MAPK1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: MAPK1 functions in intracellular signal transduction downstream of extracellular cues. Reason: Intracellular signal transduction is a supported core process for MAPK1 as the ERK2 kinase in the canonical MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0007166 cell surface receptor signaling pathway	IBA GO_REF:0000033	MODIFY	Summary: MAPK1 responds to cell-surface receptor inputs, but its core role is the downstream intracellular ERK/MAPK cascade. Reason: Cell surface receptor signaling is too broad and upstream-oriented for the MAPK1 core function; ERK/MAPK cascade terms are more specific. Proposed replacements: ERK1 and ERK2 cascade MAPK cascade Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0004672 protein kinase activity	IEA GO_REF:0000120	MODIFY	Summary: MAPK1 is a protein kinase, but this term is less specific than the supported serine/threonine MAP kinase terms. Reason: The generic protein kinase term should be replaced by protein serine/threonine kinase activity and MAP kinase activity, which capture MAPK1 specificity. Proposed replacements: protein serine/threonine kinase activity MAP kinase activity Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0004707 MAP kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: MAPK1 binds ATP as the phosphoryl donor for kinase catalysis. Reason: ATP binding is integral to the active-site chemistry of ERK2 kinase activity. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005769 early endosome	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This early endosome annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the early endosome location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005770 late endosome	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This late endosome annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the late endosome location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005794 Golgi apparatus	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This Golgi apparatus annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the Golgi apparatus location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005813 centrosome	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: This centrosome annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the centrosome location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005819 spindle	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: This spindle annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the spindle location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005901 caveola	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: This caveola annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the caveola location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005925 focal adhesion	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: This focal adhesion annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the focal adhesion location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: MAPK1 can affect transcriptional programs through downstream substrates, but broad regulation of RNA polymerase II transcription overstates the direct function. Reason: The direct MAPK1 function is kinase activity and ERK/MAPK cascade signaling; broad transcriptional regulation should not be inferred from pathway membership alone. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0007173 epidermal growth factor receptor signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0010759 positive regulation of macrophage chemotaxis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0032206 positive regulation of telomere maintenance	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Positive regulation of telomere maintenance is inferred from a high-throughput RNAi telomerase screen (PMID:21531765) plus electronic annotation. Reason: This is a high-throughput screen-derived, indirect pathway outcome rather than a direct MAPK1 function; it should not be elevated to a core ERK2 annotation without direct mechanistic evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0032872 regulation of stress-activated MAPK cascade	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This automated annotation places canonical ERK2 in a stress-activated MAPK cascade context. Reason: GO:0032872 is a stress-activated MAPK cascade term associated with JNK/p38 signaling, whereas MAPK1/ERK2 is curated here as the canonical ERK/MAPK cascade kinase. The automated inference overstates the evidence.
GO:0034198 cellular response to amino acid starvation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is an amino-acid-starvation response annotation linked to ERK signaling context. Reason: The starvation-response annotation may be retained as non-core where the source evidence supports this context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0045202 synapse	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: This synapse annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the synapse location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0051403 stress-activated MAPK cascade	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This automated annotation places canonical ERK2 in the stress-activated MAPK cascade. Reason: GO:0051403 refers to stress-activated MAPK cascade biology associated with JNK/p38 signaling, not the canonical ERK1/ERK2 cascade. The automated inference should not be retained as a valid non-core MAPK1 annotation.
GO:0051493 regulation of cytoskeleton organization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of cytoskeleton organization) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0061514 interleukin-34-mediated signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0070371 ERK1 and ERK2 cascade	IEA GO_REF:0000117	ACCEPT	Summary: MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade. Reason: ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than generic signaling process terms. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0070849 response to epidermal growth factor	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0072584 caveolin-mediated endocytosis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (caveolin-mediated endocytosis) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0090170 regulation of Golgi inheritance	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of Golgi inheritance) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0097542 ciliary tip	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This ciliary tip annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the ciliary tip location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MODIFY	Summary: MAPK1 can phosphorylate serine residues, but the serine-only term is incomplete for ERK2. Reason: ERK2 is a proline-directed serine/threonine MAP kinase; GO:0004674 and GO:0004707 better capture the supported activity than a serine-only activity term. Proposed replacements: protein serine/threonine kinase activity MAP kinase activity Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0120041 positive regulation of macrophage proliferation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:2000641 regulation of early endosome to late endosome transport	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of early endosome to late endosome transport) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0005515 protein binding	IPI PMID:10415025 Direct suppression of TCR-mediated activation of extracellul...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:10415025; ERK2 has many reported interacting partners. ERK2 partner recognition is mediated structurally by the docking groove (D-recruitment site), which binds short linear D-motifs in substrates and regulators; this is directly illustrated by ERK2 crystal structures with bound D-motif peptides (PDB 2Y9Q, 3TEI, 4FMQ) that define docking-groove binding specificity (PMID:23047924). Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support. PMID:23047924 Mitogen-activated protein kinases (MAPKs) have a docking groove that interacts with linear "docking" motifs in binding partners. PMID:23047924 Crystal structures of four complexes of MAPKs with docking peptides ... revealed that the regions located between consensus positions in the docking motifs showed conformational diversity.
GO:0005515 protein binding	IPI PMID:10601328 A novel regulatory mechanism of MAP kinases activation and n...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:10601328; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:12592337 The protein tyrosine phosphatase HePTP regulates nuclear tra...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:12592337; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:12840032 Constitutive induction of p-Erk1/2 accompanied by reduced ac...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:12840032; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:15713638 Specific inactivation and nuclear anchoring of extracellular...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:15713638; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:16038800 Conditional expression of MAP kinase phosphatase-2 protects ...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:16038800; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:16286470 Cooperation of ERK and SCFSkp2 for MKP-1 destruction provide...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:16286470; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:16288922 New insights into the catalytic activation of the MAPK phosp...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:16288922; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:17255944 A MAPK docking site is critical for downregulation of Capicu...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:17255944; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:17255949 Mxi2 promotes stimulus-independent ERK nuclear translocation...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:17255949; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:18060821 Structural insights into the enzymatic mechanism of the path...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:18060821; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:18084305 Structural basis for the catalytic mechanism of phosphothreo...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:18084305; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:18463290 Human biliverdin reductase is an ERK activator; hBVR is an E...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:18463290; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:18616943 Phosphorylation of U24 from Human Herpes Virus type 6 (HHV-6...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:18616943; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:19494114 Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhi...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:19494114; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:21826244 TRAPPC4-ERK2 interaction activates ERK1/2, modulates its nuc...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:21826244; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:21908610 Phosphorylation of the kinase interaction motif in mitogen-a...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:21908610; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:21988832; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:22521293 ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:22521293; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23241949 MEK1 inactivates Myt1 to regulate Golgi membrane fragmentati...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23241949; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23455922; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23519423 Protein-peptide complex crystallization: a case study on the...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23519423; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23560844 Metal-dependent protein phosphatase 1A functions as an extra...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23560844; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23575685 Structure of ERK2 bound to PEA-15 reveals a mechanism for ra...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23575685; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23584453 Interaction with Shc prevents aberrant Erk activation in the...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23584453; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23602568; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:25241761; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:25852190; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:26267535 ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colore...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:26267535; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:26733474 Identification of allosteric ERK2 inhibitors through in sili...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:26733474; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:27880917; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:29997244; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:31980649; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:32296183; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:32707033; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:32814053; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:33961781; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:34591642; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:35271311; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:38884001; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:40205054; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:9632734 Activation of extracellular signal-regulated kinase 2 by a n...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:9632734; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:9788880 Isolation of the human genes encoding the pyst1 and Pyst2 ph...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:9788880; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0042802 identical protein binding	IPI PMID:16627622 Direct phosphorylation and regulation of poly(ADP-ribose) po...	KEEP AS NON CORE	Summary: MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by PMID:16627622. Reason: ERK2 dimerization is a documented property relevant to its cytoplasmic retention and scaffold interactions, but it is a regulatory/structural property rather than the core catalytic MAP kinase function.
GO:0042802 identical protein binding	IPI PMID:26267534 Small Molecule Inhibition of ERK Dimerization Prevents Tumor...	KEEP AS NON CORE	Summary: MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by PMID:26267534. Reason: ERK2 dimerization is a documented property relevant to its cytoplasmic retention and scaffold interactions, but it is a regulatory/structural property rather than the core catalytic MAP kinase function.
GO:0001784 phosphotyrosine residue binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This term assigns phosphotyrosine residue binding to ERK2. Reason: ERK2 substrate and partner recognition is mediated by D-domain/KIM and DEF/FXFP docking motifs rather than by a dedicated phosphotyrosine-binding module; this automated assignment is not supported as a core ERK2 molecular function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000107	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0005739 mitochondrion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This mitochondrion annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the mitochondrion location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment. Reason: Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0008286 insulin receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This term assigns RNA polymerase II CTD heptapeptide repeat kinase activity to ERK2. Reason: ERK2 is a proline-directed Ser/Thr MAP kinase; while it phosphorylates Ser/Thr-Pro motifs, dedicated RNA Pol II CTD kinase activity is not a core supported ERK2 function and this ISS/IEA assignment overstates substrate specificity. The supported catalytic terms are MAP kinase activity and protein serine/threonine kinase activity. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0014044 Schwann cell development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0016301 kinase activity	IEA GO_REF:0000107	MODIFY	Summary: MAPK1 is a kinase, but this term is too broad for ERK2. Reason: The broad kinase activity annotation should use the more informative serine/threonine MAP kinase terms. Proposed replacements: protein serine/threonine kinase activity MAP kinase activity Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0019902 phosphatase binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: MAPK1 binds MAP kinase phosphatases such as DUSP6/MKP-3. Reason: Phosphatase binding is a supported regulatory interaction, but it is not the primary catalytic function of MAPK1. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md DUSP6/MKP-3 as cytoplasmic tether:** MKP-3/DUSP6 binds ERK2 and can dephosphorylate and tether inactive ERK2 in the cytoplasm; mutating MKP-3 NES or KIM abolishes cytoplasmic anchoring.
GO:0031143 pseudopodium	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This pseudopodium annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the pseudopodium location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0035094 response to nicotine	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (response to nicotine) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0038133 ERBB2-ERBB3 signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0042552 myelination	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0042802 identical protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by GO_REF:0000107. Reason: ERK2 dimerization is a documented property relevant to its cytoplasmic retention and scaffold interactions, but it is a regulatory/structural property rather than the core catalytic MAP kinase function.
GO:0043415 positive regulation of skeletal muscle tissue regeneration	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0048009 insulin-like growth factor receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0150078 positive regulation of neuroinflammatory response	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0004707 MAP kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0005829 cytosol	IDA PMID:22451653 Siglec-15 protein regulates formation of functional osteocla...	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment. Reason: Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0043415 positive regulation of skeletal muscle tissue regeneration	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0106310 protein serine kinase activity	ISS GO_REF:0000024	MODIFY	Summary: MAPK1 can phosphorylate serine residues, but the serine-only term is incomplete for ERK2. Reason: ERK2 is a proline-directed serine/threonine MAP kinase; GO:0004674 and GO:0004707 better capture the supported activity than a serine-only activity term. Proposed replacements: protein serine/threonine kinase activity MAP kinase activity Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:35831023 ERK2 MAP kinase regulates SUFU binding by multisite phosphor...	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0045880 positive regulation of smoothened signaling pathway	IDA PMID:35831023 ERK2 MAP kinase regulates SUFU binding by multisite phosphor...	KEEP AS NON CORE	Summary: ERK2 phosphorylation of GLI1 links MAPK1 to Smoothened/Hedgehog pathway output in this specific context. Reason: This is a supported pathway-specific downstream role from PMID:35831023, but the core MAPK1 function remains ERK2 serine/threonine MAP kinase activity in the ERK/MAPK cascade.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment. Reason: Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0004707 MAP kinase activity	TAS Reactome:R-HSA-111898	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0004707 MAP kinase activity	TAS Reactome:R-HSA-445079	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:38503280 A gut-derived hormone regulates cholesterol metabolism.	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0070371 ERK1 and ERK2 cascade	IDA PMID:15850461 The phosphorylation of CapZ-interacting protein (CapZIP) by ...	ACCEPT	Summary: MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade. Reason: ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than generic signaling process terms. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0150078 positive regulation of neuroinflammatory response	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This is a distal or cell-type-specific outcome rather than a core MAPK1 function. Reason: The available synthesis supports ERK/MAPK cascade membership as core, but warns against promoting broad developmental or disease-associated outcomes to core MAPK1 functions without direct MAPK1-specific evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0004707 MAP kinase activity	IDA PMID:38503280 A gut-derived hormone regulates cholesterol metabolism.	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0070098 chemokine-mediated signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (chemokine-mediated signaling pathway) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0000165 MAPK cascade	IDA PMID:15850461 The phosphorylation of CapZ-interacting protein (CapZIP) by ...	ACCEPT	Summary: MAPK1/ERK2 functions in the canonical MAPK cascade. Reason: MAPK cascade membership is a core biological process for ERK2, downstream of Ras-RAF-MEK signaling. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0061514 interleukin-34-mediated signaling pathway	IGI PMID:26754294 miR-28-5p-IL-34-macrophage feedback loop modulates hepatocel...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0000165 MAPK cascade	IDA PMID:24854121 Endophilin-1 regulates blood-brain barrier permeability by c...	ACCEPT	Summary: MAPK1/ERK2 functions in the canonical MAPK cascade. Reason: MAPK cascade membership is a core biological process for ERK2, downstream of Ras-RAF-MEK signaling. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:24854121 Endophilin-1 regulates blood-brain barrier permeability by c...	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0005515 protein binding	IPI PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:26942675; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0032206 positive regulation of telomere maintenance	IMP PMID:21531765 High-throughput RNAi screening reveals novel regulators of t...	MARK AS OVER ANNOTATED	Summary: Positive regulation of telomere maintenance is inferred from a high-throughput RNAi telomerase screen (PMID:21531765) plus electronic annotation. Reason: This is a high-throughput screen-derived, indirect pathway outcome rather than a direct MAPK1 function; it should not be elevated to a core ERK2 annotation without direct mechanistic evidence. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0045542 positive regulation of cholesterol biosynthetic process	IDA PMID:38503280 A gut-derived hormone regulates cholesterol metabolism.	KEEP AS NON CORE	Summary: Positive regulation of cholesterol biosynthesis is an ERK2-linked downstream metabolic outcome reported in PMID:38503280. Reason: This is a context-dependent downstream metabolic process mediated via ERK signaling rather than a core conserved MAPK1 molecular function; retained as non-core. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0005515 protein binding	IPI PMID:11489891 MKP-7, a novel mitogen-activated protein kinase phosphatase,...