Mapk1 (also known as Erk2, Prkm1, p42-MAPK) encodes ERK2, the rat ortholog of the extracellular signal-regulated kinase 2. It is a proline-directed serine/threonine protein kinase (EC 2.7.11.24) of the CMGC group and the terminal effector kinase of the canonical RAS-RAF-MEK-ERK (ERK1/2) MAPK cascade. ERK2 is activated by dual phosphorylation on the TEY activation-loop motif (Thr183/Tyr185 in rat numbering, equivalent to the TEY threonine/tyrosine pair) by the upstream MAP2Ks MEK1/MEK2 (MAP2K1/MAP2K2), downstream of receptor tyrosine kinases (EGFR and other growth factor receptors), G-protein-coupled receptors, and other stimuli that activate RAS. Once activated, ERK2 phosphorylates a Ser/Thr-Pro consensus motif on hundreds of cytoplasmic and nuclear substrates (e.g., RSK kinases, ELK1 and other transcription factors, translation-control nodes, cytoskeletal and membrane scaffold proteins such as NHE1/SLC9A1). Its core molecular function is protein serine/threonine (MAP) kinase activity using ATP, and its core biological role is transduction of the ERK1/2 MAPK cascade. Subcellular localization (cytoplasm versus nucleus) is a key regulatory feature: activated ERK2 translocates to the nucleus to drive transcriptional programs, and is sequestered/exported by binding partners such as PEA-15. ERK2 is an extremely pleiotropic signaling hub: through its many substrates it influences cell proliferation, differentiation, survival, migration, translation and organelle dynamics in a cell-type- and stimulus-dependent manner, and these diverse developmental and physiological roles are context-specific consequences of cascade activity rather than distinct activities of the protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Activated ERK2 translocates to the nucleus where it phosphorylates transcription factors; nuclear localization is well established and a core site of action. Reason: Core localization. Activated ERK2 accumulates in the nucleus to drive transcription; supported by the phylogenetic inference and by direct evidence in this review. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md transcriptional outcomes often requiring nuclear ERK |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: ERK2 resides in the cytoplasm in the basal state and is activated there by the cytoplasmic MEK1/2; cytoplasmic localization is a core feature. Reason: Core localization. ERK2 is cytoplasmic in resting cells and is subject to cytoplasmic sequestration; this is the compartment of initial activation. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ERK2 is a central intracellular signal-transducing kinase. This is a generic parent of the more specific ERK1/2 cascade terms. Reason: Correct but generic. The more specific GO:0070371 (ERK1 and ERK2 cascade) better captures the core biological process; this broad parent is retained as non-core. Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ERK2 is a proline-directed serine/threonine protein kinase. This is a core molecular function (parent of MAP kinase activity). Reason: Core molecular function. ERK2 phosphorylates Ser/Thr-Pro motifs on substrates; well supported phylogenetically and experimentally. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md ERK family proteins are annotated under a **serine/threonine kinase domain category** |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ERK2 acts downstream of cell-surface receptors (RTKs, GPCRs), but this broad term is a generic parent of the specific cascade/receptor pathways. Reason: Generic parent. The specific receptor pathways and the ERK1/2 cascade term capture this better; kept as non-core context. Supporting Evidence: UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF UniProtKB:P63086 They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic parent of protein serine/threonine kinase / MAP kinase activity. Reason: The term is correct but too general rather than an over-reach of the evidence; ERK2 is a proline-directed Ser/Thr MAP kinase, and GO:0004707 MAP kinase activity (already carried with IDA, IMP and IEA support) is the precise replacement for this InterPro-based kinase-domain mapping. Proposed replacements: MAP kinase activity |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ERK2 IS a MAP kinase; this is the most specific and accurate molecular function term for this protein. Reason: Core molecular function. ERK2 is the canonical MAP kinase; this term is the precise MF. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md Mapk1 encodes ERK2**, a serine/threonine MAP kinase in the canonical RASβRAFβMEKβERK cascade |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ERK2 binds ATP in its kinase domain and transfers the gamma-phosphate to substrates; a core molecular function of the enzyme. Reason: Core molecular function. ATP binding is required for the phosphotransfer reaction; experimentally demonstrated (PMID:15027896) and assay-confirmed in the deep research. Supporting Evidence: UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization (duplicate of the IBA nucleus annotation). Reason: Core localization, consistent with the IBA annotation and direct evidence. Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus UniProtKB:P63086 autophosphorylation at Thr-188 promote nuclear localization |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleoplasm is a more specific child of nucleus; ERK2 acts within the nucleoplasm on transcription factors. Reason: Consistent specific nuclear localization; supported by IDA evidence (PMID:7889942) elsewhere in this review. Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization (duplicate of the IBA cytoplasm annotation). Reason: Core localization. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005769 early endosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK signaling can be organized on endosomal compartments, but early endosome is a minor/context-specific localization, not a core site. Reason: Context-specific localization tied to endosomal signaling scaffolds; not a core compartment for ERK2 function. Supporting Evidence: UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005770 late endosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Context-specific endosomal localization (see early endosome). Reason: Minor/context-specific localization, not core. Supporting Evidence: UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Golgi-localized ERK pools exist and ERK can regulate Golgi dynamics, but this is a specialized localization rather than the core site of action. Reason: Specialized localized signaling pool; non-core. Supporting Evidence: UniProtKB:P63086 as well as in the fragmentation of the Golgi apparatus during mitosis |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosomal localization is reported in mitotic contexts; specialized, not core. Reason: Context-specific localization (mitosis); non-core. Supporting Evidence: UniProtKB:P63086 Cytoplasm, cytoskeleton, microtubule organizing center, centrosome |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Spindle localization in mitosis is a specialized, context-specific site. Reason: Context-specific mitotic localization; non-core. Supporting Evidence: UniProtKB:P63086 Associated with the spindle during prometaphase and metaphase UniProtKB:P63086 May play a role in the spindle assembly checkpoint |
| GO:0005901 caveola | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ERK can be recruited to caveolae (e.g., via MURC/Cavin-4) in specialized signaling, supported by IDA (PMID:24567387); specialized localization. Reason: Context-specific membrane microdomain localization; non-core but experimentally supported. Supporting Evidence: UniProtKB:P63086 Membrane, caveola |
| GO:0005925 focal adhesion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ERK localizes to focal adhesions in migration contexts; specialized localization. Reason: Context-specific localization linked to cell migration; non-core. Supporting Evidence: UniProtKB:P63086 Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Nuclear ERK2 regulates Pol II transcription by phosphorylating transcription factors (e.g., ELK1). This is a downstream consequence of cascade activity rather than the core function. Reason: Genuine but downstream/indirect process; ERK2 regulates transcription via substrate phosphorylation. Kept as non-core. Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation UniProtKB:P63086 The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1) |
| GO:0032872 regulation of stress-activated MAPK cascade | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK2 can cross-regulate stress-activated MAPK (p38/JNK) cascades, but this is a secondary crosstalk role, not core. Reason: Crosstalk/regulatory role; non-core relative to the ERK1/2 cascade itself. |
| GO:0035094 response to nicotine | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK activation downstream of nicotinic receptors is a stimulus-specific response, not a core function. Reason: Stimulus-specific response (also supported by IGI PMID:11404397); non-core. GOA no longer carries this row. |
