Mapk8 encodes c-Jun N-terminal kinase 1 (JNK1, SAPK gamma), a proline-directed serine/threonine protein kinase of the CMGC group and the MAP kinase subfamily. It is the terminal kinase of the stress-activated JNK cascade: cytokines, oxidants, metabolic stress and other cellular stresses activate MAP3Ks that drive dual phosphorylation of the Thr183-Pro-Tyr185 activation-loop motif by MAP2K4 and MAP2K7, and JIP scaffolds assemble these modules. Active JNK1 phosphorylates Ser/Thr-Pro sites in many substrates. In the nucleus these are mainly AP-1 transcription factors such as c-Jun (Ser63/Ser73) and ATF2, through which JNK1 controls stress-responsive gene expression. In the cytoplasm, and prominently in neurons, it phosphorylates SCG10/stathmin-2 (regulating microtubule dynamics, neurite length and radial migration), paxillin (cell migration), synaptotagmin-4 (capture of dense core vesicles at synapses) and AMPA receptor subunits. In rat cells JNK1 promotes apoptosis in some settings (cardiomyocyte reoxygenation, amyloid-beta-treated cortical neurons, glioma) and protects against it in others (INS-1 beta cells under glucolipotoxicity), and it drives agonist-stimulated hepatocyte DNA synthesis. Its activity is inhibited by S-nitrosylation of Cys116 and by dual-specificity phosphatases.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | ISO GO_REF:0000121 | MODIFY | Summary: MAPK cascade, transferred by RGD ISO from mouse/human JNK1. Reason: Correct but too general. JNK1 is the terminal kinase of the JNK branch of MAPK signalling, and the specific child term GO:0007254 JNK cascade is already carried by this gene (IBA, ISO, ISS). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: JNK cascade Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0000165 MAPK cascade | ISO GO_REF:0000121 | MODIFY | Summary: MAPK cascade, transferred by RGD ISO from mouse/human JNK1. Reason: Correct but too general. JNK1 is the terminal kinase of the JNK branch of MAPK signalling, and the specific child term GO:0007254 JNK cascade is already carried by this gene (IBA, ISO, ISS). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: JNK cascade Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0001503 ossification | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ossification (acts_upstream_of_or_within), ISO from mouse Mapk8 IMP (PMID:15820682). Reason: Phenotype-level inference from a mouse knockout; bone formation is a downstream, tissue-level outcome to which JNK1 contributes through signalling, not a process it executes. Retained as non-core context. |
| GO:0001764 neuron migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Neuron migration, ISO from mouse Mapk8 IMP (PMID:21297631). Reason: Supported: cytoplasmic JNK1 phosphorylates SCG10/STMN2 and thereby controls the rate of radial migration of cortical neurons (in mouse, with rat cortical neuron experiments in the same study). Peripheral to the core kinase function. Supporting Evidence: PMID:21297631 the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development |
| GO:0002052 positive regulation of neuroblast proliferation | IMP PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Positive regulation of neuroblast proliferation, IMP from WDR62/JNK1 knockdown in developing rat/mouse cortex (PMID:24388750). Reason: Abstract reports that JNK1 depletion causes premature differentiation of neural progenitors, phenocopying WDR62 loss. The kinase acts in a signalling pathway that keeps progenitors cycling; full text not cached, deferring to the curator. Non-core developmental role. Supporting Evidence: PMID:24388750 Depletion of JNK1 and WDR62 incurs very similar defects including abnormal spindle formation and mitotic division of NPCs as well as premature NPC differentiation during cortical development. |
| GO:0002102 podosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Podosome, ISO from mouse Mapk8 IDA (PMID:24127566). Reason: Localisation transferred from a mouse study of JNK in podosome formation; plausible but cell-type specific and peripheral to the core function. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Protein kinase activity (InterPro IEA / RGD ISO). Reason: Correct but uninformative: JNK1 is a proline-directed Ser/Thr MAP kinase. Replace with GO:0004707 MAP kinase activity, already carried by this gene (and its child JUN kinase activity). Proposed replacements: MAP kinase activity Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein kinase activity (InterPro IEA / RGD ISO). Reason: Correct but uninformative: JNK1 is a proline-directed Ser/Thr MAP kinase. Replace with GO:0004707 MAP kinase activity, already carried by this gene (and its child JUN kinase activity). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: MAP kinase activity Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein serine/threonine kinase activity, ISO from mouse/human JNK1. Reason: Correct but less specific than the evidence supports. GO:0004707 MAP kinase activity (is_a protein serine/threonine kinase activity) is already carried by this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: MAP kinase activity Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein serine/threonine kinase activity, ISO from mouse/human JNK1. Reason: Correct but less specific than the evidence supports. GO:0004707 MAP kinase activity (is_a protein serine/threonine kinase activity) is already carried by this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: MAP kinase activity Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004705 JUN kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: JUN kinase activity, IBA from the PAINT JNK clade node. Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). The JNK clade node is seeded by experimentally characterised fly, mouse and human JNKs and rat Mapk8 sits within it. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0004705 JUN kinase activity | IDA PMID:11849756 Mitogen-activated protein kinase kinase 7 is activated durin... | ACCEPT | Summary: JUN kinase activity, IDA (PMID:11849756), rat cerebellar granule neurons. Reason: The cached abstract measures MKK7 activity and c-Jun phosphorylation during low-K+ apoptosis; the full text (not cached) presumably contains the JNK immune-complex kinase data the curator used. The activity is well established for JNK1, so the annotation is accepted, deferring to the curator. Supporting Evidence: PMID:11849756 These data suggest that MKK7 is responsible for activating the JNK pathway during LK-induced CGN apoptosis. |
| GO:0004705 JUN kinase activity | IDA PMID:17064355 Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenou... | ACCEPT | Summary: JUN kinase activity, IDA (PMID:17064355), rat hippocampal CA1 after global ischaemia. Reason: Abstract reports JNK1/2 activation and downstream c-Jun phosphorylation in rat hippocampus; activity is consistent with the established JNK1 function. Accepted, deferring to the curator for the full-text assay. Supporting Evidence: PMID:17064355 E2 reduced downstream JNK nuclear and non-nuclear components, c-Jun and Bcl-2 phosphorylation and Fas ligand protein expression induced by ischemia/reperfusion. |
