Mapk3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	MODIFY	Summary: intracellular signal transduction is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000622075 SUPPORTS TRANSFER A deep kinase node, not an ERK-specific one: the local PAINT cache lists PTN000622075 in the files of four families - PTHR24055 (PANTHER name "MITOGEN-ACTIVATED PROTEIN KINASE", the family UniProt assigns to the target), PTHR24056 ("CELL DIVISION PROTEIN KINASE"), PTHR24057 ("GLYCOGEN SYNTHASE KINASE-3 ALPHA") and PTHR44167. THIS row's IBD seeds span fungal, slime-mould, worm, fly and vertebrate kinases of those groups; the node's plant seeds (AGI_LocusCode) sit in its GO:0004674, GO:0005634 and GO:0005737 rows, not in the GO:0035556 one under review, whose WITH/FROM carries no AGI or TAIR entry. Across a clade that broad the generic parent is the only biological-process term that holds for every member, so the node placement is sound and only the term is uninformative for mouse Mapk3. MGI:MGI:1346859 · mouse Mapk3 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Mapk3 carries an IGI at GO:0070371 ERK1 and ERK2 cascade (PMID:19047410) and an IGI at GO:0000165 MAPK cascade (PMID:21220101), both descendants of this term, which are among the descendant evidences behind the IBD. MGI:MGI:1346858 · mouse Mapk1 (ERK2, the target's closest paralog) SUPPORTS TRANSFER ERK1/ERK2 are functionally interchangeable in the cascade; the transfer between them is not at issue. FB:FBgn0003256 · Drosophila rolled (rl, the fly ERK) SUPPORTS TRANSFER The single fly ERK ortholog, one of the seeds that anchors the cascade role deep in the metazoan tree. UniProtKB:P27361 · human MAPK3 (ERK1) SUPPORTS TRANSFER The 1:1 human ortholog seed. Its presence, with the fly and mouse ERK seeds, is why the informative claim available here is the ERK1/2 cascade: GO:0070371 is a genuine descendant of GO:0035556 (via GO:0000165 MAPK cascade), so the MODIFY is a parent-to-child narrowing rather than a change of claim. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0007166 cell surface receptor signaling pathway	IBA GO_REF:0000033	MODIFY	Summary: cell surface receptor signaling pathway is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN008603019 SUPPORTS TRANSFER A different, much shallower node than the one behind the GO:0035556 row: PTN008603019 appears only in the PTHR24055 PAINT file (PANTHER family name "MITOGEN-ACTIVATED PROTEIN KINASE", the target's own family) and its IBD seeds are exactly the ERK orthologs - fly rolled, mouse Mapk1 and Mapk3, human MAPK1 and MAPK3. The clade is the right one; what is wrong is that GO:0007166 names the upstream receptor pathway that recruits ERK rather than ERK's own step in it. MGI:MGI:1346859 · mouse Mapk3 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Mapk3 carries an IGI at GO:0070371 ERK1 and ERK2 cascade (PMID:19047410) and an IGI at GO:0000165 MAPK cascade (PMID:21220101), which are among the descendant evidences behind the IBD. MGI:MGI:1346858 · mouse Mapk1 (ERK2, the target's closest paralog) SUPPORTS TRANSFER Second mouse ERK seed; ERK1 and ERK2 act in the same cascade downstream of the same receptor classes. FB:FBgn0003256 · Drosophila rolled (rl, the fly ERK) SUPPORTS TRANSFER The fly ERK ortholog seed; like the vertebrate seeds it acts downstream of RTK input rather than at the receptor itself. UniProtKB:P27361 · human MAPK3 (ERK1) SUPPORTS TRANSFER The 1:1 human ortholog seed. Note that GO:0070371 is not a descendant of GO:0007166 - its is_a/part_of ancestors run through GO:0000165 and GO:0035556 - so unlike the GO:0035556 row this MODIFY is a lateral re-scope from the receptor pathway onto the effector cascade the seeds actually share, not a narrowing, which is why no granularity failure mode is asserted. UniProtKB:P28482 · human MAPK1 (ERK2) SUPPORTS TRANSFER The human paralog seed, counterpart of the mouse Mapk1 record above. With it this block enumerates all six WITH/FROM sources; the same lateral re-scope applies to it, since it too acts downstream of receptor input rather than at the receptor itself. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0001784 phosphotyrosine residue binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: phosphotyrosine residue binding matches the experimentally supported paxillin-pTyr association of ERK1, but is not the core kinase function. Reason: This ARBA prediction mirrors the IMP evidence from PMID:14636584 that inactive ERK associates with tyrosine-phosphorylated paxillin; retained as non-core to stay consistent with that experimental row. Supporting Evidence: PMID:14636584 this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: protein kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0004707 MAP kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005739 mitochondrion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: mitochondrion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005769 early endosome	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: early endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005770 late endosome	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: late endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005794 Golgi apparatus	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Golgi apparatus is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005856 cytoskeleton	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cytoskeleton is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005901 caveola	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: caveola is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005925 focal adhesion	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: focal adhesion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0031143 pseudopodium	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: pseudopodium is a documented site of beta-arrestin-scaffolded ERK1/2 during chemotaxis, not a primary compartment. Reason: PMID:12821670 shows a PAR-2/beta-arrestin/ERK1/2 complex enriched in pseudopodia of migrating cells, so this electronically predicted localization has direct experimental backing; kept non-core because it is a transient, stimulus-dependent pool. Supporting Evidence: PMID:12821670 PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia
GO:0032872 regulation of stress-activated MAPK cascade	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: regulation of stress-activated MAPK cascade attributes cross-cascade regulatory activity to ERK1 on machine-learning evidence only. Reason: ERK1 belongs to the classical mitogen-responsive cascade; crosstalk toward the JNK/p38 stress cascades is context-dependent and no direct mouse evidence for ERK1 regulating a stress-activated cascade is available locally, so this ARBA prediction over-reaches.
GO:0042473 outer ear morphogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: outer ear morphogenesis reflects the ERK1/2 requirement in neural crest development, a pleiotropic developmental output. Reason: Concordant with the IGI evidence from PMID:18952847 in which ERK-cascade disruption perturbs craniofacial neural crest derivatives including the outer ear; a developmental phenotype rather than a core kinase function. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0043330 response to exogenous dsRNA	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to exogenous dsRNA is corroborated by mouse TLR3/Trif pathway experiments in which ERK participates. Reason: The matching IDA row from PMID:12872135 (Trif/Lps2 mutant macrophage responses to dsRNA) gives this electronically predicted response term experimental grounding in mouse innate immunity, though it is a context-specific signaling output.
GO:0051493 regulation of cytoskeleton organization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: regulation of cytoskeleton organization by ERK1/2 is documented through paxillin and actin-remodeling substrates. Reason: ERK1/2 phosphorylate cytoskeletal regulators and drive actin reorganization during chemotaxis, as in the pseudopodial ERK pool of PMID:12821670, so the prediction is biologically sound though it is a downstream regulatory output rather than the core activity. Supporting Evidence: PMID:12821670 PAR-2 activation promotes ERK1/2- and beta-arrestin-dependent reorganization of the actin cytoskeleton
GO:0060020 Bergmann glial cell differentiation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Bergmann glial cell differentiation depends on FGF/ERK signaling, matching mouse genetic evidence. Reason: Consistent with the IGI row from PMID:24431450 showing Shp2-dependent ERK activation is required for Bergmann glia specification in the mouse cerebellum; a lineage-specific developmental output of the cascade.
