Mapk1 encodes ERK2/p42 MAPK, a CMGC-family proline-directed serine/threonine protein kinase and terminal kinase of the canonical RAS-RAF-MEK-ERK cascade. MEK1/2 activates ERK2 by dual phosphorylation of its TEY activation-loop motif, after which ERK2 phosphorylates cytosolic, nuclear, cytoskeletal, and membrane-proximal substrates selected by proline-directed motifs plus D/DEF docking interactions. Its developmental, inflammatory, sensory and disease-response effects are context-specific outputs of that same MAP kinase catalytic activity in ERK1/2 signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: intracellular signal transduction is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000622075 SUPPORTS TRANSFER A deep kinase node, not an ERK-specific one: the local PAINT cache lists PTN000622075 in the files of four families - PTHR24055 (PANTHER name "MITOGEN-ACTIVATED PROTEIN KINASE", the family UniProt assigns to the target), PTHR24056 ("CELL DIVISION PROTEIN KINASE"), PTHR24057 ("GLYCOGEN SYNTHASE KINASE-3 ALPHA") and PTHR44167. THIS row's IBD seeds span fungal, slime-mould, worm, fly and vertebrate kinases of those groups; the node's plant seeds (AGI_LocusCode) sit in its GO:0004674, GO:0005634 and GO:0005737 rows, not in the GO:0035556 one under review, whose WITH/FROM carries no AGI or TAIR entry. Across a clade that broad the generic parent is the only biological-process term that holds for every member, so the node placement is sound and only the term is uninformative for mouse Mapk1. MGI:MGI:1346858 · mouse Mapk1 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Mapk1 carries IDA annotations at GO:0000165 MAPK cascade (PMID:8626447, PMID:9064344, PMID:9254656), a descendant of this term, which is among the descendant evidences behind the IBD. MGI:MGI:1346859 · mouse Mapk3 (ERK1, the target's closest paralog) SUPPORTS TRANSFER ERK1/ERK2 are functionally interchangeable in the cascade; the transfer between them is not at issue. FB:FBgn0003256 · Drosophila rolled (rl, the fly ERK) SUPPORTS TRANSFER The single fly ERK ortholog, one of the seeds that anchors the cascade role deep in the metazoan tree. UniProtKB:P28482 · human MAPK1 (ERK2) SUPPORTS TRANSFER The 1:1 human ortholog seed. Its presence, with the fly and mouse ERK seeds, is why the informative claim available here is the ERK1/2 cascade: GO:0070371 is a genuine descendant of GO:0035556 (via GO:0000165 MAPK cascade), so the MODIFY is a parent-to-child narrowing rather than a change of claim. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: cell surface receptor signaling pathway is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN008603019 SUPPORTS TRANSFER A different, much shallower node than the one behind the GO:0035556 row: PTN008603019 appears only in the PTHR24055 PAINT file (PANTHER family name "MITOGEN-ACTIVATED PROTEIN KINASE", the target's own family) and its IBD seeds are exactly the ERK orthologs - fly rolled, mouse Mapk1 and Mapk3, human MAPK1 and MAPK3. The clade is the right one; what is wrong is that GO:0007166 names the upstream receptor pathway that recruits ERK rather than ERK's own step in it. MGI:MGI:1346858 · mouse Mapk1 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Mapk1 carries IDA annotations at GO:0000165 MAPK cascade (PMID:8626447, PMID:9064344, PMID:9254656) and an IGI at GO:0000165 (PMID:21220101), which are among the descendant evidences behind the IBD. MGI:MGI:1346859 · mouse Mapk3 (ERK1, the target's closest paralog) SUPPORTS TRANSFER Second mouse ERK seed; ERK1 and ERK2 act in the same cascade downstream of the same receptor classes. FB:FBgn0003256 · Drosophila rolled (rl, the fly ERK) SUPPORTS TRANSFER The fly ERK ortholog seed; like the vertebrate seeds it acts downstream of RTK input rather than at the receptor itself. UniProtKB:P28482 · human MAPK1 (ERK2) SUPPORTS TRANSFER The 1:1 human ortholog seed. Note that GO:0070371 is not a descendant of GO:0007166 - its is_a/part_of ancestors run through GO:0000165 and GO:0035556 - so unlike the GO:0035556 row this MODIFY is a lateral re-scope from the receptor pathway onto the effector cascade the seeds actually share, not a narrowing, which is why no granularity failure mode is asserted. UniProtKB:P27361 · human MAPK3 (ERK1) SUPPORTS TRANSFER The human paralog seed, counterpart of the mouse Mapk3 record above. With it this block enumerates all six WITH/FROM sources; the same lateral re-scope applies to it, since it too acts downstream of receptor input rather than at the receptor itself. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0001784 phosphotyrosine residue binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-predicted phosphotyrosine residue binding matches the experimentally supported phosphotyrosine-dependent paxillin association of ERK2 (IMP row, PMID:14636584). Reason: Kept consistent with the IMP annotation of this same term; pTyr-dependent docking on paxillin is documented for ERK but it is an accessory interaction rather than the core catalytic function. Supporting Evidence: PMID:14636584 this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin |
| GO:0001890 placenta development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Placenta development is one of the best-genetically-supported in vivo roles of mouse ERK2; Erk2-null embryos die from placental failure (PMID:14622137). Reason: The Erk2 knockout phenotype directly demonstrates a requirement in placental development, so the electronically propagated term is retained as a developmental (non-core) output of ERK2 signaling. Supporting Evidence: PMID:14622137 the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: protein kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005769 early endosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: early endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005770 late endosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: late endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Golgi apparatus is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: centrosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: spindle is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005901 caveola | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: caveola is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005925 focal adhesion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: focal adhesion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Regulation of RNA polymerase II transcription is a downstream consequence of ERK2 phosphorylating transcription factors such as ELK1, not a function of the kinase itself. Reason: This inter-ontology inference projects the activity of ERK2 substrates (e.g. ELK1, per Reactome R-MMU-198706) onto the kinase; annotating the upstream kinase as a Pol II transcription regulator over-extends the direct molecular role already captured by MAP kinase activity. |
| GO:0031143 pseudopodium | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pseudopodium localization of ERK1/2 is experimentally shown for the beta-arrestin-scaffolded pool during PAR-2 chemotaxis (IDA row, PMID:12821670). Reason: Matches the IDA evidence for this term; a beta-arrestin-sequestered ERK1/2 pool concentrates in pseudopodia during chemotaxis, a genuine but specialized localization distinct from the canonical cytosol/nucleus distribution. Supporting Evidence: PMID:12821670 the previously identified PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia |
| GO:0032872 regulation of stress-activated MAPK cascade | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Cross-regulation of stress-activated (JNK/p38) MAPK modules by ERK is discussed in the curated ERK-compartments review (TAS row, PMID:19565474). Reason: The only evidence here is an ARBA machine-learning IEA and a TAS pointing at a general review; neither demonstrates mouse ERK2 regulating a stress-activated cascade. ERK-JNK/p38 crosstalk is real but context-dependent, so the claim is flagged as over-annotation rather than retained. Matches the treatment of the identical IEA and TAS rows on the ERK1 paralog Mapk3, and is consistent with the sibling GO:0051403 rows. |
| GO:0035094 response to nicotine | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Response to nicotine reflects alpha7 nicotinic receptor-dependent ERK MAPK activation, supported experimentally by the IGI row from PMID:11404397. Reason: Retained to match the experimental IGI evidence that hippocampal MAPK signaling is engaged through alpha7 nicotinic acetylcholine receptors; a stimulus-specific context output rather than core function. Supporting Evidence: PMID:11404397 Abeta peptide 1-42 (Abeta42) couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0042473 outer ear morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Outer ear morphogenesis is part of the craniofacial neural-crest phenotype of ERK2 loss (IGI row, PMID:18952847). Reason: Kept consistent with the IGI row from the neural crest study, in which craniofacial anomalies including ear defects arise when ERK2 is inactivated in the neural crest; a developmental, non-core output. Supporting Evidence: PMID:18952847 exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development |
| GO:0043330 response to exogenous dsRNA | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Response to exogenous dsRNA parallels the IDA row from the Trif/Lps2 study (PMID:12872135) in which TLR3-dependent responses were characterized in mice. Reason: Retained to match the curated IDA evidence from the TLR3/TLR4 adaptor study; ERK activation downstream of dsRNA sensing is an innate-immune context output rather than a core function. |
| GO:0051493 regulation of cytoskeleton organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of cytoskeleton organization by ERK (actin reorganization, paxillin and pseudopod dynamics) is covered by the TAS review row (PMID:19565474) and the PAR-2 chemotaxis study. Reason: Kept consistent with the TAS row for this term; ERK-dependent actin remodeling during chemotaxis and adhesion signaling is documented, but it is an effector output of the cascade rather than its core activity. |
