MK08_HUMAN
ID MK08_HUMAN Reviewed; 427 AA.
AC P45983; B5BTZ5; B7ZLV4; D3DX88; D3DX92; Q15709; Q15712; Q15713; Q308M2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 229.
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:10747973, ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:8654373};
DE AltName: Full=JNK-46;
DE AltName: Full=Stress-activated protein kinase 1c;
DE Short=SAPK1c;
DE AltName: Full=Stress-activated protein kinase JNK1;
DE AltName: Full=c-Jun N-terminal kinase 1;
GN Name=MAPK8; Synonyms=JNK1, PRKM8, SAPK1, SAPK1C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=8137421; DOI=10.1016/0092-8674(94)90380-8;
RA Derijard B., Hibi M., Wu I.-H., Barrett T., Su B., Deng T., Karin M.,
RA Davis R.J.;
RT "JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and
RT phosphorylates the c-Jun activation domain.";
RL Cell 76:1025-1037(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=8654373; DOI=10.1002/j.1460-2075.1996.tb00636.x;
RA Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., Derijard B.,
RA Davis R.J.;
RT "Selective interaction of JNK protein kinase isoforms with transcription
RT factors.";
RL EMBO J. 15:2760-2770(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M.,
RA Tang Z., Huang B., Li H., Yang S.;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP MUTAGENESIS OF THR-183 AND TYR-185.
RX PubMed=7839144; DOI=10.1126/science.7839144;
RA Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J.,
RA Davis R.J.;
RT "Independent human MAP-kinase signal transduction pathways defined by MEK
RT and MKK isoforms.";
RL Science 267:682-685(1995).
RN [9]
RP PHOSPHORYLATION AT THR-183 AND TYR-185, REGULATION BY MAP2K4 AND MAP2K7,
RP CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=11062067; DOI=10.1042/bj3520145;
RA Fleming Y., Armstrong C.G., Morrice N., Paterson A., Goedert M., Cohen P.;
RT "Synergistic activation of stress-activated protein kinase 1/c-Jun N-
RT terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase
RT kinase 4 (MKK4) and MKK7.";
RL Biochem. J. 352:145-154(2000).
RN [10]
RP INTERACTION WITH MECOM, AND CATALYTIC ACTIVITY.
RX PubMed=10856240; DOI=10.1093/emboj/19.12.2958;
RA Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S.,
RA Moriguchi T., Nishida E., Yazaki Y., Hirai H.;
RT "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents
RT stress-induced cell death.";
RL EMBO J. 19:2958-2968(2000).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF HSF1, CATALYTIC ACTIVITY, AND INTERACTION
RP WITH HSF1.
RX PubMed=10747973; DOI=10.1074/jbc.m000958200;
RA Dai R., Frejtag W., He B., Zhang Y., Mivechi N.F.;
RT "c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock
RT factor-1 suppress its transcriptional activity.";
RL J. Biol. Chem. 275:18210-18218(2000).
RN [12]
RP INTERACTION WITH WWOX AND TP53.
RX PubMed=12514174; DOI=10.1074/jbc.m208373200;
RA Chang N.-S., Doherty J., Ensign A.;
RT "JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1)
RT and inhibits WOX1-mediated apoptosis.";
RL J. Biol. Chem. 278:9195-9202(2003).
RN [13]
RP INTERACTION WITH SPAG9.
RX PubMed=15693750; DOI=10.1042/bj20041577;
RA Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., Herr J.C.,
RA Okumura K., Hasegawa A., Koyama K., Suri A.;
RT "Characterization of a novel human sperm-associated antigen 9 (SPAG9)
RT having structural homology with c-Jun N-terminal kinase-interacting
RT protein.";
RL Biochem. J. 389:73-82(2005).
RN [14]
RP FUNCTION, INTERACTION WITH HSF4, AND CATALYTIC ACTIVITY.
RX PubMed=16581800; DOI=10.1128/mcb.26.8.3282-3294.2006;
RA Hu Y., Mivechi N.F.;
RT "Association and regulation of heat shock transcription factor 4b with both
RT extracellular signal-regulated kinase mitogen-activated protein kinase and
RT dual-specificity tyrosine phosphatase DUSP26.";
RL Mol. Cell. Biol. 26:3282-3294(2006).
RN [15]
RP INTERACTION WITH NFATC4, AND CATALYTIC ACTIVITY.
