MAPK8 encodes c-Jun N-terminal kinase 1 (JNK1, SAPK1c), a ubiquitously expressed, proline-directed serine/threonine protein kinase of the CMGC group and the JNK subfamily of mitogen-activated protein kinases. JNK1 is the terminal kinase of the stress-activated JNK cascade: pro-inflammatory cytokines (IL-1, TNF), oxidative, genotoxic, UV and other stresses activate MAP3Ks that act through the dual-specificity kinases MKK4 (MAP2K4) and MKK7 (MAP2K7), which phosphorylate the activation-loop Thr183-Pro-Tyr185 motif (MKK7 preferring Thr183 and MKK4 Tyr185). Docking interactions organise signalling on JIP-family scaffolds and direct JNK1 to substrates carrying D-motifs; activity is terminated by MAPK phosphatases such as DUSP16 (MKP-7) and DUSP8. Activated JNK1 enters the nucleus and phosphorylates AP-1 and related transcription factors (c-Jun Ser63/Ser73, ATF2, JDP2, Elk-1, NFAT3, HSF1), and in the cytoplasm phosphorylates Bcl-2 family proteins (BAD, BIM, BMF, BCL2) and many other substrates (YAP1, SIRT1, SIRT6, CDT1, 4E-T, NLRP3, ALKBH5, BMAL1/CLOCK). Through these outputs JNK1 contributes, in a strongly context-dependent manner, to stress-induced apoptosis or survival, autophagy, inflammasome priming, circadian timing, DNA repair, neuronal development and metabolic homeostasis. JNK1 shares most substrates and functions with its paralog JNK2 (MAPK9).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IDA PMID:15850461 The phosphorylation of CapZ-interacting protein (CapZIP) by ... | ACCEPT | Summary: CapZIP paper: CapZIP is phosphorylated by stress-activated MAPKs including JNK in vitro, and JNK1 is listed among the MAPKs activated by osmotic/anisomycin stress. Reason: JNK1 is a terminal MAP kinase; MAPK cascade is correct though general. The more specific JNK cascade (GO:0007254) is also annotated and is the preferred core process. Supporting Evidence: PMID:15850461 CapZIP was also found to be a remarkably good substrate for several stress-activated MAPKs in vitro and, indeed, is far and away the best substrate for JNK that has so far been identified. file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0000165 MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-based IEA to MAPK cascade. Reason: Correct, general parent of JNK cascade; JNK1 is the terminal kinase of a three-tier MAPK module. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 file:human/MAPK8/MAPK8-uniprot.txt Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA/InterPro kinase domain) to protein kinase activity. Reason: Correct but general; the specific MF is MAP kinase activity (GO:0004707) / JUN kinase activity (GO:0004705), both annotated. A broader IEA is acceptable. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:14967141 JNK suppresses apoptosis via phosphorylation of the proapopt... | ACCEPT | Summary: JNK phosphorylates BAD on Thr201 in IL-3-dependent cells. Reason: Direct demonstration of Ser/Thr kinase activity on BAD Thr201. Supporting Evidence: PMID:14967141 JNK phosphorylates BAD at threonine 201, thereby inhibiting BAD association with the antiapoptotic molecule BCL-X(L) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:15850461 The phosphorylation of CapZ-interacting protein (CapZIP) by ... | ACCEPT | Summary: JNK phosphorylates CapZIP on Ser-Pro sites in vitro (up to >5 mol/mol). Reason: Direct in vitro kinase evidence of Ser/Thr kinase activity. Supporting Evidence: PMID:15850461 CapZIP was also found to be a remarkably good substrate for several stress-activated MAPKs in vitro and, indeed, is far and away the best substrate for JNK that has so far been identified. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: JNK1 directly phosphorylates SIRT1 on Ser27, Ser47 and Thr530. Reason: Direct in vitro kinase evidence with site mapping; supports Ser/Thr kinase activity. Supporting Evidence: PMID:20027304 JNK1 directly phosphorylates SIRT1 on three specific residues, concentrating it in the nucleus and resulting in selective activation of SIRT1, as measured by deacetylation of histone H3 (but not p53). |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: EPO-activated JNK1 phosphorylates BAD at Thr201 in erythroid cells. Reason: Direct kinase evidence for JNK1 on BAD. Supporting Evidence: PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic molecule B-cell lymphoma-extra large (Bcl-X(L)) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22966201 Phosphorylation of the eukaryotic translation initiation fac... | ACCEPT | Summary: Activated MKK7-JNK1 fusion phosphorylates purified 4E-T (EIF4ENIF1) in vitro, while kinase-dead fusion does not. Reason: Direct in vitro kinase evidence with kinase-dead control. Supporting Evidence: PMID:22966201 activated MKK7-JNK1 (CA) robustly increased 32 P incorporation PMID:22966201 We show that the c-Jun N-terminal kinase (JNK) is targeted to PBs in response to oxidative stress and promotes the phosphorylation of 4E-T. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: JNK phosphorylates SIRT6 on Ser10 in response to oxidative stress. Reason: Direct kinase evidence with site mapping. Supporting Evidence: PMID:27568560 phosphorylates SIRT6 on serine 10 in response to oxidative stress |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:28943315 NLRP3 Phosphorylation Is an Essential Priming Event for Infl... | ACCEPT | Summary: JNK1 phosphorylates NLRP3 at Ser194 as an inflammasome priming event. Reason: JNK1-specific evidence of Ser/Thr kinase activity on NLRP3. Supporting Evidence: PMID:28943315 JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:34048572 Post-translational modification of RNA m6A demethylase ALKBH... | ACCEPT | Summary: ROS-activated JNK promotes serine phosphorylation of ALKBH5 (S87, S321). Reason: Kinase evidence for ALKBH5 phosphorylation; consistent with JNK1 Ser/Thr kinase activity. JNK1/2 interact with ALKBH5 under H2O2. Supporting Evidence: PMID:34048572 ROS stress activates ERK/JNK signaling resulting in phosphorylation of ALKBH5 at serine residues S87 and S321. PMID:34048572 activated JNK promoted serine but not tyrosine and threonine phosphorylation of ALKBH5 |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-139908 | ACCEPT | Summary: Reactome: MAPK8 phosphorylates BMF on its dynein light chain-binding motif. Reason: Consistent with JNK1 Ser/Thr kinase activity on BH3-only proteins (Lei and Davis 2003). Supporting Evidence: Reactome:R-HSA-139908 MAPK8 (JNK) phosphorylates BMF on a DLC binding motif DKATQTLSP |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-139918 | ACCEPT | Summary: Reactome: MAPK8 phosphorylates BIM (BCL2L11) on JNK consensus sites. Reason: Consistent with JNK1 Ser/Thr kinase activity on BH3-only proteins. Supporting Evidence: Reactome:R-HSA-139918 MAPK8 (JNK) phosphorylates BCL2L11 (BIM) on a DLC-binding motif (DKSTQTP) |
| GO:0004705 JUN kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PAINT node PTN001171982 (JNK clade), seeded by JNK1/JNK2 and invertebrate JNK orthologs. Reason: JUN kinase activity is the defining activity of the JNK clade; MAPK8 sits inside the clade and has its own direct experimental evidence (it legitimately appears in the WITH/FROM). This IBA is the grounding used by the JNK cascade module. Supporting Evidence: PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. file:human/MAPK8/MAPK8-uniprot.txt 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:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: Erythroid JNK1 activity measured on c-Jun substrate in the BAD/EPO paper. Reason: JUN kinase activity of JNK1 is well established; accept deferring to the curator (abstract-only cache). Supporting Evidence: PMID:21095239 our results provide a molecular mechanism by which JNK1 contributes to the survival of erythroid cells PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. |