| GO:0004705 JUN kinase activity | IEA GO_REF:0000117 | ACCEPT | Summary: JUN kinase activity, IEA (ARBA). Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). The ARBA prediction agrees with the experimental and phylogenetic evidence. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0004705 JUN kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: JUN kinase activity, ISO from mouse/human JNK1. Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). Orthologs share the activity; transfer is sound. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0004705 JUN kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: JUN kinase activity, ISO from mouse/human JNK1. Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). Orthologs share the activity; transfer is sound. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0004705 JUN kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: JUN kinase activity, ISS from mouse Mapk8 (Q91Y86). Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0004705 JUN kinase activity | TAS PMID:12011047 Involvement of c-Jun N-terminal kinase in oxidative stress-m... | ACCEPT | Summary: JUN kinase activity, TAS (PMID:12011047), rat islets. Reason: JUN kinase activity is the defining activity of JNK1 (c-Jun N-terminal Ser63/Ser73 phosphorylation). The paper uses dominant-negative JNK in rat islets; the statement is consistent with the established activity. Supporting Evidence: PMID:12011047 In conclusion, activation of JNK is involved in the reduction of insulin gene expression by oxidative stress, and suppression of the JNK pathway protects beta-cells from oxidative stress. |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: MAP kinase activity, IEA (InterPro MAP kinase/JNK signatures, EC 2.7.11.24). Reason: Core activity. Rat Mapk8 carries the MAP kinase signature and TXY activation motif and has measured Ser/Thr kinase activity (EC 2.7.11.24) toward several substrates. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) file:rat/Mapk8/Mapk8-deep-research-manual.md Rat Mapk8 encodes JNK1 / SAPK gamma, a 411-aa member of the CMGC Ser/Thr kinase group |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Protein serine/threonine/tyrosine kinase activity, ISO from mouse Mapk8 IMP (PMID:29153991). Reason: JNK1 is a proline-directed Ser/Thr kinase; the tyrosine in its own TXY motif is phosphorylated by MAP2K4, not by JNK1. A loss-of-function (IMP) experiment cannot establish tyrosine-kinase specificity. Serine and threonine phosphorylation are covered by GO:0004707 and GO:0106310. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SOURCE WEAK OR INFERRED Mouse Mapk8 source is an IMP (PMID:29153991); a loss-of-function phenotype cannot establish tyrosine-kinase specificity for a proline-directed Ser/Thr MAPK. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) file:rat/Mapk8/Mapk8-uniprot.txt The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. |
| GO:0005515 protein binding | IPI PMID:18046461 JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked ... | REMOVE | Summary: Protein binding with c-Jun (P17325), IPI (PMID:18046461). Reason: Bare protein binding is uninformative. The interaction partner is a JNK1 substrate, which is captured by the kinase activity terms; removal does not dispute the reported interaction. |
| GO:0005515 protein binding | IPI PMID:18046461 JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked ... | REMOVE | Summary: Protein binding with synaptotagmin-4 (P50232), IPI (PMID:18046461). Reason: Bare protein binding is uninformative. The interaction partner is a JNK1 substrate, which is captured by the kinase activity terms; removal does not dispute the reported interaction. Supporting Evidence: PMID:18046461 JNK associated with phosphorylated synaptotagmin-4 (Syt 4), a key mediator of NGF enhancement of Ca2+-evoked release in this system. |
| GO:0005515 protein binding | IPI PMID:18188153 Rapid and bi-directional regulation of AMPA receptor phospho... | REMOVE | Summary: Protein binding with GluR2 long isoform (P19491-3), IPI (PMID:18188153). Reason: Bare protein binding is uninformative. The interaction partner is a JNK1 substrate, which is captured by the kinase activity terms; removal does not dispute the reported interaction. Supporting Evidence: PMID:18188153 JNK1 phosphorylated both GST-GluR2L and GST-GluR4 extremely effectively in vitro |
| GO:0005515 protein binding | IPI PMID:18188153 Rapid and bi-directional regulation of AMPA receptor phospho... | REMOVE | Summary: Protein binding with GluR4 (P19493), IPI (PMID:18188153). Reason: Bare protein binding is uninformative. The interaction partner is a JNK1 substrate, which is captured by the kinase activity terms; removal does not dispute the reported interaction. Supporting Evidence: PMID:18188153 JNK1 phosphorylated both GST-GluR2L and GST-GluR4 extremely effectively in vitro |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding, IEA (InterPro kinase signatures). Reason: ATP is the phospho-donor of the kinase reaction; ATP-binding glycine loop (32-40) and Lys55 are conserved. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt /ligand="ATP" file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus, IBA (is_active_in). Reason: JNK1 phosphorylates nuclear transcription factors (c-Jun, ATF2, JDP2, Elk-1) and is found in the nucleus. The PAINT node reflects nuclear MAPK activity conserved across the MAPK family. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. file:rat/Mapk8/Mapk8-uniprot.txt Nucleus {ECO:0000250|UniProtKB:Q91Y86} |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus, IEA from UniProt subcellular location. Reason: JNK1 phosphorylates nuclear transcription factors (c-Jun, ATF2, JDP2, Elk-1) and is found in the nucleus. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Nucleus {ECO:0000250|UniProtKB:Q91Y86} |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus, ISO from mouse/human JNK1. Reason: JNK1 phosphorylates nuclear transcription factors (c-Jun, ATF2, JDP2, Elk-1) and is found in the nucleus. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Nucleus {ECO:0000250|UniProtKB:Q91Y86} |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus, ISO from mouse/human JNK1. Reason: JNK1 phosphorylates nuclear transcription factors (c-Jun, ATF2, JDP2, Elk-1) and is found in the nucleus. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Nucleus {ECO:0000250|UniProtKB:Q91Y86} |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nucleus, ISS from mouse Mapk8. Reason: JNK1 phosphorylates nuclear transcription factors (c-Jun, ATF2, JDP2, Elk-1) and is found in the nucleus. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Nucleus {ECO:0000250|UniProtKB:Q91Y86} |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleoplasm (ISO / Reactome TAS). Reason: Nuclear JNK1 acts on soluble transcription factors in the nucleoplasm; consistent with the nuclear location. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0005654 nucleoplasm | TAS Reactome:R-RNO-209184 | ACCEPT | Summary: Nucleoplasm (ISO / Reactome TAS). Reason: Nuclear JNK1 acts on soluble transcription factors in the nucleoplasm; consistent with the nuclear location. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0005737 cytoplasm | EXP PMID:16618812 JNK1 phosphorylation of SCG10 determines microtubule dynamic... | ACCEPT | Summary: Cytoplasm, EXP (PMID:16618812), rat cortical neurons. Reason: JNK1 is predominantly cytoplasmic in neurons and acts on cytoplasmic substrates (SCG10/STMN2, paxillin, Syt4). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). PMID:16618812 Phosphorylation of SCG10 by the cytoplasmic pool of JNK controls its ability to influence axodendritic architecture of cortical neurons. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm, IBA (is_active_in). Reason: JNK1 is predominantly cytoplasmic in neurons and acts on cytoplasmic substrates (SCG10/STMN2, paxillin, Syt4). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm, IEA from UniProt subcellular location. Reason: JNK1 is predominantly cytoplasmic in neurons and acts on cytoplasmic substrates (SCG10/STMN2, paxillin, Syt4). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Cytoplasm, ISO from mouse Mapk8. Reason: JNK1 is predominantly cytoplasmic in neurons and acts on cytoplasmic substrates (SCG10/STMN2, paxillin, Syt4). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Cytoplasm, ISO from mouse Mapk8. Reason: JNK1 is predominantly cytoplasmic in neurons and acts on cytoplasmic substrates (SCG10/STMN2, paxillin, Syt4). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrion, ISO from mouse Mapk8 IDA (PMID:11884367). Reason: Organelle policy check: the source is a direct mouse localisation study; JNK is recruited to mitochondria under stress (binding of outer-membrane anchors), which supports an organelle association but a transient, stress-induced one. Kept as non-core; no sub-compartment term added because the association is recruitment rather than residence. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Cytosol (ISO / Reactome TAS). Reason: JNK1 is a soluble kinase; cytosolic pools phosphorylate cytoplasmic substrates and are activated there by MAP2K4/7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005829 cytosol | TAS Reactome:R-RNO-205027 | ACCEPT | Summary: Cytosol (ISO / Reactome TAS). Reason: JNK1 is a soluble kinase; cytosolic pools phosphorylate cytoplasmic substrates and are activated there by MAP2K4/7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0005829 cytosol | TAS Reactome:R-RNO-209184 | ACCEPT | Summary: Cytosol (ISO / Reactome TAS). Reason: JNK1 is a soluble kinase; cytosolic pools phosphorylate cytoplasmic substrates and are activated there by MAP2K4/7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction (PubMed:16618812). |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:12011047 Involvement of c-Jun N-terminal kinase in oxidative stress-m... | KEEP AS NON CORE | Summary: Regulation of DNA-templated transcription, IDA (PMID:12011047), rat islets. Reason: Dominant-negative JNK preserved PDX-1 binding and insulin gene expression under oxidative stress. JNK1 regulates transcription indirectly by phosphorylating transcription factors; this is a downstream, context-specific role. Supporting Evidence: PMID:12011047 adenoviral overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA binding activity |
| GO:0006979 response to oxidative stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to oxidative stress, ISO from human MAPK8. Reason: JNK1 is activated by oxidants (shown for rat heart with H2O2). A stress-response context for the kinase, not its core activity. Supporting Evidence: PMID:9516415 H2O2 activated both SAPKs/JNKs and p38-MAPK. |
| GO:0007229 integrin-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Integrin-mediated signaling pathway, ISO from mouse Mapk8 IDA (PMID:36812915). Reason: JNK1 acts downstream of integrin/focal adhesion signalling and phosphorylates paxillin; peripheral to core function. Supporting Evidence: PMID:12853963 JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. |
| GO:0007254 JNK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: JNK cascade, IBA. Reason: Core process: JNK1 is the terminal kinase of the JNK (SAPK) cascade, activated by MAP2K4/MAP2K7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0007254 JNK cascade | ISO GO_REF:0000121 | ACCEPT | Summary: JNK cascade, ISO from mouse/human JNK1. Reason: Core process: JNK1 is the terminal kinase of the JNK (SAPK) cascade, activated by MAP2K4/MAP2K7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0007254 JNK cascade | ISO GO_REF:0000121 | ACCEPT | Summary: JNK cascade, ISO from mouse/human JNK1. Reason: Core process: JNK1 is the terminal kinase of the JNK (SAPK) cascade, activated by MAP2K4/MAP2K7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0007254 JNK cascade | ISS GO_REF:0000024 | ACCEPT | Summary: JNK cascade, ISS from mouse Mapk8. Reason: Core process: JNK1 is the terminal kinase of the JNK (SAPK) cascade, activated by MAP2K4/MAP2K7. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. PMID:11849756 A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. |
| GO:0007528 neuromuscular junction development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Neuromuscular junction development, ISO from mouse Mapk8 IMP (PMID:10521398). Reason: Developmental phenotype from a mouse study; JNK signalling contributes but the kinase is not a structural or executive component of NMJ formation. Non-core. |
| GO:0009411 response to UV | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to UV (acts_upstream_of_or_within), ISO from human MAPK8. Reason: UV is a classic JNK-activating stress; a context for activation, not a distinct function. |
| GO:0009612 response to mechanical stimulus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Response to mechanical stimulus, IBA. Reason: JNKs are activated by mechanical stress (e.g. high aortic pressure in perfused rat heart activates SR-MAPKs). Stress-response context; non-core. Supporting Evidence: PMID:9516415 Perfusion of hearts at high aortic pressure (20 kilopascals) also activated the SR-MAPKs and MAPKAPK2. |
| GO:0010468 regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of gene expression (acts_upstream_of_or_within), ISO from mouse Mapk8. Reason: Very broad phenotype-level term; the specific mechanism (phosphorylation of AP-1 factors) is better represented by the kinase activity and JNK cascade terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SUPPORTS TRANSFER Ortholog source reflects a real but indirect, phenotype-level effect captured by a very broad term; transfer is not wrong but adds little information. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of gene expression, ISO from human MAPK8. Reason: Broad, indirect phenotype-level term; JNK1 effects on gene expression are mediated by phosphorylation of transcription factors and can be positive or negative depending on target. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SUPPORTS TRANSFER Ortholog source reflects a real but indirect, phenotype-level effect captured by a very broad term; transfer is not wrong but adds little information. |