GO:0061308 cardiac neural crest cell development involved in heart development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cardiac neural crest development involvement echoes the mouse ERK1/2 neural crest requirement. Reason: The IGI evidence from PMID:18952847 links ERK-cascade disruption to conotruncal cardiac outflow tract defects of neural crest origin, so this electronic prediction is grounded, though it is a pleiotropic developmental phenotype.
GO:0071356 cellular response to tumor necrosis factor	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cellular response to tumor necrosis factor is supported by mouse myotube experiments showing TNF-modulated ERK1/2 phosphorylation. Reason: Aligned with the IGI row from PMID:24349514 in which TNF-alpha treatment of C2C12 myotubes alters phospho-ERK1/2 levels; a stimulus-response context rather than the defining function.
GO:0072584 caveolin-mediated endocytosis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: caveolin-mediated endocytosis links to the caveolar ERK pool described in compartmentalized ERK signaling. Reason: ERK1/2 localize to caveolae and modulate caveolar trafficking, matching the caveola compartment rows retained in this review per PMID:19565474; the process term is kept as non-core regulatory context because ERK participates via localized signaling rather than as endocytic machinery.
GO:0090170 regulation of Golgi inheritance	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: regulation of Golgi inheritance reflects Golgi-localized ERK function during mitotic Golgi fragmentation. Reason: Golgi-resident ERK signaling regulating Golgi fragmentation before mitosis is established ERK1/2 biology summarized in PMID:19565474; a compartment-specific regulatory role, not the core kinase function.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MODIFY	Summary: protein serine kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:2000641 regulation of early endosome to late endosome transport	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: regulation of early-to-late endosome transport corresponds to the endosomal ERK1/2 signaling pool. Reason: Endosome-localized ERK signaling influencing endosomal maturation is part of the compartmentalized ERK biology already retained for the endosome localization rows; a non-core trafficking-regulation output.
GO:0005515 protein binding	IPI PMID:22307056 ERK1 and ERK2 regulate embryonic stem cell self-renewal thro...	MODIFY	Summary: ERK1/ERK2 bind the activation domain of the transcription factor Klf4 (WITH/FROM Q60793) and phosphorylate it at Ser123, suppressing Klf4 activity in embryonic stem cells. Reason: The partner is the DNA-binding transcription factor Klf4, which ERK1 binds and phosphorylates; DNA-binding transcription factor binding is the informative MF. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:22307056 We found that ERK1 or ERK2 binds the activation domain of Klf4 and directly phosphorylates Klf4 at Ser123 file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0000165 MAPK cascade	IEA GO_REF:0000107	MODIFY	Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0002841 negative regulation of T cell mediated immune response to tumor cell	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of T cell mediated immune response to tumor cell is a hyper-specific tumor-immunology claim carried only by orthology pipelines. Reason: This composite term derives from a single-context study propagated by Ensembl Compara; attributing a standing tumor-immunosuppression function to ERK1, whose T cell roles are broadly activation-promoting, over-interprets the transfer.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000107	ACCEPT	Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005635 nuclear envelope	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: nuclear envelope localization reflects transient passage of ERK1 through nuclear pores rather than residency. Reason: ERK1/2 contact nucleoporins only while shuttling between cytoplasm and nucleoplasm; annotating the nuclear envelope as a compartment of ERK1 converts a transit interaction into a standing localization.
GO:0005654 nucleoplasm	IEA GO_REF:0000120	ACCEPT	Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0007173 epidermal growth factor receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGF receptor signaling is the paradigmatic upstream activator of the ERK1/2 cascade. Reason: ERK1 is the terminal kinase of RAS-RAF-MEK signaling downstream of EGFR; the pathway-membership term is biologically solid but names only one of many receptor inputs, so it is non-core relative to the ERK1 and ERK2 cascade itself.
GO:0019902 phosphatase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: phosphatase binding captures the well-characterized docking of DUSP/MKP phosphatases on ERK1. Reason: Inactivation of ERK1/2 through docking-based interactions with dual-specificity phosphatases is central, direct ERK biology, but it describes a regulatory interaction rather than the catalytic function, so it stays non-core.
GO:0030509 BMP signaling pathway	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: BMP signaling pathway membership for ERK1 rests on crosstalk, not pathway componency. Reason: ERK1/2 phosphorylate SMAD linker regions to modulate BMP outputs, but that is crosstalk from the RTK-ERK axis; calling ERK1 a BMP pathway component via Compara propagation inflates the relationship.
GO:0034198 cellular response to amino acid starvation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to amino acid starvation is a niche stress context propagated without mouse support. Reason: ERK activation state shifts under many stresses; elevating one starvation paradigm from an ortholog study into a standing ERK1 annotation exaggerates its place in the functional profile of this gene.
GO:0042770 signal transduction in response to DNA damage	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: signal transduction in response to DNA damage is anchored by the ERK1/2-dependent SGK1 induction after DNA damage. Reason: Concordant with the IDA row from PMID:15383658 where DNA damage induces SGK1 through ERK1/2-mediated regulation in the p53-FOXO3a axis; a stress-context signaling role, not the core cascade definition. Supporting Evidence: PMID:15383658 this induction was through extracellular signal-regulated kinase 1/2-mediated posttranslational regulation
GO:0042802 identical protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ERK dimerization is directly supported by PMID:26267534, but identical protein binding is a secondary signaling-state property rather than the core ERK1 kinase function. Reason: Retain as supported non-core biology; the core molecular function remains ERK MAP kinase activity and protein phosphorylation. Supporting Evidence: PMID:26267534 Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of RNA Pol II transcription summarizes the activation of TCF/Elk-1-driven immediate-early genes by ERK1. Reason: Nuclear ERK1/2 phosphorylate Elk-1 and related transcription factors to switch on immediate-early gene transcription (compare Reactome R-MMU-198706 in the reference list); a major downstream output, though indirect relative to the kinase activity.
GO:0051403 stress-activated MAPK cascade	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Stress-activated MAPK cascade denotes the JNK/p38 modules, whereas ERK1 is a terminal kinase of the mitogen-activated ERK1/2 cascade (GO:0070371). Reason: Although some stresses can activate ERK1/2, placing ERK1 inside the stress-activated MAPK cascade conflates it with the JNK/p38 modules; the accepted ERK1 and ERK2 cascade term already captures the correct module, so this electronic row is flagged as over-annotation. Matches the treatment of the identical term on the ERK2 paralog Mapk1, which carries the same IEA and ISO rows.
GO:0061514 interleukin-34-mediated signaling pathway	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IL-34 pathway membership enumerates one of many receptor systems that converge on ERK1/2. Reason: IL-34/CSF1R engagement activates ERK like dozens of other cytokine and growth factor receptors; propagating each such upstream pathway onto ERK1 electronically produces over-annotation without adding functional information.
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of ERK1 and ERK2 cascade casts the terminal output kinase as an upstream activator of its own cascade. Reason: ERK1 executes the cascade rather than positively regulating it, and its best-documented feedback phosphorylation of RAF, SOS and MEK is inhibitory; the regulatory term likely stems from indirect readouts and over-annotates.