| GO:0004705 JUN kinase activity | IDA PMID:8654373 Selective interaction of JNK protein kinase isoforms with tr... | ACCEPT | Summary: Cloning of ten JNK isoforms; kinase activity measured on Jun family, ATF2 and Elk-1 substrates. Reason: Primary evidence that human JNK1 isoforms phosphorylate c-Jun. Core MF. Supporting Evidence: PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0004705 JUN kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Mapk8 (MGI:1346861). Reason: Consistent with direct human evidence; mouse and human JNK1 are near-identical orthologs. Supporting Evidence: PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. file:human/MAPK8/MAPK8-uniprot.txt 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 Reactome:R-HSA-168136 | ACCEPT | Summary: Reactome: activated JNKs phosphorylate c-JUN in the nucleus. Reason: Consistent with experimental evidence. Supporting Evidence: Reactome:R-HSA-168136 JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus. |
| GO:0004705 JUN kinase activity | TAS Reactome:R-HSA-205075 | ACCEPT | Summary: Reactome: JNK phosphorylates BIM, BAD and other targets (annotated as JUN kinase activity). Reason: The Reactome event concerns cytoplasmic BH3-only substrates rather than c-Jun, but GO:0004705 describes the JNK enzyme activity generally (MAP kinase activity of the JNK subfamily), so the term is appropriate. Supporting Evidence: Reactome:R-HSA-205075 Once activated, JNK phosphorylates targets in cytoplasm, including BIM and BAD |
| GO:0004705 JUN kinase activity | TAS Reactome:R-HSA-9673789 | ACCEPT | Summary: Reactome: activated JNK phosphorylates c-JUN. Reason: Consistent with experimental evidence. Supporting Evidence: Reactome:R-HSA-9673789 JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus. |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/EC-based IEA to MAP kinase activity. Reason: Correct. JNK1 is a proline-directed MAP kinase activated by TPY dual phosphorylation; this is the MF used for the MAPK tier in the JNK cascade module. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0005515 protein binding | IPI PMID:10393177 A Caenorhabditis elegans JNK signal transduction pathway reg... | MODIFY | Summary: IPI with c-Jun (P05412) cited to a C. elegans JNK-1/JKK-1 paper (abstract only). Reason: The binding of JNK1 to its substrate c-Jun through the Jun delta docking region is well established; the informative MF is DNA-binding transcription factor binding. The cached abstract does not describe the human interaction assay, so the replacement rests on the broader literature. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:10393177 The genes for the Caenorhabditis elegans homolog of JNK, JNK-1, and its direct activator, JKK-1, were isolated PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0005515 protein binding | IPI PMID:10490659 The JIP group of mitogen-activated protein kinase scaffold p... | MODIFY | Summary: JNK1 binds the scaffold JIP2 (MAPK8IP2, Q13387). Reason: JIP proteins are JNK pathway scaffolds; scaffold protein binding is the informative term (consistent with MAPK1 scaffold rows). Proposed replacements: scaffold protein binding Supporting Evidence: PMID:10490659 Both JIP1 and JIP2 form homo- and hetero-oligomeric complexes with components of the JNK signaling pathway. file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005515 protein binding | IPI PMID:10747973 c-Jun NH2-terminal kinase targeting and phosphorylation of h... | MODIFY | Summary: JNK binds HSF1 via MAPK-binding motifs and phosphorylates its regulatory domain. Reason: HSF1 is a DNA-binding transcription factor and JNK1 substrate; DNA-binding transcription factor binding is informative. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:10747973 JNK binds to HSF-1 in the conserved mitogen-activated protein kinases binding motifs and phosphorylates HSF-1 in the regulatory domain |
| GO:0005515 protein binding | IPI PMID:10856240 The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and p... | REMOVE | Summary: Evi-1 (MECOM) binds and inhibits JNK1, protecting against stress-induced death. Reason: The interaction is an inhibitory input onto JNK1 (captured better as a MECOM kinase-inhibitor function), not an activity of JNK1. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:10856240 However, Evi-1 significantly suppressed JNK1 activity when they were co-expressed. |
| GO:0005515 protein binding | IPI PMID:11517249 c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-b... | MODIFY | Summary: Human JNK1beta1 forms a complex with APP via the scaffold JIP-1b (mouse Mapk8ip1 isoform, Q9WVI9-1). Reason: JIP-1b is the canonical JNK scaffold; scaffold protein binding is the informative MF. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:11517249 human JNK1beta1 formed a complex with APP in a JIP-1b-dependent manner file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005515 protein binding | IPI PMID:15334056 Transformation suppressor protein Pdcd4 interferes with JNK-... | REMOVE | Summary: Pdcd4 (mouse, Q61823) interferes with JNK-mediated c-Jun phosphorylation. Reason: The abstract states Pdcd4 acts by binding c-Jun rather than JNK; the JNK1 interaction adds no informative MF. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:15334056 Pdcd4 interferes with the phosphorylation of c-Jun by Jun N-terminal kinase (JNK) |
| GO:0005515 protein binding | IPI PMID:15894542 Disabled-2 (Dab2) mediates transforming growth factor beta (... | MODIFY | Summary: IPI JNK1 with c-Jun in the Dab2/TGFbeta-JNK paper. Reason: c-Jun is a DNA-binding transcription factor and canonical JNK1 substrate; replace with DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:15894542 the cytosolic adaptor protein disabled-2 (Dab2) directly stimulates JNK activity PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0005515 protein binding | IPI PMID:16291755 The tyrosine kinase Syk regulates TPL2 activation signals. | MODIFY | Summary: IPI JNK1 with c-Jun in a TPL2/Syk signaling paper. Reason: c-Jun binding is informative as DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:16291755 TNF-alpha stimulates the JNK, ERK, and p38 mitogen-activated protein kinases PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0005515 protein binding | IPI PMID:16533805 Interacting JNK-docking sites in MKK7 promote binding and ac... | MODIFY | Summary: MKK7 (MAP2K7, O14733-2) binds JNK1 through three N-terminal D-site docking motifs. Reason: Upstream MAP2K docking; mitogen-activated protein kinase kinase binding is the informative MF (reciprocal of MAP2K4 review choice). Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:16533805 Full-length MKK7 containing combined D1/D2 mutations was compromised for binding to JNK1 and exhibited reduced JNK1 kinase activity when compared with wild-type MKK7. |
| GO:0005515 protein binding | IPI PMID:16533805 Interacting JNK-docking sites in MKK7 promote binding and ac... | MODIFY | Summary: MKK4 (MAP2K4, P45985) binding to JNK1 in the MKK7 D-site paper. Reason: Replace with mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:16533805 peptide versions of any of the three D-sites of MKK7 inhibited the ability of JNK1 and JNK2 to phosphorylate their transcription factor substrates c-Jun and ATF2 PMID:11062067 MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183) |
| GO:0005515 protein binding | IPI PMID:16840345 Vaccinia virus B1R kinase interacts with JIP1 and modulates ... | MODIFY | Summary: Vaccinia B1R forms a complex with JIP1 that increases JNK bound to JIP1. Reason: JNK1-JIP1 (MAPK8IP1, Q9UQF2) binding is scaffold protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:16840345 there is an increase in the phosphorylation state of JNK bound to JIP1 file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | REMOVE | Summary: JNK1 co-immunoprecipitates with a p85-CBL-CrkII/L adaptor network in AML cells. Reason: Association with CBL (P22681) is within a multi-adaptor complex; direct binding and function are unclear. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:16982329 JNK1 co-immunoprecipitated from such lysates with p85-cbl-crkII/L and bound to Crk species SH3 domain in pull-down assay |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | REMOVE | Summary: JNK1 co-immunoprecipitates with PI3K p85 (PIK3R1, P27986) in AML adaptor network. Reason: Indirect adaptor-complex association; no informative MF. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:16982329 JNK1 co-immunoprecipitated from such lysates with p85-cbl-crkII/L and bound to Crk species SH3 domain in pull-down assay |