| GO:0010666 positive regulation of cardiac muscle cell apoptotic process | IMP PMID:11259632 Inhibition of c-Jun N-terminal kinase 1, but not c-Jun N-ter... | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell apoptotic process, IMP (PMID:11259632), rat cardiac myocytes. Reason: Antisense knockdown of JNK1 (not JNK2) almost abolished reoxygenation-induced apoptosis. Valid isoform-specific evidence; context-dependent, non-core. Supporting Evidence: PMID:11259632 Pretreatment of cardiac myocytes with JNK1 AS, but not JNK2 AS, resulted in almost complete attenuation of reoxygenation-induced apoptosis. |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Kinase activity, ISO from mouse Mapk8. Reason: Correct but uninformative; replace with GO:0004707 MAP kinase activity, already carried by this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1346861 · MGI:MGI:1346861 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: MAP kinase activity Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0018105 peptidyl-serine phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Peptidyl-serine phosphorylation, ISS from human MAPK8. Reason: JNK1 phosphorylates serine residues of its substrates (c-Jun Ser63/73, SCG10 Ser62/73, paxillin Ser178, Syt4 Ser135). Supporting Evidence: PMID:12853963 JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0019894 kinesin binding | IPI PMID:18932217 Daxx functions as a scaffold of a protein assembly constitut... | UNDECIDED | Summary: Kinesin binding, IPI (PMID:18932217) with RGD:621559. Reason: The cached abstract describes JNK1 binding to Daxx and GLUT4 via D-sites and Daxx binding to kinesin light chain; it does not state that JNK1 binds kinesin directly. Full text not available, so the specific JNK1-kinesin interaction cannot be verified. Supporting Evidence: PMID:18932217 Daxx and GLUT4 interact with JNK1 through D-sites in their NH(2)-(aa 1-501) and large endofacial loop, respectively. |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Enzyme binding, ISO from human MAPK8. Reason: JNK1 binds many enzymes (upstream MKKs, phosphatases, substrates); generic binding term retained as non-core. |
| GO:0019903 protein phosphatase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Protein phosphatase binding, ISO from human MAPK8. Reason: JNK1 is bound and inactivated by dual-specificity phosphatases; a regulatory interaction rather than the gene's own activity. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1. |
| GO:0030335 positive regulation of cell migration | IDA PMID:12853963 JNK phosphorylates paxillin and regulates cell migration. | KEEP AS NON CORE | Summary: Positive regulation of cell migration, IDA (PMID:12853963), rat NBT-II cells. Reason: JNK1 phosphorylation of paxillin Ser178 is needed for rapid migration of NBT-II cells. Mechanistically direct, but a cell-type-specific role; non-core. Supporting Evidence: PMID:12853963 Here we show that JNK1 is required for the rapid movement of both fish keratocytes and rat bladder tumour epithelial cells (NBT-II). PMID:12853963 JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. |
| GO:0030424 axon | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: Axon, IDA (PMID:9714150), adult rat CNS immunostaining. Reason: JNK1 immunoreactivity in neuronal cytoplasm, dendrites and axons; neuronal sub-location of a cytoplasmic kinase. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons. |
| GO:0030424 axon | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Axon, ISO from mouse Mapk8. Reason: Consistent with rat immunostaining; neuronal sub-location, non-core. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons. |
| GO:0031116 positive regulation of microtubule polymerization | IMP PMID:16618812 JNK1 phosphorylation of SCG10 determines microtubule dynamic... | ACCEPT | Summary: Positive regulation of microtubule polymerization, IMP (PMID:16618812), rat cortical neurons. Reason: JNK1 phosphorylates SCG10/STMN2 on Ser62/Ser73, the sites that inhibit its microtubule-depolymerising activity; blocking cytoplasmic JNK or expressing non-phosphorylatable SCG10 reduced tubulin recovery after photobleaching. Direct substrate-level mechanism characterised in rat neurons. Supporting Evidence: PMID:16618812 These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development. |
| GO:0031175 neuron projection development | IMP PMID:16618812 JNK1 phosphorylation of SCG10 determines microtubule dynamic... | KEEP AS NON CORE | Summary: Neuron projection development, IMP (PMID:16618812). Reason: JNK1 phosphorylation of SCG10 determines axodendritic length; the more specific mechanistic term (positive regulation of microtubule polymerization) is accepted, this outcome term kept as non-core. Supporting Evidence: PMID:16618812 These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development. |
| GO:0031398 positive regulation of protein ubiquitination | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of protein ubiquitination, ISO from mouse Mapk8 IMP (PMID:29153991). Reason: JNK1 phosphorylates and activates the E3 ligase ITCH; a substrate-specific regulatory role, non-core. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. |
| GO:0031982 vesicle | IDA PMID:16618812 JNK1 phosphorylation of SCG10 determines microtubule dynamic... | KEEP AS NON CORE | Summary: Vesicle, IDA (PMID:16618812), rat forebrain fractionation. Reason: Active JNK co-fractionated with SCG10 in the P2 vesicle fraction (endosomal/Golgi vesicles). Valid but secondary location. Supporting Evidence: PMID:16618812 active JNK, SCG10, and S73-phosphorylated SCG10 concentrated in the P2 fraction, containing predominantly endosomal and Golgi vesicles |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process, ISO from mouse Mapk8 IMP. Reason: Downstream consequence of JNK1-dependent phosphorylation of ubiquitin ligases or their substrates (e.g. ITCH, POU5F1); non-core. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). |
| GO:0032839 dendrite cytoplasm | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: Dendrite cytoplasm, IDA (PMID:9714150). Reason: Immunostaining places JNK1 in dendrites of rat CNS neurons; neuronal sub-location of a cytoplasmic kinase. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons. |
| GO:0032880 regulation of protein localization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of protein localization, ISO from human MAPK8. Reason: JNK1 phosphorylation alters localisation of substrates (e.g. Syt4 vesicle capture, GluR2L reinsertion); generic downstream term, non-core. Supporting Evidence: PMID:29166604 Phosphorylation of serine 135 of Syt4 by JNK steers DCV trafficking by destabilizing Syt4-Kif1A interaction, leading to a transition from microtubule-dependent DCV trafficking to capture at en passant presynaptic boutons by actin. |
| GO:0034198 cellular response to amino acid starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to amino acid starvation, ISO from human MAPK8. Reason: JNK1 mediates starvation-induced BCL2 phosphorylation and autophagy; context-specific role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. |
| GO:0034349 glial cell apoptotic process | IEP PMID:14997384 Activation of c-Jun N-terminal kinase 1 and caspase 3 in the... | MARK AS OVER ANNOTATED | Summary: Glial cell apoptotic process, IEP (PMID:14997384), rat glioma cells. Reason: IEP based on increased phospho-JNK1 during tamoxifen-induced glioma apoptosis. Activation correlating with apoptosis does not make JNK1 a participant in the apoptotic process itself; the knockdown evidence from the same paper is captured by the regulation term (positive regulation of glial cell apoptotic process). Supporting Evidence: PMID:14997384 Four-hour 50-microM tamoxifen treatment increased the expression of phospho-specific JNK1 to 3.2 times that of the control level in glioma cells. |