| GO:0045727 positive regulation of translation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK2 promotes translation via downstream nodes (e.g., RSK/MNK, eIF4E pathway, EIF4EBP1, EEF2K). This is a downstream consequence of cascade activity. Reason: Downstream regulatory consequence (also IMP PMID:15027896); non-core. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md ERK2 is also linked to translation-control nodes including Eif4ebp1 and Eef2k |
| GO:0046697 decidualization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Decidualization is a tissue-specific developmental process downstream of MAPK activation; not a core ERK2 function. Reason: Tissue-specific developmental process (also IDA PMID:21248290); non-core. |
| GO:0051493 regulation of cytoskeleton organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK2 phosphorylates cytoskeletal regulators, influencing cytoskeleton organization; a downstream effect. Reason: Downstream effector consequence; non-core. Supporting Evidence: UniProtKB:P63086 cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1) |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000117 | ACCEPT | Summary: This is the defining biological process for ERK2 - it IS one of the two terminal kinases of the ERK1/2 cascade. Core BP. Reason: Core biological process. ERK2 is a defining component of the ERK1 and ERK2 cascade. GOA no longer carries this row. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md ERK1/2 (MAPK3/MAPK1) are described as **terminal kinases** in the canonical **RASβRAFβMEKβERK** cascade |
| GO:0071375 cellular response to peptide hormone stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK activation downstream of peptide hormones is a stimulus-specific response. Reason: Stimulus-specific response; non-core. GOA no longer carries this row. |
| GO:0071396 cellular response to lipid | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Stimulus-specific cellular response. Reason: Stimulus-specific response; non-core. GOA no longer carries this row. |
| GO:0072584 caveolin-mediated endocytosis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: A specialized endocytosis process where ERK has been implicated; downstream/context-specific. Reason: Context-specific process; non-core. Supporting Evidence: UniProtKB:P63086 Membrane, caveola UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0090170 regulation of Golgi inheritance | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ERK2 has been implicated in mitotic Golgi partitioning; specialized downstream process. Reason: Specialized mitotic process; non-core. Supporting Evidence: UniProtKB:P63086 as well as in the fragmentation of the Golgi apparatus during mitosis |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: ERK2 phosphorylates serine residues; a more specific child of protein serine/threonine kinase activity. Accurate. Reason: Accurate specific MF; ERK2 is a Ser/Thr (proline-directed) kinase. GOA no longer carries this row. |
| GO:2000641 regulation of early endosome to late endosome transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Specialized endosomal trafficking process linked to ERK; downstream. Reason: Context-specific process; non-core. Supporting Evidence: UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005515 protein binding | IPI PMID:21070949 Phosphorylation of DCC by ERK2 is facilitated by direct dock... | MODIFY | Summary: ERK2 directly docks onto the intracellular P1 domain of the netrin receptor DCC (WITH/FROM Q63155) and phosphorylates it. Reason: The partner is the netrin receptor DCC, whose cytoplasmic P1 domain carries a MAPK docking motif bound by ERK2; 'signaling receptor binding' is more informative than bare protein binding. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:21070949 ERK2 directly interacts with DCC, and the ERK2-binding region was mapped to the conserved intracellular P1 domain of the receptor |
| GO:0106310 protein serine kinase activity | IMP PMID:29959233 Desmoplakin maintains gap junctions by inhibiting Ras/MAPK a... | ACCEPT | Summary: ERK2 serine kinase activity demonstrated in the context of Ras/MAPK regulation of connexin-43/gap junctions. Accurate MF. Reason: Accurate specific molecular function with experimental support. Supporting Evidence: PMID:29959233 increased phosphorylation of S279/282 of Cx43, which signals clathrin-mediated internalization and subsequent lysosomal degradation of Cx43 |
| GO:0045880 positive regulation of smoothened signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Crosstalk between ERK and Hedgehog/Smoothened signaling is reported but indirect; not a core ERK2 function and based on sequence-similarity transfer. Reason: Indirect crosstalk role from ISS transfer; non-core. Supporting Evidence: UniProtKB:P63086 Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI1 |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Refers to ERK2 homodimerization. While ERK2 can dimerize, this is a relatively uninformative interaction term. Reason: ERK2 homodimerization is documented but its functional relevance is debated; retained as non-core rather than core function. Supporting Evidence: UniProtKB:P63086 the interaction requires dimerization of MAPK1/ERK2 |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleoplasm localization (ISO duplicate). Consistent. Reason: Consistent specific nuclear localization. Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Cytosolic localization; consistent with cytoplasmic localization and the site of basal ERK2 and MEK-mediated activation. Reason: Core localization (cytosolic pool), consistent with TAS and other evidence. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0004707 MAP kinase activity | IDA PMID:7889942 ERK phosphorylation potentiates Elk-1-mediated ternary compl... | ACCEPT | Summary: Direct demonstration of ERK MAP kinase activity (Elk-1 phosphorylation / ternary complex). Core MF with strong experimental support. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:7889942 is a nuclear target of two members of the MAP kinase family, ERK1 and ERK2 |
| GO:0150078 positive regulation of neuroinflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A tissue/context-specific downstream process inferred by orthology; not a core ERK2 function. Reason: Context-specific downstream process from ISO transfer; non-core. |
| GO:0061514 interleukin-34-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK acts downstream of IL-34/CSF1R signaling; a stimulus-specific pathway inferred by orthology. Reason: Stimulus-specific signaling context; non-core. |
| GO:0000165 MAPK cascade | ISO GO_REF:0000121 | ACCEPT | Summary: ERK2 is a core component of the MAPK cascade; this is the generic parent of the ERK1/2 cascade term. Reason: Core biological process (generic parent of ERK1/2 cascade). ERK2 is a terminal MAPK of this cascade. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md concludes that EGF activates the canonical MAPK pathway in this native rat tissue context |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is a key effector of EGFR signaling; this is a major upstream pathway that activates the ERK1/2 cascade. Well supported in rat tissue. Reason: Genuine and important upstream-receptor pathway, but it is the receptor context that activates ERK2 rather than ERK2's own core function. Kept as non-core; strongly corroborated by rat IMCD EGF data. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md pathway enrichment confirms engagement of **RAFβMEKβERK signaling** |
| GO:0032206 positive regulation of telomere maintenance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Downstream/indirect process inferred by orthology; not a core function. Reason: Indirect downstream process; non-core. |
| GO:0004707 MAP kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: MAP kinase activity (ISO duplicate). Core MF. Reason: Core molecular function (orthology-inferred duplicate of the IDA/IEA MAP kinase activity annotations). Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Indirect downstream metabolic process inferred by orthology. Reason: Indirect downstream process; non-core. |
| GO:0061431 cellular response to methionine | IEP PMID:22676582 Activation of Nrf2 is required for up-regulation of the Ο cl... | KEEP AS NON CORE | Summary: ERK activation under methionine starvation (Nrf2/GST context); a stimulus-specific cellular response inferred from expression/phenotype. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:22676582 Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells |
| GO:0071380 cellular response to prostaglandin E stimulus | IEP PMID:11875501 Prostaglandin E2 transactivates EGF receptor: a novel mechan... | KEEP AS NON CORE | Summary: ERK activation downstream of PGE2/EGFR transactivation; stimulus-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:11875501 triggers the extracellular signal-regulated kinase 2 (ERK2)--mitogenic signaling pathway |
| GO:0071320 cellular response to cAMP | IEP PMID:8223435 cAMP antagonizes p21ras-directed activation of extracellular... | KEEP AS NON CORE | Summary: cAMP modulates ERK2 activation (cAMP antagonizes Ras-directed ERK2 activation); stimulus-specific response. Reason: Stimulus-specific response/crosstalk (IEP); non-core. Supporting Evidence: PMID:8223435 elevation of the intracellular cAMP level results in the inhibition of ERK2 activation induced by PDGF, EGF and insulin treatment |