| GO:0005515 protein binding | IPI PMID:18003900 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppr... | MODIFY | Summary: IPI JNK1 with c-Jun in a 3-hydroxyanthranilic acid/PDK1 paper (JNK1 kinase assays with GST-cJun). Reason: c-Jun binding as substrate; replace with DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:18003900 immunoprecipitated JNK1 or IKK were incubated with their respective recombinant substrate, GST-cJun or GST-IΞΊBΞ± PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0005515 protein binding | IPI PMID:18286207 Modulation of interleukin-1 transcriptional response by the ... | MODIFY | Summary: VRK2 and JIP1 paper; JIP1 assembles JNK pathway components in a signalosome. Reason: JNK1-JIP1 is scaffold protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:18286207 JIP1 assembles all these proteins in an oligomeric signalosome. file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005515 protein binding | IPI PMID:19234442 Tyrosine dephosphorylation of H2AX modulates apoptosis and s... | REMOVE | Summary: Fe65 (APBB1, O00213) co-immunoprecipitates with JNK1 after DNA damage and recruits it to gamma-H2AX. Reason: APBB1 is an adaptor that recruits JNK1; the interaction does not describe a JNK1 molecular function. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:19234442 we found that Fe65 protein interacted with endogenous JNK1 by co-immunoprecipitation in 293T cells treated with the DNA-damage agent etoposide Reactome:R-HSA-5683986 APBB1 (FE65) binds diphosphorylated H2AFX and recruits MAPK8 (JNK1) to H2AFX |
| GO:0005515 protein binding | IPI PMID:19234442 Tyrosine dephosphorylation of H2AX modulates apoptosis and s... | REMOVE | Summary: JNK1 associates with Y142/S139-diphosphorylated H2AX (P16104) after high-dose radiation. Reason: Recruitment is Fe65-mediated and direct binding is not established; no informative MF. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:19234442 we were able to detect a robust interaction between transfected wild-type H2AX and endogenous JNK1 in 293T cells in response to high-dose radiation |
| GO:0005515 protein binding | IPI PMID:19527717 A selective small-molecule inhibitor of c-Jun N-terminal kin... | MODIFY | Summary: IPI JNK1 with c-Jun in a JNK1-selective inhibitor (AV-7) paper. Reason: c-Jun substrate binding; DNA-binding transcription factor binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:19527717 AV-7 is an isoform selective small-molecule inhibitor of JNK1 activity PMID:8654373 the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | MODIFY | Summary: Y2H interaction of JNK1 with DUSP8 (Q13202) in a signaling interaction screen. Reason: DUSP8 is a JNK-directed MAPK phosphatase; protein phosphatase binding is informative (as in MAPK14/MAPK1 reviews). Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:21900206 we searched for protein interaction partners of more than 450 signaling-related proteins by means of automated yeast two-hybrid interaction mating file:human/MAPK8/MAPK8-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1 |
| GO:0005515 protein binding | IPI PMID:22966201 Phosphorylation of the eukaryotic translation initiation fac... | REMOVE | Summary: HA-JNK1 co-immunoprecipitates with its substrate 4E-T (EIF4ENIF1, Q9NRA8). Reason: Substrate association is captured by the kinase activity annotation; no further informative MF. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:22966201 we expressed HA-tagged JNK1 and myc-tagged 4E-T in HEK293 cells and coimmunoprecipitated them with anti-HA antibodies |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: CMGC interaction proteomics: JNK1 co-purifies with JNK2 (P45984). Reason: Kinase-kinase association; protein kinase binding, consistent with MAPK14 treatment of MAPK partners in the same dataset. Proposed replacements: protein kinase binding Supporting Evidence: PMID:23602568 Here we present a global proteomic analysis of complexes of the human CMGC kinase group. |
| GO:0005515 protein binding | IPI PMID:25284480 Naturally occurring neomorphic PIK3R1 mutations activate the... | REMOVE | Summary: PIK3R1 R348* neomorph assembles a complex with MLK3/MKK7/JNK; JNK likely tethered indirectly. Reason: Authors state JNK is likely tethered via MKK7 or intermediaries; no informative MF. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:25284480 JNK is likely to be tethered to the complex through an interaction with MKK7 or other intermediary proteins |
| GO:0005515 protein binding | IPI PMID:25284480 Naturally occurring neomorphic PIK3R1 mutations activate the... | MODIFY | Summary: JNK1 and JNK2 (P45984) found together in the p85 R348*/MLK3/MKK7 complex. Reason: Protein kinase binding (co-complex with paralog), consistent with sibling MAPK reviews. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25284480 the p85Ξ± R348*/Rac1/Cdc42/MLK3/MKK7/JNK1/JNK2 complex can be detected in the cytosol |
| GO:0005515 protein binding | IPI PMID:27043084 HSF1 critically attunes proteotoxic stress sensing by mTORC1... | REMOVE | Summary: JNK1 co-precipitates with RAPTOR (Q8N122) and mTOR under proteotoxic stress. Reason: Interesting regulatory association with mTORC1, but bare binding is not informative. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:27043084 under non-reducing conditions we detected JNK1 dimers co-precipitated with RAPTOR and mTOR |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: Phosphatase interactome: DUSP8 (Q13202) interacts with JNK1. Reason: Protein phosphatase binding (DUSP8 is a JNK phosphatase). Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:27880917 we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains file:human/MAPK8/MAPK8-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Kinase interaction network AP-MS: JNK1 with MKK4 (P45985). Reason: Upstream MAP2K; mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:32707033 A well-established method for capturing stable protein interactions is affinity purification coupled to mass spectrometry (AP-MS). file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex AP-MS: JNK1 with JNK2 (P45984). Reason: Protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33961781 repeating AP-MS in HCT116 cells has revealed additional cell-specific modules |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex AP-MS: JNK1 with DUSP8 (Q13202). Reason: Protein phosphatase binding. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:33961781 repeating AP-MS in HCT116 cells has revealed additional cell-specific modules file:human/MAPK8/MAPK8-uniprot.txt Inhibited by dual specificity phosphatases, such as DUSP1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BioPlex AP-MS: JNK1 with JIP1 (MAPK8IP1, Q9UQF2). Reason: Scaffold protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:33961781 repeating AP-MS in HCT116 cells has revealed additional cell-specific modules file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: OpenCell: JNK1 with JNK2 (P45984). Reason: Protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:35271311 we provide an open-source resource of well-curated localization and interactome measurements |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: OpenCell: JNK1 with MKK4 (P45985). Reason: Mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:35271311 we provide an open-source resource of well-curated localization and interactome measurements file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0005515 protein binding | IPI PMID:36935496 CLDN6 inhibits breast cancer metastasis through WIP-dependen... | REMOVE | Summary: CLDN6 (P56747) interacts with JNK via its PDZ-binding motif in breast cancer cells (pan-JNK reagents). Reason: Not informative for JNK1 molecular function. Bare protein binding is uninformative and REMOVE is the policy for GO:0005515 when no more informative MF is supported; removal does not mean the reported interaction is false. Supporting Evidence: PMID:36935496 CLDN6 interacts with JNK via the PDZ-binding motif. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: U2OS AP-MS cell map: JNK1 with MKK4 (P45985). Reason: Mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:40205054 interacting partners were identified by tandem MS (APβMS) to yield a total of 36,842 interactions among 7,543 proteins file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: U2OS AP-MS cell map: JNK1 with JIP1 (Q9UQF2). Reason: Scaffold protein binding. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:40205054 interacting partners were identified by tandem MS (APβMS) to yield a total of 36,842 interactions among 7,543 proteins file:human/MAPK8/MAPK8-uniprot.txt Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based ATP binding. Reason: Correct: ATP is the phosphoryl donor of the kinase domain. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA nucleus (PTN000622075, MAPK family). Reason: Active JNK1 acts on nuclear transcription factors; correct. Supporting Evidence: Reactome:R-HSA-450348 c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus file:human/MAPK8/MAPK8-uniprot.txt Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus |
| GO:0005634 nucleus | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: JNK1 primarily nuclear in the SIRT1 study. Reason: Direct localization evidence. Supporting Evidence: PMID:20027304 JNK1 was primarily localized to the nucleus. |
| GO:0005634 nucleus | IDA PMID:30878395 MicroRNA-143-3p promotes human cardiac fibrosis via targetin... | ACCEPT | Summary: Nucleus, cardiac fibrosis/miR-143 paper (abstract-only cache; cited by UniProt for nuclear location). Reason: Nuclear localization of JNK1 is well supported by other evidence; defer to curator. Supporting Evidence: PMID:30878395 MiR-143-3p promoted fibrosis along with SPRY3 degradation and the activation of its downstream P38, ERK, and JNK pathways. PMID:20027304 JNK1 was primarily localized to the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to nucleus. Reason: Correct. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: nucleoplasm. Reason: Consistent with nuclear JNK1 pool. Supporting Evidence: PMID:22966201 Immunofluorescence of HA-tagged JNK1 in untreated U2OS cells resulted in uniform staining throughout the cytoplasm and the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-168053 | ACCEPT | Summary: Reactome: phosphorylated MAPKs (including JNK) phosphorylate ATF-2 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-168053 At the end of this reaction, 1 molecule of 'ADP', and 1 molecule of 'ATF-2-P' are present. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-168136 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-168136 JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-193666 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-193666 active JNK does move to the nucleus and phosphorylates and activate transcription factors such as c-JUN and ATF2 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450348 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-450348 c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683986 | ACCEPT | Summary: Reactome: APBB1 recruits MAPK8 to diphosphorylated H2AX in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-5683986 APBB1 (FE65) binds diphosphorylated H2AFX and recruits MAPK8 (JNK1) to H2AFX |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9673322 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9673322 MAPK8 moves to the nucleus and phosphorylates transcription factors such as c-JUN and ATF2 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9673789 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9673789 JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851076 | ACCEPT | Summary: Reactome: phospho-MAPK8/9 bind TP53 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9851076 Inhibition of JNK (MAPK8 and 9) phosphorylation inhibits formation of a TP53:JNK complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851079 | ACCEPT | Summary: Reactome event placing active MAPK8 in the nucleoplasm. Reason: Active JNK1 translocates to the nucleus where it phosphorylates AP-1/ATF2 and binds nuclear partners; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-9851079 After NPM1-ALK-stimulated phosphorylation, MAPK8 and 9 promote activation of nuclear targets such as JUN |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm (PTN000622075). Reason: Inactive JNK1 is largely cytoplasmic and phosphorylates cytoplasmic substrates; correct. Supporting Evidence: PMID:22966201 Immunofluorescence of HA-tagged JNK1 in untreated U2OS cells resulted in uniform staining throughout the cytoplasm and the nucleus file:human/MAPK8/MAPK8-uniprot.txt Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Correct. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Mapk8. Reason: Correct and consistent with human data. Supporting Evidence: PMID:22966201 Immunofluorescence of HA-tagged JNK1 in untreated U2OS cells resulted in uniform staining throughout the cytoplasm and the nucleus |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139908 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-139908 MAPK8 (JNK) phosphorylates BMF on a DLC binding motif DKATQTLSP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139918 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-139918 MAPK8 (JNK) phosphorylates BCL2L11 (BIM) on a DLC-binding motif (DKSTQTP) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168162 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-168162 phosphorylate Thr183 and Tyr185 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-193666 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-193666 active JNK does move to the nucleus and phosphorylates and activate transcription factors such as c-JUN and ATF2 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205075 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-205075 Once activated, JNK phosphorylates targets in cytoplasm, including BIM and BAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205136 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-205136 activation was described as essential for p75NTR to induce MAPK8 (aka JNK) and apoptosis in cortical oligodendrocytes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450348 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-450348 c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9008043 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-9008043 can activate Mitogen Activated Protein Kinase 8 (MAPK8, JNK1) signaling |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9673284 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-9673284 activation was described as essential for p75NTR to induce MAPK8 (aka JNK) and apoptosis in cortical oligodendrocytes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9673322 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-9673322 MAPK8 moves to the nucleus and phosphorylates transcription factors such as c-JUN and ATF2 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9851078 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-9851078 NPM1-ALK promotes the phosphorylation of MAPK8 and MAPK9 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9851079 | ACCEPT | Summary: Reactome event placing MAPK8 in the cytosol (activation by MKK4/MKK7 or cytosolic substrate phosphorylation). Reason: JNK1 is activated and phosphorylates BH3-only proteins in the cytosol; cytosol is appropriate. Supporting Evidence: Reactome:R-HSA-9851079 After NPM1-ALK-stimulated phosphorylation, MAPK8 and 9 promote activation of nuclear targets such as JUN |