| GO:0060020 Bergmann glial cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Bergmann glial cell differentiation requires FGF/Shp2-dependent ERK activation, supported experimentally by the IGI row (PMID:24431450). Reason: Retained to match the IGI evidence in which constitutively active MEK1 rescues Bergmann glia formation in Shp2-deficient cerebella; a lineage-specific developmental output of ERK signaling. Supporting Evidence: PMID:24431450 expressing constitutively active MEK1 rescues BG formation and cerebellar foliation in Shp2-deficient cerebella |
| GO:0061308 cardiac neural crest cell development involved in heart development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cardiac neural crest development involved in heart development mirrors the conotruncal defects of neural-crest ERK2 inactivation (IGI row, PMID:18952847). Reason: Kept consistent with the IGI row; cardiac outflow tract defects in neural-crest-specific ERK2 mutants support this developmental role, retained as a non-core pleiotropic output. Supporting Evidence: PMID:18952847 cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling |
| GO:0071356 cellular response to tumor necrosis factor | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular response to tumor necrosis factor is experimentally paralleled by the IGI row (PMID:24349514) showing TNF-alpha modulation of ERK1/2 phosphorylation in C2C12 myotubes. Reason: Retained to match the IGI evidence that TNF-alpha treatment alters phospho-ERK1/2 levels in muscle cells; a cytokine-context signaling response, not a core function. Supporting Evidence: PMID:24349514 the level of p-ERK-1/2 decreased on incubation with TNF-α at 2 or 20 ng/ml |
| GO:0071375 cellular response to peptide hormone stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cellular response to peptide hormone stimulus groups the experimentally documented insulin- and IGF-1-stimulated ERK activation (PMID:20056832, PMID:14997210). Reason: Insulin and IGF-1 robustly activate ERK1/2 in the experimental rows of this review, so this ARBA grouping term is biologically sound; kept as a non-core stimulus-context annotation. Supporting Evidence: PMID:20056832 The phosphorylation of ERK by insulin was eliminated by exposure to a Raf inhibitor (GW5074) |
| GO:0071396 cellular response to lipid | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Cellular response to lipid is an ARBA machine-learning generalization with no lipid-specific ERK2 evidence in this review. Reason: No local experimental or curated evidence links mouse ERK2 to a defined lipid-response program; the term is too vague to add information beyond the receptor- and cytokine-specific responses already annotated, so it is flagged as an electronic over-annotation. |
| GO:0072584 caveolin-mediated endocytosis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Caveolin-mediated endocytosis is carried by the curated TAS row from the ERK-compartments review (PMID:19565474) alongside the caveola localization rows. Reason: Kept consistent with the TAS row for this term and with the caveola component annotations; ERK function at caveolae is a compartment-specific, non-core aspect of the cascade. |
| GO:0090170 regulation of Golgi inheritance | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of Golgi inheritance reflects the mitotic Golgi-fragmentation role of ERK signaling covered by the TAS review row (PMID:19565474). Reason: Kept consistent with the TAS row; ERK-dependent control of Golgi partitioning during mitosis is documented compartmentalized biology but clearly non-core relative to MAP kinase catalysis. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: protein serine kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0150078 positive regulation of neuroinflammatory response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of neuroinflammatory response is supported by the mouse IDA row (PMID:31898284) on CCR1/TPR1/ERK1/2 signaling after intracerebral hemorrhage. Reason: Retained to match the experimental IDA row; ERK1/2 promotion of neuroinflammation after brain hemorrhage is a disease-context output, kept non-core. Supporting Evidence: PMID:31898284 CCR1/TPR1/ERK1/2 Signaling Pathway After Intracerebral Hemorrhage in Mice |
| GO:2000641 regulation of early endosome to late endosome transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of early-to-late endosome transport is carried by the curated TAS row from the ERK-compartments review (PMID:19565474) together with the endosome localization rows. Reason: Kept consistent with the TAS row and the endosomal component annotations; endosome-associated ERK signaling that influences trafficking is documented but peripheral to the core cascade function. |
| GO:0005515 protein binding | IPI PMID:10419510 Interaction of mitogen-activated protein kinases with the ki... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:15102471 Bioinformatics and cellular signaling. | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:16148006 ERK2 shows a restrictive and locally selective mechanism of ... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:18045539 Integrating patterning signals: Wnt/GSK3 regulates the durat... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:19455133 Targeted tandem affinity purification of PSD-95 recovers cor... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:20554783 Pseudorabies virus tegument protein Us2 recruits the mitogen... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:23644467 The collagen receptor discoidin domain receptor 2 stabilizes... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:27822540 Identification of Novel Host Interactors of Effectors Secret... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:28671696 Spatiotemporal profile of postsynaptic interactomes integrat... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0042802 identical protein binding | IPI PMID:26267534 Small Molecule Inhibition of ERK Dimerization Prevents Tumor... | KEEP AS NON CORE | Summary: ERK dimerization is directly supported by PMID:26267534, but identical protein binding is a secondary signaling-state property rather than the core ERK2 kinase function. Reason: The cached publication explicitly states that activated ERK dimerizes. Retain as supported non-core biology instead of leaving the accessible IPI evidence undecided. Supporting Evidence: PMID:26267534 Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling |
| GO:0000165 MAPK cascade | IEA GO_REF:0000107 | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000107 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005654 nucleoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ERK1/2 is the canonical terminal kinase downstream of EGFR, so epidermal growth factor receptor signaling pathway is biologically solid for ERK2. Reason: EGFR-to-ERK signaling is textbook ERK biology; retained as a non-core annotation because the receptor-specific upstream context is one of many inputs into the core ERK1/2 cascade already accepted. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0019902 phosphatase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Phosphatase binding is experimentally grounded by the IPI row with MKP-1 (PMID:8221888), which complexes with phospho-p42MAPK. Reason: Kept consistent with the IPI row; ERK2 physically engages its inactivating dual-specificity phosphatases (MKP-1) and tyrosine phosphatases (PTP-SL), a regulatory interaction that is informative but not the core catalytic function. Supporting Evidence: PMID:8221888 The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK |
| GO:0034198 cellular response to amino acid starvation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to amino acid starvation is an ortholog-projected annotation with no starvation-related ERK2 evidence in the mouse literature reviewed here. Reason: Amino acid starvation responses are canonically GCN2/mTOR territory; nothing in the reviewed mouse ERK2 literature establishes a starvation-specific role, so this Ensembl projection looks like an over-propagated one-study transfer. |
| GO:0038127 ERBB signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ERBB signaling pathway is supported by the direct mouse IDA row for ERBB2-ERBB3 signaling (PMID:24493648) and ERK function downstream of neuregulin/ErbB in Schwann cells. Reason: Retained to match the ERBB2-ERBB3 IDA evidence; ErbB receptors are established upstream activators of ERK2, but the receptor-context term is non-core relative to the cascade itself. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ERK dimerization is directly supported by PMID:26267534, but identical protein binding is a secondary signaling-state property rather than the core ERK2 kinase function. Reason: Retain as supported non-core biology; the core molecular function remains ERK MAP kinase activity and protein phosphorylation. Supporting Evidence: PMID:26267534 Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling |
| GO:0045542 positive regulation of cholesterol biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cholesterol biosynthetic process reaches ERK2 only via electronic ortholog transfer of an indirect SREBP-level effect. Reason: Any ERK influence on cholesterol synthesis runs indirectly through transcriptional regulators; annotating the kinase itself as a positive regulator of cholesterol biosynthesis stretches a downstream effect into a function, so the electronic transfer is flagged as over-annotation. |
| GO:0045880 positive regulation of smoothened signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of smoothened signaling is a niche crosstalk claim carried only by electronic transfer, with no hedgehog-related evidence in the ERK2 corpus reviewed here. Reason: ERK-SMO crosstalk is not part of the well-characterized ERK1/2 biology and no mouse experimental row supports it; the Ensembl projection of a single-context claim is treated as over-annotation. |
