ID MK08_MOUSE Reviewed; 384 AA. AC Q91Y86; DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Mitogen-activated protein kinase 8; DE Short=MAP kinase 8; DE Short=MAPK 8; DE EC=2.7.11.24 {ECO:0000269|PubMed:11562351, ECO:0000269|PubMed:11602244, ECO:0000269|PubMed:16166642, ECO:0000269|PubMed:16618812, ECO:0000269|PubMed:9096336, ECO:0000269|PubMed:9207092, ECO:0000269|PubMed:9393873}; DE AltName: Full=Stress-activated protein kinase JNK1; DE AltName: Full=c-Jun N-terminal kinase 1; GN Name=Mapk8; Synonyms=Jnk1 {ECO:0000303|PubMed:28943315}, Prkm8; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH MAPK8IP3. RC TISSUE=Brain; RX PubMed=10523642; DOI=10.1128/mcb.19.11.7539; RA Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K., RA Hibi M., Nakabeppu Y., Shiba T., Yamamoto K.; RT "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that RT functions as a scaffold factor in the JNK signaling pathway."; RL Mol. Cell. Biol. 19:7539-7548(1999). RN [2] RP FUNCTION IN PHOSPHORYLATION OF TP53, AND CATALYTIC ACTIVITY. RX PubMed=9393873; DOI=10.1038/sj.onc.1201401; RA Hu M.C., Qiu W.R., Wang Y.P.; RT "JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases."; RL Oncogene 15:2277-2287(1997). RN [3] RP CATALYTIC ACTIVITY, AND REGULATION BY MAP2K4. RC TISSUE=Embryonic stem cell; RX PubMed=9096336; DOI=10.1073/pnas.94.7.3004; RA Yang D., Tournier C., Wysk M., Lu H.-T., Xu J., Davis R.J., Flavell R.A.; RT "Targeted disruption of the MKK4 gene causes embryonic death, inhibition of RT c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional RT activity."; RL Proc. Natl. Acad. Sci. U.S.A. 94:3004-3009(1997). RN [4] RP CATALYTIC ACTIVITY, COFACTOR, AND REGULATION BY MAP2K7. RX PubMed=9207092; DOI=10.1073/pnas.94.14.7337; RA Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.; RT "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun RT NH2-terminal kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997). RN [5] RP FUNCTION, ACTIVITY REGULATION, AND INDUCTION. RC TISSUE=Embryonic stem cell, and T-cell; RX PubMed=10811224; DOI=10.1038/35011091; RA Dong C., Yang D.D., Tournier C., Whitmarsh A.J., Xu J., Davis R.J., RA Flavell R.A.; RT "JNK is required for effector T-cell function but not for T-cell RT activation."; RL Nature 405:91-94(2000). RN [6] RP FUNCTION IN PHOSPHORYLATION OF JDP2, AND CATALYTIC ACTIVITY. RX PubMed=11602244; DOI=10.1016/s0014-5793(01)02907-6; RA Katz S., Heinrich R., Aronheim A.; RT "The AP-1 repressor, JDP2, is a bona fide substrate for the c-Jun N- RT terminal kinase."; RL FEBS Lett. 506:196-200(2001). RN [7] RP CATALYTIC ACTIVITY, SUBUNIT, AND PHOSPHORYLATION AT THR-183 AND TYR-185. RC TISSUE=Hippocampus; RX PubMed=11562351; DOI=10.1101/gad.922801; RA Whitmarsh A.J., Kuan C.-Y., Kennedy N.J., Kelkar N., Haydar T.F., RA Mordes J.P., Appel M., Rossini A.A., Jones S.N., Flavell R.A., Rakic P., RA Davis R.J.; RT "Requirement of the JIP1 scaffold protein for stress-induced JNK RT activation."; RL Genes Dev. 15:2421-2432(2001). RN [8] RP INTERACTION WITH SPAG9. RX PubMed=12391307; DOI=10.1073/pnas.232310199; RA Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.; RT "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and RT transcription factors."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002). RN [9] RP IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND ARHGEF28. RX PubMed=14499478; DOI=10.1016/s0169-328x(03)00263-8; RA Wu J., Zhai J., Lin H., Nie Z., Ge W.-W., Garcia-Bermejo L., Muschel R.J., RA Schlaepfer W.W., Canete-Soler R.; RT "Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity RT to an EGFP-tagged protein."; RL Brain Res. Mol. Brain Res. 117:27-38(2003). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [11] RP CATALYTIC ACTIVITY, AND INTERACTION WITH JAMP. RX PubMed=16166642; DOI=10.1128/mcb.25.19.8619-8630.2005; RA Kadoya T., Khurana A., Tcherpakov M., Bromberg K.D., Didier C., Broday L., RA Asahara T., Bhoumik A., Ronai Z.; RT "JAMP, a Jun N-terminal kinase 1 (JNK1)-associated membrane protein, RT regulates duration of JNK activity."; RL Mol. Cell. Biol. 25:8619-8630(2005). RN [12] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=16618812; DOI=10.1083/jcb.200511055; RA Tararuk T., Ostman N., Li W., Bjorkblom B., Padzik A., Zdrojewska J., RA Hongisto V., Herdegen T., Konopka W., Courtney M.J., Coffey E.T.; RT "JNK1 phosphorylation of SCG10 determines microtubule dynamics and RT axodendritic length."; RL J. Cell Biol. 173:265-277(2006). RN [13] RP PHOSPHORYLATION BY MAP3K1. RX PubMed=17761173; DOI=10.1016/j.febslet.2007.08.008; RA Ye B., Yu W.P., Thomas G.M., Huganir R.L.; RT "GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway."; RL FEBS Lett. 581:4403-4410(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH NFE2. RX PubMed=19966288; DOI=10.1073/pnas.0909153107; RA Lee T.L., Shyu Y.C., Hsu P.H., Chang C.W., Wen S.C., Hsiao W.Y., Tsai M.D., RA Shen C.K.; RT "JNK-mediated turnover and stabilization of the transcription factor RT p45/NF-E2 during differentiation of murine erythroleukemia cells."; RL Proc. Natl. Acad. Sci. U.S.A. 107:52-57(2010). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=21297631; DOI=10.1038/nn.2755; RA Westerlund N., Zdrojewska J., Padzik A., Komulainen E., Bjorkblom B., RA Rannikko E., Tararuk T., Garcia-Frigola C., Sandholm J., Nguyen L., RA Kallunki T., Courtney M.J., Coffey E.T.; RT "Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and RT neuronal migration rate."; RL Nat. Neurosci. 14:305-313(2011). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=22441692; DOI=10.1038/embor.2012.37; RA Yoshitane H., Honma S., Imamura K., Nakajima H., Nishide S.Y., Ono D., RA Kiyota H., Shinozaki N., Matsuki H., Wada N., Doi H., Hamada T., Honma K., RA Fukada Y.; RT "JNK regulates the photic response of the mammalian circadian clock."; RL EMBO Rep. 13:455-461(2012). RN [18] RP IDENTIFICATION IN A COMPLEX WITH SH3RF1; RAC1; MAP3K11; MAPK8IP1 AND RP MAP2K7. RX PubMed=23963642; DOI=10.1002/eji.201343635; RA Cunningham C.A., Knudson K.M., Peng B.J., Teixeiro E., Daniels M.A.; RT "The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and RT effector function in CD8(+) T cells."; RL Eur. J. Immunol. 43:3361-3371(2013). RN [19] RP IDENTIFICATION IN A COMPLEX WITH SH3RF1; RAC2; MAP3K7; MAPK8IP1; MAP2K7 AND RP MAPK9. RX PubMed=27084103; DOI=10.4049/jimmunol.1501728; RA Cunningham C.A., Cardwell L.N., Guan Y., Teixeiro E., Daniels M.A.; RT "POSH regulates CD4+ T cell differentiation and survival."; RL J. Immunol. 196:4003-4013(2016). RN [20] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28943315; DOI=10.1016/j.molcel.2017.08.017; RA Song N., Liu Z.S., Xue W., Bai Z.F., Wang Q.Y., Dai J., Liu X., Huang Y.J., RA Cai H., Zhan X.Y., Han Q.Y., Wang H., Chen Y., Li H.Y., Li A.L., RA Zhang X.M., Zhou T., Li T.; RT "NLRP3 phosphorylation is an essential priming event for inflammasome RT activation."; RL Mol. Cell 68:185-197(2017). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH POU5F1, AND SUBCELLULAR RP LOCATION. RX PubMed=29153991; DOI=10.1016/j.stemcr.2017.10.017; RA Bae K.B., Yu D.H., Lee K.Y., Yao K., Ryu J., Lim D.Y., Zykova T.A., RA Kim M.O., Bode A.M., Dong Z.; RT "Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein RT Stability in Mouse Embryonic Stem Cells."; RL Stem Cell Reports 9:2050-2064(2017). RN [22] RP FUNCTION. RX PubMed=36812915; DOI=10.1016/j.cmet.2023.01.011; RA Kuramoto K., Liang H., Hong J.H., He C.; RT "Exercise-activated hepatic autophagy via the FN1-alpha5beta1 integrin RT pathway drives metabolic benefits of exercise."; RL Cell Metab. 