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:11489891; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005515 protein binding	IPI PMID:32721402 Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:32721402; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005634 nucleus	IDA PMID:32721402 Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder...	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005737 cytoplasm	IDA PMID:32721402 Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder...	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005515 protein binding	IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:32051553; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:7588608 ERF: an ETS domain protein with strong transcriptional repre...	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0010759 positive regulation of macrophage chemotaxis	IGI PMID:26754294 miR-28-5p-IL-34-macrophage feedback loop modulates hepatocel...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0120041 positive regulation of macrophage proliferation	IGI PMID:26754294 miR-28-5p-IL-34-macrophage feedback loop modulates hepatocel...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0005515 protein binding	IPI PMID:15133037 The major vault protein is a novel substrate for the tyrosin...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:15133037; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005829 cytosol	TAS Reactome:R-HSA-9652816	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005788 endoplasmic reticulum lumen	TAS Reactome:R-HSA-9636296	MARK AS OVER ANNOTATED	Summary: This is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization; secretory or granule-lumen locations are likely pathway-context over-annotations for soluble ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005829 cytosol	TAS Reactome:R-HSA-9635739	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:26996940 Regulation of Microtubule Assembly by Tau and not by Pin1.	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0005886 plasma membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This plasma membrane annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the plasma membrane location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005901 caveola	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This caveola annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the caveola location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0007611 learning or memory	NAS PMID:11404397 Beta-amyloid activates the mitogen-activated protein kinase ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0035094 response to nicotine	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (response to nicotine) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0034198 cellular response to amino acid starvation	IDA PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta...	KEEP AS NON CORE	Summary: This is an amino-acid-starvation response annotation linked to ERK signaling context. Reason: The starvation-response annotation may be retained as non-core where the source evidence supports this context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0051403 stress-activated MAPK cascade	IDA PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta...	MARK AS OVER ANNOTATED	Summary: This stress-activated MAPK cascade annotation on MAPK1/ERK2 derives from a paper focused on ASK1/JNK stress signaling, not the canonical ERK cascade. Reason: GO:0051403 (stress-activated MAPK cascade) is associated with JNK/p38 (SAPK) signaling. PMID:11096076 concerns the Gln-dependent interaction of glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1 (ASK1) and JNK/SAPK, not ERK2; assigning the stress-activated MAPK cascade to canonical ERK2 over-annotates MAPK1. Supporting Evidence: PMID:11096076 signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase (SAPK)) in Gln-deprived cells
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798751	MARK AS OVER ANNOTATED	Summary: This is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization; secretory or granule-lumen locations are likely pathway-context over-annotations for soluble ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: This is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization; secretory or granule-lumen locations are likely pathway-context over-annotations for soluble ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0035578 azurophil granule lumen	TAS Reactome:R-HSA-6798751	MARK AS OVER ANNOTATED	Summary: This is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization; secretory or granule-lumen locations are likely pathway-context over-annotations for soluble ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: This is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization; secretory or granule-lumen locations are likely pathway-context over-annotations for soluble ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005515 protein binding	IPI PMID:24735981 MFAP3L activation promotes colorectal cancer cell invasion a...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:24735981; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0006468 protein phosphorylation	IDA PMID:23184662 Phosphorylation of eukaryotic elongation factor 2 (eEF2) by ...	ACCEPT	Summary: MAPK1 directly phosphorylates protein substrates. Reason: Protein phosphorylation is the direct biochemical output of the MAPK1 kinase activity. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 directly phosphorylates defined downstream targets such as Elk-1/ETS-family and other transcription-factor substrates in vitro and in cells; docking motifs/exosites help determine substrate recognition.
GO:0005634 nucleus	HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp...	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005737 cytoplasm	HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp...	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0072686 mitotic spindle	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This mitotic spindle annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the mitotic spindle location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005515 protein binding	IPI PMID:23847209 Pseudophosphatase STYX modulates cell-fate decisions and cel...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:23847209; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-198746	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-198756	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-199959	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-203797	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3132737	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3857329	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-450325	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5674387	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5675373	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9032751	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9610166	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9632910	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9725030	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9765960	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005654 nucleoplasm	TAS Reactome:R-NUL-9009236	ACCEPT	Summary: MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of several Reactome reaction-level annotations placing ERK2 in the nucleoplasm. Reason: Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-109858	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-109862	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-109864	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-111898	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-1168459	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-2029469	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-3371531	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-418158	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-418163	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-418170	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-418176	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-418200	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-445079	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5654560	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5654562	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5654565	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5654566	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5672972	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5672973	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5672978	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5672980	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674130	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674132	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674366	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674373	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674385	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674387	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5674496	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5675194	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5675198	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5675206	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-5675376	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802910	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802911	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802912	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802914	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802918	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802919	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802921	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802922	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802925	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802926	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802932	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802933	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802934	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802935	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802942	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6802943	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6803227	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6803230	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6803233	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6803234	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6811454	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-6811472	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9610152	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9610153	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9610154	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9610156	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9610166	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9626832	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9627089	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9632910	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9635743	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9636296	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9652165	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9656209	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9656211	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9656214	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9656215	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9657599	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9657603	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9657606	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9657608	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9731111	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9732753	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9734547	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9824582	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9824977	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9825759	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-HSA-9845033	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005829 cytosol	TAS Reactome:R-NUL-9619973	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many Reactome reaction-level annotations placing ERK2 in the cytosol. Reason: Cytosolic localization is a core supported localization for ERK2, which is predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The numerous Reactome cytosol rows are group-accepted as consistent with this core localization. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0038127 ERBB signaling pathway	IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin...	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylati...	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0005515 protein binding	IPI PMID:18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylati...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:18794356; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0005634 nucleus	IDA PMID:18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylati...	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005737 cytoplasm	IDA PMID:18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylati...	ACCEPT	Summary: MAPK1/ERK2 is cytoplasmic in quiescent cells. Reason: Cytoplasmic localization is a core supported localization for ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0070849 response to epidermal growth factor	IDA PMID:18794356 Extracellular signal-regulated kinase 2 (ERK2) phosphorylati...	KEEP AS NON CORE	Summary: MAPK1 is activated in receptor and growth-factor signaling contexts, but these are stimulus-specific pathway contexts rather than the core conserved ERK2 function. Reason: Growth-factor and receptor-specific signaling annotations can be retained as non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0005515 protein binding	IPI PMID:22253824 Localization of nucleoporin Tpr to the nuclear pore complex ...	KEEP AS NON CORE	Summary: This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2 from PMID:22253824; ERK2 has many reported interacting partners. Reason: The generic protein binding term is uninformative for a multi-partner kinase like ERK2 and is retained only as a non-core interaction record. ERK partner recognition is motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate, scaffold, or phosphatase interaction is established a more informative molecular function term should be used instead of bare protein binding. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Because docking is motif-driven and structurally/biochemically dissectable, using only “protein binding” is typically uninformative and risks over-annotation. Additionally, yeast two-hybrid and peptide-based assays may capture indirect interactions or partial interfaces, so direct “binding” annotations should be limited to partners with orthogonal support.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:15850461 The phosphorylation of CapZ-interacting protein (CapZIP) by ...	ACCEPT	Summary: MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase. Reason: Serine/threonine protein kinase activity is a core molecular function of MAPK1; the more specific MAP kinase activity term should also be retained where present. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0005634 nucleus	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	ACCEPT	Summary: MAPK1/ERK2 localizes to the nucleus after stimulation. Reason: Nuclear localization is supported, but should be interpreted as stimulus-dependent rather than constitutive. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs. file:human/MAPK1/MAPK1-deep-research-falcon.md Do not infer “nuclear” localization from phospho-ERK alone. Nuclear accumulation can be partially uncoupled from TEY phosphorylation and depends on docking interactions and anchors.
GO:0005739 mitochondrion	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This mitochondrion annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the mitochondrion location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005769 early endosome	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This early endosome annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the early endosome location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005770 late endosome	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This late endosome annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the late endosome location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005794 Golgi apparatus	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This Golgi apparatus annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the Golgi apparatus location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005829 cytosol	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	ACCEPT	Summary: MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment. Reason: Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and contributes to induced gene expression programs.
GO:0005856 cytoskeleton	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This cytoskeleton annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the cytoskeleton location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005901 caveola	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This caveola annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the caveola location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0005925 focal adhesion	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This focal adhesion annotation is not a supported core MAPK1 localization in this review. Reason: Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the focal adhesion location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
GO:0032872 regulation of stress-activated MAPK cascade	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: This TAS annotation assigns regulation of the stress-activated MAPK cascade to MAPK1/ERK2, citing a general ERK compartmentalization review. Reason: GO:0032872 (regulation of stress-activated MAPK cascade) is associated with JNK/p38 (SAPK) biology rather than the canonical ERK cascade. PMID:19565474 is a review of ERK signaling across subcellular compartments and does not establish ERK2 as a regulator of the stress-activated (JNK/p38) MAPK cascade; this is an over-annotation for canonical ERK2, consistent with the corresponding IEA row. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0051493 regulation of cytoskeleton organization	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of cytoskeleton organization) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0072584 caveolin-mediated endocytosis	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (caveolin-mediated endocytosis) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0090170 regulation of Golgi inheritance	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of Golgi inheritance) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:2000641 regulation of early endosome to late endosome transport	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process (regulation of early endosome to late endosome transport) linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function, which is ERK2 MAP kinase activity in the ERK/MAPK cascade. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0010800 positive regulation of peptidyl-threonine phosphorylation	IDA PMID:16314496 Activation of TRAP/mediator subunit TRAP220/Med1 is regulate...	KEEP AS NON CORE	Summary: MAPK1 can increase phosphorylation of downstream threonine-containing protein substrates. Reason: The term is consistent with ERK2 substrate phosphorylation, but it is less central than the direct kinase activity and ERK/MAPK cascade annotations. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 directly phosphorylates defined downstream targets such as Elk-1/ETS-family and other transcription-factor substrates in vitro and in cells; docking motifs/exosites help determine substrate recognition.
GO:0070371 ERK1 and ERK2 cascade	IDA PMID:16314496 Activation of TRAP/mediator subunit TRAP220/Med1 is regulate...	ACCEPT	Summary: MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade. Reason: ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than generic signaling process terms. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0019902 phosphatase binding	IPI PMID:19494114 Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhi...	KEEP AS NON CORE	Summary: MAPK1 binds MAP kinase phosphatases such as DUSP6/MKP-3. Reason: Phosphatase binding is a supported regulatory interaction, but it is not the primary catalytic function of MAPK1. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md DUSP6/MKP-3 as cytoplasmic tether:** MKP-3/DUSP6 binds ERK2 and can dephosphorylate and tether inactive ERK2 in the cytoplasm; mutating MKP-3 NES or KIM abolishes cytoplasmic anchoring.
GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: This term assigns RNA polymerase II CTD heptapeptide repeat kinase activity to ERK2. Reason: ERK2 is a proline-directed Ser/Thr MAP kinase; while it phosphorylates Ser/Thr-Pro motifs, dedicated RNA Pol II CTD kinase activity is not a core supported ERK2 function and this ISS/IEA assignment overstates substrate specificity. The supported catalytic terms are MAP kinase activity and protein serine/threonine kinase activity. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro.
GO:0004707 MAP kinase activity	TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ...	ACCEPT	Summary: MAPK1/ERK2 has MAP kinase activity. Reason: MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the relevant phosphoryl donor in vitro. file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses.
GO:0006915 apoptotic process	TAS PMID:10958679 Hsp72-mediated suppression of c-Jun N-terminal kinase is imp...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0006935 chemotaxis	TAS PMID:10706854 Eotaxin induces degranulation and chemotaxis of eosinophils ...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.
GO:0007165 signal transduction	TAS PMID:1540184 Extracellular signal-regulated kinases in T cells: character...	MODIFY	Summary: MAPK1 participates in signal transduction, but the generic term should be replaced by more specific intracellular MAPK/ERK signaling terms. Reason: Generic signal transduction underspecifies MAPK1; intracellular signal transduction and ERK/MAPK cascade terms capture the supported biology more accurately. Proposed replacements: intracellular signal transduction ERK1 and ERK2 cascade Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK signal transduction cascade, converting extracellular cues (including growth factors/serum) into intracellular phosphorylation events and responses. file:human/MAPK1/MAPK1-deep-research-falcon.md annotate ERK2 to MAPK cascade / ERK1 and ERK2 cascade and intracellular signal transduction; optionally include response to growth factor where the evidence is directly about upstream stimuli triggering ERK activation/translocation rather than downstream phenotypes.
GO:0007268 chemical synaptic transmission	TAS PMID:10051431 Regulation of extracellular-signal regulated kinase and c-Ju...	KEEP AS NON CORE	Summary: This is a context-dependent downstream process linked to ERK signaling. Reason: The process may be retained as non-core where the source evidence supports a specific context, but it should not be treated as the core conserved MAPK1 function. Supporting Evidence: file:human/MAPK1/MAPK1-deep-research-falcon.md Many sources link ERK signaling to proliferation/differentiation and disease contexts, but these are typically emergent outcomes of the pathway rather than direct MAPK1 enzymatic functions.