| GO:0051403 stress-activated MAPK cascade | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Stress-activated MAPK cascade denotes the JNK/p38 modules, whereas ERK2 is the terminal kinase of the mitogen-activated ERK1/2 cascade (GO:0070371). Reason: Although some stresses can activate ERK1/2, placing ERK2 inside the stress-activated MAPK cascade conflates it with the JNK/p38 modules; the accepted ERK1 and ERK2 cascade term already captures the correct module, so this electronic row is flagged as over-annotation. |
| GO:0061514 interleukin-34-mediated signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Interleukin-34-mediated signaling pathway is projected from a single human CSF1R/IL-34 study and has no mouse ERK2 support in this review. Reason: IL-34 engagement of CSF1R can activate ERK as it does many receptor pathways, but propagating this single-context cytokine pathway onto mouse ERK2 electronically adds an overly specific claim; flagged as over-annotation together with the related macrophage output terms. |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000120 | ACCEPT | Summary: ERK1 and ERK2 cascade is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0070849 response to epidermal growth factor | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to epidermal growth factor captures the classic EGF-stimulated activation of ERK1/2, consistent with the EGFR pathway rows. Reason: EGF stimulation of ERK phosphorylation is among the most reproduced observations in the field; retained as a stimulus-context (non-core) annotation in line with the EGFR signaling rows. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004707 MAP kinase activity | IDA PMID:38198890 Dynamic palmitoylation of STX11 controls injury-induced fatt... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0043415 positive regulation of skeletal muscle tissue regeneration | IMP PMID:38198890 Dynamic palmitoylation of STX11 controls injury-induced fatt... | KEEP AS NON CORE | Summary: Positive regulation of skeletal muscle tissue regeneration comes from the STX11 palmitoylation study whose cached record is abstract-only, but the same paper carries the accepted ERK2 MAP kinase activity IDA row. Reason: The curator-read full text of this study evidently assayed Mapk1 directly (its MAP kinase activity IDA row is accepted above), and ERK promotion of injury-induced muscle regeneration is a credible context-specific output; deferring to the MGI curator, the row is retained as non-core rather than left undecided. |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0032991 protein-containing complex | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex is a root-level component term that conveys no information about which ERK2 assemblies are meant. Reason: Like the generic protein binding rows, this rat-transferred root complex term adds nothing beyond the specific scaffold and signaling complexes described elsewhere in the review; flagged as uninformative over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH |
| GO:0106310 protein serine kinase activity | ISS GO_REF:0000024 | MODIFY | Summary: protein serine kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0045880 positive regulation of smoothened signaling pathway | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of smoothened signaling by curator ISS transfer, matching the IEA row flagged as over-annotation. Reason: Flagged in step with the matching IEA row for consistency; hedgehog-pathway promotion is not corroborated by any mouse ERK2 evidence assembled here and rests on a single transferred source. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-MMU-198706 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-MMU-9769840 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0006468 protein phosphorylation | ISO GO_REF:0000096 | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0006468 protein phosphorylation | ISO GO_REF:0000119 | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0010800 positive regulation of peptidyl-threonine phosphorylation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of peptidyl-threonine phosphorylation recasts phosphorylation that ERK2 performs or triggers directly as an indirect regulatory activity. Reason: ERK2 directly catalyzes proline-directed serine/threonine phosphorylation (accepted GO:0004707 and GO:0006468 rows); wrapping that in a regulation-of-phosphorylation term is a contorted human-transfer framing, so it is flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION GRANULARITY MISMATCH |
| GO:0018105 peptidyl-serine phosphorylation | ISO GO_REF:0000096 | ACCEPT | Summary: peptidyl-serine phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0097542 ciliary tip | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Ciliary tip localization stems from a single human study transferred by orthology, with no ciliary evidence in the mouse ERK2 literature here. Reason: Ciliary ERK localization is not part of the reproducible ERK compartment repertoire (cytosol, nucleus, endosomes, mitochondria, adhesions) documented in this review; a one-study human transfer to so precise a subciliary location is treated as over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH |
| GO:0000165 MAPK cascade | ISO GO_REF:0000096 | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0000165 MAPK cascade | ISO GO_REF:0000119 | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0003690 double-stranded DNA binding | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: double-stranded DNA binding is not a defensible core ERK annotation. Reason: The Falcon synthesis supports ERK as a proline-directed protein kinase in MAPK signaling; this term is too indirect, too broad, or mechanistically mismatched for the gene product. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000119 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | ISO GO_REF:0000096 | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | ISO GO_REF:0000119 | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005524 ATP binding | ISO GO_REF:0000096 | ACCEPT | Summary: ATP binding is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005654 nucleoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005886 plasma membrane | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Plasma membrane recruitment of ERK2 accompanies its activation at receptor-proximal and caveolar sites, consistent with the retained caveola and focal adhesion rows. Reason: A fraction of ERK is recruited to the plasma membrane where upstream complexes assemble; retained as non-core localization in line with the other membrane-proximal component rows. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005901 caveola | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Caveola localization by rat-ortholog transfer matches the IEA and TAS caveola rows already retained as non-core. Reason: Kept for consistency with the other caveola rows in this file, which retain caveolar ERK as documented compartmentalized signaling rather than core function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005929 cilium | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Cilium localization is a human-transfer claim without support in the reviewed mouse ERK2 compartment literature. Reason: The curated ERK compartment repertoire covered by the TAS review rows does not include cilia, and no mouse experimental row places ERK2 there; the ortholog-projected ciliary terms are flagged together as over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGFR signaling pathway via human-ortholog transfer matches the IEA row for the same term; ERK1/2 is the canonical EGFR effector kinase. Reason: Retained as non-core in step with the matching IEA row; the EGFR-specific upstream context is well established but subsidiary to the accepted ERK1 and ERK2 cascade annotation. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0009636 response to toxic substance | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Response to toxic substance is consistent with the mouse experimental literature in this file on ERK activation by oxidative toxicity and ischemia. Reason: ERK activation under oxidative/toxic insult is documented in the referenced neuronal studies (PMID:11726647 nuclear retention under oxidative toxicity; PMID:12223545 ischemia), so the rat transfer is retained as a stress-context non-core annotation. |
| GO:0010759 positive regulation of macrophage chemotaxis | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of macrophage chemotaxis belongs to the IL-34/CSF1R macrophage set transferred from a single human study. Reason: This macrophage-output claim travels with the IL-34 pathway transfer and lacks any mouse ERK2 support here; a whole-cell-behavior output from one propagated study is flagged as over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH |
| GO:0014069 postsynaptic density | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Postsynaptic density localization agrees with the mouse PSD interactome studies referenced in this review that recover ERK2 in PSD-95 complexes. Reason: Mouse PSD proteomics (PMID:19455133, PMID:28671696) recovered ERK2 in core postsynaptic complexes, supporting this rat-transferred component; retained as neuronal, non-core localization. |
| GO:0015630 microtubule cytoskeleton | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Microtubule cytoskeleton association of ERK matches the retained cytoskeleton and spindle rows; a sizable ERK fraction is microtubule-associated. Reason: Consistent with the TAS cytoskeleton row kept as non-core; microtubule-associated ERK pools are documented compartment biology, peripheral to the catalytic core function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0015966 diadenosine tetraphosphate biosynthetic process | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: diadenosine tetraphosphate biosynthetic process is not a defensible core ERK annotation. Reason: The Falcon synthesis supports ERK as a proline-directed protein kinase in MAPK signaling; this term is too indirect, too broad, or mechanistically mismatched for the gene product. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0019233 sensory perception of pain | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Sensory perception of pain reflects the extensive rodent literature on ERK activation in nociceptive sensitization, transferred from rat. Reason: Spinal and dorsal-horn ERK signaling in pain sensitization is a robust rodent finding, but it is an organism-level behavioral output of the cascade; retained as non-core. |