RX PubMed=17875713; DOI=10.1158/0008-5472.can-06-4788;
RA Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y.,
RA Bode A.M., Dong Z.;
RT "Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1
RT induced cell transformation.";
RL Cancer Res. 67:8725-8735(2007).
RN [16]
RP INTERACTION WITH GRIPAP1, AND 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 [17]
RP PHOSPHORYLATION BY TAOK2.
RX PubMed=17158878; DOI=10.1074/jbc.m608336200;
RA Zihni C., Mitsopoulos C., Tavares I.A., Baum B., Ridley A.J., Morris J.D.;
RT "Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis.
RT JNK- and caspase-dependent nuclear localization is a requirement for
RT membrane blebbing.";
RL J. Biol. Chem. 282:6484-6493(2007).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF ELK1, AND CATALYTIC ACTIVITY.
RX PubMed=17296730; DOI=10.1128/mcb.02276-06;
RA Zhang L., Yang S.H., Sharrocks A.D.;
RT "Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to
RT activation of the transcription factor Elk-1.";
RL Mol. Cell. Biol. 27:2861-2869(2007).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF JDP2, AND CATALYTIC ACTIVITY.
RX PubMed=18307971; DOI=10.1016/j.ab.2008.01.038;
RA Murata T., Shinozuka Y., Obata Y., Yokoyama K.K.;
RT "Phosphorylation of two eukaryotic transcription factors, Jun dimerization
RT protein 2 and activation transcription factor 2, in Escherichia coli by Jun
RT N-terminal kinase 1.";
RL Anal. Biochem. 376:115-121(2008).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF BCL2.
RX PubMed=18570871; DOI=10.1016/j.molcel.2008.06.001;
RA Wei Y., Pattingre S., Sinha S., Bassik M., Levine B.;
RT "JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced
RT autophagy.";
RL Mol. Cell 30:678-688(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301 (ISOFORM 5), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP INTERACTION WITH SERPINB3, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19166818; DOI=10.1016/j.bbrc.2009.01.057;
RA Zheng B., Matoba Y., Kumagai T., Katagiri C., Hibino T., Sugiyama M.;
RT "Crystal structure of SCCA1 and insight about the interaction with JNK1.";
RL Biochem. Biophys. Res. Commun. 380:143-147(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301 (ISOFORM 5), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF SIRT1, AND CATALYTIC ACTIVITY.
RX PubMed=20027304; DOI=10.1371/journal.pone.0008414;
RA Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R.,
RA Bordone L.;
RT "JNK1 phosphorylates SIRT1 and promotes its enzymatic activity.";
RL PLoS ONE 4:E8414-E8414(2009).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF YAP1, AND CATALYTIC ACTIVITY.
RX PubMed=21364637; DOI=10.1038/cddis.2010.7;
RA Tomlinson V., Gudmundsdottir K., Luong P., Leung K.Y., Knebel A., Basu S.;
RT "JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis.";
RL Cell Death Dis. 1:E29-E29(2010).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP INTERACTION WITH PIN1, AND CATALYTIC ACTIVITY.
RX PubMed=21660049; DOI=10.1038/cdd.2011.82;
RA Park J.E., Lee J.A., Park S.G., Lee D.H., Kim S.J., Kim H.J., Uchida C.,
RA Uchida T., Park B.C., Cho S.;
RT "A critical step for JNK activation: isomerization by the prolyl isomerase
RT Pin1.";
RL Cell Death Differ. 19:153-161(2012).
RN [29]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [30]
RP FUNCTION IN PHOSPHORYLATION OF BAD, AND CATALYTIC ACTIVITY.
RX PubMed=21095239; DOI=10.1016/j.biocel.2010.11.011;
RA Deng H., Zhang J., Yoon T., Song D., Li D., Lin A.;
RT "Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-
RT activated c-Jun N-terminal protein kinase 1 contributes to survival of
RT erythropoietin-dependent cells.";
RL Int. J. Biochem. Cell Biol. 43:409-415(2011).
RN [31]
RP SUBCELLULAR LOCATION.
RX PubMed=21148294; DOI=10.1091/mbc.e10-06-0492;
RA Wang J., Tang R., Lv M., Wang Q., Zhang X., Guo Y., Chang H., Qiao C.,
RA Xiao H., Li X., Li Y., Shen B., Zhang J.;
RT "Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is
RT associated with resistance to Fas-mediated apoptosis.";
RL Mol. Biol. Cell 22:117-127(2011).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF CDT1, AND CATALYTIC ACTIVITY.
