MK09_HUMAN
ID MK09_HUMAN Reviewed; 424 AA.
AC P45984; A8K0S3; B5BU66; B5M0B4; D3DWQ8; D3DWQ9; Q15708; Q15710; Q15711;
AC Q8N5C5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Mitogen-activated protein kinase 9;
DE Short=MAP kinase 9;
DE Short=MAPK 9;
DE EC=2.7.11.24 {ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:21110917, ECO:0000269|PubMed:7969172, ECO:0000269|PubMed:8001819, ECO:0000269|PubMed:8654373};
DE AltName: Full=JNK-55;
DE AltName: Full=Stress-activated protein kinase 1a;
DE Short=SAPK1a;
DE AltName: Full=Stress-activated protein kinase JNK2;
DE AltName: Full=c-Jun N-terminal kinase 2;
GN Name=MAPK9; Synonyms=JNK2, PRKM9, SAPK1A;
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], AND CATALYTIC ACTIVITY.
RX PubMed=7969172; DOI=10.1128/mcb.14.12.8376-8384.1994;
RA Sluss H.K., Barrett T., Derijard B., Davis R.J.;
RT "Signal transduction by tumor necrosis factor mediated by JNK protein
RT kinases.";
RL Mol. Cell. Biol. 14:8376-8384(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RX PubMed=8001819; DOI=10.1101/gad.8.24.2996;
RA Kallunki T., Su B., Tsigelny I., Sluss H.K., Derijard B., Moore G.,
RA Davis R., Karin M.;
RT "JNK2 contains a specificity-determining region responsible for efficient
RT c-Jun binding and phosphorylation.";
RL Genes Dev. 8:2996-3007(1994).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND CATALYTIC ACTIVITY.
RX PubMed=21110917; DOI=10.5483/bmbrep.2010.43.11.738;
RA Wang P., Xiong Y., Ma C., Shi T., Ma D.;
RT "Molecular cloning and characterization of novel human JNK2 (MAPK9)
RT transcript variants that show different stimulation activities on AP-1.";
RL BMB Rep. 43:738-743(2010).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-268.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-2).
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [12]
RP INTERACTION WITH ATF7, AND FUNCTION.
RX PubMed=10376527; DOI=10.1038/sj.onc.1202723;
RA De Graeve F., Bahr A., Sabapathy K.T., Hauss C., Wagner E.F., Kedinger C.,
RA Chatton B.;
RT "Role of the ATFa/JNK2 complex in Jun activation.";
RL Oncogene 18:3491-3500(1999).
RN [13]
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 [14]
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 [15]
RP FUNCTION IN PHOSPHORYLATION OF RRN3, AND CATALYTIC ACTIVITY.
RX PubMed=15805466; DOI=10.1101/gad.333205;
RA Mayer C., Bierhoff H., Grummt I.;
RT "The nucleolus as a stress sensor: JNK2 inactivates the transcription
RT factor TIF-IA and down-regulates rRNA synthesis.";
RL Genes Dev. 19:933-941(2005).
RN [16]
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 [17]
RP INTERACTION WITH BCL10, AND CATALYTIC ACTIVITY.
RX PubMed=17189706; DOI=10.1016/j.immuni.2006.11.008;
RA Blonska M., Pappu B.P., Matsumoto R., Li H., Su B., Wang D., Lin X.;
RT "The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in
RT the T cell receptor-signaling pathway.";
RL Immunity 26:55-66(2007).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF TP53, AND CATALYTIC ACTIVITY.
RX PubMed=17525747; DOI=10.1038/sj.onc.1210526;
RA Oleinik N.V., Krupenko N.I., Krupenko S.A.;
RT "Cooperation between JNK1 and JNK2 in activation of p53 apoptotic
RT pathway.";
RL Oncogene 26:7222-7230(2007).
RN [19]
RP REVIEW ON FUNCTION.
RX PubMed=19290929; DOI=10.1111/j.1600-065x.2008.00749.x;
RA Blonska M., Lin X.;
RT "CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.";
RL Immunol. Rev. 228:199-211(2009).
RN [20]
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 [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CTNNB1.
RX PubMed=19675674; DOI=10.1371/journal.pone.0006640;
RA Hu D., Bi X., Fang W., Han A., Yang W.;
RT "GSK3beta is involved in JNK2-mediated beta-catenin inhibition.";
RL PLoS ONE 4:E6640-E6640(2009).