| GO:0014069 postsynaptic density | IEP PMID:7478291 ERK2-type mitogen-activated protein kinase (MAPK) and its su... | KEEP AS NON CORE | Summary: ERK2 detected in postsynaptic density fractions from rat brain; a neuronal localization. Specialized. Reason: Tissue-specific neuronal localization; non-core but experimentally observed in rat brain. Supporting Evidence: PMID:7478291 Only ERK2 was detected in the postsynaptic density (PSD) fraction |
| GO:0014069 postsynaptic density | IDA PMID:7478291 ERK2-type mitogen-activated protein kinase (MAPK) and its su... | KEEP AS NON CORE | Summary: Direct observation of ERK2 in postsynaptic density fractions (rat brain). Reason: Tissue-specific neuronal localization with direct evidence; non-core. Supporting Evidence: PMID:7478291 Only ERK2 was detected in the postsynaptic density (PSD) fraction |
| GO:0032355 response to estradiol | IEP PMID:15893655 17-Beta estradiol rapidly enhances extracellular signal-regu... | KEEP AS NON CORE | Summary: Estradiol rapidly enhances ERK2 phosphorylation in rat brain; stimulus-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:15893655 E2-treated rats exhibited a statistically significant increase in ERK2 phosphorylation |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IEP PMID:8246947 Epidermal growth factor induces phosphorylation of extracell... | KEEP AS NON CORE | Summary: ERK2 is activated downstream of PDGF; a growth-factor-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:8246947 inhibits activation of extracellular signal-regulated kinase 2 (ERK2) by insulin and platelet-derived growth factor in rat-1 cells |
| GO:0071364 cellular response to epidermal growth factor stimulus | IEP PMID:8246947 Epidermal growth factor induces phosphorylation of extracell... | KEEP AS NON CORE | Summary: ERK2 is activated downstream of EGF; well supported in rat tissue (IMCD EGF phosphoproteomics shows TEY phosphorylation of Mapk1). Stimulus response. Reason: Stimulus-specific response, but strongly corroborated; non-core relative to the cascade itself. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md Dual phosphorylation in the TEY activation segment region** is directly observed for rat Mapk1/ERK2 |
| GO:0033574 response to testosterone | IEP PMID:22265242 Extracellular signal-regulated kinase 2 signaling in the hip... | KEEP AS NON CORE | Summary: ERK2 in dentate gyrus mediates antidepressant effects of testosterone; stimulus-specific. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:22265242 We found a testosterone-dependent regulation of hippocampal ERK2 expression |
| GO:0044849 estrous cycle | IEP PMID:22521590 Sex differences in social interaction behaviors in rats are ... | KEEP AS NON CORE | Summary: ERK2 expression correlates with estrous-cycle-related behavior; an organism-level physiological context, not a molecular role. Reason: Physiological/behavioral context (IEP); non-core. Supporting Evidence: PMID:22521590 female rats' had lower ERK2 expression compared to male rats |
| GO:0042220 response to cocaine | IEP PMID:19457111 Signaling pathway adaptations and novel protein kinase A sub... | KEEP AS NON CORE | Summary: ERK signaling adaptations in cocaine sensitization; stimulus-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:19457111 ERK2 activation followed a parallel time-course |
| GO:0042542 response to hydrogen peroxide | IEP PMID:11679970 Defective mitogen-activated protein kinase (ERK2) signaling ... | KEEP AS NON CORE | Summary: ERK2 signaling altered by oxidative stress; stimulus-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:11679970 in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired |
| GO:0097305 response to alcohol | IEP PMID:21790671 Elevated activation of ERK1 and ERK2 accompany enhanced live... | KEEP AS NON CORE | Summary: ERK1/2 activation accompanies alcohol-induced liver injury; stimulus-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:21790671 significant increase (compared with chronic ethanol alone) in the phosphorylation of extracellular regulated kinase 1 (ERK1), ERK2, and RSK |
| GO:1990314 cellular response to insulin-like growth factor stimulus | IEP PMID:9235900 Insulin-like growth factor-I rapidly activates multiple sign... | KEEP AS NON CORE | Summary: IGF-I rapidly activates ERK2 in cardiac myocytes; growth-factor-specific response. Reason: Stimulus-specific response (IEP); non-core. Supporting Evidence: PMID:9235900 Maximal activation of ERK2 (12-fold) and ERK1 (8.3-fold) activities was attained after a 5-min exposure to IGF-I |
| GO:0048009 insulin-like growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector of IGF-1R signaling; an upstream receptor pathway context inferred by orthology. Reason: Upstream-receptor pathway context; non-core. Supporting Evidence: UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF |
| GO:0008286 insulin receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector of insulin receptor signaling; upstream pathway context inferred by orthology. Reason: Upstream-receptor pathway context; non-core. Supporting Evidence: UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF |
| GO:0014044 Schwann cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A developmental process where ERK signaling is required; tissue/lineage specific, downstream of the cascade. Reason: Developmental process inferred by orthology; non-core. |
| GO:0042552 myelination | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process where ERK signaling participates; downstream and tissue-specific. Reason: Developmental process inferred by orthology; non-core. |
| GO:0038133 ERBB2-ERBB3 signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector of ERBB2-ERBB3 signaling; upstream receptor pathway context inferred by orthology. Reason: Upstream-receptor pathway context; non-core. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nuclear localization (ISO duplicate). Consistent core localization. Reason: Core localization, consistent with other nucleus annotations. Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus UniProtKB:P63086 autophosphorylation at Thr-188 promote nuclear localization |
| GO:0010759 positive regulation of macrophage chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific downstream process inferred by orthology. Reason: Cell-type-specific downstream process; non-core. |
| GO:0120041 positive regulation of macrophage proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific downstream process inferred by orthology. Reason: Cell-type-specific downstream process; non-core. |
| GO:0042307 positive regulation of protein import into nucleus | IMP PMID:19524539 LysRS serves as a key signaling molecule in the immune respo... | KEEP AS NON CORE | Summary: From the LysRS/Ap4A study; ERK2 phosphorylation of LysRS affecting its nuclear function. A specific downstream regulatory effect. Reason: Specific downstream regulatory effect (IMP); non-core. Supporting Evidence: PMID:19524539 LysRS was phosphorylated on serine 207 in a MAPK-dependent manner, released from the multisynthetase complex, and translocated into the nucleus |
| GO:0060045 positive regulation of cardiac muscle cell proliferation | IMP PMID:26884868 MAPK1 up-regulates the expression of MALAT1 to promote the p... | KEEP AS NON CORE | Summary: MAPK1 promotes cardiomyocyte proliferation via MALAT1/PI3K-AKT; a cell-type-specific downstream process. Reason: Cell-type-specific downstream process (IMP); non-core. Supporting Evidence: PMID:26884868 MAPK1 was able to increase the proliferation of cardiomyocytes |
| GO:0003690 double-stranded DNA binding | IDA PMID:26950759 Phosphorylation or Mutation of the ERK2 Activation Loop Alte... | KEEP AS NON CORE | Summary: The cited study shows that ERK2 activation-loop phosphorylation/mutation alters oligonucleotide binding; ERK2 can bind DNA. This is an unusual, non-catalytic moonlighting activity, not the core kinase function. Reason: Experimentally observed but non-canonical moonlighting DNA-binding activity; not the core kinase function. Retained as non-core. Supporting Evidence: PMID:26950759 has been shown to bind oligonucleotides directly UniProtKB:P63086 Binds to a [GC]AAA[GC] consensus sequence |
| GO:0006468 protein phosphorylation | IDA PMID:26950759 Phosphorylation or Mutation of the ERK2 Activation Loop Alte... | KEEP AS NON CORE | Summary: Generic protein phosphorylation; the catalytic output of ERK2 kinase activity. Accurate but generic relative to the MF terms. Reason: Generic BP that is the direct output of the kinase activity; the MF terms (MAP kinase activity) capture this more precisely. Non-core. GOA no longer carries this row. |
| GO:0046697 decidualization | IDA PMID:21248290 Ovarian steroid receptors and activated MAPK in the regional... | KEEP AS NON CORE | Summary: MAPK activation in regional decidualization in rats; tissue-specific developmental process. Reason: Tissue-specific developmental process; non-core. Supporting Evidence: PMID:21248290 MAPK was activated exclusively in undifferentiated stromal cells of the junctional zone |