RX PubMed=21856198; DOI=10.1016/j.molcel.2011.06.021;
RA Miotto B., Struhl K.;
RT "JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone
RT acetylase and blocks replication licensing in response to stress.";
RL Mol. Cell 44:62-71(2011).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-55.
RX PubMed=22966201; DOI=10.1128/mcb.00544-12;
RA Cargnello M., Tcherkezian J., Dorn J.F., Huttlin E.L., Maddox P.S.,
RA Gygi S.P., Roux P.P.;
RT "Phosphorylation of the eukaryotic translation initiation factor 4E-
RT transporter (4E-T) by c-Jun N-terminal kinase promotes stress-dependent P-
RT body assembly.";
RL Mol. Cell. Biol. 32:4572-4584(2012).
RN [34]
RP FUNCTION.
RX PubMed=22327296; DOI=10.1038/nature10806;
RA Huang J., Gurung B., Wan B., Matkar S., Veniaminova N.A., Wan K.,
RA Merchant J.L., Hua X., Lei M.;
RT "The same pocket in menin binds both MLL and JUND but has opposite effects
RT on transcription.";
RL Nature 482:542-546(2012).
RN [35]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27568560; DOI=10.1016/j.celrep.2016.08.006;
RA Van Meter M., Simon M., Tombline G., May A., Morello T.D., Hubbard B.P.,
RA Bredbenner K., Park R., Sinclair D.A., Bohr V.A., Gorbunova V.,
RA Seluanov A.;
RT "JNK phosphorylates SIRT6 to stimulate DNA double-strand break repair in
RT response to oxidative stress by recruiting PARP1 to DNA Breaks.";
RL Cell Rep. 16:2641-2650(2016).
RN [36]
RP SUBCELLULAR LOCATION.
RX PubMed=30878395; DOI=10.1016/j.yjmcc.2019.03.005;
RA Li C., Li J., Xue K., Zhang J., Wang C., Zhang Q., Chen X., Gao C., Yu X.,
RA Sun L.;
RT "MicroRNA-143-3p promotes human cardiac fibrosis via targeting sprouty3
RT after myocardial infarction.";
RL J. Mol. Cell. Cardiol. 129:281-292(2019).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-363, AND CATALYTIC ACTIVITY.
RX PubMed=15141161; DOI=10.1038/sj.emboj.7600212;
RA Heo Y.S., Kim S.K., Seo C.I., Kim Y.K., Sung B.J., Lee H.S., Lee J.I.,
RA Park S.Y., Kim J.H., Hwang K.Y., Hyun Y.L., Jeon Y.H., Ro S., Cho J.M.,
RA Lee T.G., Yang C.H.;
RT "Structural basis for the selective inhibition of JNK1 by the scaffolding
RT protein JIP1 and SP600125.";
RL EMBO J. 23:2185-2195(2004).
RN [38]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-171 AND ARG-177.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as cell proliferation, differentiation, migration, transformation
CC and programmed cell death. Extracellular stimuli such as pro-
CC inflammatory cytokines or physical stress stimulate the stress-
CC activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling
CC pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and
CC MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1
CC phosphorylates a number of transcription factors, primarily components
CC of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1
CC transcriptional activity (PubMed:18307971). Phosphorylates the
CC replication licensing factor CDT1, inhibiting the interaction between
CC CDT1 and the histone H4 acetylase HBO1 to replication origins
CC (PubMed:21856198). Loss of this interaction abrogates the acetylation
CC required for replication initiation (PubMed:21856198). Promotes
CC stressed cell apoptosis by phosphorylating key regulatory factors
CC including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637).
CC In T-cells, MAPK8 and MAPK9 are required for polarized differentiation
CC of T-helper cells into Th1 cells. Contributes to the survival of
CC erythroid cells by phosphorylating the antagonist of cell death BAD
CC upon EPO stimulation (PubMed:21095239). Mediates starvation-induced
CC BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation
CC of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence
CC regulates microtubule dynamics, controlling neurite elongation in
CC cortical neurons (By similarity). 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 (By similarity). Phosphorylates several other substrates including heat
CC shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3
CC ligase ITCH (PubMed:20027304, PubMed:16581800, PubMed:17296730).