GO aspect	Recommended core GO term(s)	Evidence type	Key supporting statements	Key citation IDs	Over-annotation caveat
MF	protein serine/threonine kinase activity; mitogen-activated protein kinase activity; ATP binding	direct biochemical	ERK2 is a Ser/Thr MAPK that transfers phosphate from ATP/MgATP to Ser/Thr-Pro motifs; ATP binds in the active site, with N-lobe/glycine-rich loop contributions to nucleotide binding and catalysis.	(rainey2004astructurefunctionanalysis pages 20-24, rainey2004astructurefunctionanalysis pages 24-29, waas2003physiologicalconcentrationsof pages 1-2, novak2023mutationinthe pages 1-2)	Do not infer tyrosine kinase activity, broad “catalytic activity,” or substrate-level specificity beyond supported proline-directed Ser/Thr phosphorylation.
MF	MAP kinase kinase activity toward protein substrates	direct biochemical	Catalytic efficiency rises dramatically after dual phosphorylation; purified dually phosphorylated ERK2 phosphorylates peptide/protein substrates, including Elk-1-derived peptides and ETS/Runx-related transcription factor substrates in biochemical assays.	(rainey2004astructurefunctionanalysis pages 24-29, bardwell2003dockingsiteson pages 5-6, waas2003physiologicalconcentrationsof pages 1-2)	Do not treat every phosphoproteomics hit or motif-containing protein as a direct MAPK1 substrate.
BP	ERK1 and ERK2 cascade; MAPK cascade; intracellular signal transduction; response to growth factor	review/mechanistic plus direct pathway evidence	ERK2 is a principal effector downstream of Ras-Raf-MEK; activated by extracellular stimuli including serum/growth factors and mediates canonical MAPK/ERK signaling.	(novak2023mutationinthe pages 1-2, waas2003physiologicalconcentrationsof pages 1-2, rainey2004astructurefunctionanalysis pages 20-24)	Keep pathway terms close to the conserved cascade; avoid annotating broad disease, cancer, development, or generic transcription terms from pathway membership alone.
BP	positive regulation of protein phosphorylation of direct substrates; phosphorylation of transcription factors	direct biochemical	ERK2 directly phosphorylates defined downstream targets such as Elk-1/ETS-family and other transcription-factor substrates in vitro and in cells; docking motifs/exosites help determine substrate recognition.	(bardwell2003dockingsiteson pages 5-6, waas2003physiologicalconcentrationsof pages 1-2, rainey2004astructurefunctionanalysis pages 24-29)	Direct substrate phosphorylation can support narrower process terms only when the substrate/process link is demonstrated; do not infer all downstream transcriptional programs as direct MAPK1 functions.
BP	regulation of cell proliferation/differentiation; apoptosis/senescence; cell migration	review/mechanistic, usually non-core	Literature links ERK2 signaling to proliferation, differentiation, survival/death decisions, and motility, often through many downstream effectors and context-specific scaffolds.	(novak2023mutationinthe pages 1-2, martin–vega2025erk12mapksignalingmetabolic pages 3-5, butch1996characterizationoferk1 pages 1-2)	These are often pathway outcomes, not direct MAPK1 actions; avoid making them core GO annotations unless supported by direct loss-of-function/rescue and mechanistic evidence specific to MAPK1.
CC	cytoplasm; nucleus	cell biology localization	In quiescent cells ERK is mainly cytoplasmic; after activation it accumulates in the nucleus. ERK lacks clear intrinsic NLS/NES and relies on partner-mediated trafficking.	(karlsson2006spatiotemporalregulationof pages 1-2, caunt2006seventransmembranereceptorsignalling pages 2-3, caunt2010stimulusinduceduncouplingof pages 1-2, caunt2010stimulusinduceduncouplingof pages 2-3)	Prefer cytoplasm/nucleus over highly specific compartments unless direct localization evidence exists for MAPK1 itself in that context.
CC	cytoplasm to nucleus translocation upon stimulation	cell biology localization	MEK binds inactive ERK in the cytoplasm; TEY phosphorylation and release from anchors permit nuclear accumulation. Nuclear localization depends on phosphorylation but can also require D-domain interactions beyond phosphorylation alone.	(karlsson2006spatiotemporalregulationof pages 1-2, caunt2010stimulusinduceduncouplingof pages 1-2, caunt2010stimulusinduceduncouplingof pages 2-3)	Do not annotate constitutive nuclear localization; stimulus dependence matters, and nuclear entry should not be inferred solely from ERK phosphorylation readouts.
CC	cytoplasmic anchoring complex with MEK/DUSP6-like regulators; nuclear sequestration with DUSP5-like regulators	cell biology localization; review/mechanistic	MEK NES helps anchor inactive ERK in cytoplasm; DUSP6/MKP-3 tethers inactive ERK2 in cytoplasm; DUSP5 contains an NLS and can inactivate/sequester ERK2 in the nucleus.	(karlsson2006spatiotemporalregulationof pages 2-3, karlsson2006spatiotemporalregulationof pages 1-2, caunt2010stimulusinduceduncouplingof pages 11-11)	These support localization regulation and specific complexes, not broad stable residence in every compartment or all phosphatase-binding annotations.
MF	sequence-specific protein docking / scaffold-mediated binding	direct biochemical; review/mechanistic	ERK2 recognizes D-domain/KIM and DEF/FXFP docking motifs through common-docking and exosite regions; these interactions are crucial for MEK, MKP, Elk-1 and scaffold/substrate binding.	(rainey2004astructurefunctionanalysis pages 24-29, bardwell2003dockingsiteson pages 5-6, rainey2004astructurefunctionanalysis pages 29-33)	Avoid generic “protein binding” if a more informative docking/scaffold interaction term can be used; also avoid inferring direct binding from yeast two-hybrid or peptide competition alone without orthogonal support.
BP	scaffold-mediated spatial regulation of MAPK signaling	review/mechanistic	Scaffold and anchoring proteins such as β-arrestin, Naf1, paxillin/GIT1/IQGAP1/KSR1 shape where ERK signals and which outputs are engaged.	(rainey2004astructurefunctionanalysis pages 29-33, martin–vega2025erk12mapksignalingmetabolic pages 3-5)	Scaffold-dependent localization does not automatically justify annotating MAPK1 to every scaffold’s biological process or cellular site.
BP	nuclear transcription factor phosphorylation leading to gene expression changes	direct substrate plus mechanistic	ERK nuclear translocation enables phosphorylation of nuclear substrates such as Elk-1 and related transcription factors that contribute to induced gene expression.	(caunt2006seventransmembranereceptorsignalling pages 2-3, bardwell2003dockingsiteson pages 5-6, butch1996characterizationoferk1 pages 1-2)	Annotate the direct phosphorylation event or upstream signaling role rather than broad “regulation of transcription” unless MAPK1-specific causality is directly established.
General guidance	core set should emphasize kinase activity, MEK-dependent activation, MAPK/ERK cascade role, intracellular signaling, and cytoplasm/nucleus shuttling	synthesis	Best-supported core annotations are those nearest to direct chemistry, canonical pathway position, and experimentally observed localization dynamics.	(novak2023mutationinthe pages 1-2, karlsson2006spatiotemporalregulationof pages 1-2, caunt2010stimulusinduceduncouplingof pages 1-2)	Be cautious with inhibitor/overexpression phenotypes, cancer-context reviews, and high-throughput substrate claims; distinguish direct MAPK1 action from downstream pathway outcomes.