| GO:0006468 protein phosphorylation | IMP PMID:22441692 JNK regulates the photic response of the mammalian circadian... | ACCEPT | Summary: Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation; MKK7-JNK1 phosphorylates BMAL1/CLOCK. Reason: Protein phosphorylation is the process executed by JNK1 kinase activity; correct if general. Supporting Evidence: PMID:22441692 Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. PMID:22441692 stimulated phosphorylation of BMAL1 and CLOCK coexpressed in NIH3T3 cells |
| GO:0006979 response to oxidative stress | IDA PMID:22966201 Phosphorylation of the eukaryotic translation initiation fac... | KEEP AS NON CORE | Summary: JNK is targeted to P-bodies in response to oxidative stress and phosphorylates 4E-T. Reason: JNK1 is activated by and acts in oxidative stress responses, but this is a context-dependent downstream role. Supporting Evidence: PMID:22966201 We show that the c-Jun N-terminal kinase (JNK) is targeted to PBs in response to oxidative stress and promotes the phosphorylation of 4E-T. |
| GO:0007254 JNK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: IBA JNK cascade from PTN001171982. Reason: Core process: JNK1 is the terminal kinase of the JNK cascade. Target is in the JNK clade with direct experimental support. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 PMID:11062067 MKK4 and MKK7 together produce a synergistic increase in the activity of each SAPK1/JNK isoform in vitro |
| GO:0007254 JNK cascade | IDA PMID:8654373 Selective interaction of JNK protein kinase isoforms with tr... | ACCEPT | Summary: JNK isoforms activated by IL-1 and phosphorylate AP-1/ATF2/Elk-1. Reason: Direct evidence for JNK1 as the terminal kinase of the cascade. Supporting Evidence: PMID:8654373 Treatment of cells with interleukin-1 (IL-1) caused activation of the JNK isoforms. PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. |
| GO:0007258 JUN phosphorylation | IDA PMID:14967141 JNK suppresses apoptosis via phosphorylation of the proapopt... | ACCEPT | Summary: JUN phosphorylation (BAD survival paper, JNK activity on c-Jun). Reason: JNK1 directly phosphorylates c-Jun Ser63/73; the process term is accurate for the kinase. Supporting Evidence: PMID:14967141 IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a constitutively active JNK. file:human/MAPK8/MAPK8-uniprot.txt 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:0007258 JUN phosphorylation | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: JUN phosphorylation by EPO-activated JNK1 in erythroid cells. Reason: Accurate process for JNK1 kinase activity toward c-Jun. Supporting Evidence: PMID:21095239 our results provide a molecular mechanism by which JNK1 contributes to the survival of erythroid cells file:human/MAPK8/MAPK8-uniprot.txt 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:0009411 response to UV | IDA PMID:14967141 JNK suppresses apoptosis via phosphorylation of the proapopt... | KEEP AS NON CORE | Summary: Response to UV (BAD paper; JNK activated by UV). Reason: JNK1 is activated by UV irradiation as a stress response; a context, not a core function. Supporting Evidence: PMID:14967141 IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a constitutively active JNK. Reactome:R-HSA-111446 JNK or MAPK8 releases BIM in response to UV irradiation by phosphorylation. |
| GO:0009612 response to mechanical stimulus | IBA GO_REF:0000033 | UNDECIDED | Summary: IBA response to mechanical stimulus from PTN008602925; the only extant WITH/FROM grounding is human MAPK8 itself. Reason: The target's own experimental grounding for this process appears to be the IEP row for cellular response to mechanical stimulus citing PMID:19593445, which does not mention JNK or mechanical stimulation (treated as UNDECIDED here and in the MAP2K4/MAP3K1 reviews). Without verifiable descendant evidence we cannot confirm the node placement, although JNK activation by mechanical stress is plausible. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN008602925 UNRESOLVED PAINT node carrying the response to mechanical stimulus IBD; node placement could not be checked against verifiable descendant evidence. UniProtKB:P45983 UNRESOLVED Target itself is the only listed extant descendant; its visible experimental row for a mechanical-stimulus response (IEP, PMID:19593445) cites a paper that does not mention JNK. Supporting Evidence: PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer growth. |
| GO:0010628 positive regulation of gene expression | IMP PMID:22065586 Oncogenic Ras and B-Raf proteins positively regulate death r... | MARK AS OVER ANNOTATED | Summary: Ras/B-Raf induce DR5 expression via co-activation of ERK/RSK and JNK signaling. Reason: Pan-JNK pathway readout (no JNK1-specific perturbation found in the full text); positive regulation of gene expression is an indirect downstream effect. Supporting Evidence: PMID:22065586 Ras induces DR5 expression through co-activation of ERK/RSK and JNK signaling pathways |
| GO:0016241 regulation of macroautophagy | TAS PMID:26546165 Regulation of autophagy by Beclin 1 in the heart. | KEEP AS NON CORE | Summary: JNK1-mediated Bcl-2 phosphorylation frees Beclin 1 and induces autophagy (review). Reason: Real, JNK1-specific downstream role, but not core. Supporting Evidence: PMID:26546165 Phosphorylation of Bcl-2 in response to starvation is mediated by JNK1 file:human/MAPK8/MAPK8-uniprot.txt Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: Peptidyl-serine phosphorylation (erythroid JNK1 study; c-Jun Ser phosphorylation readout). Reason: JNK1 is a Ser/Thr kinase; accurate process consequence of its activity. Supporting Evidence: PMID:21095239 our results provide a molecular mechanism by which JNK1 contributes to the survival of erythroid cells file:human/MAPK8/MAPK8-uniprot.txt 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:0018105 peptidyl-serine phosphorylation | IDA PMID:22966201 Phosphorylation of the eukaryotic translation initiation fac... | ACCEPT | Summary: JNK phosphorylates 4E-T on multiple serines under oxidative stress. Reason: Accurate for JNK1 kinase activity. Supporting Evidence: PMID:22966201 We show that the c-Jun N-terminal kinase (JNK) is targeted to PBs in response to oxidative stress and promotes the phosphorylation of 4E-T. PMID:22966201 activated MKK7-JNK1 (CA) robustly increased 32 P incorporation |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: JNK1 phosphorylates BAD Thr201. Reason: Accurate process consequence of JNK1 activity. Supporting Evidence: PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic molecule B-cell lymphoma-extra large (Bcl-X(L)) |
| GO:0019899 enzyme binding | IPI PMID:14615289 Angiotensin-converting enzyme is involved in outside-in sign... | KEEP AS NON CORE | Summary: JNK and MKK7 co-precipitate with ACE (P12821) in endothelial cells. Reason: Enzyme binding is weakly informative; the ACE-JNK association is a context-specific signaling link (kept non-core, consistent with MAPK14). Supporting Evidence: PMID:14615289 Mitogen-activated protein kinase kinase 7 and c-Jun N-terminal kinase (JNK) coprecipitated with ACE |
| GO:0019903 protein phosphatase binding | IPI PMID:11489891 MKP-7, a novel mitogen-activated protein kinase phosphatase,... | ACCEPT | Summary: MKP-7 (DUSP16) is a JNK-specific phosphatase that binds JNK and retains it in the cytoplasm. Reason: Protein phosphatase binding reflects the physiological inactivation of JNK1 by MKPs. Supporting Evidence: PMID:11489891 MKP-7 works as a JNK-specific phosphatase in vivo PMID:11489891 Co-immunoprecipitation experiments and histological analysis suggested that MKP-7 determines the localization of MAPKs in the cytoplasm. |