RN [22]
RP FUNCTION.
RX PubMed=20595622; DOI=10.1152/ajpgi.00265.2010;
RA Samak G., Suzuki T., Bhargava A., Rao R.K.;
RT "c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction
RT disruption in the intestinal epithelium.";
RL Am. J. Physiol. 299:G572-G584(2010).
RN [23]
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 [24]
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 [25]
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 [26]
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 7-362.
RX PubMed=18801372; DOI=10.1016/j.jmb.2008.08.086;
RA Shaw D., Wang S.M., Villasenor A.G., Tsing S., Walter D., Browner M.F.,
RA Barnett J., Kuglstatter A.;
RT "The crystal structure of JNK2 reveals conformational flexibility in the
RT MAP kinase insert and indicates its involvement in the regulation of
RT catalytic activity.";
RL J. Mol. Biol. 383:885-893(2008).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-13; ASN-56; THR-246 AND ILE-366.
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).
RN [28]
RP INTERACTION WITH MAPKBP1.
RX PubMed=28089251; DOI=10.1016/j.ajhg.2016.12.011;
RA Macia M.S., Halbritter J., Delous M., Bredrup C., Gutter A., Filhol E.,
RA Mellgren A.E., Leh S., Bizet A., Braun D.A., Gee H.Y., Silbermann F.,
RA Henry C., Krug P., Bole-Feysot C., Nitschke P., Joly D., Nicoud P.,
RA Paget A., Haugland H., Brackmann D., Ahmet N., Sandford R., Cengiz N.,
RA Knappskog P.M., Boman H., Linghu B., Yang F., Oakeley E.J.,
RA Saint Mezard P., Sailer A.W., Johansson S., Roedahl E., Saunier S.,
RA Hildebrandt F., Benmerah A.;
RT "Mutations in MAPKBP1 cause juvenile or late-onset cilia-independent
RT nephronophthisis.";
RL Am. J. Hum. Genet. 100:323-333(2017).
RN [29]
RP ERRATUM OF PUBMED:28089251.
RX PubMed=28157543; DOI=10.1016/j.ajhg.2017.01.025;
RA Macia M.S., Halbritter J., Delous M., Bredrup C., Gutter A., Filhol E.,
RA Mellgren A.E., Leh S., Bizet A., Braun D.A., Gee H.Y., Silbermann F.,
RA Henry C., Krug P., Bole-Feysot C., Nitschke P., Joly D., Nicoud P.,
RA Paget A., Haugland H., Brackmann D., Ahmet N., Sandford R., Cengiz N.,
RA Knappskog P.M., Boman H., Linghu B., Yang F., Oakeley E.J.,
RA Saint Mezard P., Sailer A.W., Johansson S., Roedahl E., Saunier S.,
RA Hildebrandt F., Benmerah A.;
RL Am. J. Hum. Genet. 100:372-372(2017).
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 MAPK9/JNK2. In turn, MAPK9/JNK2
CC phosphorylates a number of transcription factors, primarily components
CC of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional
CC activity. In response to oxidative or ribotoxic stresses, inhibits rRNA
CC synthesis by phosphorylating and inactivating the RNA polymerase 1-
CC specific transcription initiation factor RRN3. Promotes stressed cell
CC apoptosis by phosphorylating key regulatory factors including TP53 and
CC YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized
CC differentiation of T-helper cells into Th1 cells. Upon T-cell receptor
CC (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and
CC MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in
CC the osmotic stress-induced epithelial tight-junctions disruption. When
CC activated, promotes beta-catenin/CTNNB1 degradation and inhibits the
CC canonical Wnt signaling pathway. Participates also in neurite growth in
CC spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1
CC heterodimer and plays a role in the regulation of the circadian clock
CC (PubMed:22441692). Phosphorylates POU5F1, which results in the
CC inhibition of POU5F1's transcriptional activity and enhances its
CC proteosomal degradation (By similarity). {ECO:0000250|UniProtKB:Q9WTU6,
CC ECO:0000269|PubMed:22441692}.
CC -!- FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1
CC and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind
CC to ATF2. However, there is no correlation between binding and
CC phosphorylation, which is achieved at about the same efficiency by all
CC isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only
CC weakly to it.