📄 View Raw YAML

id: P28482
gene_symbol: MAPK1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MAPK1 (ERK2) is an ATP-dependent, proline-directed serine/threonine MAP kinase
  in the canonical Ras-RAF-MEK-ERK cascade. It is activated by MEK1/2 dual
  phosphorylation, phosphorylates cytosolic and nuclear substrates, and shuttles
  between cytoplasmic/cytosolic and nuclear compartments after stimulation.
  Distal proliferation, differentiation, apoptosis, migration, transcriptional,
  and disease phenotypes are context-dependent ERK pathway outputs rather than
  the core MAPK1 molecular function.
alternative_products:
- name: '1'
  id: P28482-1
- name: '2'
  id: P28482-2
  sequence_note: VSP_047815
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      MAPK1 functions in intracellular signal transduction downstream of extracellular
      cues.
    action: ACCEPT
    reason: >-
      Intracellular signal transduction is a supported core process for MAPK1 as the
      ERK2 kinase in the canonical MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      MAPK1 responds to cell-surface receptor inputs, but its core role is the
      downstream intracellular ERK/MAPK cascade.
    action: MODIFY
    reason: >-
      Cell surface receptor signaling is too broad and upstream-oriented for the MAPK1
      core function; ERK/MAPK cascade terms are more specific.
    proposed_replacement_terms:
    - id: GO:0070371
      label: ERK1 and ERK2 cascade
    - id: GO:0000165
      label: MAPK cascade
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      MAPK1 is a protein kinase, but this term is less specific than the supported
      serine/threonine MAP kinase terms.
    action: MODIFY
    reason: >-
      The generic protein kinase term should be replaced by protein serine/threonine
      kinase activity and MAP kinase activity, which capture MAPK1 specificity.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    - id: GO:0004707
      label: MAP kinase activity
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      MAPK1 binds ATP as the phosphoryl donor for kinase catalysis.
    action: ACCEPT
    reason: >-
      ATP binding is integral to the active-site chemistry of ERK2 kinase activity.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This early endosome annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the early endosome location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This late endosome annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the late endosome location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This Golgi apparatus annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the Golgi apparatus location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      This centrosome annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the centrosome location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      This spindle annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the spindle location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005901
    label: caveola
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      This caveola annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the caveola location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      This focal adhesion annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the focal adhesion location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: >-
      MAPK1 can affect transcriptional programs through downstream substrates, but broad
      regulation of RNA polymerase II transcription overstates the direct function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The direct MAPK1 function is kinase activity and ERK/MAPK cascade signaling; broad
      transcriptional regulation should not be inferred from pathway membership alone.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0010759
    label: positive regulation of macrophage chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0032206
    label: positive regulation of telomere maintenance
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Positive regulation of telomere maintenance is inferred from a high-throughput RNAi
      telomerase screen (PMID:21531765) plus electronic annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a high-throughput screen-derived, indirect pathway outcome rather than a direct
      MAPK1 function; it should not be elevated to a core ERK2 annotation without direct
      mechanistic evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0032872
    label: regulation of stress-activated MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This automated annotation places canonical ERK2 in a stress-activated
      MAPK cascade context.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0032872 is a stress-activated MAPK cascade term associated with
      JNK/p38 signaling, whereas MAPK1/ERK2 is curated here as the canonical
      ERK/MAPK cascade kinase. The automated inference overstates the evidence.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is an amino-acid-starvation response annotation linked to ERK signaling
      context.
    action: KEEP_AS_NON_CORE
    reason: >-
      The starvation-response annotation may be retained as non-core where the source
      evidence supports this context, but it should not be treated as the core conserved
      MAPK1 function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: >-
      This synapse annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the synapse location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0051403
    label: stress-activated MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This automated annotation places canonical ERK2 in the stress-activated MAPK
      cascade.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0051403 refers to stress-activated MAPK cascade biology associated with JNK/p38
      signaling, not the canonical ERK1/ERK2 cascade. The automated inference should not
      be retained as a valid non-core MAPK1 annotation.
- term:
    id: GO:0051493
    label: regulation of cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of cytoskeleton organization)
      linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0061514
    label: interleukin-34-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade.
    action: ACCEPT
    reason: >-
      ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than
      generic signaling process terms.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0070849
    label: response to epidermal growth factor
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0072584
    label: caveolin-mediated endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process (caveolin-mediated endocytosis) linked to
      ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0090170
    label: regulation of Golgi inheritance
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of Golgi inheritance) linked
      to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0097542
    label: ciliary tip
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This ciliary tip annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the ciliary tip location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: >-
      MAPK1 can phosphorylate serine residues, but the serine-only term is incomplete
      for ERK2.
    action: MODIFY
    reason: >-
      ERK2 is a proline-directed serine/threonine MAP kinase; GO:0004674 and GO:0004707
      better capture the supported activity than a serine-only activity term.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    - id: GO:0004707
      label: MAP kinase activity
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0120041
    label: positive regulation of macrophage proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:2000641
    label: regulation of early endosome to late endosome transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of early endosome to late
      endosome transport) linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10415025
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:10415025; ERK2 has many reported interacting partners. ERK2 partner
      recognition is mediated structurally by the docking groove (D-recruitment site),
      which binds short linear D-motifs in substrates and regulators; this is directly
      illustrated by ERK2 crystal structures with bound D-motif peptides (PDB 2Y9Q, 3TEI,
      4FMQ) that define docking-groove binding specificity (PMID:23047924).
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
    - reference_id: PMID:23047924
      supporting_text: >-
        Mitogen-activated protein kinases (MAPKs) have a docking groove that interacts
        with linear "docking" motifs in binding partners.
    - reference_id: PMID:23047924
      supporting_text: >-
        Crystal structures of four complexes of MAPKs with docking peptides ... revealed
        that the regions located between consensus positions in the docking motifs showed
        conformational diversity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10601328
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:10601328; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12592337
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:12592337; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12840032
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:12840032; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15713638
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:15713638; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16038800
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:16038800; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16286470
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:16286470; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16288922
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:16288922; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17255944
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:17255944; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17255949
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:17255949; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18060821
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:18060821; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18084305
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:18084305; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18463290
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:18463290; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18616943
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:18616943; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19494114
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:19494114; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21826244
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:21826244; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21908610
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:21908610; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:21988832; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22521293
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:22521293; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23241949
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23241949; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23455922
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23455922; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23519423
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23519423; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23560844
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23560844; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23575685
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23575685; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23584453
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23584453; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23602568
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23602568; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:25241761; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:25852190; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26267535
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:26267535; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26733474
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:26733474; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27880917
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:27880917; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997244
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:29997244; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:31980649; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:32296183; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:32707033; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:32814053; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:33961781; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591642
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:34591642; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:35271311; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38884001
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:38884001; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:40205054; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9632734
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:9632734; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9788880
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:9788880; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:16627622
  review:
    summary: >-
      MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by
      PMID:16627622.
    action: KEEP_AS_NON_CORE
    reason: >-
      ERK2 dimerization is a documented property relevant to its cytoplasmic retention and
      scaffold interactions, but it is a regulatory/structural property rather than the core
      catalytic MAP kinase function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:26267534
  review:
    summary: >-
      MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by
      PMID:26267534.
    action: KEEP_AS_NON_CORE
    reason: >-
      ERK2 dimerization is a documented property relevant to its cytoplasmic retention and
      scaffold interactions, but it is a regulatory/structural property rather than the core
      catalytic MAP kinase function.
- term:
    id: GO:0001784
    label: phosphotyrosine residue binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This term assigns phosphotyrosine residue binding to ERK2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      ERK2 substrate and partner recognition is mediated by D-domain/KIM and DEF/FXFP docking
      motifs rather than by a dedicated phosphotyrosine-binding module; this automated
      assignment is not supported as a core ERK2 molecular function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This mitochondrion annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the mitochondrion location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment.
    action: ACCEPT
    reason: >-
      Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in
      quiescent cells before stimulus-dependent nuclear accumulation.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0008353