| GO:0034352 positive regulation of glial cell apoptotic process | IMP PMID:14997384 Activation of c-Jun N-terminal kinase 1 and caspase 3 in the... | KEEP AS NON CORE | Summary: Positive regulation of glial cell apoptotic process, IMP (PMID:14997384). Reason: JNK1 antisense reduced tamoxifen-induced apoptosis of rat glioma cells from 51% to 28%. Valid isoform-specific evidence; context-dependent, non-core. Supporting Evidence: PMID:14997384 The apoptosis fraction of glioma cells induced by 4-h treatment with 50 microM tamoxifen was decreased from 51% to 28% by pretreatment with the antisense OGN of JNK1 (P<0.003) |
| GO:0034599 cellular response to oxidative stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to oxidative stress, ISO from human MAPK8. Reason: JNK1 is activated by ROS/oxidants; stress-response context, non-core. Supporting Evidence: PMID:9516415 H2O2 activated both SAPKs/JNKs and p38-MAPK. |
| GO:0034614 cellular response to reactive oxygen species | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to reactive oxygen species, ISO from human MAPK8. Reason: JNK1 is activated by ROS/oxidants; stress-response context, non-core. Supporting Evidence: PMID:9516415 H2O2 activated both SAPKs/JNKs and p38-MAPK. |
| GO:0035033 histone deacetylase regulator activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Histone deacetylase regulator activity, ISO from human MAPK8. Reason: JNK1 phosphorylates SIRT1, altering its activity; this is kinase activity on an HDAC substrate, not a separate regulator activity. The MF is better captured by the kinase activity terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SOURCE WEAK OR INFERRED Human source reflects JNK1 phosphorylation of SIRT1; the kinase acting on an HDAC substrate was annotated as an HDAC regulator activity. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. |
| GO:0038127 ERBB signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ERBB signaling pathway, ISO from mouse Mapk8 IDA (PMID:8702681). Reason: JNK is activated downstream of ERBB receptors; signalling context, non-core. |
| GO:0042542 response to hydrogen peroxide | IDA PMID:14707549 Regulation of c-Jun N-terminal kinase activation in hydrogen... | KEEP AS NON CORE | Summary: Response to hydrogen peroxide, IDA (PMID:14707549), rat cortical neurons. Reason: H2O2 activates JNK1/2 via NMDA-R and Ca2+/CaMKII in rat cortical neurons; stress-response context. Supporting Evidence: PMID:14707549 The above results suggest that in H2O2-induced neurotoxicity, JNK1/2 activation is mainly mediated by NMDA-R and L-VGCC. |
| GO:0042752 regulation of circadian rhythm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of circadian rhythm, ISO from mouse Mapk8. Reason: JNK1 phosphorylates CLOCK-BMAL1 and modulates circadian period (mouse); peripheral role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (By similarity). |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of circadian rhythm, ISS from mouse Mapk8. Reason: JNK1 phosphorylates CLOCK-BMAL1 and modulates circadian period (mouse); peripheral role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (By similarity). |
| GO:0042826 histone deacetylase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Histone deacetylase binding, ISO from human MAPK8. Reason: Reflects JNK1 binding to its substrate SIRT1; non-core. |
| GO:0043005 neuron projection | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Neuron projection, ISO from mouse Mapk8. Reason: JNK1 is present in axons and dendrites of neurons; non-core neuronal sub-location. Supporting Evidence: PMID:9714150 All four kinases were present in the cytoplasm, dendrites, and axons of neurons. |
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of apoptotic process, IBA. Reason: JNKs promote stress-induced apoptosis in many settings (rat examples: cardiomyocytes, cortical neurons, glioma), but can also be protective; context-dependent, non-core. Supporting Evidence: PMID:12534344 These results demonstrate a significant role for JNK1 in A beta-mediated induction of the apoptotic cascade in cultured cortical neurons. |
| GO:0043065 positive regulation of apoptotic process | IEP PMID:16699462 JNK (c-Jun NH2 terminal kinase) and p38 during ischemia repe... | KEEP AS NON CORE | Summary: Positive regulation of apoptotic process, IEP (PMID:16699462), rat intestinal ischaemia/reperfusion. Reason: Correlative (JNK activity and TUNEL co-localisation) with a dual JNK/p38 inhibitor, so not JNK1-specific; the term itself is supported for JNK1 by isoform-specific knockdown studies in other rat cells. Non-core. Supporting Evidence: PMID:16699462 These results suggest that JNK and p38 both play a key role during small intestinal ischemia reperfusion injury through a proapoptotic action on the tip of villi. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:15309413 p38 and JNK have distinct regulatory functions on the develo... | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process, IDA (PMID:15309413), rat neonatal cardiomyocytes. Reason: SP600125 increased caspase-3 activation and apoptosis during simulated ischaemia/reperfusion, indicating a protective JNK role. Pharmacological, not isoform-specific; context-dependent, non-core. Supporting Evidence: PMID:15309413 JNK phosphorylation is protective in our cell model |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process, ISO from human MAPK8. Reason: JNK1 can promote survival (e.g. BAD phosphorylation in erythroid cells; protection of INS-1 beta cells). Context-dependent, non-core. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process, ISO from human MAPK8. Reason: JNK1 can promote survival (e.g. BAD phosphorylation in erythroid cells; protection of INS-1 beta cells). Context-dependent, non-core. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. |
| GO:0043204 perikaryon | IDA PMID:9714150 Immunolocalization of the mitogen-activated protein kinases ... | KEEP AS NON CORE | Summary: Perikaryon, IDA (PMID:9714150). Reason: JNK1 immunoreactivity in neuronal cell bodies; neuronal sub-location of a cytoplasmic kinase. Supporting Evidence: PMID:9714150 The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. |
| GO:0043204 perikaryon | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Perikaryon, IEA (ARBA). Reason: Consistent with rat immunostaining (PMID:9714150); non-core. Supporting Evidence: PMID:9714150 The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:12534344 A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, i... | KEEP AS NON CORE | Summary: Positive regulation of neuron apoptotic process, IMP (PMID:12534344), rat cortical neurons. Reason: JNK1 (not JNK2) antisense blocked A-beta-induced p53 stabilisation, caspase-3 activation and DNA fragmentation. Valid; context-dependent, non-core. Supporting Evidence: PMID:12534344 The results obtained demonstrate a role for JNK1 in the A beta-induced stabilization of p53, activation of caspase 3 and DNA fragmentation. |