GO:0070498 interleukin-1-mediated signaling pathway	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IL-1 pathway membership lists a single upstream stimulus among the many that activate ERK1/2. Reason: IL-1 receptor signaling reaches ERK via IRAK/TRAF6/TAK1, but ERK1 participation there is generic downstream kinase engagement; the pathway-specific annotation adds context, not function, and over-annotates by enumeration.
GO:0070849 response to epidermal growth factor	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to epidermal growth factor is the founding physiological context of ERK activation. Reason: EGF stimulation of ERK1/2 phosphorylation is the archetypal cascade trigger and amply conserved in mouse; the term describes the stimulus context of the core activity, hence non-core but sound.
GO:0071260 cellular response to mechanical stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to mechanical stimulus generalizes a mechanotransduction context onto ERK1. Reason: Mechanical stress activates many kinase pathways including ERK in specific cell types, but the propagated term gives ERK1 a standing mechanoresponse function that neither local evidence nor core ERK biology singles out.
GO:0140297 DNA-binding transcription factor binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: DNA-binding transcription factor binding reflects docking of ERK1 onto substrate transcription factors such as Elk-1. Reason: ERK1/2 engage transcription factor substrates through D-motif and DEF-site docking before phosphorylating them (see Reactome R-MMU-198706 on ELK1 activation); an informative substrate-interaction term kept as non-core.
GO:0150078 positive regulation of neuroinflammatory response	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: positive regulation of neuroinflammatory response echoes direct mouse ICH evidence for the CCR1/TPR1/ERK1/2 axis. Reason: Backed by the IDA row from PMID:31898284 in which ERK1/2 activation downstream of CCR1 promotes neuroinflammation after intracerebral hemorrhage; a pathological signaling context, so non-core.
GO:1904262 negative regulation of TORC1 signaling	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of TORC1 signaling inverts the predominant ERK-mTORC1 relationship. Reason: Canonical ERK1/2 signaling activates mTORC1 by phosphorylating and inhibiting TSC2, directly and via RSK; a propagated negative-regulation claim reflects a specialized context and misleads as a standing ERK1 function.
GO:0032991 protein-containing complex	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: protein-containing complex is a root-level component term conveying no ERK1-specific information. Reason: Like the protein binding rows already marked over-annotated in this review, assigning the generic complex root records only that ERK1 associates with scaffolds and partners; the informative statements are the specific localization and interaction annotations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH
GO:0106310 protein serine kinase activity	ISS GO_REF:0000024	MODIFY	Summary: protein serine kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-MMU-198706	ACCEPT	Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0006468 protein phosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0006468 protein phosphorylation	ISO GO_REF:0000119	ACCEPT	Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0016310 phosphorylation	ISO GO_REF:0000119	MODIFY	Summary: Phosphorylation is too broad for an ERK kinase annotation. Reason: The relevant process is protein phosphorylation catalyzed by ERK MAP kinase activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: protein phosphorylation Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0018105 peptidyl-serine phosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: peptidyl-serine phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0031281 positive regulation of cyclase activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cyclase activity is an obscure, single-context ortholog transfer. Reason: Neither local evidence nor canonical ERK1/2 biology establishes cyclase regulation as an ERK1 function; the transferred human observation is too peripheral to keep as a standing annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0038083 peptidyl-tyrosine autophosphorylation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: peptidyl-tyrosine autophosphorylation is not a defensible core ERK annotation. Reason: The Falcon synthesis supports ERK as a proline-directed protein kinase in MAPK signaling; this term is too indirect, too broad, or mechanistically mismatched for the gene product. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0097542 ciliary tip	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: ciliary tip localization stems from human ciliary studies without mouse corroboration. Reason: Reports of ERK at ciliary subdomains come from specialized human cell systems; ciliary residence is not part of established ERK1 cell biology and the transferred subcompartment claim is over-fine. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH
GO:0000045 autophagosome assembly	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: autophagosome assembly credits ERK1 with a biogenesis role beyond its regulatory input. Reason: ERK signaling modulates autophagy induction, as kept for the xenophagy and positive-regulation rows, but direct involvement in building autophagosomes overstates a kinase acting upstream of the machinery. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0000165 MAPK cascade	ISO GO_REF:0000096	MODIFY	Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0000165 MAPK cascade	ISO GO_REF:0000119	MODIFY	Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0002841 negative regulation of T cell mediated immune response to tumor cell	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Ortholog transfer of a narrow tumor-directed T cell suppression phenotype to mouse ERK1. Reason: The human-to-mouse transfer inherits one experimental context; ERK1/2 signaling in T cells is predominantly required for activation, so a blanket negative-regulation-of-antitumor-immunity annotation overstates the evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0004674 protein serine/threonine kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0004707 MAP kinase activity	ISO GO_REF:0000096	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0004707 MAP kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005524 ATP binding	ISO GO_REF:0000096	ACCEPT	Summary: ATP binding is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005635 nuclear envelope	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Human-derived nuclear envelope assignment for a kinase that shuttles through, not into, the envelope. Reason: The transferred human annotation likely captures nucleoporin-associated ERK during nucleocytoplasmic shuttling; the accepted nucleus, nucleoplasm, and cytoplasm rows already describe the steady-state distribution. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH
GO:0005654 nucleoplasm	ISO GO_REF:0000096	ACCEPT	Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005737 cytoplasm	ISO GO_REF:0000119	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005737 cytoplasm	ISO GO_REF:0000096	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005886 plasma membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: plasma membrane matches the membrane-associated ERK1/2 pool at receptors and scaffolds. Reason: A fraction of ERK1/2 is recruited to plasma membrane receptor complexes and caveolae during activation, as reflected in the retained caveola rows and the deep-research synthesis; kept as a non-core, activation-linked localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005901 caveola	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: caveola localization from rat orthology matches the retained caveolar ERK rows. Reason: This transfer duplicates the caveola annotations already kept as non-core in this review (the IEA and TAS rows citing compartmentalized ERK signaling); handled identically for consistency. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005929 cilium	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: cilium localization is an ortholog-propagated assignment outside the canonical ERK compartments. Reason: Steady-state ERK1 distribution is cytoplasmic and nuclear with organelle-associated pools; a general ciliary localization for mouse ERK1 lacks supporting evidence here and likely traces to a limited human dataset. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH
GO:0007173 epidermal growth factor receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Human-derived EGFR pathway membership for ERK1, the canonical downstream kinase. Reason: The ortholog transfer restates textbook biology in which EGF-bound receptor signaling culminates in ERK1/2 activation; kept as a non-core receptor-context annotation alongside the response-to-EGF rows.
GO:0009636 response to toxic substance	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: response to toxic substance parallels mouse studies of ERK activation by oxidative toxicity. Reason: ERK1/2 activation under oxidative or toxic insult is documented in the mouse ischemia and neuronal toxicity papers already in this reference list (PMID:12223545, PMID:11726647); a stress-response context, hence non-core.