| GO:0030424 axon | ISS PMID:22683681 Autism spectrum disorder susceptibility gene TAOK2 affects b... | KEEP AS NON CORE | Summary: ISS axon from mouse Mapk8 (pJNK1 enriched in axons of cortical neurons). Reason: Neuronal compartment localization; valid but not core. Supporting Evidence: PMID:22683681 we found that pJNK1 is preferentially enriched in the basal dendrites and the axons of cortical pyramidal neurons |
| GO:0031281 positive regulation of cyclase activity | IMP PMID:22027397 HIV-1 and IL-1Ξ² regulate astrocytic CD38 through mitogen-act... | MARK AS OVER ANNOTATED | Summary: IL-1beta induction of CD38 ADP-ribosyl cyclase activity in astrocytes blocked by MAPK inhibitors. Reason: Pharmacological inhibitor evidence does not distinguish JNK1 from JNK2/3 and the effect is indirect (transcriptional induction of CD38); consistent with MAPK14 treatment. Supporting Evidence: PMID:22027397 a panel of pharmacological inhibitors targeting MAPKs was employed |
| GO:0031343 positive regulation of cell killing | TAS Reactome:R-HSA-9664420 | MARK AS OVER ANNOTATED | Summary: Reactome Leishmania 'Killing mechanisms' pathway includes MAPK8. Reason: The pathway describes macrophage ROS/RNS production; JNK1 involvement is at most a signaling input and 'positive regulation of cell killing' over-states it. Supporting Evidence: Reactome:R-HSA-9664420 the most effective killing response is the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) |
| GO:0032091 negative regulation of protein binding | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | KEEP AS NON CORE | Summary: JNK1 phosphorylation of BAD Thr201 inhibits BAD binding to Bcl-XL. Reason: Accurate mechanistic consequence of JNK1 activity but a downstream, substrate-specific effect. Supporting Evidence: PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic molecule B-cell lymphoma-extra large (Bcl-X(L)) |
| GO:0032880 regulation of protein localization | IDA PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | KEEP AS NON CORE | Summary: JNK1 phosphorylation concentrates SIRT1 in the nucleus. Reason: Substrate-specific downstream effect; non-core. Supporting Evidence: PMID:20027304 our data suggest that phosphorylation via JNK1 is an important regulator of SIRT1 subcellular localization and function PMID:20027304 JNK1 directly phosphorylates SIRT1 on three specific residues, concentrating it in the nucleus and resulting in selective activation of SIRT1, as measured by deacetylation of histone H3 (but not p53). |
| GO:0034198 cellular response to amino acid starvation | IDA PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | KEEP AS NON CORE | Summary: JNK activation by Fas in glutamine-deprived HeLa cells. Reason: Pan-JNK readout of a stress response; non-core context (consistent with MAPK1). Supporting Evidence: PMID:11096076 Fas ligation activated apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase (SAPK)) in Gln-deprived cells but not in normal cells |
| GO:0034599 cellular response to oxidative stress | IDA PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | KEEP AS NON CORE | Summary: JNK phosphorylates SIRT6 Ser10 under oxidative stress to promote DSB repair. Reason: Real downstream role (GO-CAM 622aace900000522) but not core. Supporting Evidence: PMID:27568560 phosphorylates SIRT6 on serine 10 in response to oxidative stress file:human/MAPK8/MAPK8-uniprot.txt Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity |
| GO:0034614 cellular response to reactive oxygen species | IDA PMID:34048572 Post-translational modification of RNA m6A demethylase ALKBH... | KEEP AS NON CORE | Summary: ROS activate ERK/JNK signaling leading to ALKBH5 phosphorylation. Reason: Downstream stress-response role (GO-CAM 64e7eefa00001258); non-core. Supporting Evidence: PMID:34048572 ROS stress activates ERK/JNK signaling resulting in phosphorylation of ALKBH5 at serine residues S87 and S321. file:human/MAPK8/MAPK8-uniprot.txt Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation |
| GO:0035033 histone deacetylase regulator activity | IMP PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | MARK AS OVER ANNOTATED | Summary: JNK1 phosphorylates SIRT1 and increases its histone H3 deacetylation activity. Reason: The mechanism is JNK1 kinase activity on SIRT1 (captured by the Ser/Thr kinase annotations with SIRT1 as input); annotating the kinase with a regulator MF for its substrate over-states the MF. The regulatory consequence belongs in a causal model rather than as a JNK1 molecular function. Supporting Evidence: PMID:20027304 JNK1 directly phosphorylates SIRT1 on three specific residues, concentrating it in the nucleus and resulting in selective activation of SIRT1, as measured by deacetylation of histone H3 (but not p53). |
| GO:0038095 Fc-epsilon receptor signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: Fc-epsilon receptor signaling pathway. Reason: FCERI signaling activates JNK in mast cells; JNK1 is a downstream component, not specific to this receptor. Supporting Evidence: Reactome:R-HSA-2454202 These pathways lead to activation of the ERK, JNK and p38 MAP kinases, histamine release and cytokine production. |
| GO:0038095 Fc-epsilon receptor signaling pathway | TAS Reactome:R-HSA-2454202 | KEEP AS NON CORE | Summary: Reactome FCERI signaling includes JNK activation. Reason: Downstream MAPK arm of receptor signaling; non-core. Supporting Evidence: Reactome:R-HSA-2454202 These pathways lead to activation of the ERK, JNK and p38 MAP kinases, histamine release and cytokine production. |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Mapk8: regulation of circadian rhythm. Reason: JNK phosphorylates BMAL1/CLOCK and knockdown lengthens period; real but non-core. Supporting Evidence: PMID:22441692 Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. file:human/MAPK8/MAPK8-uniprot.txt Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock |
| GO:0042826 histone deacetylase binding | IPI PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | KEEP AS NON CORE | Summary: JNK1 interacts with SIRT1 (Q96EB6) upon activation by anisomycin/H2O2. Reason: SIRT1 is a JNK1 substrate; histone deacetylase binding is accurate for the partner class but reflects a substrate interaction. Supporting Evidence: PMID:20027304 First, we demonstrated that SIRT1 and JNK1 functionally interact, but only when JNK1 is activated by anisomycin or H2O2. |
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA positive regulation of apoptotic process (PTN008602925). Reason: JNK signaling promotes stress-induced apoptosis (BIM/BMF release, YAP, p53), but JNK1 is also anti-apoptotic in other contexts; pleiotropic, non-core. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 PMID:21364637 Here we report the identification of JNK1 and JNK2 as kinases that robustly phosphorylate YAP and regulate its function in apoptosis. |
| GO:0043065 positive regulation of apoptotic process | TAS Reactome:R-HSA-193648 | KEEP AS NON CORE | Summary: Reactome: NRAGE signals death through JNK. Reason: Context-specific pro-apoptotic role; non-core. Supporting Evidence: Reactome:R-HSA-193648 JNK controls apoptosis in two ways: it induces transcription of pro-apoptotic genes, and directly activates the cell death machinery. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:14967141 JNK suppresses apoptosis via phosphorylation of the proapopt... | KEEP AS NON CORE | Summary: JNK suppresses IL-3 withdrawal-induced apoptosis via BAD Thr201 phosphorylation. Reason: Context-dependent anti-apoptotic role; non-core. Supporting Evidence: PMID:14967141 IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a constitutively active JNK. PMID:14967141 JNK phosphorylates BAD at threonine 201, thereby inhibiting BAD association with the antiapoptotic molecule BCL-X(L) |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | KEEP AS NON CORE | Summary: JNK1 required for EPO-mediated erythroid survival via BAD phosphorylation. Reason: Context-dependent anti-apoptotic role; non-core. Supporting Evidence: PMID:21095239 our results provide a molecular mechanism by which JNK1 contributes to the survival of erythroid cells file:human/MAPK8/MAPK8-uniprot.txt Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location mapping: synapse. Reason: Neuronal localization by similarity (rat); non-core. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Increased neuronal activity increases phosphorylated form at synapses |