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:11062067, ECO:0000269|PubMed:15805466,
CC ECO:0000269|PubMed:17189706, ECO:0000269|PubMed:17525747,
CC ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:21110917,
CC ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:22441692,
CC ECO:0000269|PubMed:7969172, ECO:0000269|PubMed:8001819,
CC 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:11062067,
CC ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17189706,
CC ECO:0000269|PubMed:17525747, ECO:0000269|PubMed:17875713,
CC ECO:0000269|PubMed:21110917, ECO:0000269|PubMed:21364637,
CC ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:7969172,
CC ECO:0000269|PubMed:8001819, 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. {ECO:0000269|PubMed:11062067}.
CC -!- SUBUNIT: Interacts with MECOM (By similarity). Interacts with DCLK2 (By
CC similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-
CC 1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These
CC proteins also bind other components of the JNK signaling pathway (By
CC similarity). Interacts with NFATC4 (PubMed:17875713). Interacts with
CC ATF7; the interaction does not phosphorylate ATF7 but acts as a docking
CC site for ATF7-associated partners such as JUN (PubMed:10376527).
CC Interacts with BCL10 (PubMed:17189706). Interacts with CTNNB1 and GSK3B
CC (PubMed:19675674). Interacts with MAPKBP1 (PubMed:28089251). Interacts
CC with POU5F1; phosphorylates POU5F1 at 'Ser-355'. Found in a complex
CC with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and
CC MAPK8/JNK1 (By similarity). {ECO:0000250|UniProtKB:P49186,
CC ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10376527,
CC ECO:0000269|PubMed:17189706, ECO:0000269|PubMed:17875713,
CC ECO:0000269|PubMed:19675674, ECO:0000269|PubMed:28089251}.
CC -!- INTERACTION:
CC P45984; P49407: ARRB1; NbExp=9; IntAct=EBI-713568, EBI-743313;
CC P45984; P32121: ARRB2; NbExp=9; IntAct=EBI-713568, EBI-714559;
CC P45984; P15336: ATF2; NbExp=9; IntAct=EBI-713568, EBI-1170906;
CC P45984; P0C671: BNIP5; NbExp=3; IntAct=EBI-713568, EBI-12806802;
CC P45984; O95561: C1orf105; NbExp=5; IntAct=EBI-713568, EBI-10191951;
CC P45984; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-713568, EBI-946029;
CC P45984; Q8N7E2: CBLL2; NbExp=3; IntAct=EBI-713568, EBI-12196065;
CC P45984; Q13042: CDC16; NbExp=3; IntAct=EBI-713568, EBI-994830;
CC P45984; Q9C0F1: CEP44; NbExp=9; IntAct=EBI-713568, EBI-744115;
CC P45984; Q13363-2: CTBP1; NbExp=3; IntAct=EBI-713568, EBI-10171858;
CC P45984; O43602-2: DCX; NbExp=3; IntAct=EBI-713568, EBI-14148644;
CC P45984; Q8N9I9: DTX3; NbExp=3; IntAct=EBI-713568, EBI-2340258;
CC P45984; Q9Y6W6: DUSP10; NbExp=5; IntAct=EBI-713568, EBI-3443946;
CC P45984; Q9BY84: DUSP16; NbExp=7; IntAct=EBI-713568, EBI-3443956;
CC P45984; Q13115: DUSP4; NbExp=4; IntAct=EBI-713568, EBI-6591081;
CC P45984; Q5JST6: EFHC2; NbExp=7; IntAct=EBI-713568, EBI-2349927;
CC P45984; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-713568, EBI-744099;
CC P45984; P14136: GFAP; NbExp=3; IntAct=EBI-713568, EBI-744302;
CC P45984; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-713568, EBI-11163335;
CC P45984; O15499: GSC2; NbExp=3; IntAct=EBI-713568, EBI-19954058;
CC P45984; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-713568, EBI-8638439;
CC P45984; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-713568, EBI-712105;
CC P45984; Q9P2G9-2: KLHL8; NbExp=3; IntAct=EBI-713568, EBI-11959635;
CC P45984; O00505: KPNA3; NbExp=3; IntAct=EBI-713568, EBI-358297;