GO:0010507 negative regulation of autophagy	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of autophagy is one side of a context-dependent ERK effect, transferred without mouse support. Reason: ERK signaling can restrain autophagy through mTORC1 activation in some settings, yet the local mouse evidence in PMID:22033934 shows ERK promoting autophagy; keeping the opposite-sign electronic row as a standing function over-annotates the negative arm. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION
GO:0010508 positive regulation of autophagy	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of autophagy agrees with the mouse xenophagy genetics for ERK. Reason: Matches the IGI evidence from PMID:22033934 where autophagy of L. monocytogenes depends selectively on the ERK pathway in macrophages; a supported context-specific regulatory output. Supporting Evidence: PMID:22033934 autophagy against L. monocytogenes was dependent selectively on the ERK pathway
GO:0010759 positive regulation of macrophage chemotaxis	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of macrophage chemotaxis is a cell-type-specific output transferred from one human context. Reason: ERK contributes to chemotactic signaling in many motile cells; singling out macrophage chemotaxis as a standing mouse ERK1 function from an ortholog transfer over-specifies the biology. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0015630 microtubule cytoskeleton	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: microtubule cytoskeleton association recalls the original identification of ERK1 as a microtubule-associated protein 2 kinase. Reason: A substantial ERK1/2 fraction is microtubule-associated, in line with the retained cytoskeleton rows and the MAP2 kinase synonym recorded for this protein in UniProt; a non-core localization pool.
GO:0019902 phosphatase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Ortholog-transferred phosphatase interaction consistent with conserved DUSP docking on ERK1/2. Reason: Human ERK1 binds MKP/DUSP-family phosphatases through the common docking domain and the relevant residues are conserved in mouse; a genuine interaction annotation that is secondary to the kinase activity itself.
GO:0030509 BMP signaling pathway	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Human-derived BMP pathway assignment that conflates SMAD-linker crosstalk with core pathway membership. Reason: The transferred context reflects ERK-mediated modulation of BMP/SMAD signaling in particular cell systems; ERK1 is not part of the BMP receptor-SMAD transduction chain, so the annotation over-extends. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0031669 cellular response to nutrient levels	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: cellular response to nutrient levels is a diffuse metabolic-context transfer. Reason: ERK activity responds to countless extracellular cues; a generic nutrient-response annotation from human orthology neither pinpoints a mechanism nor reflects characterized mouse ERK1 biology. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH
GO:0032206 positive regulation of telomere maintenance	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of telomere maintenance is a specialized human-derived claim not established for mouse ERK1. Reason: Reports of ERK phosphorylating telomeric factors such as TRF2 in human cells remain a narrow context; the transferred term promotes this to a standing function without corroboration. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of proteasomal degradation generalizes substrate-level stabilization events. Reason: ERK phosphorylation can shield individual substrates from ubiquitin-dependent turnover, but a gene-level annotation that ERK1 negatively regulates proteasomal catabolism inflates those substrate-specific effects. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0034198 cellular response to amino acid starvation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Ortholog transfer of an amino acid starvation response observed in one human experimental system. Reason: No local evidence ties mouse ERK1 to starvation signaling, and the phenomenon is a generic stress modulation of the cascade rather than a distinctive ERK1 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0035556 intracellular signal transduction	ISO GO_REF:0000096	MODIFY	Summary: intracellular signal transduction is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0036064 ciliary basal body	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: ciliary basal body assignment shares the weakness of the other transferred ciliary rows. Reason: As with the cilium and ciliary tip transfers, basal body residence of ERK1 is not corroborated by mouse data or by the compartmentalized ERK literature used elsewhere in this review. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH
GO:0038202 TORC1 signaling	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: TORC1 signaling membership for a kinase that only crosstalks with mTORC1. Reason: ERK1 modulates mTORC1 through TSC2/RSK crosstalk but is not a component of TORC1 signal transduction; the transferred pathway-membership term over-assigns. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0042770 signal transduction in response to DNA damage	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Human-transferred DNA damage signaling role matching the direct mouse-relevant SGK1 evidence. Reason: The transfer parallels the experimentally supported DNA damage response row from PMID:15383658, where ERK1/2 relay p53-dependent signals to SGK1/FOXO3a; retained as non-core stress signaling.
GO:0042802 identical protein binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ERK dimerization is directly supported by PMID:26267534, but identical protein binding is a secondary signaling-state property rather than the core ERK1 kinase function. Reason: Retain as supported non-core biology; the core molecular function remains ERK MAP kinase activity and protein phosphorylation. Supporting Evidence: PMID:26267534 Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling
GO:0045727 positive regulation of translation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of translation aligns with MAPK-driven protein synthesis in mouse myelination. Reason: ERK signaling boosts translation via MNK/eIF4E and downstream effectors, and sustained MAPK activation massively up-regulates protein production in mouse Schwann cells (PMID:24493648); a downstream output, kept non-core. Supporting Evidence: PMID:24493648 MAPK activation leads to minor changes in transcript levels but massively up-regulates protein production
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Ortholog-transferred transcriptional activation output of nuclear ERK1. Reason: Matches the conserved role of activated ERK entering the nucleus to phosphorylate Pol II-associated transcription factors; kept as a non-core downstream output executed through substrate phosphorylation.
GO:0046697 decidualization	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: decidualization is a rat-derived reproductive-physiology output of ERK signaling. Reason: The mouse-rat transfer reflects experimentally observed ERK involvement in uterine decidualization; as with other tissue-level developmental outputs in this review, it is retained but marked non-core.
GO:0050821 protein stabilization	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: protein stabilization is too vague to stand as an ERK1 function. Reason: Phosphorylation by ERK alters the stability of particular substrates in particular directions; the undirected protein stabilization term communicates no mechanism and is better covered by the kinase and substrate annotations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH
GO:0050868 negative regulation of T cell activation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of T cell activation runs against the established requirement for ERK in TCR signaling. Reason: ERK1/2 activity downstream of the TCR promotes T cell activation and thymocyte selection; the transferred negative-regulation claim must derive from a specialized human context and is misleading as a general mouse ERK1 annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION
GO:0051403 stress-activated MAPK cascade	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Ortholog transfer placing ERK1 inside the stress-activated (SAPK) cascade, which denotes the JNK/p38 modules rather than the ERK1/2 cascade. Reason: The SAPK cascade term is defined by JNK/p38 module membership, and mouse ERK1 is a terminal kinase of the ERK1 and ERK2 cascade (GO:0070371), which is already accepted here. Some stresses do activate ERK1/2, so rather than calling the transfer flatly wrong this is flagged as over-annotation - the same treatment given to the identical term on the ERK2 paralog Mapk1, and to the paired IEA row on this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0061514 interleukin-34-mediated signaling pathway	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Human-derived IL-34 signaling assignment reflecting generic downstream ERK activation. Reason: The transferred annotation records that ERK is phosphorylated downstream of IL-34-bound CSF1R in a human system; this is generic cascade engagement, not a distinctive mouse ERK1 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0065003 protein-containing complex assembly	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: protein-containing complex assembly is a generic process transfer with no ERK1-specific content. Reason: That ERK1 enters scaffolded signaling complexes is captured by the interaction rows; annotating the gene to complex assembly as a process treats a byproduct of signaling as a function and over-annotates. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Ortholog-transferred claim that ERK1 positively regulates its own cascade. Reason: Known ERK1/2 feedback onto upstream cascade components is predominantly negative; a positive-regulation annotation on the terminal kinase of the cascade most likely reflects an indirect experimental readout in the human source. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION
GO:0070498 interleukin-1-mediated signaling pathway	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Human-derived IL-1 signaling assignment for ERK1 as a generic downstream kinase. Reason: The transfer captures ERK phosphorylation after IL-1 stimulation in a human context; IL-1 outputs run chiefly through NF-kB and the stress MAPKs, with ERK engagement being ancillary, so the annotation overstates the role of ERK1. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0070849 response to epidermal growth factor	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Ortholog-transferred EGF responsiveness of ERK1. Reason: The human evidence transferring here reflects the canonical EGF-to-ERK axis on which the cascade was defined; retained as a supported stimulus-response annotation secondary to the kinase function.