0:0-0(2023). CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes CC such as cell proliferation, differentiation, migration, transformation CC and programmed cell death (PubMed:9393873, PubMed:28943315). CC Extracellular stimuli such as pro-inflammatory cytokines or physical CC stress stimulate the stress-activated protein kinase/c-Jun N-terminal CC kinase (SAP/JNK) signaling pathway. In this cascade, two dual CC specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and CC activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of CC transcription factors, primarily components of AP-1 such as JUN, JDP2 CC and ATF2 and thus regulates AP-1 transcriptional activity CC (PubMed:11602244). Phosphorylates the replication licensing factor CC CDT1, inhibiting the interaction between CDT1 and the histone H4 CC acetylase HBO1 to replication origins. Loss of this interaction CC abrogates the acetylation required for replication initiation. Promotes CC stressed cell apoptosis by phosphorylating key regulatory factors CC including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 CC and MAPK9 are required for polarized differentiation of T-helper cells CC into Th1 cells (PubMed:10811224). Contributes to the survival of CC erythroid cells by phosphorylating the antagonist of cell death BAD CC upon EPO stimulation (By similarity). Mediates starvation-induced BCL2 CC phosphorylation, BCL2 dissociation from BECN1, and thus activation of CC autophagy (PubMed:36812915). Phosphorylates STMN2 and hence regulates CC microtubule dynamics, controlling neurite elongation in cortical CC neurons (PubMed:21297631). In the developing brain, through its CC cytoplasmic activity on STMN2, negatively regulates the rate of exit CC from multipolar stage and of radial migration from the ventricular zone CC (PubMed:21297631). Phosphorylates several other substrates including CC heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the CC E3 ligase ITCH. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a CC role in the regulation of the circadian clock (PubMed:22441692). CC Phosphorylates the heat shock transcription factor HSF1, suppressing CC HSF1-induced transcriptional activity (By similarity). Phosphorylates CC POU5F1, which results in the inhibition of POU5F1's transcriptional CC activity and enhances its proteasomal degradation (PubMed:29153991). CC Phosphorylates JUND and this phosphorylation is inhibited in the CC presence of MEN1 (By similarity). In neurons, phosphorylates SYT4 which CC captures neuronal dense core vesicles at synapses (By similarity). CC Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, CC promoting P-body assembly (By similarity). Phosphorylates SIRT6 in CC response to oxidative stress, stimulating its mono-ADP- CC ribosyltransferase activity (By similarity). Phosphorylates NLRP3, CC promoting assembly of the NLRP3 inflammasome (PubMed:28943315). CC {ECO:0000250|UniProtKB:P45983, ECO:0000250|UniProtKB:P49185, CC ECO:0000269|PubMed:10811224, ECO:0000269|PubMed:11602244, CC ECO:0000269|PubMed:19966288, ECO:0000269|PubMed:21297631, CC ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:28943315, CC ECO:0000269|PubMed:29153991, ECO:0000269|PubMed:36812915, CC ECO:0000269|PubMed:9393873}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC Evidence={ECO:0000269|PubMed:11562351, ECO:0000269|PubMed:11602244, CC ECO:0000269|PubMed:16166642, ECO:0000269|PubMed:16618812, CC ECO:0000269|PubMed:19966288, ECO:0000269|PubMed:21297631, CC ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:28943315, CC ECO:0000269|PubMed:29153991, ECO:0000269|PubMed:9096336, CC ECO:0000269|PubMed:9207092, ECO:0000269|PubMed:9393873}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.24; Evidence={ECO:0000269|PubMed:11562351, CC ECO:0000269|PubMed:11602244, ECO:0000269|PubMed:16166642, CC ECO:0000269|PubMed:16618812, ECO:0000269|PubMed:19966288, CC ECO:0000269|PubMed:21297631, ECO:0000269|PubMed:22441692, CC ECO:0000269|PubMed:29153991, ECO:0000269|PubMed:9096336, CC ECO:0000269|PubMed:9207092, ECO:0000269|PubMed:9393873}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:9207092}; CC -!