    label: RNA polymerase II CTD heptapeptide repeat kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This term assigns RNA polymerase II CTD heptapeptide repeat kinase activity to ERK2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      ERK2 is a proline-directed Ser/Thr MAP kinase; while it phosphorylates Ser/Thr-Pro
      motifs, dedicated RNA Pol II CTD kinase activity is not a core supported ERK2 function
      and this ISS/IEA assignment overstates substrate specificity. The supported catalytic
      terms are MAP kinase activity and protein serine/threonine kinase activity.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like
        other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the
        relevant phosphoryl donor in vitro.
- term:
    id: GO:0014044
    label: Schwann cell development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1 is a kinase, but this term is too broad for ERK2.
    action: MODIFY
    reason: >-
      The broad kinase activity annotation should use the more informative
      serine/threonine MAP kinase terms.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    - id: GO:0004707
      label: MAP kinase activity
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0019902
    label: phosphatase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      MAPK1 binds MAP kinase phosphatases such as DUSP6/MKP-3.
    action: KEEP_AS_NON_CORE
    reason: >-
      Phosphatase binding is a supported regulatory interaction, but it is not the
      primary catalytic function of MAPK1.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        DUSP6/MKP-3 as cytoplasmic tether:** MKP-3/DUSP6 binds ERK2 and can
        dephosphorylate and tether inactive ERK2 in the cytoplasm; mutating MKP-3 NES or
        KIM abolishes cytoplasmic anchoring.
- term:
    id: GO:0031143
    label: pseudopodium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This pseudopodium annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the pseudopodium location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0035094
    label: response to nicotine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This is a context-dependent downstream process (response to nicotine) linked to ERK
      signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0038133
    label: ERBB2-ERBB3 signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0042552
    label: myelination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1/ERK2 self-associates (homodimerizes); identical protein binding is supported by
      GO_REF:0000107.
    action: KEEP_AS_NON_CORE
    reason: >-
      ERK2 dimerization is a documented property relevant to its cytoplasmic retention and
      scaffold interactions, but it is a regulatory/structural property rather than the core
      catalytic MAP kinase function.
- term:
    id: GO:0043415
    label: positive regulation of skeletal muscle tissue regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0150078
    label: positive regulation of neuroinflammatory response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:22451653
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment.
    action: ACCEPT
    reason: >-
      Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in
      quiescent cells before stimulus-dependent nuclear accumulation.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0043415
    label: positive regulation of skeletal muscle tissue regeneration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      MAPK1 can phosphorylate serine residues, but the serine-only term is incomplete
      for ERK2.
    action: MODIFY
    reason: >-
      ERK2 is a proline-directed serine/threonine MAP kinase; GO:0004674 and GO:0004707
      better capture the supported activity than a serine-only activity term.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    - id: GO:0004707
      label: MAP kinase activity
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:35831023
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0045880
    label: positive regulation of smoothened signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:35831023
  review:
    summary: >-
      ERK2 phosphorylation of GLI1 links MAPK1 to Smoothened/Hedgehog pathway
      output in this specific context.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a supported pathway-specific downstream role from PMID:35831023,
      but the core MAPK1 function remains ERK2 serine/threonine MAP kinase
      activity in the ERK/MAPK cascade.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent
      nuclear accumulation of ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment.
    action: ACCEPT
    reason: >-
      Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in
      quiescent cells before stimulus-dependent nuclear accumulation.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-111898
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-445079
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:38503280
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: IDA
  original_reference_id: PMID:15850461
  review:
    summary: >-
      MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade.
    action: ACCEPT
    reason: >-
      ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than
      generic signaling process terms.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0150078
    label: positive regulation of neuroinflammatory response
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This is a distal or cell-type-specific outcome rather than a core MAPK1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The available synthesis supports ERK/MAPK cascade membership as core, but warns
      against promoting broad developmental or disease-associated outcomes to core MAPK1
      functions without direct MAPK1-specific evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: IDA
  original_reference_id: PMID:38503280
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0070098
    label: chemokine-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This is a context-dependent downstream process (chemokine-mediated signaling pathway)
      linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:15850461
  review:
    summary: >-
      MAPK1/ERK2 functions in the canonical MAPK cascade.
    action: ACCEPT
    reason: >-
      MAPK cascade membership is a core biological process for ERK2, downstream of
      Ras-RAF-MEK signaling.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0061514
    label: interleukin-34-mediated signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:26754294
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:24854121
  review:
    summary: >-
      MAPK1/ERK2 functions in the canonical MAPK cascade.
    action: ACCEPT
    reason: >-
      MAPK cascade membership is a core biological process for ERK2, downstream of
      Ras-RAF-MEK signaling.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:24854121
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26942675
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:26942675; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0032206
    label: positive regulation of telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:21531765
  review:
    summary: >-
      Positive regulation of telomere maintenance is inferred from a high-throughput RNAi
      telomerase screen (PMID:21531765) plus electronic annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a high-throughput screen-derived, indirect pathway outcome rather than a direct
      MAPK1 function; it should not be elevated to a core ERK2 annotation without direct
      mechanistic evidence.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0045542
    label: positive regulation of cholesterol biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:38503280
  review:
    summary: >-
      Positive regulation of cholesterol biosynthesis is an ERK2-linked downstream metabolic
      outcome reported in PMID:38503280.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a context-dependent downstream metabolic process mediated via ERK signaling
      rather than a core conserved MAPK1 molecular function; retained as non-core.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11489891
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:11489891; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32721402
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:32721402; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:32721402
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:32721402
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32051553
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:32051553; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:7588608
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0010759
    label: positive regulation of macrophage chemotaxis
  evidence_type: IGI
  original_reference_id: PMID:26754294
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0120041
    label: positive regulation of macrophage proliferation
  evidence_type: IGI
  original_reference_id: PMID:26754294
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15133037
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:15133037; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9652816
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9636296
  review:
    summary: >-
      This is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization; secretory or granule-lumen locations are likely pathway-context
      over-annotations for soluble ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct
        localization evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9635739
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:26996940
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This plasma membrane annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the plasma membrane location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005901
    label: caveola
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This caveola annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the caveola location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: NAS
  original_reference_id: PMID:11404397
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0035094
    label: response to nicotine
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This is a context-dependent downstream process (response to nicotine) linked to ERK
      signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: IDA
  original_reference_id: PMID:11096076
  review:
    summary: >-
      This is an amino-acid-starvation response annotation linked to ERK signaling
      context.
    action: KEEP_AS_NON_CORE
    reason: >-
      The starvation-response annotation may be retained as non-core where the source
      evidence supports this context, but it should not be treated as the core conserved
      MAPK1 function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0051403
    label: stress-activated MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:11096076
  review:
    summary: >-
      This stress-activated MAPK cascade annotation on MAPK1/ERK2 derives from a paper
      focused on ASK1/JNK stress signaling, not the canonical ERK cascade.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0051403 (stress-activated MAPK cascade) is associated with JNK/p38 (SAPK)
      signaling. PMID:11096076 concerns the Gln-dependent interaction of glutaminyl-tRNA
      synthetase with apoptosis signal-regulating kinase 1 (ASK1) and JNK/SAPK, not
      ERK2; assigning the stress-activated MAPK cascade to canonical ERK2 over-annotates
      MAPK1.
    supported_by:
    - reference_id: PMID:11096076
      supporting_text: >-
        signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known
        as stress-activated protein kinase (SAPK)) in Gln-deprived cells
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798751
  review:
    summary: >-
      This is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization; secretory or granule-lumen locations are likely pathway-context
      over-annotations for soluble ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct
        localization evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  review:
    summary: >-
      This is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization; secretory or granule-lumen locations are likely pathway-context
      over-annotations for soluble ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct
        localization evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0035578
    label: azurophil granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798751
  review:
    summary: >-
      This is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization; secretory or granule-lumen locations are likely pathway-context
      over-annotations for soluble ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct
        localization evidence exists for MAPK1 itself in that context.
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  review:
    summary: >-
      This is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization; secretory or granule-lumen locations are likely pathway-context
      over-annotations for soluble ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct
        localization evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24735981
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:24735981; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:23184662
  review:
    summary: >-
      MAPK1 directly phosphorylates protein substrates.
    action: ACCEPT
    reason: >-
      Protein phosphorylation is the direct biochemical output of the MAPK1 kinase
      activity.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 directly phosphorylates defined downstream targets such as Elk-1/ETS-family
        and other transcription-factor substrates in vitro and in cells; docking
        motifs/exosites help determine substrate recognition.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:16791210
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:16791210
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0072686
    label: mitotic spindle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This mitotic spindle annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the mitotic spindle location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23847209
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:23847209; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-198746
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-198756
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-199959
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-203797
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3132737
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3857329
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-450325
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674387
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675373
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9032751
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610166
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9632910
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9725030
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9765960
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9009236
  review:
    summary: >-
      MAPK1/ERK2 can accumulate in the nuclear compartment after stimulation; this is one of
      several Reactome reaction-level annotations placing ERK2 in the nucleoplasm.
    action: ACCEPT
    reason: >-
      Nucleoplasmic localization is compatible with the supported stimulus-dependent nuclear