| GO:0045202 synapse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS synapse from rat Mapk8 (P49185). Reason: Neuronal localization; non-core. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Increased neuronal activity increases phosphorylated form at synapses |
| GO:0051247 positive regulation of protein metabolic process | IMP PMID:22027397 HIV-1 and IL-1Ξ² regulate astrocytic CD38 through mitogen-act... | MARK AS OVER ANNOTATED | Summary: IL-1beta-induced CD38 protein expression in astrocytes reduced by MAPK inhibitors. Reason: Inhibitor-based, not JNK1-specific, and very general process term. Supporting Evidence: PMID:22027397 a panel of pharmacological inhibitors targeting MAPKs was employed |
| GO:0051403 stress-activated MAPK cascade | IDA PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | ACCEPT | Summary: JNK/SAPK activation by Fas ligation in glutamine-deprived cells (ASK1 upstream). Reason: JNK1 is a core component of the stress-activated MAPK cascade; the more specific JNK cascade is also annotated. Supporting Evidence: PMID:11096076 Fas ligation activated apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase (SAPK)) in Gln-deprived cells but not in normal cells file:human/MAPK8/MAPK8-uniprot.txt In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1 |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:23776175 SASH1 is a scaffold molecule in endothelial TLR4 signaling. | KEEP AS NON CORE | Summary: SASH1 scaffolds TLR4 signaling and promotes LPS-induced JNK activation in endothelial cells. Reason: JNK activation downstream of TLR4 is a context; non-core (consistent with MAPK14). Supporting Evidence: PMID:23776175 promotes LPS-induced NF-ΞΊB, JNK, and p38 activation |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | UNDECIDED | Summary: IEP cellular response to mechanical stimulus citing a BAD/prostate cancer paper. Reason: The cached full text does not mention JNK or mechanical stimulation; this appears to be a batch mis-citation also seen on MAP2K4 and MAP3K1 rows. Cannot verify. Supporting Evidence: PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer growth. |
| GO:0090398 cellular senescence | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: cellular senescence. Reason: JNK signaling contributes to stress-induced senescence; non-core. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death |
| GO:0090398 cellular senescence | TAS Reactome:R-HSA-2559583 | KEEP AS NON CORE | Summary: Reactome Cellular Senescence pathway includes MAPK8. Reason: Stress-MAPK arm of oxidative stress-induced senescence; non-core (as for MAPK14). Supporting Evidence: Reactome:R-HSA-2559583 Cellular senescence involves irreversible growth arrest |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Mapk8: energy homeostasis (Jnk1 knockout protects from obesity/insulin resistance). Reason: Organism-level physiological role; non-core (GO-CAM 6494e2e900002525). Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death |
| GO:0097441 basal dendrite | ISS PMID:22683681 Autism spectrum disorder susceptibility gene TAOK2 affects b... | KEEP AS NON CORE | Summary: ISS basal dendrite from mouse Mapk8. Reason: pJNK1 enriched in basal dendrites; non-core neuronal localization. Supporting Evidence: PMID:22683681 we found that pJNK1 is preferentially enriched in the basal dendrites and the axons of cortical pyramidal neurons PMID:22683681 Over-expression of a constitutively active JNK1 (MKK7-JNK1) restores basal dendrite formation in cortical neurons following TAO2 down-regulation. |
| GO:0106310 protein serine kinase activity | EXP PMID:10747973 c-Jun NH2-terminal kinase targeting and phosphorylation of h... | ACCEPT | Summary: JNK phosphorylates HSF1 in its regulatory domain. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:10747973 JNK binds to HSF-1 in the conserved mitogen-activated protein kinases binding motifs and phosphorylates HSF-1 in the regulatory domain |
| GO:0106310 protein serine kinase activity | EXP PMID:10856240 The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and p... | ACCEPT | Summary: JNK1 kinase activity on GST-c-Jun (inhibited by Evi-1). Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:10856240 JNK1 activity was measured by immunoprecipitation followed by in vitro kinase assay using GSTβc-Jun as a substrate PMID:10856240 However, Evi-1 significantly suppressed JNK1 activity when they were co-expressed. |
| GO:0106310 protein serine kinase activity | EXP PMID:11062067 Synergistic activation of stress-activated protein kinase 1/... | ACCEPT | Summary: MKK4/MKK7-activated JNK1 isoforms assayed in vitro. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:11062067 MKK4 and MKK7 together produce a synergistic increase in the activity of each SAPK1/JNK isoform in vitro |
| GO:0106310 protein serine kinase activity | EXP PMID:15141161 Structural basis for the selective inhibition of JNK1 by the... | ACCEPT | Summary: JNK1 kinase activity toward substrates is inhibited by JIP1 peptide. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:15141161 Overexpression of JIP1 deactivates the JNK pathway selectively by cytoplasmic retention of JNK |
| GO:0106310 protein serine kinase activity | EXP PMID:16581800 Association and regulation of heat shock transcription facto... | ACCEPT | Summary: HSF4b phosphorylation study using JNK1 immunoprecipitates (paper focuses on ERK). Reason: The cached full text mainly concerns ERK phosphorylation of Hsf4b; UniProt nonetheless cites this paper for JNK1 phosphorylation of HSF4 and the curator had the full figures. Serine kinase activity of JNK1 is independently well established, so accept deferring to the curator. Supporting Evidence: PMID:16581800 polyclonal rabbit antibody to ERK1/2, JNK1, or p38 |
| GO:0106310 protein serine kinase activity | EXP PMID:17296730 Rev7/MAD2B links c-Jun N-terminal protein kinase pathway sig... | ACCEPT | Summary: JNK phosphorylates Elk-1, promoted by hRev7. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:17296730 hRev7 acts to promote Elk-1 phosphorylation by the c-Jun N-terminal protein kinase (JNK) MAP kinases |
| GO:0106310 protein serine kinase activity | EXP PMID:17875713 Nuclear factor of activated T3 is a negative regulator of Ra... | ACCEPT | Summary: JNK1 phosphorylates NFAT3 at Ser213/Ser217. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:17875713 the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217) |
| GO:0106310 protein serine kinase activity | EXP PMID:18307971 Phosphorylation of two eukaryotic transcription factors, Jun... | ACCEPT | Summary: Human JNK1 phosphorylates JDP2 and ATF2 when co-expressed in E. coli. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:18307971 we were able to phosphorylate mouse and human Jun dimerization protein 2 (JDP2) and human activation transcription factor 2 (ATF-2) by the action of human JNK1 that was expressed simultaneously |
| GO:0106310 protein serine kinase activity | EXP PMID:19166818 Crystal structure of SCCA1 and insight about the interaction... | ACCEPT | Summary: SCCA1 inhibits JNK1 kinase activity. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:19166818 We show that the inhibitory effect of SCCA1 on the kinase activity of JNK1 is lost when the RCL was truncated. |
| GO:0106310 protein serine kinase activity | EXP PMID:20027304 JNK1 phosphorylates SIRT1 and promotes its enzymatic activit... | ACCEPT | Summary: JNK1 phosphorylates SIRT1 Ser27/Ser47. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:20027304 JNK1 directly phosphorylates SIRT1 on three specific residues, concentrating it in the nucleus and resulting in selective activation of SIRT1, as measured by deacetylation of histone H3 (but not p53). |