CC Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in
CC the regulation of the circadian clock (PubMed:22441692). Phosphorylates
CC the heat shock transcription factor HSF1, suppressing HSF1-induced
CC transcriptional activity (PubMed:10747973). Phosphorylates POU5F1,
CC which results in the inhibition of POU5F1's transcriptional activity
CC and enhances its proteosomal degradation (By similarity).
CC Phosphorylates JUND and this phosphorylation is inhibited in the
CC presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4
CC which captures neuronal dense core vesicles at synapses (By
CC similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative
CC stress, promoting P-body assembly (PubMed:22966201). Phosphorylates
CC SIRT6 in response to oxidative stress, stimulating its mono-ADP-
CC ribosyltransferase activity (PubMed:27568560).
CC {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86,
CC ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800,
CC ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971,
CC ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304,
CC ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637,
CC ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296,
CC ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201,
CC ECO:0000269|PubMed:27568560}.
CC -!- FUNCTION: JNK1 isoforms display different binding patterns: beta-1
CC preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2
CC have a similar low level of binding to both c-Jun or ATF2. However,
CC there is no correlation between binding and phosphorylation, which is
CC achieved at about the same efficiency by all isoforms.
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:10747973, ECO:0000269|PubMed:10856240,
CC ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:15141161,
CC ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730,
CC ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:18307971,
CC ECO:0000269|PubMed:19166818, ECO:0000269|PubMed:20027304,
CC ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637,
CC ECO:0000269|PubMed:21660049, ECO:0000269|PubMed:21856198,
CC ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201,
CC ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:8654373};
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:10747973,
CC ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:11062067,
CC ECO:0000269|PubMed:15141161, ECO:0000269|PubMed:16581800,
CC ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17875713,
CC ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:19166818,
CC ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239,
CC ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21660049,
CC ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22441692,
CC ECO:0000269|PubMed:8654373};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11062067};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by either of two dual specificity kinases, MAP2K4 and
CC MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7
CC phosphorylates Tyr-183 preferentially. Inhibited by dual specificity
CC phosphatases, such as DUSP1. Inhibited by SERPINB3.
CC {ECO:0000269|PubMed:19166818}.
CC -!- SUBUNIT: Forms a complex with MAPK8IP1 and ARHGEF28 (By similarity).
CC Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and
CC MAPK8IP1/JIP1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1,
CC MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 (By similarity). Binds to at
CC least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2,
CC MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 (PubMed:15693750). These
CC proteins also bind other components of the JNK signaling pathway.
CC Interacts with TP53 and WWOX (PubMed:12514174). Interacts with JAMP (By
CC similarity). Interacts with HSF1 (via D domain and preferentially with
CC hyperphosphorylated form); this interaction occurs under both normal
CC growth conditions and immediately upon heat shock (PubMed:10747973).
CC Interacts (phosphorylated form) with NFE2; the interaction
CC phosphorylates NFE2 in undifferentiated cells (By similarity).
CC Interacts with NFATC4 (PubMed:17875713). Interacts with MECOM;
CC regulates JNK signaling (PubMed:10856240). Interacts with PIN1; this
CC interaction mediates MAPK8 conformational changes leading to the
CC binding of MAPK8 to its substrates (PubMed:21660049). Interacts with
CC GRIPAP1 (PubMed:17761173). Interacts with POU5F1; phosphorylates POU5F1
CC at 'Ser-355'. Interacts with STMN2, STMN3 and STMN4 (By similarity).
CC Interacts with HSF4 (PubMed:16581800). {ECO:0000250|UniProtKB:P49185,
CC ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973,
CC ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:12514174,
CC ECO:0000269|PubMed:15693750, ECO:0000269|PubMed:16581800,
CC ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:17875713,
CC ECO:0000269|PubMed:19166818, ECO:0000269|PubMed:21660049}.