| GO:0019902 phosphatase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 binds dual-specificity phosphatases (DUSPs/MKPs) that dephosphorylate it; a genuine regulatory interaction but not a core function. Reason: Regulatory protein interaction (with MKPs); non-core, more informative than generic protein binding. Supporting Evidence: UniProtKB:P63086 Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9 |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Protein serine/threonine kinase activity (ISO duplicate). Core MF. Reason: Core molecular function (orthology-inferred duplicate). Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0071356 cellular response to tumor necrosis factor | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stimulus-specific cellular response inferred by orthology. Reason: Stimulus-specific response; non-core. |
| GO:0030641 regulation of cellular pH | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Reflects ERK2 phosphorylation of the NHE1/SLC9A1 Na+/H+ exchanger; a specific downstream effect, corroborated in rat IMCD (ERK2 phosphorylates NHE1 at Ser727/Ser730). Reason: Specific downstream effector consequence (NHE1 phosphorylation); non-core but corroborated. GOA no longer carries this row. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md NHE1/Slc9a1** can act as a **membrane scaffold** for ERK2 |
| GO:0005515 protein binding | IPI PMID:24567387 MURC/Cavin-4 facilitates recruitment of ERK to caveolae and ... | REMOVE | Summary: ERK1/2 associate with MURC/Cavin-4 (WITH/FROM B1PRL5) in cardiomyocyte caveolae, facilitating ERK recruitment to caveolae. Reason: Cavin-4 is a caveolar structural protein; no more informative MF term for ERK2 is supported. Removal does not mean the reported interaction is false; the bare protein binding term simply carries no functional information about MAPK1/ERK2. Supporting Evidence: PMID:24567387 MURC/Cavin-4 bound to Ξ±1A- and Ξ±1B-ARs as well as ERK1/2 in caveolae |
| GO:0005737 cytoplasm | IDA PMID:24567387 MURC/Cavin-4 facilitates recruitment of ERK to caveolae and ... | ACCEPT | Summary: Cytoplasmic localization with direct evidence. Core localization. Reason: Core localization with direct experimental support. Supporting Evidence: UniProtKB:P63086 Cytoplasm {ECO:0000269|PubMed:24567387} |
| GO:0005886 plasma membrane | IDA PMID:24567387 MURC/Cavin-4 facilitates recruitment of ERK to caveolae and ... | KEEP AS NON CORE | Summary: ERK recruited to plasma membrane/caveolae in cardiac hypertrophy context; a specialized localized pool. Reason: Context-specific membrane recruitment; non-core. Supporting Evidence: PMID:24567387 MURC/Cavin-4 bound to Ξ±1A- and Ξ±1B-ARs as well as ERK1/2 in caveolae |
| GO:0005901 caveola | IDA PMID:24567387 MURC/Cavin-4 facilitates recruitment of ERK to caveolae and ... | KEEP AS NON CORE | Summary: Direct evidence of ERK recruitment to caveolae via MURC/Cavin-4. Specialized localization. Reason: Context-specific membrane microdomain localization with direct evidence; non-core. Supporting Evidence: PMID:24567387 MURC/Cavin-4 bound to Ξ±1A- and Ξ±1B-ARs as well as ERK1/2 in caveolae UniProtKB:P63086 Membrane, caveola |
| GO:0005515 protein binding | IPI PMID:12944431 DOC1R: a MAP kinase substrate that control microtubule organ... | REMOVE | Summary: Yeast two-hybrid interaction of MAPK with DOC1R (WITH/FROM Q9CPY4), a MAPK substrate regulating oocyte microtubules. Reason: DOC1R is a MAPK phosphorylation substrate; the interaction is captured by kinase activity and no more informative binding MF applies. Removal does not mean the reported interaction is false; the bare protein binding term simply carries no functional information about MAPK1/ERK2. Supporting Evidence: PMID:12944431 Using the same screen, we identify another MAPK partner, DOC1R |
| GO:0035094 response to nicotine | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stimulus-specific response (ISO duplicate of the nicotine annotations). Reason: Stimulus-specific response; non-core. Supporting Evidence: PMID:11404397 couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0035094 response to nicotine | IGI PMID:11404397 Beta-amyloid activates the mitogen-activated protein kinase ... | KEEP AS NON CORE | Summary: Beta-amyloid activates MAPK cascade via alpha7 nicotinic receptors; stimulus-specific response with genetic-interaction evidence. Reason: Stimulus-specific response (IGI); non-core. Supporting Evidence: PMID:11404397 couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0034198 cellular response to amino acid starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stimulus-specific cellular response inferred by orthology. Reason: Stimulus-specific response; non-core. |
| GO:0051403 stress-activated MAPK cascade | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: ERK2 is not part of the stress-activated (p38/JNK) MAPK cascade itself; this annotation conflates the ERK cascade with stress-activated cascades. Reason: ERK2 is the terminal kinase of the ERK1/2 (mitogen-activated) cascade, not a component of the stress-activated (p38/JNK) cascade. This orthology-inferred term likely over-annotates; ERK2's relationship to stress cascades is regulatory crosstalk (captured by GO:0032872), not membership. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P28482 Β· human MAPK1 SUPPORTS SOURCE BUT NOT TARGET Human MAPK1 carries the term by IDA (PMID:11096076), but ERK2's relationship to the stress-activated cascades is crosstalk; membership in the p38/JNK cascade does not transfer. |
| GO:0004707 MAP kinase activity | IMP PMID:19524539 LysRS serves as a key signaling molecule in the immune respo... | ACCEPT | Summary: MAP kinase activity demonstrated via LysRS phosphorylation. Core MF. Reason: Core molecular function with experimental support. Supporting Evidence: PMID:19524539 LysRS was phosphorylated on serine 207 in a MAPK-dependent manner |
| GO:0015966 diadenosine tetraphosphate biosynthetic process | IMP PMID:19524539 LysRS serves as a key signaling molecule in the immune respo... | KEEP AS NON CORE | Summary: ERK2 phosphorylation of LysRS triggers Ap4A production in immune signaling; an indirect downstream consequence, not an ERK2 enzymatic activity. Reason: Indirect downstream consequence via substrate (LysRS); ERK2 does not itself synthesize Ap4A. Non-core. Supporting Evidence: PMID:19524539 LysRS was phosphorylated on serine 207 in a MAPK-dependent manner |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:19524539 LysRS serves as a key signaling molecule in the immune respo... | KEEP AS NON CORE | Summary: ERK2 promotes transcription via substrate phosphorylation; downstream regulatory consequence. Reason: Downstream transcriptional regulation via substrates; non-core. Supporting Evidence: PMID:19524539 enabling MITF to transcribe its target genes |
| GO:0070371 ERK1 and ERK2 cascade | IMP PMID:19524539 LysRS serves as a key signaling molecule in the immune respo... | ACCEPT | Summary: ERK1/2 cascade (IMP). Core biological process. Reason: Core biological process with experimental support. Supporting Evidence: PMID:19524539 LysRS was phosphorylated on serine 207 in a MAPK-dependent manner |
| GO:0030278 regulation of ossification | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process where ERK signaling participates; tissue-specific, downstream. Reason: Developmental process inferred by orthology; non-core. |
| GO:0007507 heart development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK1/2 signaling is required for heart development; a pleiotropic developmental process downstream of the cascade. Reason: Developmental process inferred by orthology; non-core. |
| GO:0014032 neural crest cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process where ERK signaling participates; downstream. Reason: Developmental process inferred by orthology; non-core. |
| GO:0030878 thyroid gland development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0042473 outer ear morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology (RASopathy-related); downstream. Reason: Developmental process; non-core. |
| GO:0048538 thymus development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0060324 face development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology (RASopathy-related); downstream. Reason: Developmental process; non-core. |
| GO:0061308 cardiac neural crest cell development involved in heart development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0060020 Bergmann glial cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell-type-specific developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0070371 ERK1 and ERK2 cascade | ISO GO_REF:0000121 | ACCEPT | Summary: ERK1/2 cascade (ISO duplicate). Core biological process. Reason: Core biological process (orthology-inferred duplicate). Supporting Evidence: UniProtKB:P63086 MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade |
| GO:0006468 protein phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic protein phosphorylation (the catalytic output). Generic relative to the MF terms. Reason: Generic BP output of kinase activity; non-core. GOA no longer carries this row. |