| GO:0019901 protein kinase binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Protein kinase binding covers documented ERK2 interactions with upstream kinases (MEK1) and kinase substrates via docking-site contacts. Reason: ERK2 docking interactions with MEK1 and substrate kinases (e.g. RSK) are mechanistically established; kept as a non-core interaction annotation since the D-site docking system, not generic binding, underlies specificity. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0019902 phosphatase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Phosphatase binding by human-ortholog transfer matches the mouse IPI row with MKP-1 and the PTP-SL interaction study in this file. Reason: Consistent with the IPI evidence (PMID:8221888, PMID:10419510) that ERK2 physically engages its inactivating phosphatases; a regulatory, non-core interaction. Supporting Evidence: PMID:8221888 The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK |
| GO:0030424 axon | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Axon localization is a rat-transferred neuronal compartment consistent with broad ERK distribution in neurons and its retrograde injury signaling roles. Reason: ERK is present and locally activated in axons (retrograde signaling after nerve injury is a classic rodent finding); kept as neuronal non-core localization alongside perikaryon and dendrite rows. |
| GO:0031435 mitogen-activated protein kinase kinase kinase binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Mitogen-activated protein kinase kinase kinase binding reflects documented ERK2 contact with Raf-family MAP3Ks during feedback phosphorylation. Reason: ERK2 physically engages RAF kinases for inhibitory feedback phosphorylation, a documented but regulatory interaction; retained as non-core rather than left undecided. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0032206 positive regulation of telomere maintenance | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of telomere maintenance is a single-study human claim propagated by orthology, outside the characterized ERK2 functional repertoire. Reason: Telomere maintenance regulation is not corroborated anywhere in the mouse ERK2 evidence assembled here, and the effect in the human source is indirect (substrate-level); flagged as over-propagated over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION |
| GO:0032839 dendrite cytoplasm | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Dendrite cytoplasm localization is a rat-transferred neuronal refinement of the accepted cytoplasm annotation. Reason: Dendritic ERK pools underlie synapse-to-nucleus signaling in rodent neurons (cf. the retained long-term potentiation row); kept as fine-grained neuronal localization, non-core. |
| GO:0034198 cellular response to amino acid starvation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Cellular response to amino acid starvation by human transfer matches the IEA row flagged as over-annotation. Reason: Flagged in step with the matching IEA row; starvation sensing is not an established ERK2 function and the transferred claim traces to a single study outside the core corpus. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH |
| GO:0035094 response to nicotine | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Response to nicotine by rat transfer matches the mouse IGI row linking alpha7 nicotinic receptors to MAPK cascade activation. Reason: Kept consistent with the experimental IGI row from PMID:11404397; nicotinic-receptor-evoked ERK activation is a stimulus-context output. Supporting Evidence: PMID:11404397 Abeta peptide 1-42 (Abeta42) couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000096 | MODIFY | Summary: intracellular signal transduction is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0036064 ciliary basal body | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Ciliary basal body localization travels with the other single-source ciliary transfers (ciliary tip, cilium) rejected above. Reason: Flagged together with the ciliary tip and cilium rows for consistency; a precise basal-body placement for ERK2 rests on one propagated human study and is not part of the documented compartment repertoire. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH |
| GO:0038127 ERBB signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ERBB signaling pathway by human transfer matches the IEA row and the direct mouse ERBB2-ERBB3 IDA evidence. Reason: Kept in step with the matching IEA row and the IDA ERBB2-ERBB3 row; ErbB receptors are established ERK activators, and the receptor context is non-core. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination |
| GO:0042307 positive regulation of protein import into nucleus | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein import into nucleus recasts substrate phosphorylation effects on partner localization as a trafficking function of ERK2. Reason: ERK2 phosphorylation can alter the localization of individual substrates, but promoting nuclear import is not an ERK2 function per se; the rat-transferred regulation-of-transport framing is flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ERK dimerization is directly supported by PMID:26267534, but identical protein binding is a secondary signaling-state property rather than the core ERK2 kinase function. Reason: Retain as supported non-core biology; the core molecular function remains ERK MAP kinase activity and protein phosphorylation. Supporting Evidence: PMID:26267534 Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling |
| GO:0043204 perikaryon | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Perikaryon localization is a rat-transferred neuronal compartment consistent with somatic ERK pools observed in neuronal studies. Reason: ERK is abundant in neuronal somata (perikarya) in the rodent studies underlying these transfers; retained as fine-grained neuronal localization, non-core, together with the axon and dendrite rows. |
| GO:0043627 response to estrogen | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Response to estrogen is a rat-transferred stimulus term with no estrogen-related evidence anywhere in this review's mouse ERK2 corpus. Reason: Rapid estrogen-evoked ERK activation is reported in some rat systems, but with no corroborating mouse evidence here and only an ortholog transfer carrying it, this stimulus-specific claim is flagged as over-annotation rather than kept. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cholesterol biosynthetic process by human transfer matches the IEA row flagged as over-annotation. Reason: Flagged in step with the matching IEA row; the cholesterol-synthesis effect is indirect and substrate-mediated, not a function of the kinase. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION |
| GO:0045727 positive regulation of translation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Positive regulation of translation is supported in mouse by MAPK-driven up-regulation of myelin protein synthesis (PMID:24493648). Reason: Sustained MAPK activation massively increases protein production in myelinating Schwann cells, giving in vivo mouse support for a translation-promoting output; retained as non-core since it runs through downstream effectors. Supporting Evidence: PMID:24493648 MAPK activation leads to minor changes in transcript levels but massively up-regulates protein production |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Positive regulation of DNA-templated transcription projects the activity of ERK2 substrates (ELK1 and other TFs) onto the kinase, as with the Pol II regulation row. Reason: Flagged consistently with the GO:0006357 row; transcriptional activation is achieved by ERK2 substrates after phosphorylation, and annotating the kinase as the transcription regulator over-extends its direct function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION |
| GO:0046697 decidualization | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Decidualization is a narrow uterine developmental claim carried only by rat-ortholog transfer in this file. Reason: The mouse-rat ortholog transfer (donor RGD:70500) reflects experimentally observed ERK involvement in uterine decidualization. As with the other tissue-level developmental outputs in this review it is retained but marked non-core. The ERK1 paralog Mapk3 carries the parallel row from its own rat ortholog (RGD:3046) and is treated the same way. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:70500 · the rat ortholog cited in this row's GOA WITH/FROM SUPPORTS TRANSFER The rat donor's decidualization evidence transfers soundly to the mouse ortholog; the annotation is defensible but contextual rather than a core ERK2 function, which is what NO_FAILURE_NON_CORE records. The ERK1 paralog Mapk3 receives the parallel transfer from a different rat ortholog (RGD:3046). |
| GO:0051403 stress-activated MAPK cascade | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Stress-activated MAPK cascade by human transfer matches the IEA row flagged as over-annotation; ERK2 belongs to the ERK1/2 cascade. Reason: Flagged in step with the matching IEA row; the stress-activated cascade designation fits JNK/p38 modules, and the correct GO:0070371 assignment is already accepted for ERK2. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION |
| GO:0060045 positive regulation of cardiac muscle cell proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell proliferation aligns with neuregulin/ErbB-ERK-driven cardiomyocyte proliferation and the retained heart development row. Reason: ERK signaling downstream of neuregulin/ErbB promotes cardiomyocyte cell-cycle activity in rodents, and cardiac roles for ERK2 are independently supported here (PMID:18952847); retained as a tissue-specific non-core output. |
