MAPK3

Summary: EGFR-ERK1/2 pathway activation downstream of endophilin-1 in brain endothelial cells.

Reason: ERK1 is a core MAPK cascade kinase; the term is correct although the paper measures p-ERK1/2 rather than ERK1 specifically.

Summary: MAPK cascade transferred from mouse Erk1.

Reason: Correct core process (ERK1 and ERK2 cascade is the more specific child).

Summary: IL-1beta activates ERK1/2 upstream of EGR1 transcription in smooth muscle cells.

Reason: Core process for ERK1; evidence is pathway-level (MEK inhibitor).

Summary: lncRNA ARHGAP5-AS1/CSDE1 axis activates ERK signaling in HCC.

Reason: Term correct for ERK1 as a core cascade member; the paper only reads out phospho-ERK1/2.

Summary: Phosphotyrosine residue binding transferred from mouse Erk1.

Reason: ERK1 is not a phosphotyrosine-reading domain protein; the mouse source reflects interactions with phosphorylated partners rather than a pTyr-binding function. Consistent with the MAPK1 review.

Summary: ERK1 phosphorylates PD-1 Thr234, stabilizing it via USP5 and dampening antitumor T cell responses.

Reason: ERK1-specific kinase screen and direct phosphorylation; physiological immune output is context-specific, non-core.

Summary: Generic protein kinase activity from InterPro/ortholog mapping.

Reason: Correct but too general; ERK1 is a proline-directed Ser/Thr MAP kinase (matching the MAPK1 review replacement).

Proposed replacements: protein serine/threonine kinase activity MAP kinase activity

Summary: Phylogenetic inference of protein serine/threonine kinase activity for ERK1.

Reason: ERK1 is a CMGC-family proline-directed Ser/Thr kinase; the PAINT node covering MAPKs is sound and ERK1 itself has direct biochemical evidence.

Summary: Purified ERK1 phosphorylates the Mediator subunit MED1 in vitro.

Reason: Direct kinase assay using ERK1 on a protein substrate supports Ser/Thr kinase activity; MAP kinase activity is the more specific core term.

Summary: Recombinant activated ERK1 directly phosphorylates DEPTOR on Ser235 in vitro.

Reason: ERK1-specific in vitro kinase assay and ERK1 knockdown establish Ser/Thr kinase activity on a physiological substrate.

Summary: Reactome: ERK1 phosphorylates SOS1 in GRB2:SOS1:p-SHC1 complexes (feedback phosphorylation).

Reason: ERK-mediated feedback phosphorylation of SOS1 on Ser/Thr residues is a well-established ERK1/2 kinase activity.

Summary: Reactome: ERK1 phosphorylates SOS1 in GRB2:SOS1:p-IRS complexes.

Reason: Consistent with ERK1 Ser/Thr kinase activity and negative feedback on SOS1.

Summary: MEK1/MEK2 dually phosphorylate recombinant human ERK1 and activate its kinase activity >100-fold.

Reason: Direct demonstration that human ERK1 is a MEK-activated MAP kinase; this is the most specific core MF for MAPK3.

Summary: Combined IEA assignment of MAP kinase activity from InterPro MAPK signatures and orthology.

Reason: Correct and appropriately specific core MF for ERK1.

Summary: Cloning paper describing human p44erk1 as a mitogen-activated protein kinase with MBP phosphotransferase activity.

Reason: MAP kinase activity is the core MF; the cloning paper directly measured ERK1 kinase activity toward MBP.

Summary: IPI protein binding between ERK1 and PTPRR (mouse PTP-SL/PTPBR7), a KIM-containing tyrosine phosphatase that dephosphorylates ERK1 (Q62132), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and PTPRR (mouse PTP-SL/PTPBR7), a KIM-containing tyrosine phosphatase that dephosphorylates ERK1 (Q62132), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and DUSP1/MKP-1, a MAP kinase phosphatase that is also an ERK substrate (P28562), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and HSF1, a heat shock transcription factor phosphorylated by ERK (Q00613), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a DNA-binding transcription factor that ERK1 docks onto and phosphorylates; DNA-binding transcription factor binding is the informative replacement (matching the MAPK1 review).

Proposed replacements: DNA-binding transcription factor binding

Summary: IPI protein binding between ERK1 and MAPK14/p38alpha MAP kinase (Q16539), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a protein kinase; protein kinase binding is the informative replacement for the generic term.

