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. Because ERK2 is an extremely pleiotropic signaling hub, it is annotated to a very large number of downstream and developmental processes; most of these are context-specific consequences of cascade activity rather than the core function 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: file:rat/Mapk1/Mapk1-deep-research-falcon.md NHE1/Slc9a1** can act as a **membrane scaffold** for ERK2 |
| 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. |
| 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. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic parent of protein serine/threonine kinase / MAP kinase activity. Reason: Over-general. The specific MF terms (MAP kinase activity, protein serine/threonine kinase activity) are present and preferred. |
| 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 RAS→RAF→MEK→ERK 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: file:rat/Mapk1/Mapk1-deep-research-falcon.md an in vitro kinase assay with active TEY-phosphorylated ERK2 and an ATPγS analog |
| 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. |
| 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. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization (duplicate of the IBA cytoplasm annotation). Reason: Core localization. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. Supporting Evidence: file:rat/Mapk1/Mapk1-deep-research-falcon.md ERK1/2 (MAPK3/MAPK1) are described as **terminal kinases** in the canonical **RAS→RAF→MEK→ERK** 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| GO:0005515 protein binding | IPI PMID:21070949 Phosphorylation of DCC by ERK2 is facilitated by direct dock... | MARK AS OVER ANNOTATED | Summary: This IPI annotation reflects the ERK2-DCC docking interaction (ERK2 phosphorylates DCC via direct docking). The generic protein binding term is uninformative. Reason: The protein binding term is non-informative per curation guidelines. The underlying interaction (DCC docking/substrate) is better captured by the kinase activity and substrate-docking functions. |
| 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. |
| 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. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleoplasm localization (ISO duplicate). Consistent. Reason: Consistent specific nuclear localization. |
| 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: file:rat/Mapk1/Mapk1-deep-research-falcon.md NHE1/Slc9a1** can act as a **membrane scaffold** for ERK2 |
| 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. |
| 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 **RAF–MEK–ERK 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). |
| 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 π 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. 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 ... | MARK AS OVER ANNOTATED | Summary: ERK interaction with MURC/Cavin-4 (caveolar recruitment). The generic protein binding term is uninformative. Reason: The protein binding term is non-informative per curation guidelines; the caveolar localization is captured by the caveola term. |
| 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. |
| 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. |
| 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. |
| GO:0005515 protein binding | IPI PMID:12944431 DOC1R: a MAP kinase substrate that control microtubule organ... | MARK AS OVER ANNOTATED | Summary: DOC1R interaction (a MAP kinase substrate in oocytes). The generic protein binding term is uninformative. Reason: The protein binding term is non-informative; the substrate relationship is captured by kinase activity. |
| 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. |
| 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. |
| 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 · 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization (ISS duplicate). Core localization. Reason: Core localization. |
| 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. |
| 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. |
| 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. |
| GO:0019901 protein kinase binding | IPI PMID:16943189 cGMP-dependent protein kinase type I inhibits TAB1-p38 mitog... | KEEP AS NON CORE | Summary: ERK2 binds upstream/partner kinases (e.g., TAB1 context); a more informative interaction term than generic protein binding. Reason: Informative protein-interaction term reflecting ERK2 binding to kinases in its signaling module; non-core. |
| 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). |
| 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. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Cytoplasmic localization (ISO duplicate). Core localization. Reason: Core localization. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| GO:0005515 protein binding | IPI PMID:19200235 Dopamine promotes striatal neuronal apoptotic death via ERK ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a dopamine/ERK apoptosis study; uninformative. Reason: The protein binding term is non-informative per curation guidelines. |
| 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. |
| 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 · 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. |
| 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. |
| 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. |
| GO:0005515 protein binding | IPI PMID:15781236 Caveolin-2 regulation of the cell cycle in response to insul... | MARK AS OVER ANNOTATED | Summary: Caveolin-2/insulin/cell-cycle interaction context; the generic protein binding term is uninformative. Reason: The protein binding term is non-informative per curation guidelines. |
| GO:0032991 protein-containing complex | IDA PMID:15781236 Caveolin-2 regulation of the cell cycle in response to insul... | MARK AS OVER ANNOTATED | Summary: ERK in a protein complex; generic and uninformative as a cellular component. Reason: Generic component term that adds little functional information; the specific complexes/scaffolds are not characterized here. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic parent of the specific kinase MF terms. Reason: Over-general MF; the specific MAP kinase / protein serine/threonine kinase terms are present and preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 · 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. |
| 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 · 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. |
| 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. |
| 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. |
| GO:0016301 kinase activity | TAS PMID:11687663 Cyclic changes in estradiol regulate synaptic plasticity thr... | MARK AS OVER ANNOTATED | Summary: Generic kinase activity (TAS). Over-general. Reason: Over-general MF; specific kinase terms preferred. |
| 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. |
| 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. |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic parent of the specific kinase MF terms (ISO duplicate). Reason: Over-general MF; specific MAP kinase / Ser/Thr kinase terms preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346858 · 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. |
| 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 · 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. |
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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?
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.
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