| GO:0060425 lung morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0060440 trachea formation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0060291 long-term synaptic potentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK signaling contributes to LTP; a neuronal physiological process downstream of the cascade. Reason: Neuronal physiological process inferred by orthology; non-core. Supporting Evidence: PMID:11687663 the magnitude of long-term potentiation in hippocampus |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization (ISS duplicate). Core localization. Reason: Core localization. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0072686 mitotic spindle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitotic spindle localization (specific child of spindle). Specialized mitotic localization. Reason: Context-specific mitotic localization; non-core. Supporting Evidence: UniProtKB:P63086 Associated with the spindle during prometaphase and metaphase |
| GO:0004707 MAP kinase activity | IMP PMID:16955078 Alterations in mammalian target of rapamycin signaling pathw... | ACCEPT | Summary: MAP kinase activity (mTOR signaling/TBI context). Core MF. Reason: Core molecular function with experimental support. The cached abstract (traumatic brain injury and mTOR signalling) does not itself describe the ERK2 assay, so this rests on deference to the curator, who read the full text; the activity is in any case well established for ERK2. Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway |
| GO:0018105 peptidyl-serine phosphorylation | IMP PMID:16955078 Alterations in mammalian target of rapamycin signaling pathw... | KEEP AS NON CORE | Summary: ERK2 phosphorylates serine residues on substrates; a specific child of protein phosphorylation describing the catalytic output. Reason: Describes the catalytic output (serine phosphorylation); the MF terms capture this more precisely. Non-core. GOA no longer carries this row. |
| GO:0019901 protein kinase binding | IPI PMID:16943189 cGMP-dependent protein kinase type I inhibits TAB1-p38 mitog... | UNDECIDED | Summary: IPI for ERK2 binding the cGMP-dependent protein kinase PKG I (Prkg1, RGD:1587390) from a cardiac ischemia/reperfusion study centred on TAB1-p38 MAPK; protein kinase binding would be more informative than generic protein binding if the interaction is confirmed. Reason: The cached record of PMID:16943189 is abstract-only and the abstract concerns PKG I inhibiting TAB1-p38 MAPK signalling without mentioning ERK2; the curator-recorded ERK2-PKG I (RGD:1587390, Prkg1) interaction presumably comes from the full text, which could not be checked here. The interaction cannot be adjudicated from the available evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-3245934 | ACCEPT | Summary: Nucleoplasm localization, from a Reactome reaction (Mapk1 phosphorylates ERF). Consistent core nuclear localization. Reason: Consistent specific nuclear localization (TAS from Reactome). Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation |
| GO:0038127 ERBB signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector of ERBB receptor signaling; upstream pathway context inferred by orthology. Reason: Upstream-receptor pathway context; non-core. Supporting Evidence: UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Cytoplasmic localization (ISO duplicate). Core localization. Reason: Core localization. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0070849 response to epidermal growth factor | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ERK2 responds to EGF; strongly supported in rat tissue (IMCD EGF phosphoproteomics). Stimulus response. Reason: Stimulus-specific response; non-core but well corroborated. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md concludes that EGF activates the canonical MAPK pathway in this native rat tissue context |
| GO:0070849 response to epidermal growth factor | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to EGF (ISO duplicate). Stimulus response. Reason: Stimulus-specific response; non-core. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md concludes that EGF activates the canonical MAPK pathway in this native rat tissue context |
| GO:0018105 peptidyl-serine phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Serine phosphorylation output (ISO duplicate). Generic catalytic output. Reason: Describes the catalytic output; non-core relative to MF terms. GOA no longer carries this row. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:7768935 Phosphorylation of tristetraprolin, a potential zinc finger ... | KEEP AS NON CORE | Summary: Direct demonstration of ERK2 serine phosphorylation of tristetraprolin in vitro. Catalytic output. Reason: Direct evidence for the catalytic output (serine phosphorylation); the MF terms capture this more precisely. Non-core. Supporting Evidence: PMID:7768935 serine 220 was phosphorylated by p42 MAP kinase in vitro |
| GO:0005634 nucleus | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | ACCEPT | Summary: Nuclear localization from a review of ERK signaling across compartments. Core localization. Reason: Core localization (TAS). Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 Many of these substrates are localized in the nucleus |
| GO:0005739 mitochondrion | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: A mitochondrial ERK pool is reported; a minor specialized localization. Reason: Minor/specialized localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution |
| GO:0005769 early endosome | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Endosomal ERK signaling pool; context-specific localization. Reason: Context-specific localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005770 late endosome | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Endosomal ERK signaling pool; context-specific localization. Reason: Context-specific localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005794 Golgi apparatus | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Golgi-associated ERK pool; specialized localization. Reason: Specialized localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 as well as in the fragmentation of the Golgi apparatus during mitosis |
| GO:0005829 cytosol | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | ACCEPT | Summary: Cytosolic localization. Core localization (the basal pool). Reason: Core localization (cytosolic pool, TAS). Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005856 cytoskeleton | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: ERK associates with cytoskeletal structures in some contexts; specialized localization. Reason: Context-specific localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 Associated with the spindle during prometaphase and metaphase |
| GO:0005901 caveola | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Caveolar ERK pool; specialized localization. Reason: Specialized localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 Membrane, caveola |
| GO:0005925 focal adhesion | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Focal-adhesion-associated ERK pool; specialized localization. Reason: Specialized localization; non-core. Supporting Evidence: PMID:19565474 the cascade exhibits versatile and dynamic subcellular distribution UniProtKB:P63086 Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions |
| GO:0032872 regulation of stress-activated MAPK cascade | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: ERK crosstalk regulating stress-activated MAPK cascades; secondary regulatory role. Reason: Crosstalk/regulatory role; non-core. |
| GO:0051493 regulation of cytoskeleton organization | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: ERK phosphorylation of cytoskeletal regulators; downstream effect. Reason: Downstream effector consequence; non-core. Supporting Evidence: UniProtKB:P63086 cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1) |
| GO:0072584 caveolin-mediated endocytosis | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Specialized endocytic process where ERK is implicated; downstream. Reason: Context-specific process; non-core. Supporting Evidence: UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0090170 regulation of Golgi inheritance | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: ERK role in mitotic Golgi partitioning; specialized process. Reason: Specialized mitotic process; non-core. Supporting Evidence: UniProtKB:P63086 as well as in the fragmentation of the Golgi apparatus during mitosis |
| 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: Specialized endosomal trafficking process linked to ERK; downstream. Reason: Context-specific process; non-core. Supporting Evidence: UniProtKB:P63086 the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics |
| GO:0005515 protein binding | IPI PMID:19200235 Dopamine promotes striatal neuronal apoptotic death via ERK ... | MODIFY | Summary: Phospho-ERK co-immunoprecipitates with the scaffold protein beta-arrestin2 (WITH/FROM RGD:2157) and the D1 dopamine receptor in striatal neurons, causing cytosolic retention of p-ERK. Reason: The partner beta-arrestin2 is explicitly described as a scaffold protein that binds p-ERK; 'scaffold protein binding' is the informative MF. GOA no longer carries this row; the MODIFY judgment is retained as the record of how the IPI should be represented if the annotation is re-instated. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:19200235 The scaffold protein beta-arrestin2 interacted with both p-ERK and D1 DA receptor |