- ACTIVITY REGULATION: Inhibited by SERPINB3 (By similarity). Activated CC by threonine and tyrosine phosphorylation by either of two dual CC specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong CC preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 CC preferentially. Inhibited by dual specificity phosphatases, such as CC DUSP1. {ECO:0000250|UniProtKB:P45983, ECO:0000269|PubMed:10811224}. CC -!- SUBUNIT: Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, CC MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 CC (PubMed:10523642, PubMed:12391307, PubMed:11562351). These proteins CC also bind other components of the JNK signaling pathway. Forms a CC complex with MAPK8IP1 and ARHGEF28 (PubMed:14499478). Interacts with CC TP53 and WWOX (By similarity). Interacts with JAMP (PubMed:16166642). CC Interacts with NFATC4 (By similarity). Interacts with MECOM; regulates CC JNK signaling (By similarity). Interacts with PIN1; this interaction CC mediates MAPK8 conformational changes leading to the binding of MAPK8 CC to its substrates (By similarity). Interacts with HSF1 (via D domain CC and preferentially with hyperphosphorylated form); this interaction CC occurs under both normal growth conditions and immediately upon heat CC shock (By similarity). Interacts (phosphorylated form) with NFE2; the CC interaction phosphorylates NFE2 in undifferentiated cells CC (PubMed:19966288). Interacts with GRIPAP1 (By similarity). Interacts CC with POU5F1; phosphorylates POU5F1 at 'Ser-347' (PubMed:29153991). CC Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and CC MAPK8IP1/JIP1 (PubMed:23963642). Found in a complex with SH3RF1, RAC2, CC MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 CC (PubMed:27084103). {ECO:0000250|UniProtKB:P45983, CC ECO:0000250|UniProtKB:P49185, ECO:0000269|PubMed:10523642, CC ECO:0000269|PubMed:11562351, ECO:0000269|PubMed:12391307, CC ECO:0000269|PubMed:14499478, ECO:0000269|PubMed:16166642, CC ECO:0000269|PubMed:19966288, ECO:0000269|PubMed:23963642, CC ECO:0000269|PubMed:27084103, ECO:0000269|PubMed:29153991}. CC -!- INTERACTION: CC Q91Y86; P05627: Jun; NbExp=2; IntAct=EBI-298784, EBI-764369; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16618812}. Nucleus CC {ECO:0000269|PubMed:29153991}. Synapse {ECO:0000250|UniProtKB:P49185}. CC Note=In the cortical neurons, predominantly cytoplasmic and associated CC with the Golgi apparatus and endosomal fraction. Increased neuronal CC activity increases phosphorylated form at synapses (By similarity). CC Colocalizes with POU5F1 in the nucleus (By similarity) CC (PubMed:29153991). {ECO:0000250|UniProtKB:P49185, CC ECO:0000269|PubMed:29153991}. CC -!- TISSUE SPECIFICITY: Brain (at protein level). CC {ECO:0000269|PubMed:22441692}. CC -!- DEVELOPMENTAL STAGE: At 15.5 dpc, mid to low expression throughout the CC midbrain, with more prominent levels in the telencephalon, especially CC in the intermediate zone, the midbrain roof, the olfactory epithelium, CC the inferior colliculus, and the medulla oblongata. telencephalon CC revealed concentrated (at protein level). CC {ECO:0000269|PubMed:16618812}. CC -!- INDUCTION: In T-cells, following T-cell receptor (TCR) activation. CC Levels peak 48 hours after TCR and CD-28 costimulation. CC {ECO:0000269|PubMed:10811224}. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Phosphorylated by TAOK2 (By similarity). Dually phosphorylated on CC Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme CC (PubMed:11562351). May be phosphorylated at Thr-183 and Tyr-185 by CC MAP3K1/MEKK1 (PubMed:17761173). Phosphorylated form is more CC concentrated at synapses than none-phosphorylated (By similarity). CC {ECO:0000250|UniProtKB:P45983, ECO:0000250|UniProtKB:P49185, CC ECO:0000269|PubMed:11562351, ECO:0000269|PubMed:17761173}. CC -!- DISRUPTION PHENOTYPE: At 14.5 dpc, brain intermediate zone and cortical CC plate are significantly thicker in mutant mice compared to wild type. CC The number of neuronal cells is increased in the cortical plate and CC intermediate zone. Cell cycle exit is decreased by 13% in the CC ventricular and subventricular zones. In 17.5 dpc brains, the CC ventricular zone was thinner in mutant mice compared to wild type CC animals, consistent with the increased number of neurons in the CC cortical plate. TUBB3 is consistently more diffuse and less structured CC in mutant telencephalon than in wild type. CC {ECO:0000269|PubMed:21297631}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. MAP kinase subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB005663; BAA85875.1; -; mRNA. DR CCDS; CCDS36869.1; -. DR RefSeq; NP_057909.1; NM_016700.4. DR AlphaFoldDB; Q91Y86; -. DR SMR; Q91Y86; -. DR BioGRID; 204971; 24. DR DIP; DIP-31075N; -. DR ELM; Q91Y86; -. DR IntAct; Q91Y86; 8. DR MINT; Q91Y86; -. DR BindingDB; Q91Y86; -. DR ChEMBL; CHEMBL1795174; -. DR iPTMnet; Q91Y86; -. DR PhosphoSitePlus; Q91Y86; -. DR MaxQB; Q91Y86; -. DR PaxDb; 10090-ENSMUSP00000107576; -. DR ProteomicsDB; 295946; -. DR Pumba; Q91Y86; -. DR Antibodypedia; 3846; 2034 antibodies from 47 providers. DR DNASU; 26419; -. DR Ensembl; ENSMUST00000111945.9; ENSMUSP00000107576.3; ENSMUSG00000021936.15. DR GeneID; 26419; -. DR KEGG; mmu:26419; -. DR UCSC; uc007szt.3; mouse. DR AGR; MGI:1346861; -. DR CTD; 5599; -. DR MGI; MGI:1346861; Mapk8. DR VEuPathDB; HostDB:ENSMUSG00000021936; -. DR eggNOG; KOG0665; Eukaryota. DR GeneTree; ENSGT00940000153692; -. DR InParanoid; Q91Y86; -. DR OrthoDB; 158564at2759; -. DR PhylomeDB; Q91Y86; -. DR TreeFam; TF105100; -. DR BRENDA; 2.7.11.24; 3474. DR Reactome; R-MMU-111446; Activation of BIM and translocation to mitochondria. DR Reactome; R-MMU-139910; Activation of BMF and translocation to mitochondria. DR Reactome; R-MMU-193648; NRAGE signals death through JNK. DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation. DR Reactome; R-MMU-376172; DSCAM interactions. DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-MMU-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-MMU-9007892; Interleukin-38 signaling. DR BioGRID-ORCS; 26419; 1 hit in 78 CRISPR screens. DR ChiTaRS; Mapk8; mouse. DR PRO; PR:Q91Y86; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; Q91Y86; Protein. DR Bgee; ENSMUSG00000021936; Expressed in animal zygote and 270 other cell types or tissues. DR ExpressionAtlas; Q91Y86; baseline and differential. DR GO; GO:0030424; C:axon; IMP:ARUK-UCL. DR GO; GO:0097441; C:basal dendrite; IMP:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0043204; C:perikaryon; ISO:MGI. DR GO; GO:0002102; C:podosome; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0031982; C:vesicle; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0035033; F:histone deacetylase regulator activity; ISO:MGI. DR GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB. DR GO; GO:0016301; F:kinase activity; IDA:MGI. DR GO; GO:0019894; F:kinesin binding; ISO:MGI. DR GO; GO:0004672; F:protein kinase activity; IDA:MGI. DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0120283; F:protein serine/threonine kinase binding; ISO:MGI. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; IGI:MGI. DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI. DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:MGI. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI. DR GO; GO:0071732; P:cellular response to nitric oxide; IMP:MGI. DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI. DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; ISO:MGI. DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:CACAO. DR GO; GO:0048263; P:determination of dorsal identity; ISO:MGI. DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:SynGO. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI. DR GO; GO:0001764; P:neuron migration; IMP:CACAO. DR GO; GO:0031175; P:neuron projection development; ISO:MGI. DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:MGI. DR GO; GO:0001503; P:ossification; IMP:MGI. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IGI:MGI. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:2000017; P:positive regulation of determination of dorsal identity; IDA:MGI. DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0034352; P:positive regulation of glial cell apoptotic process; ISO:MGI. DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISO:MGI. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:MGI. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI. DR GO; GO:2001224; P:positive regulation of neuron migration; ISO:MGI. DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0071803; P:positive regulation of podosome assembly; IMP:MGI. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB. DR GO; GO:0097300; P:programmed necrotic cell death; IMP:MGI. DR GO; GO:0061833; P:protein localization to tricellular tight junction; IMP:MGI. DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB. DR GO; GO:0046605; P:regulation of centrosome cycle; ISO:MGI. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:1904809; P:regulation of dense core granule transport; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:MGI. DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI. DR GO; GO:0046686; P:response to cadmium ion; IGI:MGI. DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI. DR GO; GO:0009612; P:response to mechanical stimulus; IBA:GO_Central. DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI. DR GO; GO:0009411; P:response to UV; ISO:MGI. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:MGI. DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:MGI. DR GO; GO:0097050; P:type B pancreatic cell apoptotic process; ISO:MGI. DR CDD; cd07850; STKc_JNK; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR008351; MAPK_JNK. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF222; MITOGEN-ACTIVATED PROTEIN KINASE 8; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01772; JNKMAPKINASE. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q91Y86; MM. PE 1: Evidence at protein level; KW ATP-binding; Biological rhythms; Cytoplasm; Kinase; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; S-nitrosylation; KW Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..384 FT /note="Mitogen-activated protein kinase 8" FT /id="PRO_0000186263" FT DOMAIN 26..321 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOTIF 183..185 FT /note="TXY" FT ACT_SITE 151 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 32..40 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 55 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 116 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P49185" FT MOD_RES 183 FT /note="Phosphothreonine; by MAP2K7" FT /evidence="ECO:0000269|PubMed:11562351" FT MOD_RES 185 FT /note="Phosphotyrosine; by MAP2K4" FT /evidence="ECO:0000269|PubMed:11562351" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747" SQ SEQUENCE 384 AA; 44229 MW; A7320EF933E9CF85 CRC64; MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV MDLEERTKNG VIRGQPSPLA QVQQ //