Proposed replacements: protein kinase binding

Summary: IPI protein binding between ERK1 and PTPRB (VE-PTP), a receptor protein tyrosine phosphatase (P23467), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and DUSP6/MKP-3, the ERK-selective cytoplasmic MAP kinase phosphatase (Q16828), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and DAPK1, a death-associated protein kinase that docks on ERK via its death domain (P53355), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a protein kinase; protein kinase binding is the informative replacement for the generic term.

Proposed replacements: protein kinase binding

Summary: IPI protein binding between ERK1 and RPS3, a ribosomal protein phosphorylated by ERK at Thr42 (P23396), from a targeted study.

Reason: Generic protein binding is uninformative. The partner RPS3, a ribosomal protein phosphorylated by ERK at Thr42 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and ELK1, a ternary complex ETS transcription factor and canonical ERK substrate (P19419), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a DNA-binding transcription factor that ERK1 docks onto and phosphorylates; DNA-binding transcription factor binding is the informative replacement (matching the MAPK1 review).

Proposed replacements: DNA-binding transcription factor binding

Summary: IPI protein binding between ERK1 and TPR, a nuclear pore protein that is an ERK substrate (P12270), from a targeted study.

Reason: Generic protein binding is uninformative. The partner TPR, a nuclear pore protein that is an ERK substrate does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PTPRB (VE-PTP), a receptor protein tyrosine phosphatase (P23467), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and PTPRJ/DEP-1, a receptor tyrosine phosphatase that dephosphorylates ERK1 pTyr204 via a KIM-like docking motif (Q12913), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and MAP2K1/MEK1, the upstream MAP kinase kinase that activates ERK1 (Q02750), from a targeted study.

Reason: Generic protein binding is uninformative. MEK1 binds and dually phosphorylates ERK1 on the TEY motif; mitogen-activated protein kinase kinase binding captures this.

Proposed replacements: mitogen-activated protein kinase kinase binding

Summary: IPI protein binding between ERK1 and PTPRJ/DEP-1, a receptor tyrosine phosphatase that dephosphorylates ERK1 pTyr204 via a KIM-like docking motif (Q12913), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and mouse Eps8, an actin regulator phosphorylated by ERK (Q08509), from a targeted study.

Reason: Generic protein binding is uninformative. The partner mouse Eps8, an actin regulator phosphorylated by ERK does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DUSP1/MKP-1, a MAP kinase phosphatase that is also an ERK substrate (P28562), from a targeted study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and SCRIB (hScrib), a polarity scaffold that docks ERK through KIM motifs (Q14160), from a targeted study.

Reason: Generic protein binding is uninformative. The partner acts as a scaffold/anchor that regulates ERK subcellular distribution and access to substrates; scaffold protein binding matches the MAPK1 review choice.

Proposed replacements: scaffold protein binding

Summary: IPI protein binding between ERK1 and PEA15, a cytoplasmic ERK-anchoring scaffold protein (Q15121), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner acts as a scaffold/anchor that regulates ERK subcellular distribution and access to substrates; scaffold protein binding matches the MAPK1 review choice. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: scaffold protein binding

Summary: IPI protein binding between ERK1 and mouse Klf4, a transcription factor phosphorylated by ERK1/2 at Ser123 (Q60793), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a DNA-binding transcription factor that ERK1 docks onto and phosphorylates; DNA-binding transcription factor binding is the informative replacement (matching the MAPK1 review).

Proposed replacements: DNA-binding transcription factor binding

Summary: IPI protein binding between ERK1 and MAPK14/p38alpha MAP kinase (Q16539), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner is a protein kinase; protein kinase binding is the informative replacement for the generic term. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein kinase binding

Summary: IPI protein binding between ERK1 and rat Nsmf/Jacob, a synapto-nuclear messenger phosphorylated by ERK1/2 (Q9EPI6), from a targeted study.

Reason: Generic protein binding is uninformative. The partner rat Nsmf/Jacob, a synapto-nuclear messenger phosphorylated by ERK1/2 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PKM2 (pyruvate kinase M2) (P14618-1), from a targeted study.

Reason: Generic protein binding is uninformative. The partner PKM2 (pyruvate kinase M2) does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and CDKN2AIP/CARF (Q9NXV6), from a targeted study.

Reason: Generic protein binding is uninformative. The partner CDKN2AIP/CARF does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PNKD/MR-1 (Q8N490), from a targeted study.