GO:0097110 scaffold protein binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: scaffold protein binding describes ERK1 engagement with KSR- and beta-arrestin-type scaffolds. Reason: Scaffold binding governs where and how long ERK1/2 signal, exemplified locally by the beta-arrestin-scaffolded pseudopodial ERK pool of PMID:12821670; an informative regulatory interaction, non-core to the catalytic function. Supporting Evidence: PMID:12821670 PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia
GO:0097237 cellular response to toxic substance	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to toxic substance mirrors the broader toxic-response row and mouse oxidative-stress data. Reason: Same rationale as the response to toxic substance transfer, with cellular-level ERK activation by oxidative toxicants shown in the neuronal systems cited here (PMID:11726647); kept as non-core stress context.
GO:0120041 positive regulation of macrophage proliferation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of macrophage proliferation reflects generic mitogenic ERK signaling in one lineage. Reason: Proliferative signaling is the textbook ERK cascade output in essentially every mitogen-responsive cell; a macrophage-specific proliferation term transferred from human adds enumeration, not information. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH
GO:0140297 DNA-binding transcription factor binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Ortholog-transferred transcription factor docking interaction of ERK1. Reason: Conserved docking-groove contacts between ERK1/2 and TCF-family transcription factors underlie immediate-early gene induction; retained as a mechanistically meaningful, non-core interaction annotation.
GO:0150078 positive regulation of neuroinflammatory response	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Human-transferred neuroinflammatory role congruent with the direct mouse ICH study. Reason: This transfer duplicates biology already shown in mouse by PMID:31898284 (CCR1/TPR1/ERK1/2 after intracerebral hemorrhage); kept as non-core to match the experimental row for the same term.
GO:1904262 negative regulation of TORC1 signaling	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Ortholog-transferred TORC1-inhibition claim contrary to the usual ERK-TSC2-mTORC1 activation axis. Reason: Whatever human context generated this row, the dominant documented ERK1/2 effect on mTORC1 is stimulatory; transferring the opposite sign onto mouse ERK1 without local support is over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION
GO:0150078 positive regulation of neuroinflammatory response	IDA PMID:31898284 CCR1 Activation Promotes Neuroinflammation Through CCR1/TPR1...	KEEP AS NON CORE	Summary: Direct mouse evidence that ERK1/2 signaling downstream of CCR1/TPR1 promotes neuroinflammation after intracerebral hemorrhage. Reason: The study used an ERK1/2 activator to restore CCR1-driven inflammation blocked by receptor antagonism, placing ERK1/2 causally in the pro-inflammatory pathway; a disease-context output annotation, retained as non-core. Supporting Evidence: PMID:31898284 the mechanism of CCR1/tetratricopeptide repeat 1 (TPR1)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in CCR1-mediated neuroinflammation
GO:0090370 negative regulation of cholesterol efflux	IMP PMID:20037141 Inhibition of ERK1/2 and activation of liver X receptor syne...	KEEP AS NON CORE	Summary: ERK1/2 activity suppresses macrophage ABCA1 expression and cholesterol efflux. Reason: Direct inhibitor and activator experiments in macrophages show ERK1/2 activation lowers, and inhibition raises, ABCA1-dependent cholesterol efflux; a metabolic regulatory output of the cascade rather than a core function. Supporting Evidence: PMID:20037141 activation of ERK1/2 reduced macrophage cholesterol efflux and ABCA1 expression
GO:0050804 modulation of chemical synaptic transmission	IMP PMID:12062026 Knockout of ERK1 MAP kinase enhances synaptic plasticity in ...	KEEP AS NON CORE	Summary: Erk1 knockout mice show enhanced striatal synaptic plasticity, demonstrating synaptic modulation. Reason: Loss of ERK1 facilitates long-term potentiation in the nucleus accumbens and alters striatal plasticity, establishing a genuine but region-specific neuromodulatory role for ERK1; non-core relative to the kinase and cascade functions. Supporting Evidence: PMID:12062026 a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens
GO:0050804 modulation of chemical synaptic transmission	IDA PMID:12062026 Knockout of ERK1 MAP kinase enhances synaptic plasticity in ...	KEEP AS NON CORE	Summary: Direct electrophysiological evidence from the same Erk1 mutant study of altered synaptic transmission. Reason: This IDA row records the direct plasticity measurements in ERK1-deficient striatum from the paper; treated identically to the IMP row for consistency, as a neuronal-context output annotation. Supporting Evidence: PMID:12062026 a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens
GO:0098978 glutamatergic synapse	IMP PMID:12062026 Knockout of ERK1 MAP kinase enhances synaptic plasticity in ...	KEEP AS NON CORE	Summary: glutamatergic synapse reflects ERK1 function at corticostriatal and accumbens synapses. Reason: The plasticity phenotypes of Erk1-null mice localize ERK1 action to glutamatergic synapses of the striatum and nucleus accumbens; a synaptic-context component annotation kept as non-core. Supporting Evidence: PMID:12062026 a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens
GO:0098978 glutamatergic synapse	IDA PMID:12062026 Knockout of ERK1 MAP kinase enhances synaptic plasticity in ...	KEEP AS NON CORE	Summary: Direct-assay counterpart of the glutamatergic synapse annotation from the Erk1 knockout study. Reason: Matches the IMP row from the same paper; the synaptic localization and context of ERK1 during striatal long-term potentiation is well supported but peripheral to the core kinase activity. Supporting Evidence: PMID:12062026 a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens
GO:0005829 cytosol	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	ACCEPT	Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0004707 MAP kinase activity	IDA PMID:1717989 Mouse Erk-1 gene product is a serine/threonine protein kinas...	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0048009 insulin-like growth factor receptor signaling pathway	IDA PMID:14997210 Specific roles for the PI3K and the MEK-ERK pathway in IGF-1...	KEEP AS NON CORE	Summary: MEK-ERK signaling mediates specific IGF-1 outputs in the mouse 5T33MM model. Reason: IGF-1 stimulation activated ERK1/2 and MEK-ERK inhibition abolished IGF-1-driven VEGF secretion while reducing proliferation in mouse myeloma cells, placing ERK1 downstream of the IGF-1 receptor; one receptor context among many, hence non-core. Supporting Evidence: PMID:14997210 only the MEK-ERK pathway is involved in IGF-1-stimulated VEGF production
GO:0048009 insulin-like growth factor receptor signaling pathway	ISO PMID:17348861 IGF-I-induced oligodendrocyte progenitor proliferation requi...	KEEP AS NON CORE	Summary: Rat oligodendrocyte progenitor data transferred to mouse for IGF-1 receptor signaling. Reason: In rat oligodendrocyte progenitors IGF-I-driven proliferation requires MEK1/ERK signaling; the ortholog transfer is congruent with the direct mouse IDA row for this pathway term and is kept non-core with it. Supporting Evidence: PMID:17348861 stimulation of oligodendrocyte progenitor proliferation by IGF-I requires Src-like tyrosine kinases as well as the PI3K/Akt and MEK1/ERK signaling pathways
GO:0008286 insulin receptor signaling pathway	IDA PMID:20889126 Insulin signaling to the glomerular podocyte is critical for...	KEEP AS NON CORE	Summary: Insulin signals to podocytes through the MAPK pathway via the insulin receptor. Reason: The podocyte study demonstrates insulin receptor-dependent MAPK-arm signaling important for kidney function, situating ERK1 downstream of the insulin receptor in a defined physiological context; receptor-pathway membership, so non-core. Supporting Evidence: PMID:20889126 insulin signals through the MAPK and PI3K pathways via the insulin receptor
GO:0014044 Schwann cell development	IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ...	KEEP AS NON CORE	Summary: Schwann cell development annotation from the erbB2 conditional mutant study. Reason: The cached abstract covers Neuregulin/ErbB2 control of Schwann cell development without naming ERK1; the full-text basis used by the curator cannot be checked locally, but ERK1/2 are the established effectors of this axis, so the annotation is credible as a non-core developmental role. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination
GO:0042552 myelination	IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ...	KEEP AS NON CORE	Summary: Myelination role inferred from erbB2 mutant neuropathy with ERK as the downstream effector. Reason: erbB2 ablation causes hypomyelination and the annotation reflects ERK1 acting downstream of Neuregulin/ErbB in Schwann cells, a link proven directly by MAPK gain-of-function driving continuous myelin growth in PMID:24493648; a developmental output, non-core. Supporting Evidence: PMID:24493648 sustained activation of MAPK signaling by expression of the Mek1DD allele in mice overcomes the signals that end myelination
GO:0042552 myelination	IMP PMID:18760695 Neuregulin-1/ErbB signaling serves distinct functions in mye...	KEEP AS NON CORE	Summary: Second myelination row, from the Nrg1/ErbB conditional mutant series. Reason: PMID:18760695 dissects NRG1/ErbB requirements for peripheral versus central myelination; ERK1 is annotated as the downstream kinase of this pathway, consistent with the direct MAPK myelination evidence in PMID:24493648, and is kept as a non-core developmental role. Supporting Evidence: PMID:24493648 sustained activation of MAPK signaling by expression of the Mek1DD allele in mice overcomes the signals that end myelination
GO:0004674 protein serine/threonine kinase activity	ISO PMID:33331896 Merlin cooperates with neurofibromin and Spred1 to suppress ...	ACCEPT	Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0038133 ERBB2-ERBB3 signaling pathway	IDA PMID:24493648 Activation of MAPK overrides the termination of myelin growt...	KEEP AS NON CORE	Summary: ERK1 acts downstream of ERBB2-ERBB3 in Schwann cell myelination signaling. Reason: The study shows activated MAPK signaling substitutes for ErbB3/Shp2 during Schwann cell development, functionally placing ERK1/2 within the ERBB2-ERBB3 pathway; a receptor-pathway context annotation, non-core. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination
GO:0000165 MAPK cascade	IGI PMID:21220101 Specific functions for ERK/MAPK signaling during PNS develop...	MODIFY	Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-198706	ACCEPT	Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005515 protein binding	IPI PMID:14636584 Phosphorylation-dependent paxillin-ERK association mediates ...	MODIFY	Summary: HGF induces tyrosine phosphorylation-dependent association of inactive ERK with the focal adhesion scaffold paxillin (WITH/FROM Q8VI36), which also binds Raf and MEK to localise ERK activation. Reason: Paxillin acts as a scaffold assembling Raf, MEK and ERK at cell-matrix adhesions; scaffold protein binding is the informative MF. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:14636584 tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin PMID:14636584 paxillin was found to associate with the upstream MAP kinases Raf and MEK, resulting in a complex that can mediate localized ERK activation file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0005515 protein binding	IPI PMID:15537391 Vanishin is a novel ubiquitinylated death-effector domain pr...	REMOVE	Summary: The death-effector-domain protein Vanishin (WITH/FROM MGI:3525016) binds ERK/MAPK and blocks its activation. Reason: ERK is the target regulated by Vanishin; the interaction does not describe an ERK1 molecular function and no informative MF applies. Removal does not mean the reported interaction is false; the bare protein binding term simply carries no functional information about ERK1. Supporting Evidence: PMID:15537391 We further show that Vanishin binds ERK/MAPK but not the DED proteins file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0071356 cellular response to tumor necrosis factor	IGI PMID:24349514 MicroRNA-494, upregulated by tumor necrosis factor-α, desens...	KEEP AS NON CORE	Summary: TNF-alpha alters ERK1/2 phosphorylation in mouse C2C12 myotubes. Reason: The full text documents changed p-ERK-1/2 levels upon TNF-alpha incubation during inflammation-induced insulin resistance; a genuine but context-specific cellular response annotation. Supporting Evidence: PMID:24349514 the level of p-ERK-1/2 decreased on incubation with TNF-α at 2 or 20 ng/ml
GO:0004707 MAP kinase activity	IMP PMID:26375174 Regulation of neuronal pH by the metabotropic Zn(2+)-sensing...	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0051453 regulation of intracellular pH	IMP PMID:26375174 Regulation of neuronal pH by the metabotropic Zn(2+)-sensing...	KEEP AS NON CORE	Summary: ERK1/2-dependent up-regulation of NHE activity mediates neuronal pH recovery downstream of mZnR/GPR39. Reason: Zinc-receptor signaling raises Na+/H+ exchanger activity in hippocampal neurons in an ERK1/2-dependent manner, giving a defined physiological pH-regulation output for the kinase; non-core relative to the cascade itself. Supporting Evidence: PMID:26375174 the Na(+)/H(+) exchanger (NHE), is induced by mZnR/GPR39 activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons
GO:0005886 plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer of plasma membrane association for ERK1. Reason: Consistent with the ISO plasma membrane row and the membrane-associated ERK pool described in the deep research synthesis; a transient signaling localization, so retained as non-core. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005901 caveola	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator similarity-based caveola assignment consistent with the other caveolar rows. Reason: Kept in line with the IEA, ISO and TAS caveola annotations retained as non-core localization context per the compartmentalized ERK literature. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0030278 regulation of ossification	IGI PMID:20053668 Gain-of-function mutation in FGFR3 in mice leads to decrease...	KEEP AS NON CORE	Summary: Elevated Erk1/2 activity downstream of FGFR3 impairs bone matrix mineralization. Reason: In the achondroplasia FGFR3 gain-of-function model, enhanced Erk1/2 activity is causally tied to defective mineralization, supporting a role in ossification regulation; a skeletal-context output of ERK signaling, non-core. Supporting Evidence: PMID:20053668 enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization
GO:1904417 positive regulation of xenophagy	IGI PMID:22033934 TLR2 and RIP2 pathways mediate autophagy of Listeria monocyt...	KEEP AS NON CORE	Summary: The ERK pathway is selectively required for antibacterial autophagy of Listeria in mouse macrophages. Reason: ERK inhibition or deficiency reduced autophagosome targeting of L. monocytogenes downstream of TLR2/NOD2, giving direct genetic support for a xenophagy-promoting role; an immune-context output rather than core function. Supporting Evidence: PMID:22033934 autophagy against L. monocytogenes was dependent selectively on the ERK pathway
GO:0014032 neural crest cell development	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Neural crest development depends on the RAF/MEK/ERK cascade in mouse. Reason: The genetic series in this paper establishes neural crest development as critically ERK-cascade dependent, with Mapk3 annotated through the combined ERK1/2 analysis; a major but pleiotropic developmental role, hence non-core. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0030878 thyroid gland development	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Thyroid gland defects are among the neural crest derivative phenotypes of ERK pathway disruption. Reason: Thyroid development is one of the pharyngeal, neural crest derived structures perturbed in the ERK cascade mutants of this study; an organ-level developmental consequence, retained as non-core. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0042473 outer ear morphogenesis	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Outer ear defects arise in mice with disrupted ERK1/2 neural crest signaling. Reason: PMID:18952847 reports craniofacial anomalies from RAF/MEK/ERK pathway inactivation in the developing neural crest; this genetic-interaction phenotype is a downstream developmental output of the cascade, so it is kept but not core. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0048538 thymus development	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Thymus development phenotype from the same ERK cascade neural crest series. Reason: Thymic defects in the DiGeorge-spectrum phenocopy of the ERK pathway mutants tie ERK1/2 signaling to pharyngeal organ development; kept as a non-core developmental annotation consistent with its sibling rows. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0060324 face development	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Craniofacial development requires intact ERK cascade signaling in neural crest. Reason: Craniofacial anomalies were replicated across mutants of B-Raf and C-Raf, MEK1/2, ERK2 and SRF in this work, embedding ERK1/2 in facial morphogenesis; a developmental output annotation, non-core. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0061308 cardiac neural crest cell development involved in heart development	IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol...	KEEP AS NON CORE	Summary: Cardiac outflow tract neural crest defects follow ERK cascade inactivation in mice. Reason: The study reports conotruncal anomalies from perturbation of neural crest ERK signaling, replicated across cascade components; retained as a developmental, non-core output of ERK1/2 activity. Supporting Evidence: PMID:18952847 mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway
GO:0060020 Bergmann glial cell differentiation	IGI PMID:24431450 Shp2-dependent ERK signaling is essential for induction of B...	KEEP AS NON CORE	Summary: Genetic evidence that ERK activation downstream of Shp2/FGF drives Bergmann glia specification. Reason: PMID:24431450 shows loss of Shp2 blocks ERK activation in radial glia and prevents Bergmann glia formation, rescued by constitutively active MEK1; a well-supported developmental role executed through the core cascade, hence non-core. Supporting Evidence: PMID:24431450 essential role of Shp2 in BG specification via fibroblast growth factor/extracellular signal-regulated protein kinase signaling
GO:0070371 ERK1 and ERK2 cascade	IGI PMID:19047410 Phosphoinositide 3-kinase-dependent inhibition of dendritic ...	ACCEPT	Summary: ERK1 and ERK2 cascade is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0060425 lung morphogenesis	IGI PMID:25100655 Crucial requirement of ERK/MAPK signaling in respiratory tra...	KEEP AS NON CORE	Summary: Lung morphogenesis requires epithelial ERK/MAPK signaling in mouse. Reason: Mutating Erk1 and Erk2 in airway epithelium phenocopies the Mek mutant lung agenesis, demonstrating an ERK1/2 requirement in respiratory development; a pleiotropic organogenesis output, non-core. Supporting Evidence: PMID:25100655 these anomalies were phenocopied when the Erk1 and Erk2 genes were mutated in airway epithelium
GO:0060440 trachea formation	IGI PMID:25100655 Crucial requirement of ERK/MAPK signaling in respiratory tra...	KEEP AS NON CORE	Summary: Trachea formation depends on the ERK/MAPK pathway in respiratory progenitors. Reason: The same genetic series shows tracheal progenitor maintenance and differentiation need ERK/MAPK signaling, with Erk1;Erk2 epithelial mutants phenocopying Mek loss; a developmental annotation kept non-core. Supporting Evidence: PMID:25100655 these anomalies were phenocopied when the Erk1 and Erk2 genes were mutated in airway epithelium
GO:0005829 cytosol	IDA PMID:22451653 Siglec-15 protein regulates formation of functional osteocla...	ACCEPT	Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0070849 response to epidermal growth factor	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator sequence-similarity transfer of EGF responsiveness. Reason: This ISS row repeats the well-founded EGF-responsive behavior of ERK1 orthologs; handled consistently with the other response-to-EGF rows kept as non-core context.
GO:0005634 nucleus	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	ACCEPT	Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005739 mitochondrion	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: mitochondrion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005769 early endosome	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: early endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005770 late endosome	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: late endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005794 Golgi apparatus	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: Golgi apparatus is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005856 cytoskeleton	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: cytoskeleton is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005901 caveola	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: caveola is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0005925 focal adhesion	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: focal adhesion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments
GO:0032872 regulation of stress-activated MAPK cascade	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	MARK AS OVER ANNOTATED	Summary: Review-derived claim that compartmentalized ERK signaling regulates stress-activated MAPK cascades. Reason: The cited Yao and Seger review discusses ERK localization broadly; attributing regulation of the JNK/p38 stress cascades to ERK1 itself stretches a general statement about cascade crosstalk beyond what is demonstrated for mouse ERK1.
GO:0051493 regulation of cytoskeleton organization	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: Author statement that cytoskeleton-localized ERK regulates cytoskeletal processes. Reason: The Yao and Seger review describes ERK targeting many compartments whose local substrates in turn regulate diverse cellular processes, including cytoskeletal organization; retained as a supported but non-core regulatory role. Supporting Evidence: PMID:19565474 induce and regulate a large number of cellular processes
GO:0072584 caveolin-mediated endocytosis	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: Author statement connecting caveolar ERK signaling to caveolin-mediated endocytosis. Reason: Follows the same review used for the retained caveola localization rows; the endocytosis process is one of the compartment-linked activities ERK modulates, kept as non-core context. Supporting Evidence: PMID:19565474 induce and regulate a large number of cellular processes
GO:0090170 regulation of Golgi inheritance	TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ...	KEEP AS NON CORE	Summary: Author statement on Golgi-localized ERK regulating Golgi partitioning. Reason: The review supporting the retained Golgi apparatus localization row also covers the mitotic Golgi fragmentation role of Golgi-associated ERK; kept as non-core organelle-level regulation. Supporting Evidence: PMID:19565474 induce and regulate a large number of cellular processes
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: Author statement that endosomal ERK modulates endosome maturation and transport. Reason: Same review as the retained early and late endosome compartment rows; the transport-regulation process is the functional counterpart of that localization, kept as non-core. Supporting Evidence: PMID:19565474 induce and regulate a large number of cellular processes
GO:0031143 pseudopodium	IDA PMID:12821670 A beta-arrestin-dependent scaffold is associated with prolon...	KEEP AS NON CORE	Summary: Direct localization of scaffolded ERK1/2 to pseudopodia during PAR-2-induced chemotaxis. Reason: The paper physically isolated pseudopodial proteins and found the beta-arrestin-sequestered ERK1/2 pool enriched at the leading edge; a genuine but context-specific localization during chemotaxis rather than a core compartment. Supporting Evidence: PMID:12821670 PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia
GO:0005634 nucleus	IDA PMID:11254359 Pecam-1 is a modulator of stat family member phosphorylation...	ACCEPT	Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005634 nucleus	IDA PMID:11726647 Prolonged nuclear retention of activated extracellular signa...	ACCEPT	Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0005737 cytoplasm	IDA PMID:11726647 Prolonged nuclear retention of activated extracellular signa...	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0004707 MAP kinase activity	IDA PMID:15314156 MUC20 suppresses the hepatocyte growth factor-induced Grb2-R...	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0051216 cartilage development	IDA PMID:17644814 Cytokine-like 1 (Cytl1) regulates the chondrogenesis of mese...	KEEP AS NON CORE	Summary: Cartilage development annotation from the Cytl1 chondrogenesis study. Reason: The cached abstract describes Cytl1-driven chondrogenesis without detailing the ERK assays, which are in the full text the curator used; ERK1/2 signaling in chondrogenic differentiation is well established (compare the FGFR3 bone study PMID:20053668), so the row is retained as a non-core skeletal-development role.