CC -!- INTERACTION:
CC P45983; P22681: CBL; NbExp=2; IntAct=EBI-286483, EBI-518228;
CC P45983; P16104: H2AX; NbExp=3; IntAct=EBI-286483, EBI-494830;
CC P45983; P05412: JUN; NbExp=5; IntAct=EBI-286483, EBI-852823;
CC P45983; P45985: MAP2K4; NbExp=2; IntAct=EBI-286483, EBI-447868;
CC P45983; O14733-2: MAP2K7; NbExp=3; IntAct=EBI-286483, EBI-492627;
CC P45983; Q9UQF2: MAPK8IP1; NbExp=7; IntAct=EBI-286483, EBI-78404;
CC P45983; P27986: PIK3R1; NbExp=6; IntAct=EBI-286483, EBI-79464;
CC P45983; Q8N122: RPTOR; NbExp=6; IntAct=EBI-286483, EBI-1567928;
CC P45983; Q9WVI9-1: Mapk8ip1; Xeno; NbExp=2; IntAct=EBI-286483, EBI-288461;
CC P45983-1; P05412: JUN; NbExp=2; IntAct=EBI-288687, EBI-852823;
CC P45983-4; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-18121963, EBI-3443946;
CC P45983-4; Q9BY84: DUSP16; NbExp=3; IntAct=EBI-18121963, EBI-3443956;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus
CC {ECO:0000269|PubMed:21148294, ECO:0000269|PubMed:30878395}. Synapse
CC {ECO:0000250|UniProtKB:P49185}. Note=In the cortical neurons,
CC predominantly cytoplasmic and associated with the Golgi apparatus and
CC endosomal fraction. Increased neuronal activity increases
CC phosphorylated form at synapses (By similarity). Colocalizes with
CC POU5F1 in the nucleus. {ECO:0000250|UniProtKB:P49185,
CC ECO:0000250|UniProtKB:Q91Y86}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2; Synonyms=JNK1-alpha-2;
CC IsoId=P45983-1; Sequence=Displayed;
CC Name=1; Synonyms=JNK1-alpha-1;
CC IsoId=P45983-2; Sequence=VSP_004833;
CC Name=3; Synonyms=JNK1-beta-1;
CC IsoId=P45983-3; Sequence=VSP_004831, VSP_004832, VSP_004833;
CC Name=4; Synonyms=JNK1-beta-2;
CC IsoId=P45983-4; Sequence=VSP_004831, VSP_004832;
CC Name=5;
CC IsoId=P45983-5; Sequence=VSP_054554, VSP_004833;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4,
CC which activates the enzyme (PubMed:11062067). Phosphorylated by TAOK2
CC (PubMed:17158878). 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:P49185, ECO:0000269|PubMed:11062067,
CC ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17761173}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/JNK1ID196.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=C-Jun N-terminal kinases entry;
CC URL="https://en.wikipedia.org/wiki/C-Jun_N-terminal_kinases";
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DR EMBL; L26318; AAA36131.1; -; mRNA.
DR EMBL; U34822; AAC50607.1; -; mRNA.
DR EMBL; U35004; AAC50610.1; -; mRNA.
DR EMBL; U35005; AAC50611.1; -; mRNA.
DR EMBL; DQ234352; ABB29981.1; -; mRNA.
DR EMBL; AC016397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB451231; BAG70045.1; -; mRNA.
DR EMBL; CH471187; EAW93132.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93129.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93130.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93133.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93134.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93136.1; -; Genomic_DNA.
DR EMBL; BC144063; AAI44064.1; -; mRNA.
DR CCDS; CCDS60527.1; -. [P45983-5]
DR CCDS; CCDS7223.1; -. [P45983-4]
DR CCDS; CCDS7224.1; -. [P45983-1]
DR CCDS; CCDS7225.1; -. [P45983-2]
DR CCDS; CCDS7226.1; -. [P45983-3]
DR PIR; S71097; S71097.
DR PIR; S71099; S71099.
DR RefSeq; NP_001265476.1; NM_001278547.1. [P45983-4]
DR RefSeq; NP_001265477.1; NM_001278548.1. [P45983-5]
DR RefSeq; NP_001310231.1; NM_001323302.1. [P45983-2]
DR RefSeq; NP_001310250.1; NM_001323321.1. [P45983-3]
DR RefSeq; NP_001310251.1; NM_001323322.1. [P45983-4]
DR RefSeq; NP_001310252.1; NM_001323323.1. [P45983-4]
DR RefSeq; NP_001310253.1; NM_001323324.1. [P45983-2]
DR RefSeq; NP_001310254.1; NM_001323325.1. [P45983-3]
DR RefSeq; NP_001310255.1; NM_001323326.1. [P45983-2]
DR RefSeq; NP_001310256.1; NM_001323327.1. [P45983-2]
DR RefSeq; NP_001310257.1; NM_001323328.1. [P45983-1]
DR RefSeq; NP_001310258.1; NM_001323329.1. [P45983-1]
DR RefSeq; NP_001310259.1; NM_001323330.1. [P45983-4]
DR RefSeq; NP_001310260.1; NM_001323331.1. [P45983-1]
DR RefSeq; NP_620634.1; NM_139046.3. [P45983-3]
DR RefSeq; NP_620637.1; NM_139049.3. [P45983-1]
DR PDB; 1UKH; X-ray; 2.35 A; A=1-363.