Reason: Generic protein binding is uninformative. The partner PNKD/MR-1 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and ELK1, a ternary complex ETS transcription factor and canonical ERK substrate (P19419), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner is a DNA-binding transcription factor that ERK1 docks onto and phosphorylates; DNA-binding transcription factor binding is the informative replacement (matching the MAPK1 review). The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: DNA-binding transcription factor binding

Summary: IPI protein binding between ERK1 and DUSP1/MKP-1, a MAP kinase phosphatase that is also an ERK substrate (P28562), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and DAPK1, a death-associated protein kinase that docks on ERK via its death domain (P53355), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner is a protein kinase; protein kinase binding is the informative replacement for the generic term. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein kinase binding

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DUSP6/MKP-3, the ERK-selective cytoplasmic MAP kinase phosphatase (Q16828), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DUSP6/MKP-3, the ERK-selective cytoplasmic MAP kinase phosphatase (Q16828), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and ZNF263, a KRAB zinc-finger transcription factor stabilized by ERK binding (O14978), from a targeted study.

Reason: Generic protein binding is uninformative. The partner is a DNA-binding transcription factor that ERK1 docks onto and phosphorylates; DNA-binding transcription factor binding is the informative replacement (matching the MAPK1 review).

Proposed replacements: DNA-binding transcription factor binding

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PEA15, a cytoplasmic ERK-anchoring scaffold protein (Q15121), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner acts as a scaffold/anchor that regulates ERK subcellular distribution and access to substrates; scaffold protein binding matches the MAPK1 review choice. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: scaffold protein binding

Summary: IPI protein binding between ERK1 and DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor (P49366), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner DHPS (deoxyhypusine synthase), a recurrent high-throughput interactor does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and DUSP6/MKP-3, the ERK-selective cytoplasmic MAP kinase phosphatase (Q16828), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. ERK1 activity is terminated by tyrosine and dual-specificity phosphatases that dock on its common docking site; binding to this phosphatase is better captured as protein phosphatase binding. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: protein phosphatase binding

Summary: IPI protein binding between ERK1 and UNG (uracil-DNA glycosylase) isoform (P13051-2), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner UNG (uracil-DNA glycosylase) isoform does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and FAM135B isoform (Q49AJ0-4), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner FAM135B isoform does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and OTUD7B isoform (Q6GQQ9-2), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner OTUD7B isoform does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and MRFAP1L1 (Q96HT8), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner MRFAP1L1 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and KLHL32 (Q96NJ5), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner KLHL32 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and CD248/endosialin (Q9HCU0), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner CD248/endosialin does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PADI3 (Q9ULW8), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner PADI3 does not define a specific molecular function of ERK1 beyond its kinase activity toward substrates, so no more informative MF replacement is justified from this evidence. Removal of the GO:0005515 row does not mean the reported interaction is false.

Summary: IPI protein binding between ERK1 and PEA15, a cytoplasmic ERK-anchoring scaffold protein (Q15121), from a high-throughput interactome study.

Reason: Generic protein binding is uninformative. The partner acts as a scaffold/anchor that regulates ERK subcellular distribution and access to substrates; scaffold protein binding matches the MAPK1 review choice. The interaction comes from a high-throughput screen, but the partner class is well established for ERK1/2.

Proposed replacements: scaffold protein binding

Summary: ATP binding from InterPro kinase-domain signatures.

Reason: ERK1 binds ATP in the kinase active-site cleft as phosphoryl donor; required for catalysis.

Summary: Phylogenetic inference that ERK1 is active in the nucleus.

Reason: Activated ERK1 translocates to the nucleus and phosphorylates nuclear substrates.

Summary: Nucleus from UniProt subcellular location/orthology.

Reason: Core site of action for activated ERK1.

Summary: Review of ERK cascade compartmentalization, including nuclear ERK.

Reason: Nuclear ERK is a well-established core pool.

Summary: Insulin-activated ERK is translocated to the nuclear envelope by caveolin-2.

Reason: Stimulus- and caveolin-2-specific localization; supported but not a general site of ERK1 action.

Summary: Human Protein Atlas immunofluorescence places MAPK3 in the nucleoplasm.

Reason: Consistent with nuclear ERK1 pool.