      accumulation of ERK2. The repeated Reactome nucleoplasm rows are group-accepted as
      consistent with this core localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-109858
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-109862
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-109864
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-111898
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1168459
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2029469
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371531
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-418158
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-418163
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-418170
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-418176
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-418200
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-445079
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654560
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654562
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654565
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654566
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672972
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672973
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672978
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672980
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674130
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674132
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674366
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674373
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674385
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674387
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674496
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675194
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675198
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675206
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675376
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802910
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802911
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802912
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802914
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802918
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802919
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802921
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802922
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802925
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802926
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802932
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802933
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802934
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802935
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802942
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802943
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803227
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803230
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803233
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803234
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6811454
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6811472
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610152
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610153
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610154
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610156
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9610166
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9626832
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9627089
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9632910
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9635743
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9636296
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9652165
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656209
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656211
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656214
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656215
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657599
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657603
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657606
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657608
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9731111
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9732753
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9734547
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824582
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824977
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9825759
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9845033
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9619973
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment; this is one of many
      Reactome reaction-level annotations placing ERK2 in the cytosol.
    action: ACCEPT
    reason: >-
      Cytosolic localization is a core supported localization for ERK2, which is predominantly
      cytoplasmic in quiescent cells before stimulus-dependent nuclear accumulation. The
      numerous Reactome cytosol rows are group-accepted as consistent with this core
      localization.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the nucleus after
        activation by certain stimuli; nuclear ERK phosphorylates nuclear targets and
        contributes to induced gene expression programs.
- term:
    id: GO:0038127
    label: ERBB signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15133037
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:18794356
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18794356
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:18794356; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18794356
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18794356
  review:
    summary: >-
      MAPK1/ERK2 is cytoplasmic in quiescent cells.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is a core supported localization for ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0070849
    label: response to epidermal growth factor
  evidence_type: IDA
  original_reference_id: PMID:18794356
  review:
    summary: >-
      MAPK1 is activated in receptor and growth-factor signaling contexts, but these are
      stimulus-specific pathway contexts rather than the core conserved ERK2 function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Growth-factor and receptor-specific signaling annotations can be retained as
      non-core contexts; the core MAPK1 process is the intracellular ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22253824
  review:
    summary: >-
      This is a generic protein-binding (GO:0005515) interaction annotation for MAPK1/ERK2
      from PMID:22253824; ERK2 has many reported interacting partners.
    action: KEEP_AS_NON_CORE
    reason: >-
      The generic protein binding term is uninformative for a multi-partner kinase like ERK2
      and is retained only as a non-core interaction record. ERK partner recognition is
      motif/exosite-driven (KIM/D-domain, DEF/FXFP) and where a specific docking, substrate,
      scaffold, or phosphatase interaction is established a more informative molecular
      function term should be used instead of bare protein binding.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Because docking is motif-driven and structurally/biochemically dissectable, using only
        “protein binding” is typically uninformative and risks over-annotation. Additionally,
        yeast two-hybrid and peptide-based assays may capture indirect interactions or partial
        interfaces, so direct “binding” annotations should be limited to partners with
        orthogonal support.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15850461
  review:
    summary: >-
      MAPK1/ERK2 is an ATP-dependent protein serine/threonine kinase.
    action: ACCEPT
    reason: >-
      Serine/threonine protein kinase activity is a core molecular function of MAPK1;
      the more specific MAP kinase activity term should also be retained where present.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      MAPK1/ERK2 localizes to the nucleus after stimulation.
    action: ACCEPT
    reason: >-
      Nuclear localization is supported, but should be interpreted as stimulus-dependent
      rather than constitutive.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        **Do not infer “nuclear” localization from phospho-ERK alone.** Nuclear
        accumulation can be partially uncoupled from TEY phosphorylation and depends on
        docking interactions and anchors.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This mitochondrion annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the mitochondrion location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This early endosome annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the early endosome location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This late endosome annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the late endosome location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This Golgi apparatus annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the Golgi apparatus location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      MAPK1/ERK2 is present in the cytosolic/cytoplasmic compartment.
    action: ACCEPT
    reason: >-
      Cytosolic localization is consistent with ERK2 being predominantly cytoplasmic in
      quiescent cells before stimulus-dependent nuclear accumulation.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK is predominantly cytoplasmic in quiescent cells and accumulates in the
        nucleus after activation by certain stimuli; nuclear ERK phosphorylates nuclear
        targets and contributes to induced gene expression programs.
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This cytoskeleton annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the cytoskeleton location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005901
    label: caveola
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This caveola annotation is not a supported core MAPK1 localization in this review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the caveola location is a context-/pathway-specific or high-
      throughput-derived assignment that should not be promoted to a core ERK2 localization
      without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This focal adhesion annotation is not a supported core MAPK1 localization in this
      review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear
      localization as core; the focal adhesion location is a context-/pathway-specific or
      high-throughput-derived assignment that should not be promoted to a core ERK2
      localization without direct MAPK1-specific evidence in that compartment.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Prefer cytoplasm/nucleus over highly specific compartments unless direct localization
        evidence exists for MAPK1 itself in that context.
- term:
    id: GO:0032872
    label: regulation of stress-activated MAPK cascade
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This TAS annotation assigns regulation of the stress-activated MAPK cascade to
      MAPK1/ERK2, citing a general ERK compartmentalization review.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0032872 (regulation of stress-activated MAPK cascade) is associated with JNK/p38
      (SAPK) biology rather than the canonical ERK cascade. PMID:19565474 is a review of
      ERK signaling across subcellular compartments and does not establish ERK2 as a
      regulator of the stress-activated (JNK/p38) MAPK cascade; this is an over-annotation
      for canonical ERK2, consistent with the corresponding IEA row.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0051493
    label: regulation of cytoskeleton organization
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of cytoskeleton organization)
      linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0072584
    label: caveolin-mediated endocytosis
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This is a context-dependent downstream process (caveolin-mediated endocytosis) linked to
      ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0090170
    label: regulation of Golgi inheritance
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of Golgi inheritance) linked
      to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:2000641
    label: regulation of early endosome to late endosome transport
  evidence_type: TAS
  original_reference_id: PMID:19565474
  review:
    summary: >-
      This is a context-dependent downstream process (regulation of early endosome to late
      endosome transport) linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a specific
      context, but it should not be treated as the core conserved MAPK1 function, which is
      ERK2 MAP kinase activity in the ERK/MAPK cascade.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease contexts,
        but these are typically emergent outcomes of the pathway rather than direct MAPK1
        enzymatic functions.
- term:
    id: GO:0010800
    label: positive regulation of peptidyl-threonine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:16314496
  review:
    summary: >-
      MAPK1 can increase phosphorylation of downstream threonine-containing protein
      substrates.
    action: KEEP_AS_NON_CORE
    reason: >-
      The term is consistent with ERK2 substrate phosphorylation, but it is less central
      than the direct kinase activity and ERK/MAPK cascade annotations.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 directly phosphorylates defined downstream targets such as Elk-1/ETS-family
        and other transcription-factor substrates in vitro and in cells; docking
        motifs/exosites help determine substrate recognition.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: IDA
  original_reference_id: PMID:16314496
  review:
    summary: >-
      MAPK1/ERK2 is a central component of the ERK1 and ERK2 cascade.
    action: ACCEPT
    reason: >-
      ERK1 and ERK2 cascade is a core pathway term for MAPK1 and is more specific than
      generic signaling process terms.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0019902
    label: phosphatase binding
  evidence_type: IPI
  original_reference_id: PMID:19494114
  review:
    summary: >-
      MAPK1 binds MAP kinase phosphatases such as DUSP6/MKP-3.
    action: KEEP_AS_NON_CORE
    reason: >-
      Phosphatase binding is a supported regulatory interaction, but it is not the
      primary catalytic function of MAPK1.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        DUSP6/MKP-3 as cytoplasmic tether:** MKP-3/DUSP6 binds ERK2 and can
        dephosphorylate and tether inactive ERK2 in the cytoplasm; mutating MKP-3 NES or
        KIM abolishes cytoplasmic anchoring.
- term:
    id: GO:0008353
    label: RNA polymerase II CTD heptapeptide repeat kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      This term assigns RNA polymerase II CTD heptapeptide repeat kinase activity to ERK2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      ERK2 is a proline-directed Ser/Thr MAP kinase; while it phosphorylates Ser/Thr-Pro