CC P45984; Q96JM7: L3MBTL3; NbExp=3; IntAct=EBI-713568, EBI-2686809;
CC P45984; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-713568, EBI-11985629;
CC P45984; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-713568, EBI-12039345;
CC P45984; Q8TBB1: LNX1; NbExp=7; IntAct=EBI-713568, EBI-739832;
CC P45984; Q8N448: LNX2; NbExp=3; IntAct=EBI-713568, EBI-2340947;
CC P45984; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-713568, EBI-1216080;
CC P45984; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-713568, EBI-348259;
CC P45984; Q86YW9: MED12L; NbExp=3; IntAct=EBI-713568, EBI-3957138;
CC P45984; P50221: MEOX1; NbExp=7; IntAct=EBI-713568, EBI-2864512;
CC P45984; Q5VWP3-2: MLIP; NbExp=5; IntAct=EBI-713568, EBI-12320785;
CC P45984; Q5HYW2: NHSL2; NbExp=5; IntAct=EBI-713568, EBI-2859639;
CC P45984; Q02548: PAX5; NbExp=3; IntAct=EBI-713568, EBI-296331;
CC P45984; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-713568, EBI-10302990;
CC P45984; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-713568, EBI-79165;
CC P45984; P78424: POU6F2; NbExp=3; IntAct=EBI-713568, EBI-12029004;
CC P45984; P37231: PPARG; NbExp=3; IntAct=EBI-713568, EBI-781384;
CC P45984; Q96S79: RASL10B; NbExp=3; IntAct=EBI-713568, EBI-3919507;
CC P45984; Q2I0M5: RSPO4; NbExp=3; IntAct=EBI-713568, EBI-12821217;
CC P45984; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-713568, EBI-3957636;
CC P45984; O00560: SDCBP; NbExp=3; IntAct=EBI-713568, EBI-727004;
CC P45984; Q15427: SF3B4; NbExp=7; IntAct=EBI-713568, EBI-348469;
CC P45984; P34896: SHMT1; NbExp=7; IntAct=EBI-713568, EBI-715117;
CC P45984; A2RU48: SMCO3; NbExp=6; IntAct=EBI-713568, EBI-10173195;
CC P45984; P40763: STAT3; NbExp=2; IntAct=EBI-713568, EBI-518675;
CC P45984; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-713568, EBI-3923210;
CC P45984; Q8IYF3: TEX11; NbExp=3; IntAct=EBI-713568, EBI-742397;
CC P45984; Q8IYF3-3: TEX11; NbExp=3; IntAct=EBI-713568, EBI-11523345;
CC P45984; O43379: WDR62; NbExp=5; IntAct=EBI-713568, EBI-714790;
CC P45984; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-713568, EBI-14104088;
CC P45984; P52744: ZNF138; NbExp=3; IntAct=EBI-713568, EBI-10746567;
CC P45984; Q9BR84: ZNF559; NbExp=3; IntAct=EBI-713568, EBI-746605;
CC P45984; O43257: ZNHIT1; NbExp=3; IntAct=EBI-713568, EBI-347522;
CC P45984-1; P40763: STAT3; NbExp=3; IntAct=EBI-713586, EBI-518675;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19675674}. Nucleus
CC {ECO:0000269|PubMed:19675674}. Note=Colocalizes with POU5F1 in the
CC nucleus. {ECO:0000250|UniProtKB:Q9WTU6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=Alpha-2;
CC IsoId=P45984-1; Sequence=Displayed;
CC Name=Alpha-1;
CC IsoId=P45984-2; Sequence=VSP_004835;
CC Name=Beta-1;
CC IsoId=P45984-3; Sequence=VSP_004834, VSP_004835;
CC Name=Beta-2;
CC IsoId=P45984-4; Sequence=VSP_004834;
CC Name=5;
CC IsoId=P45984-5; Sequence=VSP_041908, VSP_041909;
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. Autophosphorylated in vitro.
CC {ECO:0000269|PubMed:11062067}.
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/JNK2ID426.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mapk9/";
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DR EMBL; L31951; AAA56831.1; -; mRNA.
DR EMBL; U09759; AAA74740.1; -; mRNA.
DR EMBL; U34821; AAC50606.1; -; mRNA.
DR EMBL; U35002; AAC50608.1; -; mRNA.
DR EMBL; U35003; AAC50609.1; -; mRNA.
DR EMBL; EU927388; ACH57450.1; -; mRNA.
DR EMBL; CR536580; CAG38817.1; -; mRNA.
