M3K20_HUMAN
ID M3K20_HUMAN Reviewed; 800 AA.
AC Q9NYL2; B3KPG2; Q53SX1; Q580W8; Q59GY5; Q86YW8; Q9HCC4; Q9HCC5; Q9HDD2;
AC Q9NYE9;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 20 {ECO:0000312|HGNC:HGNC:17797};
DE EC=2.7.11.25;
DE AltName: Full=Human cervical cancer suppressor gene 4 protein;
DE Short=HCCS-4;
DE AltName: Full=Leucine zipper- and sterile alpha motif-containing kinase;
DE AltName: Full=MLK-like mitogen-activated protein triple kinase;
DE AltName: Full=Mitogen-activated protein kinase kinase kinase MLT;
DE AltName: Full=Mixed lineage kinase-related kinase;
DE Short=MLK-related kinase;
DE Short=MRK;
DE AltName: Full=Sterile alpha motif- and leucine zipper-containing kinase AZK;
GN Name=MAP3K20 {ECO:0000312|HGNC:HGNC:17797};
GN Synonyms=MLTK, ZAK {ECO:0000303|PubMed:10924358}; ORFNames=HCCS4;
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] {ECO:0000305, ECO:0000312|EMBL:AAF63490.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP HOMODIMERIZATION, AND VARIANT LEU-531.
RC TISSUE=Placenta {ECO:0000269|PubMed:10924358};
RX PubMed=10924358; DOI=10.1006/bbrc.2000.3236;
RA Liu T.-C., Huang C.-J., Chu Y.-C., Wei C.-C., Chou C.-C., Chou M.-Y.,
RA Chou C.-K., Yang J.-J.;
RT "Cloning and expression of ZAK, a mixed lineage kinase-like protein
RT containing a leucine-zipper and a sterile-alpha motif.";
RL Biochem. Biophys. Res. Commun. 274:811-816(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION (ISOFORM 1),
RP PHOSPHORYLATION AT SER-429 (ISOFORM 2), AND VARIANT LEU-531.
RC TISSUE=Fetal brain;
RX PubMed=11042189; DOI=10.1074/jbc.m008595200;
RA Gotoh I., Adachi M., Nishida E.;
RT "Identification and characterization of a novel MAP kinase kinase kinase,
RT MLTK.";
RL J. Biol. Chem. 276:4276-4286(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RX PubMed=11549352; DOI=10.1006/jmcc.2001.1437;
RA Bloem L.J., Pickard T.R., Acton S., Donoghue M., Beavis R.C.,
RA Knierman M.D., Wang X.;
RT "Tissue distribution and functional expression of a cDNA encoding a novel
RT mixed lineage kinase.";
RL J. Mol. Cell. Cardiol. 33:1739-1750(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, MUTAGENESIS OF LYS-45, AND VARIANT LEU-531.
RC TISSUE=T-cell {ECO:0000269|PubMed:11836244};
RX PubMed=11836244; DOI=10.1074/jbc.m111994200;
RA Gross E.A., Callow M.G., Waldbaum L., Thomas S., Ruggieri R.;
RT "MRK, a mixed lineage kinase-related molecule that plays a role in gamma-
RT radiation-induced cell cycle arrest.";
RL J. Biol. Chem. 277:13873-13882(2002).
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAB12040.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lymphoid tissue;
RA Abe Y., Ueda N.;
RT "Placible mixed-lineage kinase derived from LAK cell.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:BAB12040.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-531.
RA McNee J.J., Frima N., Diamond T.E., Dower S.K., Guesdon F.;
RT "Cloning and characterisation of AZK, a mixed lineage kinase containing a
RT sterile-alpha motif.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305, ECO:0000312|EMBL:BAB12040.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kim J.W.;
RT "Identification of a new tumor suppressor in human cancers.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [9] {ECO:0000305, ECO:0000312|EMBL:BAB12040.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-784.
RC TISSUE=Brain {ECO:0000312|EMBL:BAD92211.1};
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [10] {ECO:0000312|EMBL:AAX82002.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [11] {ECO:0000305, ECO:0000312|EMBL:BAB12040.1}
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 [12] {ECO:0000305, ECO:0000312|EMBL:AAH01401.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon {ECO:0000312|EMBL:AAH01401.1};
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 [13]
RP INTERACTION WITH ZNF33A.
RX PubMed=12535642; DOI=10.1016/s0006-291x(02)02980-7;
RA Yang J.-J.;
RT "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the
RT ZAK-expressing cells re-entering the cell cycle.";
RL Biochem. Biophys. Res. Commun. 301:71-77(2003).
RN [14] {ECO:0000305}
RP PHOSPHORYLATION, AND INTERACTION WITH PKN1.
RX PubMed=12761180; DOI=10.1093/jb/mvg022;
RA Takahashi M., Gotoh Y., Isagawa T., Nishimura T., Goyama E., Kim H.-S.,
RA Mukai H., Ono Y.;
RT "Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by
RT PKN.";
RL J. Biochem. 133:181-187(2003).
RN [15] {ECO:0000305}
RP FUNCTION (ISOFORM 1).