| GO:0106310 protein serine kinase activity | EXP PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: Erythroid JNK1 activity (c-Jun, BAD). Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic molecule B-cell lymphoma-extra large (Bcl-X(L)) |
| GO:0106310 protein serine kinase activity | EXP PMID:21364637 JNK phosphorylates Yes-associated protein (YAP) to regulate ... | ACCEPT | Summary: JNK1 robustly phosphorylates YAP. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:21364637 Here we report the identification of JNK1 and JNK2 as kinases that robustly phosphorylate YAP and regulate its function in apoptosis. |
| GO:0106310 protein serine kinase activity | EXP PMID:21660049 A critical step for JNK activation: isomerization by the pro... | ACCEPT | Summary: Pin1 isomerizes phospho-Thr-Pro in JNK1, enhancing its activity. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:21660049 phospho-Thr-Pro motif in JNK1 from trans- to cis-conformation PMID:21660049 knockdown of Pin1 in a human breast cancer cell line decreased JNK1 activity |
| GO:0106310 protein serine kinase activity | EXP PMID:21856198 JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 hi... | ACCEPT | Summary: JNK phosphorylates Cdt1 (Thr29) and Jun. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:21856198 JNK phosphorylates Cdt1 on threonine 29, leading to rapid dissociation of HBO1 from replication origins |
| GO:0106310 protein serine kinase activity | EXP PMID:22441692 JNK regulates the photic response of the mammalian circadian... | ACCEPT | Summary: MKK7-JNK1 phosphorylates BMAL1 and CLOCK. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:22441692 stimulated phosphorylation of BMAL1 and CLOCK coexpressed in NIH3T3 cells |
| GO:0106310 protein serine kinase activity | EXP PMID:22966201 Phosphorylation of the eukaryotic translation initiation fac... | ACCEPT | Summary: Activated JNK1 phosphorylates 4E-T. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:22966201 activated MKK7-JNK1 (CA) robustly increased 32 P incorporation |
| GO:0106310 protein serine kinase activity | EXP PMID:27568560 JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Brea... | ACCEPT | Summary: JNK phosphorylates SIRT6 Ser10. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:27568560 phosphorylates SIRT6 on serine 10 in response to oxidative stress |
| GO:0106310 protein serine kinase activity | EXP PMID:28943315 NLRP3 Phosphorylation Is an Essential Priming Event for Infl... | ACCEPT | Summary: JNK1 phosphorylates NLRP3 Ser194. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:28943315 JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation |
| GO:0106310 protein serine kinase activity | EXP PMID:34048572 Post-translational modification of RNA m6A demethylase ALKBH... | ACCEPT | Summary: JNK promotes Ser phosphorylation of ALKBH5. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:34048572 activated JNK promoted serine but not tyrosine and threonine phosphorylation of ALKBH5 |
| GO:0106310 protein serine kinase activity | EXP PMID:8654373 Selective interaction of JNK protein kinase isoforms with tr... | ACCEPT | Summary: JNK isoforms phosphorylate Jun, ATF2 and Elk-1. Reason: Experimental evidence of JNK1 serine kinase activity (EXP, as asserted by UniProt EC evidence); correct and consistent with MAPK14 treatment of GO:0106310 EXP rows. Supporting Evidence: PMID:8654373 The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based IEA (RHEA:17989) to protein serine kinase activity. Reason: Correct. Supporting Evidence: file:human/MAPK8/MAPK8-uniprot.txt Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:11865055 IAP suppression of apoptosis involves distinct mechanisms: t... | MODIFY | Summary: JNK1 binds TAK1 (MAP3K7) in the IAP/TAK1/JNK1 antiapoptotic cascade. Reason: The full text studies TAK1 = MAP3K7 (TGF-beta-activated kinase), an upstream MAP3K, whereas the GOA WITH/FROM is UniProtKB:P27448 (MARK3, also called C-TAK1); the partner identifier appears mis-mapped from the name 'TAK1'. The MF itself is correct (MAP3K7 is a Ser/Thr kinase); the more informative term is mitogen-activated protein kinase kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:11865055 XIAP, NAIP, and JNK1 bind to TAK1 PMID:11865055 TAK1 is an upstream MAP3 kinase that activates JNK1 and p38 in response to transforming growth factor Ξ²1 (TGF-Ξ²1) stimulation |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IDA PMID:28943315 NLRP3 Phosphorylation Is an Essential Priming Event for Infl... | KEEP AS NON CORE | Summary: JNK1 phosphorylation of NLRP3 S194 promotes NLRP3 deubiquitination, self-association and inflammasome assembly. Reason: Direct, JNK1-specific mechanism (GO-CAM 635b1e3e00002004), but a downstream, cell-type-specific output of the kinase rather than its core cascade role. Supporting Evidence: PMID:28943315 JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly file:human/MAPK8/MAPK8-uniprot.txt Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome |
| GO:1903749 obsolete positive regulation of protein localization to mitochondrion | TAS Reactome:R-HSA-111446 | MODIFY | Summary: Reactome: JNK/MAPK8 phosphorylation releases BIM from dynein, allowing translocation to mitochondria (term now obsolete). Reason: GO:1903749 is obsolete (QuickGO: represents a phenotype and was added in error; annotate to the specific regulated process). The regulated process is BIM-driven intrinsic apoptosis; replace with positive regulation of intrinsic apoptotic signaling pathway (non-core). Proposed replacements: positive regulation of intrinsic apoptotic signaling pathway Supporting Evidence: Reactome:R-HSA-111446 JNK or MAPK8 releases BIM in response to UV irradiation by phosphorylation. |
| GO:1903749 obsolete positive regulation of protein localization to mitochondrion | TAS Reactome:R-HSA-139910 | MODIFY | Summary: Reactome: MAPK8 phosphorylation releases BMF from the myosin V motor complex (term now obsolete). Reason: GO:1903749 is obsolete; replace with positive regulation of intrinsic apoptotic signaling pathway (non-core). Proposed replacements: positive regulation of intrinsic apoptotic signaling pathway Supporting Evidence: Reactome:R-HSA-139910 UV irradiation or anoikis induces MAPK8 (JNK) to phosphorylate Dynein Light Chain 2 (DLC2) to release BMF. |
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Download this section (compressed HTML)Q: What is the correct source publication for the IEP 'cellular response to mechanical stimulus' row attributed to PMID:19593445 (a BAD/prostate cancer paper that does not mention JNK), and does the PAINT IBD for response to mechanical stimulus at PTN008602925 rest on any other verifiable descendant evidence?
Q: The GOA WITH/FROM for the JNK1-TAK1 interaction (PMID:11865055) is UniProtKB:P27448 (MARK3/C-TAK1), whereas the paper studies TAK1 = MAP3K7 (O43318); should the partner identifier be corrected?
Q: Many process rows (DR5 induction, CD38 cyclase activity, response to glutamine deprivation) rest on pan-JNK inhibitors or antibodies; which of these are JNK1-specific rather than shared with JNK2 (MAPK9)?
Q: Should the many JNK1 substrates (c-Jun, ATF2, BAD, BIM, BMF, SIRT1, SIRT6, NLRP3, ALKBH5, 4E-T, YAP1) be captured as has_input on JUN/MAP kinase activity in JNK-cascade GO-CAMs rather than as regulator MFs or bare binding rows?
Experiment: Analog-sensitive JNK1 (MAPK8) allele expressed in MAPK8/MAPK9 double-knockout cells, combined with thiophosphate labelling and quantitative phosphoproteomics after anisomycin, UV or TNF stimulation, to define direct JNK1 substrates and separate JNK1-specific from JNK2-shared outputs.
Experiment: Isoform-selective genetic perturbation (MAPK8 vs MAPK9 knockout with rescue) in cells subjected to cyclic stretch or shear stress to test whether JNK1 is required for mechanical-stimulus responses.
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