Summary: Reactome reaction 'ERK1/2/5 activate RSK1/2/3' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'ERK1/2 phosphorylates MSK1' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'ERKs are inactivated by protein phosphatase 2A' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'ERKs are inactivated by dual-specific phosphatases (DUSPs)' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'MAPKs phosphorylate ETS1 and ETS2' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'MAPK3 (ERK1) and MAPK1 (ERK2) phosphorylate CEBPB' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'c-FOS activation by phospho ERK1/2' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'Phosphorylated MAPKs translocate into the nucleus' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'Nuclear DUSPs dephosphorylate MAPKs' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'Phosphorylation of UBTF' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'Estrogen-independent phosphorylation of ESR1 S118 by MAPK1 and MAPK3' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'p-T,Y MAPK dimers translocate to nucleus' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Reactome reaction 'ERKs phosphorylate MCRIP1' places ERK1 in the nucleoplasm.

Reason: Activated ERK1 accumulates in the nucleus where it phosphorylates transcription factors and nuclear substrates, and is inactivated by nuclear phosphatases; nucleoplasm is a core site of action.

Summary: Phylogenetic inference that ERK1 is active in the cytoplasm.

Reason: ERK1 is predominantly cytoplasmic in resting cells and acts on cytoplasmic substrates.

Summary: ERK phosphorylates the cytoplasmic tail of PD-1 in T cells.

Reason: Cytoplasmic activity of ERK1 is core; the paper identifies ERK1 as the kinase acting on the PD-1 cytoplasmic tail.

Summary: Cytoplasm from UniProt subcellular location/orthology.

Reason: Core localization.

Summary: Cytoplasm transferred from rat ERK1 (P21708).

Reason: Consistent with core cytoplasmic localization.

Summary: Mitochondrion from the ARBA rule ARBA00026962 (IEA); a minor, stimulus-dependent ERK1 pool at mitochondria is shown in HeLa cells.

Reason: ORGANELLES check (2026-11-03), previously MARK_AS_OVER_ANNOTATED. ARBA00026962 is a multi-condition-set association rule that carries no evidence of its own and is presumably learned from existing mitochondrion annotations such as the parallel TAS row, so it is not used as support. The organelle claim is supported directly for human ERK1: in HeLa cells endogenous and recombinant ERK1 was found in purified mitochondria whose ER contamination was checked by 5'-nucleotidase and glucose-6-phosphatase, about 15% of ERK1-GFP co-localised with MitoTracker after serum starvation, and serum stimulation moved it out towards the nucleus (PMID:19847302). Rodent studies with ERK1/2 antibodies agree (outer-membrane and intermembrane-space subfractions in mouse LP07 cells, PMID:18545666; rat brain outer membrane/intermembrane space fraction, PMID:15030409). The claim therefore holds as a minor, stimulus-dependent signalling pool, non-core beside the cytoplasmic and nuclear ERK1 pools; the earlier MARK_AS_OVER_ANNOTATED read the term as a resident-location claim. Stays at the root: ERK1 has no transit peptide or membrane anchor, the pool is transient trafficking (TRAF3/BRAF precedent), and the sub-mitochondrial lines disagree (outer membrane and IMS by subfractionation; histone partners of ERK1 placed at the outer membrane by proteinase K, while the HeLa paper speculates about a matrix role via TFAM), so no sub-compartment row is added.

Summary: Mitochondrion (TAS) from the Yao and Seger review of ERK-cascade compartments; a minor, stimulus-dependent ERK1 pool at mitochondria is shown in HeLa cells.

Reason: ORGANELLES check (2026-11-03), previously MARK_AS_OVER_ANNOTATED. The TAS source PMID:19565474 is a review whose cached text is abstract-only and does not name the mitochondrion, so the row is judged on primary papers. The organelle claim is supported directly for human ERK1: in HeLa cells endogenous and recombinant ERK1 was found in purified mitochondria whose ER contamination was checked by 5'-nucleotidase and glucose-6-phosphatase, about 15% of ERK1-GFP co-localised with MitoTracker after serum starvation, and serum stimulation moved it out towards the nucleus (PMID:19847302). Rodent studies with ERK1/2 antibodies agree (outer-membrane and intermembrane-space subfractions in mouse LP07 cells, PMID:18545666; rat brain outer membrane/intermembrane space fraction, PMID:15030409). The claim therefore holds as a minor, stimulus-dependent signalling pool, non-core beside the cytoplasmic and nuclear ERK1 pools; the earlier MARK_AS_OVER_ANNOTATED read the term as a resident-location claim. Stays at the root: ERK1 has no transit peptide or membrane anchor, the pool is transient trafficking (TRAF3/BRAF precedent), and the sub-mitochondrial lines disagree (outer membrane and IMS by subfractionation; histone partners of ERK1 placed at the outer membrane by proteinase K, while the HeLa paper speculates about a matrix role via TFAM), so no sub-compartment row is added.