DR PDB; 1UKI; X-ray; 2.70 A; A=1-363.
DR PDB; 2G01; X-ray; 3.50 A; A/B=1-364.
DR PDB; 2GMX; X-ray; 3.50 A; A/B=1-364.
DR PDB; 2H96; X-ray; 3.00 A; A/B=1-364.
DR PDB; 2NO3; X-ray; 3.20 A; A/B=1-364.
DR PDB; 2XRW; X-ray; 1.33 A; A=2-364.
DR PDB; 2XS0; X-ray; 2.60 A; A=1-379.
DR PDB; 3ELJ; X-ray; 1.80 A; A=1-364.
DR PDB; 3O17; X-ray; 3.00 A; A/B=1-364.
DR PDB; 3O2M; X-ray; 2.70 A; A/B=1-364.
DR PDB; 3PZE; X-ray; 2.00 A; A=7-364.
DR PDB; 3V3V; X-ray; 2.70 A; A=1-366.
DR PDB; 3VUD; X-ray; 3.50 A; A=1-364.
DR PDB; 3VUG; X-ray; 3.24 A; A=1-364.
DR PDB; 3VUH; X-ray; 2.70 A; A=1-364.
DR PDB; 3VUI; X-ray; 2.80 A; A=1-364.
DR PDB; 3VUK; X-ray; 2.95 A; A=1-364.
DR PDB; 3VUL; X-ray; 2.81 A; A=1-364.
DR PDB; 3VUM; X-ray; 2.69 A; A=1-364.
DR PDB; 4AWI; X-ray; 1.91 A; A=1-364.
DR PDB; 4E73; X-ray; 2.27 A; A=1-363.
DR PDB; 4G1W; X-ray; 2.45 A; A=1-363.
DR PDB; 4HYS; X-ray; 2.42 A; A=1-363.
DR PDB; 4HYU; X-ray; 2.15 A; A=1-363.
DR PDB; 4IZY; X-ray; 2.30 A; A=1-363.
DR PDB; 4L7F; X-ray; 1.95 A; A=7-362.
DR PDB; 4QTD; X-ray; 1.50 A; A=1-363.
DR PDB; 4UX9; X-ray; 2.34 A; A/B/C/D=1-364.
DR PDB; 4YR8; X-ray; 2.40 A; A/C/E/F=1-363.
DR PDB; 5LW1; X-ray; 3.20 A; B/E/H=2-363.
DR PDB; 6F5E; X-ray; 2.70 A; B=2-363.
DR PDB; 6ZR5; X-ray; 2.70 A; A/B=1-364.
DR PDBsum; 1UKH; -.
DR PDBsum; 1UKI; -.
DR PDBsum; 2G01; -.
DR PDBsum; 2GMX; -.
DR PDBsum; 2H96; -.
DR PDBsum; 2NO3; -.
DR PDBsum; 2XRW; -.
DR PDBsum; 2XS0; -.
DR PDBsum; 3ELJ; -.
DR PDBsum; 3O17; -.
DR PDBsum; 3O2M; -.
DR PDBsum; 3PZE; -.
DR PDBsum; 3V3V; -.
DR PDBsum; 3VUD; -.
DR PDBsum; 3VUG; -.
DR PDBsum; 3VUH; -.
DR PDBsum; 3VUI; -.
DR PDBsum; 3VUK; -.
DR PDBsum; 3VUL; -.
DR PDBsum; 3VUM; -.
DR PDBsum; 4AWI; -.
DR PDBsum; 4E73; -.
DR PDBsum; 4G1W; -.
DR PDBsum; 4HYS; -.
DR PDBsum; 4HYU; -.
DR PDBsum; 4IZY; -.
DR PDBsum; 4L7F; -.