      motifs, dedicated RNA Pol II CTD kinase activity is not a core supported ERK2 function
      and this ISS/IEA assignment overstates substrate specificity. The supported catalytic
      terms are MAP kinase activity and protein serine/threonine kinase activity.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro motifs; like
        other protein kinases it binds ATP in an active-site cleft, with MgATP2− serving as the
        relevant phosphoryl donor in vitro.
- term:
    id: GO:0004707
    label: MAP kinase activity
  evidence_type: TAS
  original_reference_id: PMID:10706854
  review:
    summary: >-
      MAPK1/ERK2 has MAP kinase activity.
    action: ACCEPT
    reason: >-
      MAP kinase activity is the most specific core catalytic function for MAPK1/ERK2.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
        motifs; like other protein kinases it binds ATP in an active-site cleft, with
        MgATP2− serving as the relevant phosphoryl donor in vitro.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: TAS
  original_reference_id: PMID:10958679
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: TAS
  original_reference_id: PMID:10706854
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:1540184
  review:
    summary: >-
      MAPK1 participates in signal transduction, but the generic term should be replaced
      by more specific intracellular MAPK/ERK signaling terms.
    action: MODIFY
    reason: >-
      Generic signal transduction underspecifies MAPK1; intracellular signal
      transduction and ERK/MAPK cascade terms capture the supported biology more
      accurately.
    proposed_replacement_terms:
    - id: GO:0035556
      label: intracellular signal transduction
    - id: GO:0070371
      label: ERK1 and ERK2 cascade
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
        signal transduction cascade, converting extracellular cues (including growth
        factors/serum) into intracellular phosphorylation events and responses.
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        annotate ERK2 to **MAPK cascade / ERK1 and ERK2 cascade** and **intracellular
        signal transduction**; optionally include **response to growth factor** where
        the evidence is directly about upstream stimuli triggering ERK
        activation/translocation rather than downstream phenotypes.
- term:
    id: GO:0007268
    label: chemical synaptic transmission
  evidence_type: TAS
  original_reference_id: PMID:10051431
  review:
    summary: >-
      This is a context-dependent downstream process linked to ERK signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process may be retained as non-core where the source evidence supports a
      specific context, but it should not be treated as the core conserved MAPK1
      function.
    supported_by:
    - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
      supporting_text: >-
        Many sources link ERK signaling to proliferation/differentiation and disease
        contexts, but these are typically emergent outcomes of the pathway rather than
        direct MAPK1 enzymatic functions.
references:
- id: GO_REF:0000002
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000024
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000033
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000044
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000052
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000107
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000108
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000116
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000117
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000120
  title: 'TODO: Fetch title'
  findings: []
- id: PMID:10051431
  title: Regulation of extracellular-signal regulated kinase and c-Jun N-terminal kinase by G-protein-linked muscarinic acetylcholine
    receptors.
  findings: []
- id: PMID:10415025
  title: Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine
    phosphatase, a tyrosine-specific phosphatase.
  findings: []
- id: PMID:10601328
  title: A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine
    phosphatase.
  findings: []
- id: PMID:10706854
  title: Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated
    protein kinases.
  findings: []
- id: PMID:10958679
  title: Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in development of tolerance to caspase-independent
    cell death.
  findings: []
- id: PMID:11096076
  title: Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating
    kinase 1.
  findings: []
- id: PMID:11404397
  title: 'Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer''s disease.'
  findings: []
- id: PMID:11489891
  title: MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein.
  findings: []
- id: PMID:12592337
  title: The protein tyrosine phosphatase HePTP regulates nuclear translocation of ERK2 and can modulate megakaryocytic differentiation
    of K562 cells.
  findings: []
- id: PMID:12840032
  title: Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due
    to reactive oxygen species during cellular senescence.
  findings: []
- id: PMID:15133037
  title: The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal
    growth factor signaling.
  findings: []
- id: PMID:1540184
  title: 'Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs.'
  findings: []
- id: PMID:15713638
  title: Specific inactivation and nuclear anchoring of extracellular signal-regulated kinase 2 by the inducible dual-specificity
    protein phosphatase DUSP5.
  findings: []
- id: PMID:15850461
  title: The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation
    from CapZ.
  findings: []
- id: PMID:16038800
  title: Conditional expression of MAP kinase phosphatase-2 protects against genotoxic stress-induced apoptosis by binding
    and selective dephosphorylation of nuclear activated c-jun N-terminal kinase.
  findings: []
- id: PMID:16286470
  title: Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling.
  findings: []
- id: PMID:16288922
  title: New insights into the catalytic activation of the MAPK phosphatase PAC-1 induced by its substrate MAPK ERK2 binding.
  findings: []
- id: PMID:16314496
  title: Activation of TRAP/mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation.
  findings: []
- id: PMID:16627622
  title: Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by extracellular signal-regulated kinases
    1/2.
  findings: []
- id: PMID:16791210
  title: Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins.
  findings: []
- id: PMID:17255944
  title: A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling.
  findings: []
- id: PMID:17255949
  title: Mxi2 promotes stimulus-independent ERK nuclear translocation.
  findings: []
- id: PMID:18060821
  title: Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase.
  findings: []
- id: PMID:18084305
  title: Structural basis for the catalytic mechanism of phosphothreonine lyase.
  findings: []
- id: PMID:18463290
  title: Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling.
  findings: []
- id: PMID:18616943
  title: Phosphorylation of U24 from Human Herpes Virus type 6 (HHV-6) and its potential role in mimicking myelin basic protein
    (MBP) in multiple sclerosis.
  findings: []
- id: PMID:18794356
  title: Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex
    protein Tpr cooperatively regulate ERK2-Tpr interaction.
  findings: []
- id: PMID:19494114
  title: Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2
    kinases.
  findings: []
- id: PMID:19565474
  title: The ERK signaling cascade--views from different subcellular compartments.
  findings: []
- id: PMID:21531765
  title: High-throughput RNAi screening reveals novel regulators of telomerase.
  findings: []
- id: PMID:21826244
  title: TRAPPC4-ERK2 interaction activates ERK1/2, modulates its nuclear localization and regulates proliferation and apoptosis
    of colorectal cancer cells.
  findings: []
- id: PMID:21908610
  title: Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates
    cross-talk between protein kinase A and MAP kinase signaling pathways.
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
- id: PMID:22253824
  title: Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export
    of unspliced RNA.
  findings: []
- id: PMID:22451653
  title: Siglec-15 protein regulates formation of functional osteoclasts in concert with DNAX-activating protein of 12 kDa
    (DAP12).
  findings: []
- id: PMID:22521293
  title: ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant
    proximal tubule cells.
  findings: []
- id: PMID:23047924
  title: Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Comparative crystallographic study (ERK2 structures PDB 2Y9Q/3TEI/4FMQ with
      bound D-motif peptides) defining the structural basis of MAPK docking-groove specificity
      for short linear D-motifs.
- id: PMID:23184662
  title: Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition
    by eEF2 kinase.
  findings: []
- id: PMID:23241949
  title: MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells.
  findings: []
- id: PMID:23455922
  title: Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS.
  findings: []
- id: PMID:23519423
  title: 'Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase.'
  findings: []
- id: PMID:23560844
  title: Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase.
  findings: []
- id: PMID:23575685
  title: Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK.
  findings: []
- id: PMID:23584453
  title: Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli.
  findings: []
- id: PMID:23602568
  title: The protein interaction landscape of the human CMGC kinase group.
  findings: []
- id: PMID:23847209
  title: Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2.
  findings: []
- id: PMID:24735981
  title: MFAP3L activation promotes colorectal cancer cell invasion and metastasis.
  findings: []
- id: PMID:24854121
  title: Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2
    pathway.
  findings: []
- id: PMID:25241761
  title: Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a
    pathway network.
  findings: []
- id: PMID:25852190
  title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination
    therapy.
  findings: []
- id: PMID:26267534
  title: Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.
  findings: []
- id: PMID:26267535
  title: ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development.
  findings: []
- id: PMID:26733474
  title: Identification of allosteric ERK2 inhibitors through in silico biased screening and competitive binding assay.
  findings: []
- id: PMID:26754294
  title: miR-28-5p-IL-34-macrophage feedback loop modulates hepatocellular carcinoma metastasis.
  findings: []
- id: PMID:26942675
  title: Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis.
  findings: []
- id: PMID:26996940
  title: Regulation of Microtubule Assembly by Tau and not by Pin1.
  findings: []
- id: PMID:27880917
  title: Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators.
  findings: []
- id: PMID:29997244
  title: 'LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein
    interactions in mammalian cells.'
  findings: []
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
  findings: []
- id: PMID:32051553
  title: The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma epigenetically.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
  findings: []
- id: PMID:32721402
  title: Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation
    in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34591642
  title: A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:35831023
  title: ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1.
  findings: []
- id: PMID:38503280
  title: A gut-derived hormone regulates cholesterol metabolism.
  findings: []
- id: PMID:38884001
  title: Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:7588608
  title: 'ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis
    and is regulated by phosphorylation during cell cycle and mitogenic stimulation.'
  findings: []
- id: PMID:9632734
  title: Activation of extracellular signal-regulated kinase 2 by a novel Abl-binding protein, ST5.
  findings: []
- id: PMID:9788880
  title: 'Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic
    dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases.'
  findings: []
- id: Reactome:R-HSA-109858
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-109862
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-109864
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-111898
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1168459
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- id: file:human/MAPK1/MAPK1-deep-research-falcon.md
  title: Falcon deep research report on MAPK1
  findings: []
core_functions:
- molecular_function:
    id: GO:0004707
    label: MAP kinase activity
  description: >-
    MAPK1/ERK2 is an ATP-dependent, proline-directed serine/threonine MAP
    kinase. After MEK1/2-mediated activation, ERK2 phosphorylates protein
    substrates and transmits canonical Ras-RAF-MEK-ERK signals to cytosolic and
    nuclear targets.
  directly_involved_in:
  - id: GO:0070371
    label: ERK1 and ERK2 cascade
  - id: GO:0000165
    label: MAPK cascade
  - id: GO:0006468
    label: protein phosphorylation
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
    supporting_text: >-
      ERK2 is a Ser/Thr MAPK that transfers the γ-phosphate of ATP to Ser/Thr-Pro
      motifs; like other protein kinases it binds ATP in an active-site cleft, with
      MgATP2− serving as the relevant phosphoryl donor in vitro.
  - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
    supporting_text: >-
      ERK2 is consistently positioned as a downstream effector in the Ras–Raf–MEK–ERK
      signal transduction cascade, converting extracellular cues (including growth
      factors/serum) into intracellular phosphorylation events and responses.
- molecular_function:
    id: GO:0005524
    label: ATP binding
  description: >-
    ATP binding is a core active-site function of MAPK1 because ATP/MgATP
    provides the phosphoryl group used for ERK2 serine/threonine protein kinase
    catalysis.
  directly_involved_in:
  - id: GO:0006468
    label: protein phosphorylation
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: file:human/MAPK1/MAPK1-deep-research-falcon.md
    supporting_text: >-
      ERK2 is a Ser/Thr MAPK that transfers phosphate from ATP/MgATP to Ser/Thr-Pro
      motifs; ATP binds in the active site, with N-lobe/glycine-rich loop contributions
      to nucleotide binding and catalysis.
proposed_new_terms: []
suggested_questions:
- question: >-
    Which generic protein-binding annotations correspond to direct MAPK1
    docking, substrate, scaffold, or phosphatase interactions that should be
    curated with more specific terms?
- question: >-
    Which downstream proliferation, apoptosis, migration, immune, neuronal, or
    developmental annotations have direct MAPK1-specific evidence rather than
    general ERK pathway membership?
suggested_experiments:
- description: >-
    Prioritize source-level review of MAPK1-specific substrate phosphorylation
    papers to separate direct ERK2 substrates from phosphoproteomics or
    inhibitor-based pathway effects.
- description: >-
    Review compartment-specific MAPK1 localization evidence with stimulus and
    cell-type context, especially endosome, Golgi, mitochondrion, focal
    adhesion, and caveola annotations.