Summary: ARBA prediction of early endosome.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Review mentions endosomal ERK signaling.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: ARBA prediction of late endosome.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Review mentions late endosomal ERK scaffolds.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Reactome reaction 'Mce3E binds MAPK3' (Mycobacterium tuberculosis effector) placed in the ER lumen.

Reason: ERK1 is a cytosolic/nuclear kinase with no signal peptide; ER lumen placement reflects modelling of a pathogen-effector interaction, not a physiological location (same call as MAPK1).

Summary: ARBA prediction of Golgi apparatus.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Review mentions Golgi-associated ERK.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Cytosol transferred from mouse Erk1.

Reason: Core cytosolic localization.

Summary: Review of ERK cascade compartmentalization, including cytosolic ERK.

Reason: Cytosol is the principal resting-state location of ERK1.

Summary: Reactome reaction 'MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y-IRS1,p-Y-IRS2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2K1 binds MAPK3' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2K1 phosphorylates MAPK3' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of p-T,Y-MAPK3:MAP2K1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Lyn activates ERK' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'ISGylation of host proteins' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'p-ERK phosphorylates WAVEs and ABI' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Constitutive phosphorylation by pERK1/2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'SRC-1 is activated (in F2R:ARRB1:MAPKs:SRC-1)' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated SRC-1 activates MAPKs (in F2R:ARRB1:MAPKs:active SRC-1)' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'F2R:ARRB1 binds MAPKs, SRC-1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'F2R:ARRB2 binds MAPKs, SRC-1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'SRC-1 bound to ARRB2 is not activated' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated ERK1/2 threonine-phosphorylates FGFR2-associated FRS2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated ERK1/2 threonine-phosphorylates FGFR3-associated FRS2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated ERK1/2 threonine-phosphorylates FGFR4-associated FRS2' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks and MAPKs bind to the activated RAF complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks phosphorylate MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAF phosphorylates MAP2K dimer' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of RAS:RAF complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks and MAPKs are phosphorylated at the endosome membrane' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'WDR83:LAMTOR2:LAMTOR3 binds MAPK components' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'IL17RD binds p-2S MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks phosphorylate MAPK at the Golgi membrane' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'p-T,Y MAPKs dimerize' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Phosphorylated MAPKs translocate into the nucleus' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAPKs phosphorylate MAP2K1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAPK phosphorylates RAF1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAPKs phosphorylate BRAF' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'PEA15 binds MAPK monomers and dimers' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Cytosolic DUSPs dephosphorylate MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'High kinase activity BRAF complexes phosphorylate MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'High kinase activity BRAF mutants bind MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Mutant RAS:p-RAF complexes phosphorylate MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of BRAF/RAF fusion complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'p-BRAF and RAF fusion dimers phosphorylate MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of high activity BRAF complexes' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of moderate activity BRAF complexes' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of oncogenic RAS:RAF complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of paradoxically activated RAS:BRAF complexes' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPKs phosphorylate PP2A' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'IER3 recruits MAPKs to PP2A-B56-beta,gamma' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated BRAF recruits MAP2Ks and MAPKs to the endosome' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Activated BRAF phosphorylates MAP2K dimers downstream of RAP1 and NGF' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of phosphorylated MAP2Ks and MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks phosphorylate MAPKs downstream of BRAF and NGF' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'p-T,Y MAPK dimers translocate to nucleus' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPK1 or MAPK3 phosphorylates NCF1 at Ser345' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'CASP9 is phosphorylated at T412' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'PTPN7 dephosphorylates p-T,Y-MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'PTPN7 binds p-T,Y-MAPK' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2K mutants constitutively phosphorylate MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dissociation of RAS:RAF1 mutant complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks and MAPKs bind to the activated mutant RAF1 complex' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'RAF1 mutant complexes phosphorylate MAP2K dimer' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dual mechanism MAP2K inhibitors bind MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Dual mechanism MAPK inhibitors bind MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'Single mechanism MAPK inhibitors bind phosphorylated MAPK' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPK1 and MAPK3 phosphorylate SMAD2 and SMAD3' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'JAK1-activated RAF1 phosphorylates MAPKs' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'JAK2-activated MAPKs phosphorylate YBX1' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'MAPK-dependent phosphorylation of KARS' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: Reactome reaction 'CLIP1-LTK promotes MAPK1 and MAPK3 phosphorylation' places ERK1 (MAPK3) in the cytosol.