| GO:0010800 positive regulation of peptidyl-threonine phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A downstream regulatory consequence (promoting threonine phosphorylation of targets) inferred by orthology. Reason: Downstream regulatory consequence; non-core. GOA no longer carries this row. |
| GO:0031143 pseudopodium | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pseudopodium localization inferred by orthology (migration context); specialized localization. Reason: Context-specific localization; non-core. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial ERK pool (ISO duplicate); minor specialized localization. Reason: Minor/specialized localization; non-core. |
| GO:0033598 mammary gland epithelial cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell-type-specific downstream proliferation process inferred by orthology. Reason: Cell-type-specific downstream process; non-core. |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: This term implies ERK2 phosphorylates the Pol II CTD as a CTD kinase. ERK2 is a proline-directed kinase and can phosphorylate Ser-Pro sites including in the CTD, but assigning a dedicated CTD-kinase MF (typically reserved for CDKs) is likely an over-annotation by orthology transfer. Reason: ERK2's role as a bona fide Pol II CTD kinase is not its established core function; this orthology-inferred specific MF over-annotates the protein. The canonical CTD kinases are CDK7/CDK9/CDK12. Marked as over-annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 Β· mouse Mapk1 SUPPORTS SOURCE BUT NOT TARGET The mouse donor (UniProtKB:P63085) carries a single GO:0008353 annotation, an IDA cited to PMID:12721286 (verified against QuickGO; that paper is titled for the SCP1 CTD phosphatase, and the cached record here is abstract-only, so the ERK2 assay supporting the IDA is visible to the curator but not in this cache). ERK2 being proline-directed makes such an in vitro CTD-phosphorylation result unsurprising, but a dedicated Pol II CTD-kinase molecular function over-reads that single donor IDA for the rat gene. |
| GO:0009636 response to toxic substance | IDA PMID:17651772 MAPK-ERK activation in kidney of male rats chronically fed o... | KEEP AS NON CORE | Summary: ERK activation in kidney upon ochratoxin A exposure; stimulus-specific response. Reason: Stimulus-specific response; non-core. Supporting Evidence: PMID:17651772 selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:7768935 Phosphorylation of tristetraprolin, a potential zinc finger ... | ACCEPT | Summary: Direct evidence of ERK2 Ser/Thr kinase activity (TTP phosphorylation). Core MF. The deep research notes that ERK1/2 substrates contain a Ser/Thr-Pro consensus. Reason: Core molecular function with direct experimental support. Supporting Evidence: PMID:7768935 serine 220 was phosphorylated by p42 MAP kinase in vitro |
| GO:0060716 labyrinthine layer blood vessel development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Placental developmental process inferred by orthology; downstream. Reason: Developmental process; non-core. |
| GO:0005654 nucleoplasm | IDA PMID:7889942 ERK phosphorylation potentiates Elk-1-mediated ternary compl... | ACCEPT | Summary: Direct evidence of nucleoplasmic ERK (Elk-1 phosphorylation context). Core nuclear localization. Reason: Core nuclear localization with direct evidence. Supporting Evidence: PMID:7889942 is a nuclear target of two members of the MAP kinase family, ERK1 and ERK2 |
| GO:0005515 protein binding | IPI PMID:15781236 Caveolin-2 regulation of the cell cycle in response to insul... | REMOVE | Summary: ERK co-immunoprecipitates with caveolin-2 (WITH/FROM RGD:620348) in insulin-stimulated Hirc-B fibroblasts. Reason: Caveolin-2 is a caveolar membrane protein; no more informative MF term for ERK2 is supported by this study. Removal does not mean the reported interaction is false; the bare protein binding term simply carries no functional information about MAPK1/ERK2. Supporting Evidence: PMID:15781236 Direct interaction between ERK and caveolin-2 was confirmed by immunoprecipitation |
| GO:0032991 protein-containing complex | IDA PMID:15781236 Caveolin-2 regulation of the cell cycle in response to insul... | KEEP AS NON CORE | Summary: ERK co-immunoprecipitates with caveolin-2 in insulin-stimulated Hirc-B fibroblasts; a generic complex membership term. Reason: The co-immunoprecipitation of ERK with caveolin-2 does place ERK in a protein-containing complex, so the term does not exceed the evidence; it is generic and the specific complex is not a defined GO complex, so it is retained as non-core rather than marked as over-annotated. Supporting Evidence: PMID:15781236 Direct interaction between ERK and caveolin-2 was confirmed by immunoprecipitation |
| GO:0031435 mitogen-activated protein kinase kinase kinase binding | IPI PMID:12049732 The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and m... | KEEP AS NON CORE | Summary: ERK2 interacts with MEKK1 (a MAP3K) which ubiquitinates ERK1/2. An informative interaction within the cascade module. Reason: Informative protein-interaction term reflecting ERK2 binding within the MAPK module; non-core. Supporting Evidence: PMID:12049732 exhibited E3 ubiquitin ligase activity toward ERK2 in vitro and in vivo |
| GO:0030424 axon | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: ERK2 (p42MAPK) immunolocalized to axons in rat CNS; neuronal subcellular localization. Reason: Tissue-specific neuronal localization with direct evidence; non-core. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons |
| GO:0032839 dendrite cytoplasm | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: ERK2 immunolocalized to dendritic cytoplasm in rat CNS; neuronal localization. Reason: Tissue-specific neuronal localization with direct evidence; non-core. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons |
| GO:0043204 perikaryon | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: ERK2 immunolocalized to the perikaryon (neuronal cell body) in rat CNS. Reason: Tissue-specific neuronal localization with direct evidence; non-core. Supporting Evidence: PMID:9714150 in dendrites and axons, as well as in cell bodies |
| GO:0005829 cytosol | TAS Reactome:R-NUL-997411 | ACCEPT | Summary: Cytosolic localization from a Reactome reaction (AGER binds rat ERK1/2). Core localization. Reason: Core localization (cytosolic pool, TAS). Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0050853 B cell receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector downstream of the B cell receptor; immune-cell pathway context inferred by orthology. Reason: Cell-type-specific upstream pathway context; non-core. |
| GO:0050852 T cell receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 is an effector downstream of the T cell receptor; immune-cell pathway context inferred by orthology. Reason: Cell-type-specific upstream pathway context; non-core. |
| GO:0004674 protein serine/threonine kinase activity | IC PMID:15027896 Angiotensin II-induced ERK1/ERK2 activation and protein synt... | ACCEPT | Summary: Ser/Thr kinase activity inferred by curator. Core MF. Reason: Core molecular function. GOA no longer carries this row. |
| GO:0004707 MAP kinase activity | IDA PMID:15027896 Angiotensin II-induced ERK1/ERK2 activation and protein synt... | ACCEPT | Summary: Direct evidence of ERK1/2 (MAP kinase) activation in mesangial cells. Core MF. Reason: Core molecular function with direct evidence. Supporting Evidence: PMID:15027896 Ang II activates ERK1/ERK2 via the AT1 receptor UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway |
| GO:0005524 ATP binding | IDA PMID:15027896 Angiotensin II-induced ERK1/ERK2 activation and protein synt... | ACCEPT | Summary: ATP binding/use directly demonstrated. Core MF. The deep research independently describes an in vitro kinase assay using active TEY-phosphorylated ERK2 and an ATP-gamma-S analog. Reason: Core molecular function with direct experimental support. Supporting Evidence: UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0006468 protein phosphorylation | IDA PMID:15027896 Angiotensin II-induced ERK1/ERK2 activation and protein synt... | KEEP AS NON CORE | Summary: Generic protein phosphorylation (catalytic output) with direct evidence. Reason: Generic BP output of kinase activity; the MF terms capture this more precisely. Non-core. GOA no longer carries this row. |
| GO:0045727 positive regulation of translation | IMP PMID:15027896 Angiotensin II-induced ERK1/ERK2 activation and protein synt... | KEEP AS NON CORE | Summary: ERK promotes protein synthesis in mesangial cells; downstream consequence. Reason: Downstream regulatory consequence; non-core. Supporting Evidence: PMID:15027896 protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor |
| GO:0000165 MAPK cascade | IMP PMID:17310240 Growth factor-induced MAPK network topology shapes Erk respo... | ACCEPT | Summary: ERK response within the growth-factor-induced MAPK network. Core BP. Reason: Core biological process (generic parent of ERK1/2 cascade) with experimental support. Supporting Evidence: PMID:17310240 bi-stable Erk activation dynamics, which were indeed observed |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK acts downstream of LPS/TLR signaling; stimulus-specific pathway context inferred by orthology. Reason: Stimulus-specific pathway context; non-core. |