| GO:0061514 interleukin-34-mediated signaling pathway | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Interleukin-34-mediated signaling pathway by human transfer matches the IEA row flagged as over-annotation. Reason: Flagged in step with the matching IEA row and the related macrophage-output transfers; a single-study cytokine pathway propagated onto mouse ERK2 is over-specific. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH |
| GO:0070371 ERK1 and ERK2 cascade | ISO GO_REF:0000096 | ACCEPT | Summary: ERK1 and ERK2 cascade is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0070371 ERK1 and ERK2 cascade | ISO GO_REF:0000119 | ACCEPT | Summary: ERK1 and ERK2 cascade is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0070849 response to epidermal growth factor | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Response to epidermal growth factor by human transfer matches the IEA row; EGF-evoked ERK activation is canonical. Reason: Retained in step with the matching IEA row as a stimulus-context annotation; EGF is the archetypal upstream activator of the ERK1/2 cascade. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0097237 cellular response to toxic substance | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Cellular response to toxic substance parallels the response to toxic substance row and the in-file neuronal oxidative-toxicity studies. Reason: Kept consistent with the sibling GO:0009636 row; ERK activation and nuclear retention under oxidative toxicity are documented in the referenced neuronal work (PMID:11726647), supporting a stress-context non-core annotation. |
| GO:0120041 positive regulation of macrophage proliferation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of macrophage proliferation belongs to the same single-study IL-34/CSF1R transfer set as the chemotaxis and IL-34 rows. Reason: Flagged with the IL-34 pathway and macrophage chemotaxis rows for consistency; a cell-type proliferation output propagated from one human study is over-specific for mouse ERK2. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH |
| GO:0005515 protein binding | IPI PMID:18590835 Identification of ERK2-binding domain of EBITEIN1, a novel E... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0150078 positive regulation of neuroinflammatory response | IDA PMID:31898284 CCR1 Activation Promotes Neuroinflammation Through CCR1/TPR1... | KEEP AS NON CORE | Summary: Direct mouse evidence that CCR1/TPR1/ERK1/2 signaling promotes neuroinflammation after intracerebral hemorrhage. Reason: The IDA study places ERK1/2 in the pro-inflammatory CCR1/TPR1 axis in mouse brain after hemorrhage; a valid disease-context output retained as non-core. Supporting Evidence: PMID:31898284 CCR1/TPR1/ERK1/2 Signaling Pathway After Intracerebral Hemorrhage in Mice |
| GO:0005515 protein binding | IPI PMID:20418913 The synergistic effect of Mig-6 and Pten ablation on endomet... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004674 protein serine/threonine kinase activity | ISO PMID:33331896 Merlin cooperates with neurofibromin and Spred1 to suppress ... | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005829 cytosol | IDA PMID:22451653 Siglec-15 protein regulates formation of functional osteocla... | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:26240334 FXR1P is a GSK3β substrate regulating mood and emotion proce... | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IDA PMID:14997210 Specific roles for the PI3K and the MEK-ERK pathway in IGF-1... | KEEP AS NON CORE | Summary: IGF-1 stimulation activates ERK1/2 and MEK-ERK mediates IGF-1-driven proliferation and VEGF secretion in the 5T33MM model. Reason: The full-text study shows IGF-1-stimulated ERK1/2 activation with MEK-ERK-dependent downstream outputs, supporting ERK2 participation in IGF receptor signaling as a receptor-context, non-core annotation. Supporting Evidence: PMID:14997210 Insulin-like growth factor-1 induced an increase in DNA synthesis in MM cells, which was mediated by a PI3K/Akt-MEK/ERK pathway |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IDA PMID:24381169 α6 integrin transactivates insulin-like growth factor recept... | KEEP AS NON CORE | Summary: Second IDA row for IGF receptor signaling, from the alpha6 integrin/IGF-1R lens differentiation study; the cached abstract omits the ERK read-outs the curator saw in full text. Reason: Consistent with the other IGF receptor signaling IDA row; ERK2 as an IGF-1R pathway effector is well established, and the lens epithelial context is a further receptor-context instance, retained non-core in deference to the curator-read full text. |
| GO:0004707 MAP kinase activity | ISO PMID:8828504 Comparison of the insulin and insulin-like growth factor 1 m... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | IDA PMID:1659995 Functional expression in mammalian cells of a full-length cD... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:20056832 Acute insulin signaling in pancreatic beta-cells is mediated... | KEEP AS NON CORE | Summary: Insulin activates ERK via Raf-1 in pancreatic beta-cells, directly demonstrated with Raf inhibition and dominant-negative Raf-1. Reason: The study shows insulin-stimulated, Raf-1-dependent ERK phosphorylation in mouse islets and beta-cells, placing ERK2 in insulin receptor signaling as a receptor-context, non-core annotation. Supporting Evidence: PMID:20056832 The phosphorylation of ERK by insulin was eliminated by exposure to a Raf inhibitor (GW5074) |
| GO:0014044 Schwann cell development | IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ... | KEEP AS NON CORE | Summary: Schwann cell development annotation from the erbB2 conditional-knockout study; ERK acts downstream of NRG1/ErbB2-ErbB3 in the Schwann cell lineage. Reason: The cached full text centers on ErbB2, but ERK/MAPK is the established effector of neuregulin signaling in Schwann cells and MAPK activation can substitute for ErbB3/Shp2 in this lineage (PMID:24493648); the curated IMP is retained as a developmental non-core role. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination |
| GO:0042552 myelination | IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ... | KEEP AS NON CORE | Summary: Myelination annotation from the peripheral-nerve erbB2 study, where ERK operates downstream of the NRG1/ErbB axis controlling myelin sheath growth. Reason: ERK/MAPK dependence of PNS myelin growth is directly demonstrated in mouse by sustained MAPK activation overriding myelination termination (PMID:24493648), corroborating this curated IMP; kept as a lineage-specific non-core output. Supporting Evidence: PMID:24493648 overcomes the signals that end myelination, resulting in continuous myelin growth |
| GO:0042552 myelination | IMP PMID:18760695 Neuregulin-1/ErbB signaling serves distinct functions in mye... | KEEP AS NON CORE | Summary: Second myelination IMP row, from the CNS neuregulin/ErbB study; retained on the same grounds as the PNS row. Reason: Kept consistent with the other myelination IMP row; MAPK signaling is a demonstrated driver of myelin growth in mouse, so the curated annotation from this neuregulin study is retained as non-core developmental biology. Supporting Evidence: PMID:24493648 sustained activation of MAPK signaling by expression of the Mek1DD allele in mice overcomes the signals that end myelination |
| GO:0038133 ERBB2-ERBB3 signaling pathway | IDA PMID:24493648 Activation of MAPK overrides the termination of myelin growt... | KEEP AS NON CORE | Summary: ERBB2-ERBB3 signaling pathway is directly supported; activated MAPK replaces Nrg1/ErbB3 signals in Schwann cell development and myelination. Reason: The full-text study establishes ERK/MAPK as the downstream arm of ERBB2-ERBB3 signaling in myelinating glia; retained as receptor-context non-core annotation. Supporting Evidence: PMID:24493648 activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination |
| GO:0000165 MAPK cascade | IGI PMID:21220101 Specific functions for ERK/MAPK signaling during PNS develop... | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-198706 | ACCEPT | Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9769840 | ACCEPT | Summary: nucleoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005515 protein binding | IPI PMID:15537391 Vanishin is a novel ubiquitinylated death-effector domain pr... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0019902 phosphatase binding | IPI PMID:8221888 MKP-1 (3CH134), an immediate early gene product, is a dual s... | KEEP AS NON CORE | Summary: Direct physical-interaction evidence that the MKP-1 phosphatase complexes with phosphorylated p42MAPK to inactivate it. Reason: The IPI is explicit in the cached abstract, where a catalytically inactive MKP-1 mutant traps phospho-p42MAPK; phosphatase binding is a genuine, regulatory (non-core) ERK2 interaction. Supporting Evidence: PMID:8221888 The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK |
| GO:0071356 cellular response to tumor necrosis factor | IGI PMID:24349514 MicroRNA-494, upregulated by tumor necrosis factor-α, desens... | KEEP AS NON CORE | Summary: TNF-alpha treatment of mouse C2C12 myotubes modulates phospho-ERK1/2 levels in the full-text miR-494 study. Reason: The full text documents ERK1/2 phosphorylation changes on TNF-alpha exposure in mouse muscle cells, supporting cellular response to TNF as a cytokine-context, non-core annotation. Supporting Evidence: PMID:24349514 the level of p-ERK-1/2 decreased on incubation with TNF-α at 2 or 20 ng/ml |