DR EMBL; AK289638; BAF82327.1; -; mRNA.
DR EMBL; DQ066599; AAY46156.1; -; Genomic_DNA.
DR EMBL; AB451302; BAG70116.1; -; mRNA.
DR EMBL; AB451355; BAG70169.1; -; mRNA.
DR EMBL; AC008610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471165; EAW53759.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53757.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53758.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53762.1; -; Genomic_DNA.
DR EMBL; BC032539; AAH32539.1; -; mRNA.
DR CCDS; CCDS43409.1; -. [P45984-2]
DR CCDS; CCDS43410.1; -. [P45984-3]
DR CCDS; CCDS4453.1; -. [P45984-1]
DR CCDS; CCDS4454.1; -. [P45984-4]
DR CCDS; CCDS47356.1; -. [P45984-5]
DR PIR; A55480; A55480.
DR PIR; S71102; S71102.
DR RefSeq; NP_001128516.1; NM_001135044.1. [P45984-5]
DR RefSeq; NP_001295173.1; NM_001308244.1.
DR RefSeq; NP_002743.3; NM_002752.4. [P45984-1]
DR RefSeq; NP_620707.1; NM_139068.2. [P45984-2]
DR RefSeq; NP_620708.1; NM_139069.2. [P45984-3]
DR RefSeq; NP_620709.1; NM_139070.2. [P45984-4]
DR RefSeq; XP_006714954.1; XM_006714891.2.
DR RefSeq; XP_016865127.1; XM_017009638.1.
DR RefSeq; XP_016865130.1; XM_017009641.1.
DR PDB; 3E7O; X-ray; 2.14 A; A/B=7-362.
DR PDB; 3NPC; X-ray; 2.35 A; A/B=1-364.
DR PDB; 7CML; X-ray; 2.15 A; A/B=1-364.
DR PDBsum; 3E7O; -.
DR PDBsum; 3NPC; -.
DR PDBsum; 7CML; -.
DR AlphaFoldDB; P45984; -.
DR SMR; P45984; -.
DR BioGRID; 111587; 170.
DR DIP; DIP-270N; -.
DR ELM; P45984; -.
DR IntAct; P45984; 105.
DR MINT; P45984; -.
DR STRING; 9606.ENSP00000394560; -.
DR BindingDB; P45984; -.
DR ChEMBL; CHEMBL4179; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB15624; Halicin.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB07020; N-{3-[5-(1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl]phenyl}furan-2-carboxamide.
DR DrugCentral; P45984; -.
DR GuidetoPHARMACOLOGY; 1497; -.
DR GlyConnect; 1515; 1 N-Linked glycan (1 site).
DR GlyGen; P45984; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P45984; -.
DR MetOSite; P45984; -.
DR PhosphoSitePlus; P45984; -.
DR BioMuta; MAPK9; -.
DR DMDM; 85700366; -.
DR REPRODUCTION-2DPAGE; P45984; -.
DR CPTAC; CPTAC-893; -.
DR CPTAC; CPTAC-894; -.
DR EPD; P45984; -.
DR jPOST; P45984; -.
DR MassIVE; P45984; -.
DR MaxQB; P45984; -.
DR PaxDb; P45984; -.
DR PeptideAtlas; P45984; -.
DR PRIDE; P45984; -.
DR ProteomicsDB; 55698; -. [P45984-1]
DR ProteomicsDB; 55699; -. [P45984-2]
DR ProteomicsDB; 55700; -. [P45984-3]
DR ProteomicsDB; 55701; -. [P45984-4]
DR ProteomicsDB; 55702; -. [P45984-5]
DR Antibodypedia; 4557; 916 antibodies from 47 providers.
DR DNASU; 5601; -.
DR Ensembl; ENST00000343111.10; ENSP00000345524.6; ENSG00000050748.18. [P45984-3]
DR Ensembl; ENST00000393360.7; ENSP00000377028.3; ENSG00000050748.18. [P45984-2]
DR Ensembl; ENST00000425491.6; ENSP00000397422.2; ENSG00000050748.18. [P45984-5]
DR Ensembl; ENST00000452135.7; ENSP00000394560.2; ENSG00000050748.18. [P45984-1]
DR Ensembl; ENST00000455781.5; ENSP00000389338.1; ENSG00000050748.18. [P45984-4]
DR GeneID; 5601; -.