| GO:0045202 synapse | IDA PMID:29166604 Capture of Dense Core Vesicles at Synapses by JNK-Dependent ... | ACCEPT | Summary: Synapse, IDA (PMID:29166604), rat hippocampal neurons. Reason: Active (phosphorylated) JNK concentrates at synapses with neuronal activity, where it phosphorylates Syt4 to capture dense core vesicles. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Increased neuronal activity increases phosphorylated form at synapses (PubMed:29166604). PMID:29166604 neuronal activity increased DCV capture via JNK-dependent phosphorylation of the S135 site of Syt4 |
| GO:0045202 synapse | IEA GO_REF:0000044 | ACCEPT | Summary: Synapse, IEA from UniProt subcellular location. Reason: Supported by the rat hippocampal data (PMID:29166604). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Increased neuronal activity increases phosphorylated form at synapses (PubMed:29166604). |
| GO:0045664 regulation of neuron differentiation | IMP PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Regulation of neuron differentiation, IMP (PMID:24388750). Reason: JNK1 depletion causes premature differentiation of neural progenitors; deferring to the curator (abstract only). Non-core. Supporting Evidence: PMID:24388750 Depletion of JNK1 and WDR62 incurs very similar defects including abnormal spindle formation and mitotic division of NPCs as well as premature NPC differentiation during cortical development. |
| GO:0045740 positive regulation of DNA replication | IMP PMID:9487126 The Ras/Rac1/Cdc42/SEK/JNK/c-Jun cascade is a key pathway by... | KEEP AS NON CORE | Summary: Positive regulation of DNA replication, IMP (PMID:9487126), primary rat hepatocytes. Reason: Dominant-negative JNK1 blunted agonist-stimulated c-Jun Ser63 phosphorylation and DNA synthesis. Valid, cell-type-specific proliferative role; non-core. Supporting Evidence: PMID:9487126 JNK1- blunted the abilities of glucose, TNFalpha, or HGF to increase JNK1 activity, to increase phosphorylation of c-Jun at serine 63, and to stimulate DNA synthesis. PMID:9487126 These data demonstrate that multiple agonists stimulate DNA synthesis in primary cultures of hepatocytes via a Ras/Rac1/Cdc42/SEK/JNK/c-Jun pathway. |
| GO:0046605 regulation of centrosome cycle | IMP PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Regulation of centrosome cycle, IMP (PMID:24388750). Reason: Abstract reports abnormal spindle formation and mitosis of neural progenitors after JNK1 depletion; centrosome-cycle detail is in the full text (not cached). Deferring to the curator; non-core. Supporting Evidence: PMID:24388750 Depletion of JNK1 and WDR62 incurs very similar defects including abnormal spindle formation and mitotic division of NPCs as well as premature NPC differentiation during cortical development. |
| GO:0046686 response to cadmium ion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to cadmium ion (acts_upstream_of_or_within), ISO from mouse IGI. Reason: Cadmium is a JNK-activating stress; stress-response context, non-core. |
| GO:0048545 response to steroid hormone | IEP PMID:14512437 Regulation of cytokine-induced neuron death by ovarian hormo... | KEEP AS NON CORE | Summary: Response to steroid hormone, IEP (PMID:14512437), differentiated PC12 cells. Reason: Progesterone increased TNF-induced JNK1 activity 5-8 fold; a JNK1 peptide inhibitor blocked progesterone-enhanced death. Context-specific, non-core. Supporting Evidence: PMID:14512437 TNFalpha induced a 3-fold increased activity of c-JUN-N-terminal kinase (JNK) 1 in d PC12 cells within 20 min that could be increased 5- to 8-fold by P together with TNFalpha. |
| GO:0048666 neuron development | IEP PMID:17568197 TNFalpha induces apoptosis through JNK/Bax-dependent pathway... | MARK AS OVER ANNOTATED | Summary: Neuron development, IEP (PMID:17568197), PC12 cells. Reason: The abstract reports increased JNK1 mRNA in differentiated PC12 cells during TNF-alpha-induced apoptosis; this is an expression change associated with apoptosis in a differentiated state, not evidence that JNK1 participates in neuron development. Full text not cached; marked over-annotated rather than removed. Supporting Evidence: PMID:17568197 the mRNA levels of bim, c-Jun N-terminal protein kinase 1 and 2 (JNK1 and JNK2) increased noticeably in differentiated PC12 cells |
| GO:0048813 dendrite morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Dendrite morphogenesis, ISO from mouse Mapk8 IMP (PMID:16000625). Reason: JNK1 regulates dendrite architecture through cytoplasmic substrates (e.g. MAP2, SCG10); non-core developmental role. Supporting Evidence: PMID:16618812 These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development. |
| GO:0050804 modulation of chemical synaptic transmission | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Modulation of chemical synaptic transmission, ISO from mouse Mapk8 (PMID:17284179). Reason: JNK1 regulates AMPA receptor phosphorylation/trafficking and LTD at hippocampal synapses; supported in rat by GluR2L/GluR4 phosphorylation. Non-core. Supporting Evidence: PMID:18188153 JNK1 phosphorylated both GST-GluR2L and GST-GluR4 extremely effectively in vitro |
| GO:0051247 positive regulation of protein metabolic process | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein metabolic process, ISO from human MAPK8. Reason: Very broad grouping term with little information; specific substrate effects are captured elsewhere. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SUPPORTS TRANSFER Ortholog source reflects a real but indirect, phenotype-level effect captured by a very broad term; transfer is not wrong but adds little information. |
| GO:0051403 stress-activated MAPK cascade | ISO GO_REF:0000121 | MODIFY | Summary: Stress-activated MAPK cascade, ISO from human MAPK8. Reason: Correct but more general than warranted: GO:0007254 JNK cascade (is_a stress-activated MAPK cascade) is the specific branch and is already carried by this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P45983 · UniProtKB:P45983 SUPPORTS TRANSFER Source JNK1 annotation is correct for the ortholog and transfers soundly; the issue is only that the term is broader than the specific JNK term this gene already carries. Proposed replacements: JNK cascade Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. |
| GO:0060395 SMAD protein signal transduction | IMP PMID:27769861 Activin A/Smads signaling pathway negatively regulates Oxyge... | MARK AS OVER ANNOTATED | Summary: SMAD protein signal transduction, IMP (PMID:27769861), PC12 cells. Reason: The abstract reports that activin A/Smad signalling suppresses JNK and p38 activation during oxygen-glucose deprivation; JNK is a downstream target regulated by the Smad pathway, not a participant in Smad signal transduction, and the abstract does not show JNK1-specific perturbation. Supporting Evidence: PMID:27769861 Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells. |
| GO:0061833 protein localization to tricellular tight junction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Protein localization to tricellular tight junction (acts_upstream_of_or_within), ISO from mouse Mapk8 IMP (PMID:24889144). Reason: Phenotype-level, cell-type-specific role transferred from mouse; non-core. |