Gene Description

Existing Annotations Review

Core Functions

MAPK1/ERK2 is an ATP-dependent, proline-directed serine/threonine MAP kinase. After MEK1/2-mediated activation, ERK2 phosphorylates protein substrates and transmits canonical Ras-RAF-MEK-ERK signals to cytosolic and nuclear targets.

ATP binding is a core active-site function of MAPK1 because ATP/MgATP provides the phosphoryl group used for ERK2 serine/threonine protein kinase catalysis.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Concise GO annotation research report: human MAPK1 / ERK2 (UniProt P28482)

Scope and principles (GO-relevant evidence only)

1) Key concepts and definitions (current understanding)

1.1 Core Molecular Function (MF)

1.2 Activation mechanism (upstream regulation)

2) Core Biological Process (BP) annotations (conservative, evidence-driven)

2.1 MAPK cascade / ERK1-ERK2 cascade / intracellular signal transduction

2.2 Downstream outcomes: core vs non-core

3) Cellular Component (CC): localization and stimulus-dependent translocation

3.1 Basal distribution and stimulus-dependent nuclear accumulation

3.2 ERK lacks obvious intrinsic NLS/NES → partner-mediated trafficking

3.3 Cytoplasmic anchoring and nuclear sequestration (directly relevant regulators)

3.4 Docking-domain dependence of nuclear localization (caution)

4) Protein binding / scaffold & docking annotations (avoid generic binding)

4.1 Motif/exosite-mediated docking is central to ERK specificity

4.2 Avoid over-annotation to “protein binding”

5) Substrates and downstream processes: direct vs indirect; 2023–2024 developments

5.1 Direct phosphorylation: what is strong enough for GO use?

5.2 2024 mechanistic advance: kinase-independent ERK2 function via direct binding

5.3 Processes like proliferation/migration/apoptosis/senescence: typically non-core for MAPK1

6) Current applications and real-world implementations (annotation-relevant)

7) Recommended conservative GO annotation set (with over-annotation warnings)

Key caveats for curators (high priority)

References (URLs, dates, identifiers)

Citations

📚 Additional Documentation

Notes

MAPK1 notes

📄 View Raw YAML