GO:0031663 lipopolysaccharide-mediated signaling pathway	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: LPS-mediated signaling annotation from the Trif(Lps2) identification study. Reason: The paper defines Trif-dependent TLR4 signaling in mouse; ERK1 activation is part of the macrophage LPS response assayed in the full text, and MAPK activation downstream of TLR4 is core innate-immunity biology, so this pathway-context row is kept non-core.
GO:0032496 response to lipopolysaccharide	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: response to lipopolysaccharide sits alongside the LPS pathway row from the same study. Reason: Adjudicated with its sibling annotation from PMID:12872135; ERK1 phosphorylation is a standard readout of the mouse macrophage LPS response, a stimulus-context annotation rather than a core function.
GO:0043330 response to exogenous dsRNA	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: ERK1 participates in macrophage responses to dsRNA downstream of TLR3/Trif. Reason: The cached abstract of the Trif(Lps2) study covers cytokine responses to double-stranded RNA; the ERK1-specific assay is in the full text the curator read, and ERK activation downstream of TLR3 engagement is standard innate-immune signaling, so the annotation is retained as a non-core immune output.
GO:0019233 sensory perception of pain	IMP PMID:11356865 Metabotropic glutamate receptor subtypes 1 and 5 are activat...	KEEP AS NON CORE	Summary: Spinal ERK1/2 activation downstream of group I mGluRs drives inflammatory pain sensitivity. Reason: The study shows mGluR1/5 activation engages ERK1 and ERK2 in dorsal horn neurons and that this signaling underlies nociceptive plasticity, supporting a pain-modulation role; a systems-level behavioral output, hence non-core. Supporting Evidence: PMID:11356865 activation of these group I mGluRs leads to activation of ERK1 and ERK2, resulting in enhanced pain sensitivity
GO:0004672 protein kinase activity	IDA PMID:15383658 p53-dependent inhibition of FKHRL1 in response to DNA damage...	MODIFY	Summary: protein kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0006468 protein phosphorylation	IDA PMID:15383658 p53-dependent inhibition of FKHRL1 in response to DNA damage...	ACCEPT	Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0006974 DNA damage response	IDA PMID:15383658 p53-dependent inhibition of FKHRL1 in response to DNA damage...	KEEP AS NON CORE	Summary: ERK1/2 mediate p53-dependent SGK1 induction after DNA damage. Reason: DNA damage-induced SGK1 up-regulation, required for FOXO3a inhibition, occurs through ERK1/2-mediated posttranslational regulation, placing ERK1 within a DNA damage signaling circuit; a stress-context role, retained as non-core. Supporting Evidence: PMID:15383658 this induction was through extracellular signal-regulated kinase 1/2-mediated posttranslational regulation
GO:0004707 MAP kinase activity	IMP PMID:11841548 Role of the nude gene in epithelial terminal differentiation...	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0006468 protein phosphorylation	IDA PMID:11841548 Role of the nude gene in epithelial terminal differentiation...	ACCEPT	Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0005515 protein binding	IPI PMID:15544353 Treatment of cells with the angiogenic inhibitor fumagillin ...	REMOVE	Summary: The eIF2-associated glycoprotein p67/METAP2 (WITH/FROM O08663) binds ERK1/2 and inhibits their phosphorylation. Reason: ERK is the target inhibited by p67; the interaction does not describe an ERK1 molecular function. Removal does not mean the reported interaction is false; the bare protein binding term simply carries no functional information about ERK1. Supporting Evidence: PMID:15544353 p67 binds to these ERKs, and the 108-480 amino acid segment is sufficient for this binding file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0001784 phosphotyrosine residue binding	IMP PMID:14636584 Phosphorylation-dependent paxillin-ERK association mediates ...	KEEP AS NON CORE	Summary: phosphotyrosine residue binding is supported in a specific HGF/paxillin cell-matrix interaction context, but is not the core ERK1 kinase function. Reason: The cited evidence supports a context-specific tyrosine-phosphorylation-dependent ERK association. Supporting Evidence: PMID:14636584 this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin
GO:0005737 cytoplasm	IDA PMID:12223545 Copper/zinc superoxide dismutase attenuates neuronal cell de...	ACCEPT	Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are described as present in cytoplasmic, nuclear, and membrane-associated pools.
GO:0016310 phosphorylation	TAS PMID:12223545 Copper/zinc superoxide dismutase attenuates neuronal cell de...	MODIFY	Summary: Phosphorylation is too broad for an ERK kinase annotation. Reason: The relevant process is protein phosphorylation catalyzed by ERK MAP kinase activity. Proposed replacements: protein phosphorylation Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0004707 MAP kinase activity	TAS PMID:11684667 Erk MAP kinase regulates branching morphogenesis in the deve...	ACCEPT	Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 are proline-directed Ser/Thr protein kinases, with strong preference for PX(S/T)P motifs
GO:0007165 signal transduction	TAS PMID:11684667 Erk MAP kinase regulates branching morphogenesis in the deve...	MODIFY	Summary: signal transduction is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk3/Mapk3-deep-research-falcon.md ERK1/2 function as the final kinases in the RAS-RAF-MEK-ERK cascade
GO:0009887 animal organ morphogenesis	IDA PMID:11684667 Erk MAP kinase regulates branching morphogenesis in the deve...	MODIFY	Summary: Animal organ morphogenesis is far broader than the actual finding, which is that Erk MAP kinase activity is required for branching morphogenesis of the ureteric bud in kidney development. Reason: The experiment specifically shows MEK-inhibitor-sensitive, Erk-dependent ureteric bud branching; the generic organ morphogenesis term should be narrowed to the branching-specific term that matches the assay. PD98059 inhibits MEK, so the assay cannot distinguish ERK1 from ERK2 - the identical row on the ERK2 paralog Mapk1 is narrowed the same way. Proposed replacements: branching involved in ureteric bud morphogenesis Supporting Evidence: PMID:11684667 MAP kinase is therefore essential for normal branching morphogenesis of the ureteric bud

Gene Description

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Core Functions

ERK1 catalyzes proline-directed phosphorylation of protein substrates at serine/threonine residues after MEK-mediated dual activation-loop phosphorylation.

Acts with ERK2 as the final kinase tier of the RAS-RAF-MEK-ERK cascade, with output shaped by localization, docking motifs, and signal duration.

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