Reason: ERK1 is predominantly cytoplasmic/cytosolic in unstimulated cells and phosphorylates many cytosolic substrates; the Reactome cytosol placement is consistent with this core localization.

Summary: ARBA prediction of cytoskeleton.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Review mentions cytoskeleton-associated ERK.

Reason: Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association.

Summary: Plasma membrane transferred from rat ERK1.

Reason: ERK1 is recruited transiently to membrane-proximal scaffolds; not a plasma membrane resident. Consistent with MAPK1.

Summary: Caveola from UniProt subcellular location.

Reason: Derived from the rat ERK1 caveolar pool; non-core.

Summary: Caveola transferred from rat ERK1 (P21708).

Reason: ERK1-specific ortholog evidence places a pool in caveolae; plausible but minor, non-core.

Summary: Review mentions caveolar ERK.

Reason: Minor membrane microdomain pool; non-core.

Summary: Focal adhesion from UniProt subcellular location (rat Erk1 GIT1-dependent localization).

Reason: ERK1 is recruited to focal adhesions via GIT1 and phosphorylates paxillin there; real but non-core.

Summary: Review mentions focal adhesion ERK.

Reason: Focal adhesion ERK pool phosphorylates paxillin; non-core localization.

Summary: Cloned human ERK1 phosphorylates myelin basic protein.

Reason: Core catalytic process.

Summary: Phylogenetic inference of cell surface receptor signaling pathway.

Reason: Very general; ERK1 acts in the ERK1/ERK2 MAPK cascade downstream of many receptors. Replacement matches MAPK1 review.

Proposed replacements: ERK1 and ERK2 cascade

Summary: EGFR-ERK1/2 pathway in brain endothelial cells.

Reason: Receptor-specific context of the ERK cascade; pathway-level evidence.

Summary: ARBA: EGFR signaling pathway.

Reason: ERK1 is a downstream kinase in EGFR signaling; one of many receptor contexts.

Summary: Insulin receptor signaling pathway from mouse Erk1.

Reason: ERK1 is activated downstream of insulin; receptor context, non-core.

Summary: ARBA: positive regulation of macrophage chemotaxis.

Reason: Downstream cell-behavior output of ERK signaling; non-core.

Summary: IL-34-driven macrophage chemotaxis requiring ERK (acts upstream of).

Reason: Downstream, context-specific output; non-core (consistent with MAPK1).

Summary: Schwann cell development transferred from mouse Erk1.

Reason: Mouse ERK1 loss affects Schwann cell myelination; developmental output of the cascade, non-core.

Summary: ERK phosphorylates ribosomal protein S3 at Thr42.

Reason: Phosphorylation is too general; this is protein phosphorylation of a substrate.

Proposed replacements: protein phosphorylation

Summary: Sensory perception of pain transferred from mouse Erk1.

Reason: Organismal phenotype of Erk1-null mice; indirect, non-core.

Summary: ARBA prediction of phosphatase binding.

Reason: ERK1 binds several phosphatases (DUSPs, PTPRJ, PTPRR) that inactivate it; genuine but regulatory, not a core function.

Summary: DEP-1/PTPRJ binds ERK1/2 via a KIM-like motif and dephosphorylates pTyr204.

Reason: Well-supported interaction with a negative regulator; non-core (matches MAPK1 treatment).

Summary: BMP2 induces ERK1/2 phosphorylation; ERK1/2 inhibition reduces BMP2-induced osteopontin.

Reason: Non-canonical ERK arm of BMP signaling, pathway-level inhibitor evidence; non-core.

Summary: Pseudopodium transferred from mouse Erk1.

Reason: Mouse ERK1 localizes to pseudopodia in migrating cells; context-specific, non-core.

Summary: ERK inhibition reduces IL-1beta-induced CD38 ADP-ribosyl cyclase activity in astrocytes.