| GO:0070301 cellular response to hydrogen peroxide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to hydrogen peroxide (acts_upstream_of_or_within), ISO from mouse. Reason: H2O2 activates JNK1 (rat heart and neurons); stress-response context, non-core. Supporting Evidence: PMID:9516415 H2O2 activated both SAPKs/JNKs and p38-MAPK. |
| GO:0071222 cellular response to lipopolysaccharide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to lipopolysaccharide (acts_upstream_of_or_within), ISO from human MAPK8. Reason: LPS/TLR signalling activates JNK in macrophages; context, non-core. |
| GO:0071260 cellular response to mechanical stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to mechanical stimulus, ISO from human MAPK8. Reason: Mechanical stress activates JNKs (rat heart pressure-overload data); non-core. Supporting Evidence: PMID:9516415 Perfusion of hearts at high aortic pressure (20 kilopascals) also activated the SR-MAPKs and MAPKAPK2. |
| GO:0071347 cellular response to interleukin-1 | IEP PMID:9513050 Activation of c-Jun NH2-terminal kinases by interleukin-1 be... | KEEP AS NON CORE | Summary: Cellular response to interleukin-1, IEP (PMID:9513050), rat UMR-106 osteoblastic cells. Reason: IL-1 beta activates JNK1 and JNK2; activation by a cytokine is a response context, non-core. Supporting Evidence: PMID:9513050 Both JNK1 and JNK2 were activated by IL-1 beta. |
| GO:0071732 cellular response to nitric oxide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to nitric oxide (acts_upstream_of_or_within), ISO from mouse IMP. Reason: NO inhibits JNK1 by S-nitrosylation of Cys116 (shown with rat alveolar macrophages among others). Regulatory context, non-core. Supporting Evidence: PMID:11121042 Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-gamma or SNAP on JNK1 activity in vivo or in vitro, respectively. |
| GO:0071803 positive regulation of podosome assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of podosome assembly (acts_upstream_of_or_within), ISO from mouse IMP (PMID:24127566). Reason: Cell-type-specific role from mouse; non-core. |
| GO:0090650 cellular response to oxygen-glucose deprivation | IEP PMID:27769861 Activin A/Smads signaling pathway negatively regulates Oxyge... | KEEP AS NON CORE | Summary: Cellular response to oxygen-glucose deprivation, IEP (PMID:27769861). Reason: JNK pathway activated by OGD in PC12 cells; response context, non-core. Supporting Evidence: PMID:27769861 we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy |
| GO:0090650 cellular response to oxygen-glucose deprivation | IMP PMID:27769861 Activin A/Smads signaling pathway negatively regulates Oxyge... | KEEP AS NON CORE | Summary: Cellular response to oxygen-glucose deprivation, IMP (PMID:27769861). Reason: Abstract implicates the JNK pathway in OGD-induced autophagy; full text not cached, deferring to the curator on the perturbation. Non-core. Supporting Evidence: PMID:27769861 we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy |
| GO:0097009 energy homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Energy homeostasis, ISO from mouse Mapk8 IDA (PMID:36977414). Reason: JNK1 influences systemic metabolism and insulin sensitivity (e.g. palmitate-induced JNK activation impairs insulin signalling in rat hepatocytes). Organism-level, non-core. Supporting Evidence: PMID:19332540 These results suggest that JNK activation by palmitate contributed to palmitate-induced insulin resistance. |
| GO:0097050 type B pancreatic cell apoptotic process | IMP PMID:24475223 JNK1 protects against glucolipotoxicity-mediated beta-cell a... | MODIFY | Summary: Type B pancreatic cell apoptotic process, IMP (PMID:24475223), INS-1 cells. Reason: JNK1 shRNA increased palmitate/high-glucose-induced apoptosis, so JNK1 protects beta cells; JNK1 does not execute apoptosis. The evidence supports the regulatory term with negative sign, GO:2000675 negative regulation of type B pancreatic cell apoptotic process. Proposed replacements: negative regulation of type B pancreatic cell apoptotic process Supporting Evidence: PMID:24475223 These data suggest that JNK1 protects against palmitate and high glucose-induced β-cell apoptosis associated with reduced ER and mitochondrial stress. |
| GO:0097150 neuronal stem cell population maintenance | IGI PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Neuronal stem cell population maintenance (acts_upstream_of_or_within), IGI with Wdr62 (PMID:24388750). Reason: WDR62 acts upstream of JNK1 to prevent premature progenitor differentiation; developmental, non-core. Supporting Evidence: PMID:24388750 Thus, our findings indicate that WDR62 is required for proper neurogenesis via JNK1 and provide an insight into the molecular mechanisms underlying MCPH pathogenesis. |
| GO:0097150 neuronal stem cell population maintenance | IMP PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Neuronal stem cell population maintenance (acts_upstream_of_or_within), IMP (PMID:24388750). Reason: As above; non-core developmental role. Supporting Evidence: PMID:24388750 Thus, our findings indicate that WDR62 is required for proper neurogenesis via JNK1 and provide an insight into the molecular mechanisms underlying MCPH pathogenesis. |
| GO:0097300 programmed necrotic cell death | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Programmed necrotic cell death (acts_upstream_of_or_within), ISO from mouse IMP (PMID:18007661). Reason: JNK1 contributes to TNF/ROS-induced necrotic death in mouse cells; context-dependent, non-core. |
| GO:0097441 basal dendrite | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Basal dendrite, ISO from mouse Mapk8 (PMID:22683681). Reason: Neuronal sub-location; non-core. |
| GO:0098685 Schaffer collateral - CA1 synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Schaffer collateral - CA1 synapse (is_active_in), ISO from mouse Mapk8 (PMID:17284179). Reason: JNK1 acts at hippocampal synapses (mouse LTD/AMPA-R study; rat synapse localisation, PMID:29166604). Non-core location. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Increased neuronal activity increases phosphorylated form at synapses (PubMed:29166604). |
| GO:0106310 protein serine kinase activity | EXP PMID:11121042 Nitric oxide negatively regulates c-Jun N-terminal kinase/st... | ACCEPT | Summary: Protein serine kinase activity, EXP (PMID:11121042). Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). UniProt cites this paper for the catalytic activity; JNK1 kinase activity was assayed and shown to be inhibited by S-nitrosylation of Cys116. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) PMID:11121042 Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-gamma or SNAP on JNK1 activity in vivo or in vitro, respectively. |
| GO:0106310 protein serine kinase activity | EXP PMID:16618812 JNK1 phosphorylation of SCG10 determines microtubule dynamic... | ACCEPT | Summary: Protein serine kinase activity, EXP (PMID:16618812). Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). JNK1 phosphorylates SCG10 on Ser62/Ser73 in vivo. Supporting Evidence: PMID:16618812 SCG10-S73 phosphorylation is significantly decreased in JNK1-/- cortex, indicating that JNK1 phosphorylates SCG10 in developing forebrain. |