DR KEGG; hsa:5601; -.
DR MANE-Select; ENST00000452135.7; ENSP00000394560.2; NM_002752.5; NP_002743.3.
DR UCSC; uc003mls.5; human. [P45984-1]
DR CTD; 5601; -.
DR DisGeNET; 5601; -.
DR GeneCards; MAPK9; -.
DR HGNC; HGNC:6886; MAPK9.
DR HPA; ENSG00000050748; Low tissue specificity.
DR MIM; 602896; gene.
DR neXtProt; NX_P45984; -.
DR OpenTargets; ENSG00000050748; -.
DR PharmGKB; PA30630; -.
DR VEuPathDB; HostDB:ENSG00000050748; -.
DR eggNOG; KOG0665; Eukaryota.
DR GeneTree; ENSGT00940000158327; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P45984; -.
DR OMA; IESVGNW; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P45984; -.
DR TreeFam; TF105100; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; P45984; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
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 SignaLink; P45984; -.
DR SIGNOR; P45984; -.
DR BioGRID-ORCS; 5601; 8 hits in 1112 CRISPR screens.
DR ChiTaRS; MAPK9; human.
DR EvolutionaryTrace; P45984; -.
DR GeneWiki; Mitogen-activated_protein_kinase_9; -.
DR GenomeRNAi; 5601; -.
DR Pharos; P45984; Tchem.
DR PRO; PR:P45984; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P45984; protein.
DR Bgee; ENSG00000050748; Expressed in middle temporal gyrus and 212 other tissues.
DR ExpressionAtlas; P45984; baseline and differential.
DR Genevisible; P45984; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA.
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:0018105; P:peptidyl-serine phosphorylation; IDA:CAFA.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
DR GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; IEA:Ensembl.
DR GO; GO:0061833; P:protein localization to tricellular tight junction; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; TAS:Reactome.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..424
FT /note="Mitogen-activated protein kinase 9"
FT /id="PRO_0000186273"
FT DOMAIN 26..321
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 368..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 183..185
FT /note="TXY"
FT COMPBIAS 376..416
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 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 VAR_SEQ 216..230
FT /note="GELVKGCVIFQGTDH -> AEMVLHKVLFPGRDY (in isoform Beta-
FT 1 and isoform Beta-2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_004834"
FT VAR_SEQ 230..242
FT /note="HIDQWNKVIEQLG -> RILPRDLGPAMLS (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:21110917"
FT /id="VSP_041908"
FT VAR_SEQ 243..424
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:21110917"
FT /id="VSP_041909"
FT VAR_SEQ 378..424
FT /note="DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR -> A
FT QMQQ (in isoform Alpha-1 and isoform Beta-1)"
FT /evidence="ECO:0000305"
FT /id="VSP_004835"
FT VARIANT 13
FT /note="V -> M (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042260"
FT VARIANT 56
FT /note="K -> N (in a head & Neck squamous cell carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042261"
FT VARIANT 246
FT /note="A -> T (in dbSNP:rs35421153)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042262"
FT VARIANT 268
FT /note="G -> A (in dbSNP:rs35693958)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_025175"
FT VARIANT 366
FT /note="R -> I (in dbSNP:rs55736180)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042263"
FT CONFLICT 51
FT /note="N -> S (in Ref. 1; AAA56831 and 3; AAC50606/
FT AAC50608/AAC50609)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="S -> P (in Ref. 2; AAA74740)"
FT /evidence="ECO:0000305"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:7CML"
FT STRAND 10..15
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:3E7O"
FT TURN 46..49
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:7CML"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:3E7O"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 125..144
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:3E7O"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:3E7O"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:3NPC"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:3NPC"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:7CML"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 206..220
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 246..250
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 254..261
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 286..301
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:7CML"
FT HELIX 312..316
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 319..322
FT /evidence="ECO:0007829|PDB:3E7O"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:7CML"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:3NPC"
FT HELIX 349..360
FT /evidence="ECO:0007829|PDB:3E7O"
SQ SEQUENCE 424 AA; 48139 MW; 9C15DA79981290AF CRC64;
MSDSKCDSQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP
FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH
MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF
MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ
LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV
MDWEERSKNG VVKDQPSDAA VSSNATPSQS SSINDISSMS TEQTLASDTD SSLDASTGPL
EGCR