| GO:0004707 MAP kinase activity | IMP PMID:26375174 Regulation of neuronal pH by the metabotropic Zn(2+)-sensing... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0051453 regulation of intracellular pH | IMP PMID:26375174 Regulation of neuronal pH by the metabotropic Zn(2+)-sensing... | KEEP AS NON CORE | Summary: Regulation of intracellular pH via ERK1/2-dependent up-regulation of the Na+/H+ exchanger downstream of the Zn2+ receptor mZnR/GPR39 in hippocampal neurons. Reason: The study shows NHE-mediated pH recovery requires ERK1/2 activity, a specific downstream physiological output of the cascade; retained as non-core. Supporting Evidence: PMID:26375174 the Na(+)/H(+) exchanger (NHE), is induced by mZnR/GPR39 activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged sequence-similarity transfer of plasma membrane localization, consistent with the ISO plasma membrane row and the caveola/focal adhesion rows. Reason: Kept in step with the matching ISO row; receptor-proximal membrane recruitment of ERK during activation is documented compartment biology, non-core relative to catalysis. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005901 caveola | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ISS transfer of caveola localization, matching the IEA, ISO and TAS caveola rows retained as non-core. Reason: Kept for cross-row consistency; caveolar ERK pools are covered by the curated compartments review and retained as specialized localization. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0035094 response to nicotine | IGI PMID:11404397 Beta-amyloid activates the mitogen-activated protein kinase ... | KEEP AS NON CORE | Summary: Genetic-interaction evidence that beta-amyloid engages the MAPK cascade through alpha7 nicotinic acetylcholine receptors in hippocampus. Reason: The study directly couples nicotinic receptor activation to ERK MAPK signaling in vivo and in slices, supporting response to nicotine as a stimulus-context, non-core annotation for ERK2. Supporting Evidence: PMID:11404397 Abeta peptide 1-42 (Abeta42) couples to the mitogen-activated protein kinase (MAPK) cascade via alpha7 nicotinic acetylcholine receptors |
| GO:0005634 nucleus | IDA PMID:20554783 Pseudorabies virus tegument protein Us2 recruits the mitogen... | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005737 cytoplasm | IDA PMID:20554783 Pseudorabies virus tegument protein Us2 recruits the mitogen... | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0030278 regulation of ossification | IGI PMID:20053668 Gain-of-function mutation in FGFR3 in mice leads to decrease... | KEEP AS NON CORE | Summary: Regulation of ossification from the activating-FGFR3 mouse study, where MAPK signaling mediates FGFR3 effects on osteoblasts and osteoclasts. Reason: The cached abstract does not spell out the ERK read-outs the MGI curator saw in full text, but ERK1/2 is the established mediator of FGFR3 signaling in bone and ERK-dependent osteoclast regulation is independently shown in this file (PMID:14970190); retained as a skeletal, non-core output. |
| GO:0007507 heart development | IMP PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Heart development is directly supported; loss of neural-crest ERK2 produces cardiac outflow tract defects modeling the human 22q11.2 deletion phenotype. Reason: Cardiac outflow anomalies in ERK2 mutant mice give solid IMP support for a heart development role, retained as a developmental non-core output of the cascade. Supporting Evidence: PMID:18952847 cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling |
| GO:0014032 neural crest cell development | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Neural crest cell development is the central claim of this study; conditional ERK2 inactivation in neural crest replicates the human deletion phenotype. Reason: Conditional-knockout genetics make this one of the strongest developmental annotations for mouse ERK2; retained as non-core because it is a lineage-specific developmental deployment of the core cascade. Supporting Evidence: PMID:18952847 these defects are replicated in mice by conditional inactivation of ERK2 in the developing neural crest |
| GO:0030878 thyroid gland development | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Thyroid gland development is part of the DiGeorge-spectrum organ phenotype arising from neural-crest ERK2 deficiency. Reason: Pharyngeal-organ anomalies (thyroid among the DiGeorge spectrum) in the ERK2 neural-crest mutants support this curated IGI; a downstream organ-level developmental output, non-core. Supporting Evidence: PMID:18952847 exhibit defects comparable to the DiGeorge syndrome spectrum |
| GO:0042473 outer ear morphogenesis | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Outer ear morphogenesis is among the craniofacial anomalies of the neural-crest ERK2 mutant mice. Reason: Craniofacial (including ear) malformations in neural-crest ERK2 mutants underpin this IGI row; retained as a specific developmental non-core output. Supporting Evidence: PMID:18952847 exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development |
| GO:0048538 thymus development | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Thymus development belongs to the DiGeorge-like pharyngeal phenotype of ERK2 neural-crest inactivation. Reason: Thymic defects are a canonical component of the DiGeorge spectrum reproduced in these ERK2 mutants; the curated IGI is retained as an organ-level developmental non-core annotation. Supporting Evidence: PMID:18952847 exhibit defects comparable to the DiGeorge syndrome spectrum |
| GO:0060324 face development | IMP PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Face development (IMP) is directly evidenced by craniofacial anomalies in mice with ERK2 inactivated in the neural crest. Reason: The mutant-phenotype evidence for craniofacial malformation is explicit in the cached abstract; face development is retained as a developmental non-core role of ERK2. Supporting Evidence: PMID:18952847 the craniofacial and cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling |
| GO:0060324 face development | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Face development (IGI) duplicates the IMP row through the genetic-interaction arm of the same neural-crest study. Reason: Same underlying craniofacial phenotype as the IMP row, adjudicated identically for consistency; a developmental non-core deployment of ERK2 signaling. Supporting Evidence: PMID:18952847 these defects are replicated in mice by conditional inactivation of ERK2 in the developing neural crest |
| GO:0061308 cardiac neural crest cell development involved in heart development | IGI PMID:18952847 Mouse and human phenotypes indicate a critical conserved rol... | KEEP AS NON CORE | Summary: Cardiac neural crest development involved in heart development captures the conotruncal outflow-tract phenotype of the ERK2 neural-crest mutants precisely. Reason: The outflow-tract defects arise specifically from cardiac neural crest dysfunction in these mutants, making this specific term well matched to the data; retained as developmental non-core. Supporting Evidence: PMID:18952847 exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development |
| GO:0060020 Bergmann glial cell differentiation | IGI PMID:24431450 Shp2-dependent ERK signaling is essential for induction of B... | KEEP AS NON CORE | Summary: Bergmann glial cell differentiation depends on FGF/Shp2-ERK signaling; activated MEK1 rescues Bergmann glia loss in Shp2 mutants. Reason: The MEK1 rescue experiment places ERK activation squarely in Bergmann glia specification, supporting this precise IGI annotation; retained as a lineage-specific developmental non-core role. Supporting Evidence: PMID:24431450 expressing constitutively active MEK1 rescues BG formation and cerebellar foliation in Shp2-deficient cerebella |
| GO:0070371 ERK1 and ERK2 cascade | IGI PMID:19047410 Phosphoinositide 3-kinase-dependent inhibition of dendritic ... | ACCEPT | Summary: ERK1 and ERK2 cascade is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0060425 lung morphogenesis | IGI PMID:25100655 Crucial requirement of ERK/MAPK signaling in respiratory tra... | KEEP AS NON CORE | Summary: Lung morphogenesis requires epithelial ERK/MAPK signaling; Erk1/Erk2 double mutation in airway epithelium phenocopies Mek loss and causes lung agenesis. Reason: The study explicitly mutated Erk1 and Erk2 in airway epithelium and reproduced the respiratory phenotype, giving direct genetic support; retained as a developmental non-core output. Supporting Evidence: PMID:25100655 these anomalies were phenocopied when the Erk1 and Erk2 genes were mutated in airway epithelium |
| GO:0060440 trachea formation | IGI PMID:25100655 Crucial requirement of ERK/MAPK signaling in respiratory tra... | KEEP AS NON CORE | Summary: Trachea formation depends on ERK/MAPK signaling for tracheal progenitor maintenance and epithelial differentiation. Reason: Loss of ERK/MAPK signaling abolished tracheal epithelial differentiation and SOX2-positive progenitors in this study; retained as a specific developmental non-core annotation. Supporting Evidence: PMID:25100655 No tracheal epithelial cell differentiation occurred and no SOX2-positive progenitor cells were detected in mutants |
| GO:0060291 long-term synaptic potentiation | IGI PMID:20661302 Long-term potentiation in the CA1 hippocampus induced by NR2... | KEEP AS NON CORE | Summary: Long-term synaptic potentiation in CA1 hippocampus induced by NR2A-containing NMDA receptors is mediated by Ras-GRF2/Erk signaling. Reason: The full-text study identifies Erk MAP kinase as the downstream effector through which Ras-GRF2 supports NR2A-dependent LTP; retained as a neuronal plasticity (non-core) output of the cascade. Supporting Evidence: PMID:20661302 the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase |
| GO:0072686 mitotic spindle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitotic spindle localization by curator ISS transfer, matching the spindle IEA row retained as non-core. Reason: Kept consistent with the GO:0005819 spindle row; spindle-associated ERK during mitosis is documented compartment biology peripheral to the core cascade. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005515 protein binding | IPI PMID:15196959 The forkhead genes, Foxc1 and Foxc2, regulate paraxial versu... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:11854404 Activation of p42 mitogen-activated protein kinase (MAPK), b... | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005515 protein binding | IPI PMID:15544353 Treatment of cells with the angiogenic inhibitor fumagillin ... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0070849 response to epidermal growth factor | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Response to epidermal growth factor by curator ISS transfer, matching the IEA and ISO rows for the same term. Reason: Kept consistent with the sibling rows for this term; EGF is the archetypal ERK1/2 cascade stimulus and the annotation is retained as stimulus-context, non-core. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:15284227 MAP kinase phosphatase 3 (MKP3) interacts with and is phosph... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:17187070 Scaffold protein Dlgh1 coordinates alternative p38 kinase ac... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0005515 protein binding | IPI PMID:18241670 Molecular cloning of Ebitein1: a novel extracellular signal-... | MARK AS OVER ANNOTATED | Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004707 MAP kinase activity | IDA PMID:18084034 ERK is a novel regulatory kinase for poly(A) polymerase. | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | IMP PMID:18084034 ERK is a novel regulatory kinase for poly(A) polymerase. | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:18084034 ERK is a novel regulatory kinase for poly(A) polymerase. | ACCEPT | Summary: peptidyl-serine phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0018105 peptidyl-serine phosphorylation | IMP PMID:18084034 ERK is a novel regulatory kinase for poly(A) polymerase. | ACCEPT | Summary: peptidyl-serine phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0018105 peptidyl-serine phosphorylation | ISO GO_REF:0000008 | ACCEPT | Summary: peptidyl-serine phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005634 nucleus | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005739 mitochondrion | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: mitochondrion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005769 early endosome | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: early endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005770 late endosome | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: late endosome is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005794 Golgi apparatus | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Golgi apparatus is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005829 cytosol | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005856 cytoskeleton | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: cytoskeleton is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005901 caveola | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: caveola is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0005925 focal adhesion | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: focal adhesion is supported as ERK subcellular localization context but is not a core molecular activity. Reason: PMID:19565474 supports ERK targeting to distinct subcellular compartments; retain this as non-core localization/context rather than the primary kinase function. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0032872 regulation of stress-activated MAPK cascade | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | MARK AS OVER ANNOTATED | Summary: Regulation of stress-activated MAPK cascade traced to the curated ERK-compartments review, reflecting ERK crosstalk onto JNK/p38 modules. Reason: The cited Yao and Seger review discusses ERK cascade organization and crosstalk in general terms; attributing regulation of the JNK/p38 stress cascades to ERK2 itself stretches that statement beyond what is demonstrated for the mouse protein. Flagged as over-annotation rather than removed, since ERK-stress-cascade crosstalk is documented. Matches the identical TAS row on the ERK1 paralog Mapk3. |
| GO:0051493 regulation of cytoskeleton organization | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Regulation of cytoskeleton organization from the ERK-compartments review, where cytoskeleton-associated ERK modulates actin and microtubule dynamics. Reason: Consistent with the retained cytoskeleton localization row from the same review; ERK-dependent cytoskeletal remodeling (adhesion, chemotaxis) is documented output biology, non-core. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0072584 caveolin-mediated endocytosis | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Caveolin-mediated endocytosis from the ERK-compartments review, matching the caveola localization rows. Reason: The review-supported caveolar ERK pool ties the cascade to caveolin-dependent internalization; retained as compartment-specific non-core biology alongside the caveola rows. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0090170 regulation of Golgi inheritance | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Regulation of Golgi inheritance from the ERK-compartments review, reflecting ERK-driven Golgi fragmentation during mitosis. Reason: MEK/ERK-dependent mitotic Golgi fragmentation is established cell-biology supported by the review; retained as a compartmentalized non-core function. Supporting Evidence: PMID:19565474 induce and regulate a large number of cellular processes |
| GO:2000641 regulation of early endosome to late endosome transport | TAS PMID:19565474 The ERK signaling cascade--views from different subcellular ... | KEEP AS NON CORE | Summary: Regulation of early-to-late endosome transport from the ERK-compartments review, matching the endosome localization rows. Reason: The endosomal ERK pool described in the review links the cascade to endosome maturation control; retained as compartment-specific non-core biology consistent with the early/late endosome rows. Supporting Evidence: PMID:19565474 targets at distinct subcellular compartments |
| GO:0031143 pseudopodium | IDA PMID:12821670 A beta-arrestin-dependent scaffold is associated with prolon... | KEEP AS NON CORE | Summary: Direct evidence that a beta-arrestin-scaffolded ERK1/2 pool is enriched in pseudopodia during PAR-2-induced chemotaxis. Reason: Subcellular fractionation and confocal imaging localize the PAR-2/beta-arrestin/ERK1/2 complex to pseudopodia; a specialized, well-documented localization retained as non-core. Supporting Evidence: PMID:12821670 the previously identified PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia |
| GO:0005739 mitochondrion | IDA PMID:11884367 Mitochondrial PKCepsilon and MAPK form signaling modules in ... | KEEP AS NON CORE | Summary: Direct evidence that ERKs co-localize with cardiac mitochondria and form PKCepsilon-MAPK modules during cardioprotection. Reason: Immunoblotting and immunofluorescence place ERKs at cardiac mitochondria, matching the TAS mitochondrion row retained as non-core compartmentalized signaling. Supporting Evidence: PMID:11884367 PKCepsilon, ERKs, JNKs, and p38 MAPK co-localized with cardiac mitochondria |
| GO:0005829 cytosol | IDA PMID:11884367 Mitochondrial PKCepsilon and MAPK form signaling modules in ... | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0033598 mammary gland epithelial cell proliferation | IDA PMID:18604197 IQGAP3 regulates cell proliferation through the Ras/ERK sign... | KEEP AS NON CORE | Summary: Mammary gland epithelial cell proliferation driven by IQGAP3-Ras signaling with ERK acting downstream in mouse mammary epithelial cells. Reason: The study shows ERK activity is required for IQGAP3-driven epithelial proliferation; the tissue-specific proliferation term is a context output of the core cascade, retained non-core. Supporting Evidence: PMID:18604197 IQGAP3 is necessary and sufficient for driving cell proliferation and ERK acts downstream of IQGAP3 |
| GO:0005634 nucleus | IDA PMID:11726647 Prolonged nuclear retention of activated extracellular signa... | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005634 nucleus | IDA PMID:12925581 Spatial and temporal patterns of ERK signaling during mouse ... | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0005737 cytoplasm | IDA PMID:11726647 Prolonged nuclear retention of activated extracellular signa... | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IDA PMID:12721286 A novel RNA polymerase II C-terminal domain phosphatase that... | KEEP AS NON CORE | Summary: RNA polymerase II CTD heptapeptide repeat kinase activity reflects the documented in vitro capability of ERK2 to phosphorylate the CTD consensus repeat, used as a CTD kinase in this SCP1 phosphatase study. Reason: ERK2 phosphorylation of Ser5-type sites in the Pol II CTD repeat is a long-established in vitro activity exploited to generate phospho-CTD substrate in the source paper; a genuine but accessory catalytic capability relative to the canonical MAPK substrate repertoire, retained non-core. |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000008 | ACCEPT | Summary: protein serine/threonine kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0060716 labyrinthine layer blood vessel development | IMP PMID:14622137 Essential role for ERK2 mitogen-activated protein kinase in ... | KEEP AS NON CORE | Summary: Labyrinthine layer blood vessel development is directly evidenced by the thin, poorly vascularized labyrinth of Erk2-null placentas. Reason: The knockout phenotype pinpoints defective labyrinthine vascularization as the cause of lethality; retained as a precise developmental non-core annotation together with the placenta development rows. Supporting Evidence: PMID:14622137 the labyrinthine layer of the placenta is very thin and few foetal blood vessels are observed |
| GO:0005829 cytosol | IDA PMID:9447983 A novel, multifuntional c-Cbl binding protein in insulin rec... | ACCEPT | Summary: cytosol is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0000165 MAPK cascade | IDA PMID:9254656 The motheaten mutation rescues B cell signaling and developm... | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004707 MAP kinase activity | IDA PMID:9064344 Signaling capacity of the T cell antigen receptor is negativ... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | IDA PMID:9254656 The motheaten mutation rescues B cell signaling and developm... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:9254656 The motheaten mutation rescues B cell signaling and developm... | KEEP AS NON CORE | Summary: B cell receptor signaling pathway is supported by BCR-induced MAP kinase activation in the CD45/SHP-1 double-mutant B cell study. Reason: The full-text study measures MAPK activation as a proximal read-out of BCR engagement, placing ERK2 in this antigen-receptor pathway; an immune-context, non-core annotation. Supporting Evidence: PMID:9254656 cells undergo appropriate induction of protein kinase activity, mitogen-activated protein kinase activation, and proliferative responses after BCR aggregation |