Reason: Effect is via induction of CD38 expression, measured with pan-ERK pharmacological blockers; ERK1 does not directly regulate cyclase activity.

Summary: ARBA: positive regulation of telomere maintenance.

Reason: Derived from an RNAi screen hit; indirect and weak, over-annotation (as in MAPK1).

Summary: Kinome RNAi screen for telomerase activity regulators.

Reason: High-throughput RNAi screen whose abstract highlights ERK8/MAPK15, not ERK1; any MAPK3 effect is indirect. Not REMOVE because the full text is unavailable.

Summary: ARBA: regulation of stress-activated MAPK cascade.

Reason: ERK1 is not a component or specific regulator of the JNK/p38 cascades; cross-talk only. Consistent with MAPK1.

Summary: Review of ERK compartmentalization.

Reason: Cross-talk with stress MAPK cascades is not a core ERK1 role.

Summary: IDA cellular response to amino acid starvation (glutamine deprivation).

Reason: The cached abstract discusses ASK1 and JNK only and does not mention ERK1; full text not available to verify the ERK1 readout.

Summary: ARBA: cellular response to amino acid starvation.

Reason: Stress-response context; non-core (consistent with MAPK1).

Summary: Phylogenetic inference of intracellular signal transduction.

Reason: Correct general parent of the MAPK cascade; consistent with MAPK1.

Summary: Peptidyl-tyrosine autophosphorylation of ERK1.

Reason: Recombinant ERK1 shows only low-stoichiometry in vitro autophosphorylation; physiological TEY tyrosine phosphorylation is catalysed by MEK1/2, as the cited paper demonstrates.

Summary: ERBB2-ERBB3 signaling pathway from mouse Erk1.

Reason: Receptor context of ERK1 activation; non-core.

Summary: Myelination transferred from mouse Erk1.

Reason: Developmental downstream phenotype in mouse; non-core.

Summary: ERK1/2-mediated phosphorylation of rpS3 T42 drives its nuclear translocation after genotoxic stress.

Reason: Supported downstream DNA-damage signaling role; non-core.

Summary: ERK1 self-interaction recorded from the PARP-1 phosphorylation study.

Reason: ERK1/2 can dimerize after activation; self-interaction is real but not a core function. Consistent with MAPK1 treatment.

Summary: ERK1 self-interaction recorded from the Klf4 phosphorylation study.

Reason: ERK dimerization is non-core; the paper primarily shows ERK1/2 binding and phosphorylating Klf4.

Summary: ERK1/2 activity required for IL-1beta-induced EGR1 transcription.

Reason: ERK signaling induces immediate-early gene transcription via TF phosphorylation; indirect, non-core.

Summary: IGF receptor signaling pathway from mouse Erk1.

Reason: Receptor context of ERK1 activation; non-core.

Summary: Modulation of chemical synaptic transmission transferred from mouse Erk1.

Reason: Neuronal output of ERK signaling; non-core.

Summary: Glutamine deprivation/Fas study of QRS-ASK1 interaction.

Reason: The abstract describes ASK1/JNK activation; ERK1 is not a stress-activated MAPK. Regardless of ERK1 readouts in the full text, the term over-extends ERK1 function (same call as MAPK1).

Summary: ARBA: stress-activated MAPK cascade.

Reason: ERK1 is a classical mitogen-activated MAPK; stress-activated MAPK cascade refers to JNK/p38.

Summary: ARBA: regulation of cytoskeleton organization.

Reason: ERK1 phosphorylates cytoskeletal substrates; downstream output, non-core.

Summary: Review: cytoskeletal ERK functions.

Reason: Downstream output; non-core.

Summary: ARBA: interleukin-34-mediated signaling pathway.

Reason: Cytokine-receptor context of ERK activation; non-core.

Summary: IL-34 signaling in tumor-associated macrophages (miR-28-5p/IL-34 HCC study).

Reason: Abstract does not mention ERK; the curator presumably used full-text data. Accepted as a receptor-context, non-core role consistent with MAPK1.

Summary: ARBA prediction of ERK1 and ERK2 cascade.

Reason: The most specific core process for ERK1.

Summary: ERK1/2 cascade activation in HCC downstream of CSDE1.

Reason: Correct core process term.

Summary: BMP2 induces ERK1/2 phosphorylation in aortic valve interstitial cells.