| GO:0106310 protein serine kinase activity | EXP PMID:21297631 Phosphorylation of SCG10/stathmin-2 determines multipolar st... | ACCEPT | Summary: Protein serine kinase activity, EXP (PMID:21297631). Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). JNK1 phosphorylation of SCG10 controls neuronal migration. Supporting Evidence: PMID:21297631 the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development |
| GO:0106310 protein serine kinase activity | EXP PMID:9516415 Stimulation of "stress-regulated" mitogen-activated protein ... | ACCEPT | Summary: Protein serine kinase activity, EXP (PMID:9516415), perfused rat heart. Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). SAPK/JNK activity measured in heart extracts after H2O2 and ischaemia/reperfusion. Supporting Evidence: PMID:9516415 H2O2 activated both SAPKs/JNKs and p38-MAPK. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity, IEA (Rhea mapping). Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0106310 protein serine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Protein serine kinase activity, ISO from mouse/human JNK1. Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0106310 protein serine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Protein serine kinase activity, ISO from mouse/human JNK1. Reason: JNK1 phosphorylates serine residues of protein substrates (EC 2.7.11.24). Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0120283 protein serine/threonine kinase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Protein serine/threonine kinase binding, ISO from human MAPK8. Reason: JNK1 binds upstream kinases (MAP2K4/7, MLKs on JIP scaffolds) and kinase substrates; an interaction term peripheral to its catalytic function. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8IP1/JIP1. |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of NLRP3 inflammasome complex assembly, ISO from mouse Mapk8. Reason: JNK1 phosphorylates NLRP3, promoting inflammasome assembly (by similarity to human/mouse); a substrate-specific, immune-cell role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of NLRP3 inflammasome complex assembly, ISO from human MAPK8. Reason: JNK1 phosphorylates NLRP3, promoting inflammasome assembly (by similarity to human/mouse); a substrate-specific, immune-cell role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of NLRP3 inflammasome complex assembly, ISS from human MAPK8. Reason: JNK1 phosphorylates NLRP3, promoting inflammasome assembly (by similarity to human/mouse); a substrate-specific, immune-cell role. Supporting Evidence: file:rat/Mapk8/Mapk8-uniprot.txt Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). |
| GO:1904646 cellular response to amyloid-beta | IEP PMID:12534344 A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, i... | KEEP AS NON CORE | Summary: Cellular response to amyloid-beta, IEP (PMID:12534344), rat cortical neurons. Reason: A-beta transiently activated JNK1 (peak 1 h); response context, non-core. Supporting Evidence: PMID:12534344 Evaluation of the nature of the JNK isoforms activated by A beta revealed a transient increase in JNK1 activity that reached its peak at 1 h and a later activation (at 24 h) of JNK2. |
| GO:1904809 regulation of dense core granule transport | IDA PMID:29166604 Capture of Dense Core Vesicles at Synapses by JNK-Dependent ... | ACCEPT | Summary: Regulation of dense core granule transport, IDA (PMID:29166604), rat hippocampal neurons. Reason: JNK phosphorylates Syt4 Ser135, destabilising the Syt4-KIF1A interaction and switching DCVs from microtubule transport to capture at presynaptic boutons; dominant-negative JNK1 and active MKK7-JNK1 were used. Direct, mechanistically defined neuronal function. Supporting Evidence: PMID:29166604 Phosphorylation of serine 135 of Syt4 by JNK steers DCV trafficking by destabilizing Syt4-Kif1A interaction, leading to a transition from microtubule-dependent DCV trafficking to capture at en passant presynaptic boutons by actin. PMID:29166604 neuronal activity increased DCV capture via JNK-dependent phosphorylation of the S135 site of Syt4 |
| GO:2000017 positive regulation of determination of dorsal identity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of determination of dorsal identity (acts_upstream_of_or_within), ISO from mouse IDA (PMID:18316368). Reason: Developmental patterning outcome transferred from a single study; JNK signalling acts upstream. Non-core. |
| GO:2001224 positive regulation of neuron migration | IMP PMID:24388750 Microcephaly-associated protein WDR62 regulates neurogenesis... | KEEP AS NON CORE | Summary: Positive regulation of neuron migration, IMP (PMID:24388750). Reason: Reported with WDR62/JNK1 knockdown in developing cortex (abstract only). Note that cytoplasmic JNK1-SCG10 signalling restrains radial migration rate (PMID:21297631), so the direction is context dependent. Non-core. Supporting Evidence: PMID:21297631 the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development |
| GO:2001235 positive regulation of apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of apoptotic signaling pathway (acts_upstream_of_or_within), ISO from mouse IGI (PMID:16458303). Reason: JNK1 promotes stress-induced apoptotic signalling (e.g. Bcl-2 family phosphorylation); context-dependent, non-core. |
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Download this section (compressed HTML)Q: GO:0097050 type B pancreatic cell apoptotic process (IMP, PMID:24475223): the paper shows that JNK1 knockdown increases INS-1 apoptosis. Should RGD replace the term with GO:2000675 negative regulation of type B pancreatic cell apoptotic process?
Q: GO:0060395 SMAD protein signal transduction (IMP, PMID:27769861): the abstract places JNK downstream of, and suppressed by, activin A/Smad signalling. Does the full text show a JNK1-specific perturbation that affects Smad signalling itself, or should the annotation be withdrawn?
Q: GO:0048666 neuron development (IEP, PMID:17568197): the abstract reports increased JNK1 mRNA during TNF-induced apoptosis of differentiated PC12 cells. Is there evidence in the full text that supports a neuron development annotation?
Q: GO:0019894 kinesin binding (IPI, PMID:18932217, with RGD:621559): does the full text show direct JNK1 binding to the kinesin component, or is the interaction bridged by Daxx?
Q: Rat-specific data on JNK1 in apoptosis point in opposite directions (pro-apoptotic in cardiomyocyte reoxygenation, cortical neurons and glioma; protective in INS-1 beta cells). Which substrates (for example BIM/BMF versus BAD) account for the sign in each cell type?
Experiment: Use JNK1-selective knockdown or analogue-sensitive JNK1 knock-in in H4IIEC3 hepatocytes to test whether the palmitate-induced, ROS-dependent inhibition of insulin signalling seen with SP600125 is mediated by JNK1 rather than JNK2, and identify the phosphorylated IRS2 serine sites.
Hypothesis: JNK1 is the isoform that couples palmitate-derived mitochondrial ROS to serine phosphorylation of IRS2 in rat hepatocytes.
Experiment: Phosphoproteomics of rat INS-1 cells expressing JNK1 shRNA versus control under palmitate/high glucose, to identify the JNK1 substrates that mediate its protective effect on beta-cell survival.
Hypothesis: The anti-apoptotic action of JNK1 in beta cells is mediated by phosphorylation of specific Bcl-2 family or UPR proteins distinct from its pro-apoptotic substrates in neurons.
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