| GO:0000165 MAPK cascade | IDA PMID:9064344 Signaling capacity of the T cell antigen receptor is negativ... | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:9064344 Signaling capacity of the T cell antigen receptor is negativ... | KEEP AS NON CORE | Summary: T cell receptor signaling pathway is supported by TCR-induced MAPK activation in PTP1C-deficient motheaten thymocytes. Reason: The study documents TCR-coupled MAPK activation (aberrantly prolonged without PTP1C), evidencing ERK2 participation downstream of the TCR; an immune-context, non-core annotation. Supporting Evidence: PMID:9064344 the aberrant prolongation of TCR-induced, mitogen-associated kinase (MAPK) activation observed in PTP1C-deficient thymocytes |
| GO:0004707 MAP kinase activity | IDA PMID:15896720 Presenilin acts as a positive regulator of basal level activ... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0006468 protein phosphorylation | IMP PMID:15896720 Presenilin acts as a positive regulator of basal level activ... | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ... | KEEP AS NON CORE | Summary: Lipopolysaccharide-mediated signaling pathway from the Trif/Lps2 study, where MAPK activation downstream of TLR4 was among the curator-read read-outs. Reason: The cached abstract centers on Trif, but MAPK activation is a standard read-out in this TLR study and the MGI curator read the full text; ERK activation downstream of LPS/TLR4 is well established, so the row is retained as an innate-immune, non-core annotation. |
| GO:0032496 response to lipopolysaccharide | IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ... | KEEP AS NON CORE | Summary: Response to lipopolysaccharide parallels the LPS-mediated signaling row from the same Trif/Lps2 study. Reason: Adjudicated identically to the sibling GO:0031663 row from this paper; LPS-evoked ERK activation in macrophages is canonical innate-immune signaling, retained non-core. |
| GO:0043330 response to exogenous dsRNA | IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ... | KEEP AS NON CORE | Summary: Response to exogenous dsRNA from the Trif/Lps2 study, in which dsRNA (TLR3) responses were a primary phenotype examined. Reason: The study defines Trif-dependent responses to dsRNA and LPS; MAPK read-outs in the curator-read full text support ERK2 involvement in the dsRNA response, retained as an innate-immune, non-core annotation. Supporting Evidence: PMID:12872135 abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin lipopolysaccharide |
| GO:0045596 negative regulation of cell differentiation | IGI PMID:14970190 Amylin inhibits bone resorption while the calcitonin recepto... | KEEP AS NON CORE | Summary: Negative regulation of cell differentiation reflects ERK1/2-dependent amylin inhibition of osteoclast precursor fusion. Reason: The study shows amylin blocks osteoclastogenesis in an ERK1/2-dependent manner; the broad differentiation term summarizes that finding and is kept as a context-specific, non-core output. Supporting Evidence: PMID:14970190 amylin inhibits fusion of mononucleated osteoclast precursors into multinucleated osteoclasts in an ERK1/2-dependent manner |
| GO:0006468 protein phosphorylation | IDA PMID:15284227 MAP kinase phosphatase 3 (MKP3) interacts with and is phosph... | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0016301 kinase activity | IDA PMID:15284227 MAP kinase phosphatase 3 (MKP3) interacts with and is phosph... | MODIFY | Summary: kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0019858 cytosine metabolic process | IDA PMID:15284227 MAP kinase phosphatase 3 (MKP3) interacts with and is phosph... | MARK AS OVER ANNOTATED | Summary: cytosine metabolic process is not a defensible core ERK annotation. Reason: The Falcon synthesis supports ERK as a proline-directed protein kinase in MAPK signaling; this term is too indirect, too broad, or mechanistically mismatched for the gene product. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005634 nucleus | IDA PMID:16251435 Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-in... | ACCEPT | Summary: nucleus is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0004707 MAP kinase activity | IDA PMID:15314156 MUC20 suppresses the hepatocyte growth factor-induced Grb2-R... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0006974 DNA damage response | IDA PMID:15383658 p53-dependent inhibition of FKHRL1 in response to DNA damage... | KEEP AS NON CORE | Summary: DNA damage response is supported by ERK1/2-mediated post-translational induction of SGK1 in the p53-FKHRL1 crosstalk pathway after DNA damage. Reason: The study places ERK1/2 activity inside a p53-dependent DNA damage signaling circuit controlling SGK1 and FOXO3a; a stress-context, non-core role for the cascade. Supporting Evidence: PMID:15383658 this induction was through extracellular signal-regulated kinase 1/2-mediated posttranslational regulation |
| GO:0000165 MAPK cascade | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | MODIFY | Summary: MAPK cascade is a broad parent for ERK1/2 signaling. Reason: The more specific biological process for these ERK proteins is the ERK1 and ERK2 cascade. Proposed replacements: ERK1 and ERK2 cascade Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a terminal kinase in the canonical **RAS-RAF-MEK-ERK** (ERK1/2 MAPK) cascade |
| GO:0004707 MAP kinase activity | IDA PMID:8626447 Reconstitution of B cell antigen receptor-induced signaling ... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004707 MAP kinase activity | IMP PMID:11841548 Role of the nude gene in epithelial terminal differentiation... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0006468 protein phosphorylation | IDA PMID:11841548 Role of the nude gene in epithelial terminal differentiation... | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0004672 protein kinase activity | IDA PMID:14744933 Suppression of mitochondrial respiration through recruitment... | MODIFY | Summary: protein kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0006468 protein phosphorylation | IDA PMID:14744933 Suppression of mitochondrial respiration through recruitment... | ACCEPT | Summary: protein phosphorylation is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0016301 kinase activity | IDA PMID:12808090 Gab1 is an integrator of cell death versus cell survival sig... | MODIFY | Summary: kinase activity is less specific than ERK MAP kinase activity. Reason: MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity. Proposed replacements: MAP kinase activity Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0001784 phosphotyrosine residue binding | IMP PMID:14636584 Phosphorylation-dependent paxillin-ERK association mediates ... | KEEP AS NON CORE | Summary: phosphotyrosine residue binding is supported in a specific HGF/paxillin cell-matrix interaction context, but is not the core ERK2 kinase function. Reason: The cited evidence supports a context-specific tyrosine-phosphorylation-dependent ERK association. Supporting Evidence: PMID:14636584 this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin |
| GO:0005737 cytoplasm | IDA PMID:12925581 Spatial and temporal patterns of ERK signaling during mouse ... | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0004707 MAP kinase activity | IDA PMID:12223545 Copper/zinc superoxide dismutase attenuates neuronal cell de... | ACCEPT | Summary: MAP kinase activity is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 is a **proline-directed serine/threonine protein kinase**, preferentially phosphorylating substrates containing **PX(S/T)P** |
| GO:0005737 cytoplasm | IDA PMID:12223545 Copper/zinc superoxide dismutase attenuates neuronal cell de... | ACCEPT | Summary: cytoplasm is consistent with core ERK MAP kinase activity, phosphorylation, cascade function, or localization. Reason: This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization. Supporting Evidence: file:mouse/Mapk1/Mapk1-deep-research-falcon.md ERK2 continuously exchanges between cytoplasm and nucleus |
| GO:0009887 animal organ morphogenesis | IDA PMID:11684667 Erk MAP kinase regulates branching morphogenesis in the deve... | MODIFY | Summary: Animal organ morphogenesis is far broader than the actual finding, which is that Erk MAP kinase activity is required for branching morphogenesis of the ureteric bud in kidney development. Reason: The experiment specifically shows MEK-inhibitor-sensitive, Erk-dependent ureteric bud branching; the generic organ morphogenesis term should be narrowed to the branching-specific term that matches the assay. Proposed replacements: branching involved in ureteric bud morphogenesis Supporting Evidence: PMID:11684667 inhibiting Erk activation with the MAP kinase kinase inhibitor, PD98059, reversibly inhibits branching in a dose-dependent manner |
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Download this section (compressed HTML)Q: Which ERK2 substrate classes are sufficiently direct and recurring to support more specific substrate- or compartment-scoped GO-CAM modeling?
Q: Which Mapk1 developmental annotations remain valid when separated from overlapping ERK1 activity?
Experiment: Map direct ERK2 substrates in cytosolic versus nuclear compartments after acute MEK activation using analog-sensitive or proximity-labeled ERK2 alleles.
Hypothesis: Mapk1 core function is shared MAP kinase catalysis, but biologically specific outputs depend on compartment-restricted substrate access.
Type: Compartment-resolved phosphoproteomics
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