Reason: ERK1 is itself the terminal kinase of the ERK1/2 cascade rather than a regulator of it; the finding (BMP2-induced ERK1/2 phosphorylation, inhibitor-sensitive osteopontin expression) is better captured as participation in the ERK1 and ERK2 cascade.

Proposed replacements: ERK1 and ERK2 cascade

Summary: IL-1beta-induced ERK1/2 activation drives EGR1 transcription.

Reason: Cytokine context of ERK cascade; pathway-level (MEK inhibitor) evidence; non-core.

Summary: EGF-stimulated ERK activation and nuclear translocation (Tpr study).

Reason: Stimulus-response context; non-core (consistent with MAPK1).

Summary: EGF-induced ERK phosphorylation modulated by PAQR10/PAQR11 in the Golgi.

Reason: Stimulus-response context; non-core.

Summary: ARBA: response to epidermal growth factor.

Reason: ERK1 is activated by EGF; stimulus context, non-core.

Summary: IEP cellular response to mechanical stimulus citing a BAD/prostate cancer paper.

Reason: Documented batch mis-citation (projects/MISCITATIONS.md): the cited paper contains no mechanical-stimulation experiment and does not mention MAPK3/ERK1. Cannot verify the intended evidence.

Summary: ARBA: caveolin-mediated endocytosis.

Reason: Regulatory role in endocytic dynamics; non-core.

Summary: Review: ERK and caveolar endocytosis.

Reason: Non-core.

Summary: ARBA: regulation of Golgi inheritance.

Reason: ERK phosphorylation contributes to mitotic Golgi fragmentation; non-core.

Summary: Review: ERK and Golgi fragmentation.

Reason: Non-core.

Summary: Negative regulation of cholesterol efflux transferred from mouse Erk1.

Reason: Metabolic phenotype observed in Erk1-deficient mouse macrophages; indirect, non-core.

Summary: Glutamatergic synapse transferred from mouse Erk1.

Reason: Neuronal-context localization supported in mouse; non-core.

Summary: ERK1 phosphorylates DEPTOR on Ser235.

Reason: The experiment is sound (ERK1-specific in vitro kinase assay), but ERK1 is a Ser/Thr MAP kinase; the Ser-only term under-describes the activity. Replace with MAP kinase activity (same choice as in MAPK1).

Proposed replacements: protein serine/threonine kinase activity MAP kinase activity

Summary: Rhea-based mapping of protein serine kinase activity (RHEA:17989).

Reason: ERK1 phosphorylates both Ser and Thr residues in S/T-P motifs; the Ser-only term is incomplete. Replace with Ser/Thr kinase and MAP kinase activity, as in the MAPK1 review.

Proposed replacements: protein serine/threonine kinase activity MAP kinase activity

Summary: Protein serine kinase activity transferred from rat ERK1 (P21708).

Reason: Correct but split-residue term; ERK1 is a Ser/Thr MAP kinase. Replace with MAP kinase activity (consistent with MAPK1).

Proposed replacements: protein serine/threonine kinase activity MAP kinase activity

Summary: ARBA: positive regulation of macrophage proliferation.

Reason: Downstream proliferative output; non-core.

Summary: IL-34-driven macrophage proliferation requiring ERK (acts upstream of).

Reason: Downstream, context-specific output; non-core.

Summary: EBF4 co-immunoprecipitates MAPK3/ERK1.

Reason: Binding to transcription factors reflects ERK1 substrate docking; supported but not a core function of its own.

Summary: IDA positive regulation of neuroinflammatory response citing an endophilin-1/BBB permeability paper.

Reason: The cached abstract concerns EGFR-ERK1/2 control of tight-junction proteins and BBB permeability and does not describe a neuroinflammatory response; full text unavailable, so the basis for this term cannot be verified.

Summary: Positive regulation of neuroinflammatory response from mouse Erk1.

Reason: Context-specific downstream output; non-core.

Summary: Positive regulation of neuroinflammatory response transferred from mouse Erk1.

Reason: Context-specific downstream output; non-core.

Summary: ERK1 phosphorylation of DEPTOR S235 controls DEPTOR turnover in myeloma cells.

Reason: ERK1-specific substrate-level regulatory role in mTOR signaling; non-core.

Summary: ARBA: regulation of early endosome to late endosome transport.

Reason: Endosomal dynamics output of ERK signaling; non-core.

Summary: Review: ERK in endosome dynamics.

Reason: Non-core.