| GO:0032496 response to lipopolysaccharide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stimulus-specific cellular response inferred by orthology. Reason: Stimulus-specific response; non-core. |
| GO:0043330 response to exogenous dsRNA | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stimulus-specific cellular response inferred by orthology. Reason: Stimulus-specific response; non-core. |
| GO:0045596 negative regulation of cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK signaling modulates differentiation; a pleiotropic, context-dependent downstream process inferred by orthology. Reason: Context-dependent downstream process; non-core. |
| GO:0008284 positive regulation of cell population proliferation | IEP PMID:15583728 The indazole derivative YD-3 inhibits thrombin-induced vascu... | KEEP AS NON CORE | Summary: ERK1/2 drives proliferation (thrombin-induced VSMC proliferation context). A major but downstream pleiotropic outcome of cascade activity. Reason: Major downstream consequence of ERK activity, but context-dependent and not the protein's core molecular role. Kept as non-core. Supporting Evidence: PMID:15583728 YD-3 inhibits thrombin-induced VSMC growth via the Ras- and ERK1/2-mediated signaling pathway |
| GO:0030335 positive regulation of cell migration | IEP PMID:15917991 Reactive oxygen species and ERK 1/2 mediate monocyte chemota... | KEEP AS NON CORE | Summary: ERK1/2 promotes cell migration (MCP-1-stimulated VSMC migration). A downstream pleiotropic outcome. Reason: Downstream consequence of ERK activity; non-core. Supporting Evidence: PMID:15917991 MCP-1-stimulated migration requires both ROS production and ERK 1/2 activation |
| GO:0043627 response to estrogen | IDA PMID:11751611 Impact of progestins on estrogen-induced neuroprotection: sy... | KEEP AS NON CORE | Summary: ERK2 activation in estrogen-induced neuroprotection; stimulus-specific response. Reason: Stimulus-specific response; non-core. Supporting Evidence: PMID:11751611 Estrogen and all three progestins tested, alone or in combination, activated MAPK |
| GO:0097237 cellular response to toxic substance | IDA PMID:12487375 Acrolein activates mitogen-activated protein kinase signal t... | KEEP AS NON CORE | Summary: ERK activation by acrolein in vascular smooth muscle; stimulus-specific response. Reason: Stimulus-specific response; non-core. Supporting Evidence: PMID:12487375 are effectively and transiently activated by acrolein in a concentration and time-dependent fashion |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Generic parent of the specific kinase MF terms. Reason: The term is correct but too general rather than an over-reach of the evidence; ERK2 is a MAP kinase, and GO:0004707 MAP kinase activity is the precise replacement. The mouse source no longer carries generic kinase activity (see propagation_review). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 Β· mouse Mapk1 SOURCE STALE OR MISSING The current mouse Mapk1 record carries no generic kinase activity annotation (QuickGO, checked 2026-08); its evidence is for MAP kinase and protein serine/threonine kinase activity. Proposed replacements: MAP kinase activity |
| GO:0019858 cytosine metabolic process | ISO GO_REF:0000121 | REMOVE | Summary: ERK2 has no established role in cytosine metabolism as a function it executes; the donor mouse Mapk1 annotation is experimentally grounded (IDA, PMID:15284227), but the term does not describe an ERK2 function. Reason: ERK2 is a protein kinase; it does not execute a function in pyrimidine/cytosine metabolism, so the term fails the review standard for a process annotation regardless of the donor evidence. Source tracing shows the mouse donor annotation rests on a real IDA (PMID:15284227, an MKP3/CK2alpha study), so the defect is the term choice/transfer, not a fabricated source; REMOVE stands on the biology. Propagation Review Root cause: PROPAGATION BAD Sources checked: MGI:MGI:1346858 Β· mouse Mapk1 SUPPORTS SOURCE BUT NOT TARGET The mouse donor does carry this term (IDA, PMID:15284227, a study of MKP3 and CK2alpha), but nothing in ERK2 biology connects it to cytosine metabolism, so the transfer is unsafe for the rat gene. |
| GO:0019233 sensory perception of pain | IMP PMID:11356865 Metabotropic glutamate receptor subtypes 1 and 5 are activat... | KEEP AS NON CORE | Summary: ERK signaling required for inflammatory pain (via mGluR1/5); an organism-level physiological process downstream of the cascade. Reason: Physiological process; non-core. Supporting Evidence: PMID:11356865 We show that activation of mGluR1 and mGluR5 leads to activation of ERK1 and ERK2 in the spinal cord |
| GO:0006974 DNA damage response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK signaling participates in DNA damage responses in some contexts; downstream/context-specific. Reason: Context-specific downstream process; non-core. |
| GO:0004707 MAP kinase activity | TAS PMID:9779826 Expression of mitogen-activated protein kinase pathways duri... | ACCEPT | Summary: MAP kinase activity (TAS, postnatal heart development study). Core MF. Reason: Core molecular function. Supporting Evidence: PMID:9779826 Mitogen-activated protein kinases (MAPKs) mediate signaling pathways for cell proliferation/differentiation and stress responses such as ischemia |
| GO:0006468 protein phosphorylation | TAS PMID:9779826 Expression of mitogen-activated protein kinase pathways duri... | KEEP AS NON CORE | Summary: Generic protein phosphorylation (catalytic output, TAS). Reason: Generic BP output; non-core relative to MF terms. GOA no longer carries this row. |
| GO:0016301 kinase activity | TAS PMID:11687663 Cyclic changes in estradiol regulate synaptic plasticity thr... | MODIFY | Summary: Generic kinase activity (TAS). Over-general. Reason: The term is correct but too general rather than an over-reach of the evidence; the cited study measured ERK2/MAP kinase activation, so GO:0004707 MAP kinase activity is the precise replacement. Proposed replacements: MAP kinase activity |
| GO:0035556 intracellular signal transduction | IDA PMID:12072413 1alpha,25-dihydroxyvitamin D(3) and 24R,25-dihydroxyvitamin ... | KEEP AS NON CORE | Summary: ERK1/2 in vitamin-D-modulated chondrocyte signaling; generic signal-transduction parent. Reason: Generic BP parent; the ERK1/2 cascade term is preferred. Non-core. Supporting Evidence: PMID:12072413 In both cells the effect was due to ERK1/2 activation |
| GO:0035556 intracellular signal transduction | TAS PMID:9779826 Expression of mitogen-activated protein kinase pathways duri... | KEEP AS NON CORE | Summary: Generic intracellular signal transduction (TAS). Reason: Generic BP parent; non-core. Supporting Evidence: PMID:9779826 Mitogen-activated protein kinases (MAPKs) mediate signaling pathways for cell proliferation/differentiation and stress responses such as ischemia |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Generic parent of the specific kinase MF terms (ISO duplicate). Reason: The term is correct but too general rather than an over-reach of the evidence; the specific activity of ERK2 is MAP kinase activity (GO:0004707), which the gene carries with direct experimental support, so the generic parent should be replaced by it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 Β· mouse Mapk1 SUPPORTS SOURCE BUT NOT TARGET The mouse donor carries the term by IDA (PMID:14744933), but the specific MAP kinase and serine/threonine kinase terms are already present on the rat gene and are preferred. Proposed replacements: MAP kinase activity |
| GO:0001784 phosphotyrosine residue binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: This implies ERK2 binds phosphotyrosine residues. ERK2 does engage phosphorylated docking partners, but a dedicated phosphotyrosine-binding MF is not an established ERK2 function and likely over-annotates by orthology transfer. Reason: Not an established ERK2 molecular function; ERK2 lacks a canonical phosphotyrosine-binding module (e.g., SH2/PTB). Likely an erroneous/over-broad orthology transfer. Propagation Review Root cause: PROPAGATION BAD Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 Β· mouse Mapk1 SUPPORTS SOURCE BUT NOT TARGET The mouse donor support is an IMP (PMID:14636584) reflecting engagement with phosphorylated partners; ERK2 has no canonical phosphotyrosine-binding module, so a dedicated molecular function over-reads the donor. |
| GO:0009887 animal organ morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic developmental morphogenesis process inferred by orthology; pleiotropic and downstream. Reason: Generic developmental process; non-core. |
| GO:0000165 MAPK cascade | ISO GO_REF:0000121 | ACCEPT | Summary: ERK2 is a terminal MAPK of the canonical MAPK cascade; orthology transfer from mouse Mapk1 (MGI:1346858) with the involved_in qualifier. Reason: Core biological process, consistent with the sibling ISO row from the same mouse donor (acts_upstream_of_or_within) and with the rat IMP evidence (PMID:17310240). The more specific ERK1 and ERK2 cascade term is also accepted. Supporting Evidence: UniProtKB:P63086 MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade |
| GO:0000165 MAPK cascade | ISO GO_REF:0000121 | ACCEPT | Summary: ERK2 is a terminal MAPK of the canonical MAPK cascade; orthology transfer from human MAPK1 (UniProtKB:P28482). Reason: Core biological process; the human MAPK1 donor is the direct ortholog with extensive experimental evidence for its role in the cascade. Consistent with the mouse-donor ISO rows. Supporting Evidence: UniProtKB:P63086 MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Protein serine/threonine kinase activity transferred from human MAPK1 (UniProtKB:P28482). Reason: Core molecular function; same claim as the sibling ISO row from mouse Mapk1 and the rat IDA row (PMID:7768935). ERK2 phosphorylates both Ser and Thr residues in Ser/Thr-Pro motifs. Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004707 MAP kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: MAP kinase activity transferred from human MAPK1 (UniProtKB:P28482). Reason: Core molecular function; same claim as the mouse-donor ISO row and the rat IDA/IMP rows (e.g. PMID:7889942, PMID:15027896). Supporting Evidence: UniProtKB:P63086 Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway UniProtKB:P63086 Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nuclear localization transferred from human MAPK1 (UniProtKB:P28482). Reason: Core localization; activated ERK2 enters the nucleus to phosphorylate transcription factors. Consistent with the mouse-donor ISO row, the IBA row and the rat IDA nucleoplasm row (PMID:7889942). Supporting Evidence: UniProtKB:P63086 Many of these substrates are localized in the nucleus UniProtKB:P63086 Phosphorylation at Ser- 244 and Ser- 246 as well as autophosphorylation at Thr-188 promote nuclear localization |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Cytoplasmic localization transferred from human MAPK1 (UniProtKB:P28482). Reason: Core localization (basal and cytoplasmically retained ERK2 pool); consistent with the mouse-donor ISO row and the rat IDA row (PMID:24567387). Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization transferred by sequence similarity from human MAPK1 (UniProtKB:P28482). Reason: Core localization; same claim as the sibling ISS row from Xenopus mapk1 (UniProtKB:P26696) and the ISO rows. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Cytosol as a site of activity, transferred from human MAPK1 (UniProtKB:P28482). Reason: Core localization; MEK-mediated activation of ERK2 and phosphorylation of many cytosolic substrates (RSKs, translation regulators) occur in the cytosol. Consistent with the mouse-donor is_active_in row. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Cytosolic localization transferred from mouse Mapk1 (MGI:1346858) with the located_in qualifier. Reason: Core localization, consistent with the is_active_in sibling from the same donor and the Reactome TAS cytosol rows. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Cytosolic localization transferred from human MAPK1 (UniProtKB:P28482) with the located_in qualifier. Reason: Core localization, consistent with the mouse-donor rows and the Reactome TAS cytosol rows. Supporting Evidence: UniProtKB:P63086 PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention |
| GO:0019902 phosphatase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 binds dual-specificity MAPK phosphatases (DUSPs/MKPs) that dephosphorylate and inactivate it; transferred from human MAPK1 (UniProtKB:P28482). Reason: Genuine regulatory interaction with its inactivating phosphatases, more informative than generic protein binding, but a regulatory input rather than ERK2's core activity. Consistent with the mouse-donor sibling row. Supporting Evidence: UniProtKB:P63086 Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9 UniProtKB:P63086 Interacts with DUSP6 (PubMed:16567630) |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERK2 homodimerization, transferred from human MAPK1 (UniProtKB:P28482). Reason: ERK2 dimerization is documented and is required for some interactions (e.g. with TPR), but it is a regulatory property rather than the core activity. Consistent with the mouse-donor sibling row. Supporting Evidence: UniProtKB:P63086 the interaction requires dimerization of MAPK1/ERK2 |
| GO:0043415 positive regulation of skeletal muscle tissue regeneration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of skeletal muscle tissue regeneration, transferred from mouse Mapk1 (MGI:1346858), whose annotation is an IMP (PMID:38198890, per QuickGO). Reason: A tissue-specific downstream outcome of ERK signalling in a mouse loss-of-function setting; plausible for rat ERK2 but not a core function. The mouse source paper is not cached here, so the specific mechanism was not assessed. |
| GO:0045880 positive regulation of smoothened signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of smoothened signaling, transferred from human MAPK1 (UniProtKB:P28482). Reason: ERK phosphorylates GLI1 downstream of smoothened activation, promoting its nuclear translocation; a specific regulatory output, non-core. Consistent with the ISS sibling row from the same donor. Supporting Evidence: UniProtKB:P63086 Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI1 |
| GO:0051453 regulation of intracellular pH | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of intracellular pH, transferred from mouse Mapk1 (MGI:1346858; mouse IMP, PMID:26375174, per QuickGO). Replaces the retired row for the obsolete term GO:0030641 regulation of cellular pH. Reason: Plausibly reflects ERK2 phosphorylation of the Na+/H+ exchanger NHE1/SLC9A1, a specific downstream effector output also seen in rat IMCD; non-core. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md ERK2 phosphorylates NHE1 |
| GO:0070371 ERK1 and ERK2 cascade | ISO GO_REF:0000121 | ACCEPT | Summary: ERK1 and ERK2 cascade, transferred from human MAPK1 (UniProtKB:P28482). Reason: Core biological process; ERK2 is one of the two defining kinases of this cascade. Consistent with the mouse-donor ISO row and rat IMP row (PMID:19524539). Supporting Evidence: UniProtKB:P63086 MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade |
| GO:0097237 cellular response to toxic substance | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular response to toxic substance from an ARBA rule (ARBA:ARBA00027337). Reason: ERK activation by toxicants (e.g. acrolein in vascular smooth muscle, the IDA sibling PMID:12487375) is a stimulus-specific consequence of cascade activation, not a core function; kept non-core consistent with that row. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine kinase activity from an ARBA rule with the Rhea serine-phosphorylation reaction (RHEA:17989). Reason: Accurate core MF; ERK2 is a Ser/Thr kinase and the rat IMP row (PMID:29959233) shows ERK phosphorylation of Cx43 Ser279/Ser282. Same claim as the retired GO_REF:0000116 row this IEA now supersedes. Supporting Evidence: UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0106310 protein serine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Protein serine kinase activity transferred from human MAPK1 (UniProtKB:P28482). Reason: Accurate core MF, consistent with the rat IMP row (PMID:29959233) and the IEA row. Supporting Evidence: UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0106310 protein serine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Protein serine kinase activity transferred by sequence similarity from human MAPK1 (UniProtKB:P28482). Reason: Accurate core MF, consistent with the rat IMP row (PMID:29959233); same claim as the ISO row from the same donor. Supporting Evidence: UniProtKB:P63086 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) UniProtKB:P63086 Phosphorylates GJA1 at 'Ser- 279' and 'Ser-282' |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: To what extent are the many ISO-inferred developmental and tissue-specific process annotations (e.g., thyroid/thymus/face/lung development) representative of an endogenous rat Mapk1 requirement versus general ERK1/2 pathway pleiotropy shared redundantly with Mapk3/ERK1?
Q: Which ERK2 substrates and localized signaling pools are most relevant in rat-specific physiology (e.g., the IMCD EGF-ERK network and NHE1/SLC9A1 phosphorylation), and how does ERK2 nuclear translocation versus cytoplasmic sequestration (PEA-15) shape these outputs?
Q: Does the full text of PMID:16943189 (PKG I and TAB1-p38 MAPK in cardiac ischemia/reperfusion) actually show a direct ERK2-PKG I (Prkg1) interaction supporting the IPI protein kinase binding annotation, or was ERK2 assayed only as a control MAPK?
Experiment: Use compartment-restricted ERK2 (constitutively nuclear vs. cytoplasm-tethered) in a relevant rat cell system and perform RNA-seq plus phosphoproteomics to dissect which downstream processes require nuclear ERK2 versus cytoplasmic ERK2 activity.
Hypothesis: Endogenous rat ERK2 (Mapk1) activation drives a defined transcriptional program through nuclear translocation, separable from cytoplasmic substrate phosphorylation.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)