DR PDBsum; 4QTD; -.
DR PDBsum; 4UX9; -.
DR PDBsum; 4YR8; -.
DR PDBsum; 5LW1; -.
DR PDBsum; 6F5E; -.
DR PDBsum; 6ZR5; -.
DR AlphaFoldDB; P45983; -.
DR SMR; P45983; -.
DR BioGRID; 111585; 222.
DR DIP; DIP-249N; -.
DR ELM; P45983; -.
DR IntAct; P45983; 113.
DR MINT; P45983; -.
DR STRING; 9606.ENSP00000378974; -.
DR BindingDB; P45983; -.
DR ChEMBL; CHEMBL2276; -.
DR DrugBank; DB07268; 2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)BENZAMIDE.
DR DrugBank; DB07845; 2-fluoro-6-{[2-({2-methoxy-4-[(methylsulfonyl)methyl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide.
DR DrugBank; DB07276; 5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXYPYRIDINE-2-CARBOXAMIDE.
DR DrugBank; DB07218; 6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHYDRO-4H-PYRAZOLO[3,4-B]QUINOLIN-4-ONE.
DR DrugBank; DB15624; Halicin.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB07272; N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE.
DR DrugBank; DB01782; Pyrazolanthrone.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; P45983; -.
DR GuidetoPHARMACOLOGY; 1496; -.
DR iPTMnet; P45983; -.
DR PhosphoSitePlus; P45983; -.
DR BioMuta; MAPK8; -.
DR DMDM; 2507195; -.
DR CPTAC; CPTAC-889; -.
DR CPTAC; CPTAC-890; -.
DR CPTAC; CPTAC-891; -.
DR CPTAC; CPTAC-892; -.
DR EPD; P45983; -.
DR jPOST; P45983; -.
DR MassIVE; P45983; -.
DR MaxQB; P45983; -.
DR PaxDb; P45983; -.
DR PeptideAtlas; P45983; -.
DR PRIDE; P45983; -.
DR ProteomicsDB; 55694; -. [P45983-1]
DR ProteomicsDB; 55695; -. [P45983-2]
DR ProteomicsDB; 55696; -. [P45983-3]
DR ProteomicsDB; 55697; -. [P45983-4]
DR ProteomicsDB; 61569; -.
DR Antibodypedia; 3846; 1695 antibodies from 47 providers.
DR CPTC; P45983; 1 antibody.
DR DNASU; 5599; -.
DR Ensembl; ENST00000360332.7; ENSP00000353483.4; ENSG00000107643.17. [P45983-5]
DR Ensembl; ENST00000374176.8; ENSP00000363291.4; ENSG00000107643.17. [P45983-4]
DR Ensembl; ENST00000374179.8; ENSP00000363294.3; ENSG00000107643.17. [P45983-3]
DR Ensembl; ENST00000374182.7; ENSP00000363297.3; ENSG00000107643.17. [P45983-2]
DR Ensembl; ENST00000374189.6; ENSP00000363304.1; ENSG00000107643.17. [P45983-1]
DR Ensembl; ENST00000395611.7; ENSP00000378974.4; ENSG00000107643.17. [P45983-4]
DR GeneID; 5599; -.
DR KEGG; hsa:5599; -.
DR MANE-Select; ENST00000374189.6; ENSP00000363304.1; NM_001323329.2; NP_001310258.1.
DR UCSC; uc001jgm.5; human. [P45983-1]
DR CTD; 5599; -.
DR DisGeNET; 5599; -.
DR GeneCards; MAPK8; -.
DR HGNC; HGNC:6881; MAPK8.
DR HPA; ENSG00000107643; Low tissue specificity.
DR MIM; 601158; gene.
DR neXtProt; NX_P45983; -.
DR OpenTargets; ENSG00000107643; -.
DR PharmGKB; PA283; -.
DR VEuPathDB; HostDB:ENSG00000107643; -.
DR eggNOG; KOG0665; Eukaryota.
DR GeneTree; ENSGT00940000153692; -.
DR InParanoid; P45983; -.
DR OMA; HADSEHN; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P45983; -.
DR TreeFam; TF105100; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; P45983; -.
DR Reactome; R-HSA-111446; Activation of BIM and translocation to mitochondria.
DR Reactome; R-HSA-139910; Activation of BMF and translocation to mitochondria.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-376172; DSCAM interactions.
DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-9007892; Interleukin-38 signaling.
DR Reactome; R-HSA-9673324; WNT5:FZD7-mediated leishmania damping.
DR SignaLink; P45983; -.
DR SIGNOR; P45983; -.
DR BioGRID-ORCS; 5599; 21 hits in 1118 CRISPR screens.
DR ChiTaRS; MAPK8; human.
DR EvolutionaryTrace; P45983; -.
DR GeneWiki; MAPK8; -.
DR GenomeRNAi; 5599; -.
DR Pharos; P45983; Tchem.
DR PRO; PR:P45983; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P45983; protein.
DR Bgee; ENSG00000107643; Expressed in cortical plate and 181 other tissues.
DR ExpressionAtlas; P45983; baseline and differential.
DR Genevisible; P45983; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0097441; C:basal dendrite; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR GO; GO:0035033; F:histone deacetylase regulator activity; IMP:BHF-UCL.
DR GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
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; IPI:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:CAFA.
DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA.
DR GO; GO:0090398; P:cellular senescence; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0007258; P:JUN phosphorylation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0031343; P:positive regulation of cell killing; TAS:Reactome.
DR GO; GO:0031281; P:positive regulation of cyclase activity; IMP:CACAO.
DR GO; GO:0090045; P:positive regulation of deacetylase activity; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:CACAO.
DR GO; GO:0006468; P:protein phosphorylation; IDA:CAFA.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:1902595; P:regulation of DNA replication origin binding; IMP:CAFA.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; TAS:Reactome.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032880; P:regulation of protein localization; IDA:BHF-UCL.
DR GO; GO:0009612; P:response to mechanical stimulus; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:CAFA.
DR IDEAL; IID00270; -.
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 Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01772; JNKMAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Biological rhythms;
KW Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; S-nitrosylation; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..427
FT /note="Mitogen-activated protein kinase 8"
FT /id="PRO_0000186262"
FT DOMAIN 26..321
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 371..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 183..185
FT /note="TXY"
FT COMPBIAS 381..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:11062067"
FT MOD_RES 185
FT /note="Phosphotyrosine; by MAP2K4"
FT /evidence="ECO:0000269|PubMed:11062067"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Y86"
FT VAR_SEQ 206..281
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_054554"
FT VAR_SEQ 208
FT /note="L -> I (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004831"
FT VAR_SEQ 219..230
FT /note="VCHKILFPGRDY -> IKGGVLFPGTDH (in isoform 3 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004832"
FT VAR_SEQ 380..427
FT /note="GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR ->
FT AQVQQ (in isoform 1, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:19054851, ECO:0000303|Ref.3"
FT /id="VSP_004833"
FT VARIANT 171
FT /note="G -> S (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042258"
FT VARIANT 177
FT /note="G -> R (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042259"
FT VARIANT 365
FT /note="E -> K (in dbSNP:rs45483593)"
FT /id="VAR_050592"
FT MUTAGEN 55
FT /note="K->D: Abolished protein kinase activity."
FT /evidence="ECO:0000269|PubMed:22966201"
FT MUTAGEN 183
FT /note="T->A: Phosphorylation blocked."
FT /evidence="ECO:0000269|PubMed:7839144"
FT MUTAGEN 185
FT /note="Y->F: Phosphorylation blocked."
FT /evidence="ECO:0000269|PubMed:7839144"
FT HELIX 4..9
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 10..15
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 26..34
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 36..45
FT /evidence="ECO:0007829|PDB:2XRW"
FT TURN 46..49
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4QTD"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:2GMX"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:3VUM"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 115..120
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 125..144
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:2XRW"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:2H96"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:2XRW"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:3O2M"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:2NO3"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3ELJ"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:2G01"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3PZE"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 206..220
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 230..241
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 254..261
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 285..301
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 312..317
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 319..322
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:2XRW"
FT TURN 339..342
FT /evidence="ECO:0007829|PDB:2XRW"
FT HELIX 349..363
FT /evidence="ECO:0007829|PDB:2XRW"
FT MOD_RES P45983-2:377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES P45983-3:377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES P45983-5:301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
SQ SEQUENCE 427 AA; 48296 MW; 94FB6BE0358B9B60 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 VIRGQPSPLG AAVINGSQHP SSSSSVNDVS SMSTDPTLAS DTDSSLEAAA
GPLGCCR