RX PubMed=15172994; DOI=10.1158/0008-5472.can-04-0201;
RA Cho Y.-Y., Bode A.M., Mizuno H., Choi B.Y., Choi H.S., Dong Z.;
RT "A novel role for mixed-lineage kinase-like mitogen-activated protein
RT triple kinase alpha in neoplastic cell transformation and tumor
RT development.";
RL Cancer Res. 64:3855-3864(2004).
RN [16] {ECO:0000305}
RP FUNCTION IN DNA DAMAGE CHECKPOINTS, FUNCTION IN PHOSPHORYLATION OF CHEK2,
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-161 AND SER-165, AND
RP MUTAGENESIS OF THR-161; THR-162 AND SER-165.
RX PubMed=15342622; DOI=10.1074/jbc.m409961200;
RA Tosti E., Waldbaum L., Warshaw G., Gross E.A., Ruggieri R.;
RT "The stress kinase MRK contributes to regulation of DNA damage checkpoints
RT through a p38gamma-independent pathway.";
RL J. Biol. Chem. 279:47652-47660(2004).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3 (ISOFORM 1), AND SUBCELLULAR
RP LOCATION.
RX PubMed=15684425; DOI=10.1074/jbc.m410521200;
RA Choi H.S., Choi B.Y., Cho Y.-Y., Zhu F., Bode A.M., Dong Z.;
RT "Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-
RT like mitogen-activated protein triple kinase alpha.";
RL J. Biol. Chem. 280:13545-13553(2005).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; SER-302; THR-628;
RP SER-727 AND SER-733, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339;
RP SER-434 AND SER-454 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-599; THR-628; SER-633;
RP SER-727 AND SER-733, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454
RP (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-275; THR-628; SER-633 AND SER-727, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-339; SER-434 AND SER-454 (ISOFORM 2), CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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 IDENTIFICATION IN A COMPLEX WITH AKAP13; PKN1; MAPK14 AND
RP MAP2K3.
RX PubMed=21224381; DOI=10.1074/jbc.m110.185645;
RA Cariolato L., Cavin S., Diviani D.;
RT "A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling
RT complex involved in alpha1-adrenergic receptor-induced p38 activation.";
RL J. Biol. Chem. 286:7925-7937(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567; SER-593; THR-628;
RP SER-633; SER-637; SER-648; SER-649; SER-685; SER-727 AND SER-733, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-267; THR-281; VAL-281; LEU-531;
RP TRP-580; THR-740; HIS-773 AND THR-784.
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 [31]
RP INVOLVEMENT IN SFMMP, FUNCTION, SUBUNIT, VARIANT SFMMP CYS-368, AND
RP CHARACTERIZATION OF VARIANT SFMMP CYS-368.
RX PubMed=26755636; DOI=10.1101/gr.199430.115;
RA Spielmann M., Kakar N., Tayebi N., Leettola C., Nuernberg G., Sowada N.,
RA Lupianez D.G., Harabula I., Floettmann R., Horn D., Chan W.L., Wittler L.,
RA Yilmaz R., Altmueller J., Thiele H., van Bokhoven H., Schwartz C.E.,
RA Nuernberg P., Bowie J.U., Ahmad J., Kubisch C., Mundlos S., Borck G.;
RT "Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK
RT as a cause of limb defects in humans and mice.";
RL Genome Res. 26:183-191(2016).
RN [32]
RP INVOLVEMENT IN CNM6, VARIANTS CNM6 95-ASN--PHE-800 DEL AND 172-TRP--PHE-800
RP DEL, AND CHARACTERIZATION OF VARIANTS CNM6 95-ASN--PHE-800 DEL AND
RP 172-TRP--PHE-800 DEL.
RX PubMed=27816943; DOI=10.1093/brain/aww257;
RA Vasli N., Harris E., Karamchandani J., Bareke E., Majewski J., Romero N.B.,
RA Stojkovic T., Barresi R., Tasfaout H., Charlton R., Malfatti E., Bohm J.,
RA Marini-Bettolo C., Choquet K., Dicaire M.J., Shao Y.H., Topf A.,
RA O'Ferrall E., Eymard B., Straub V., Blanco G., Lochmueller H., Brais B.,
RA Laporte J., Tetreault M.;
RT "Recessive mutations in the kinase ZAK cause a congenital myopathy with
RT fibre type disproportion.";
RL Brain 140:37-48(2017).
RN [33]
RP VARIANT CNM6 TRP-250.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Stress-activated component of a protein kinase signal
CC transduction cascade. Regulates the JNK and p38 pathways. Part of a
CC signaling cascade that begins with the activation of the adrenergic
CC receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic.
CC Role in regulation of S and G2 cell cycle checkpoint by direct
CC phosphorylation of CHEK2 (PubMed:10924358, PubMed:11836244,
CC PubMed:15342622, PubMed:21224381). Involved in limb development
CC (PubMed:26755636). {ECO:0000269|PubMed:10924358,
CC ECO:0000269|PubMed:11836244, ECO:0000269|PubMed:15342622,
CC ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:26755636}.
CC -!- FUNCTION: [Isoform 1]: Phosphorylates histone H3 at 'Ser-28'
CC (PubMed:15684425). May have role in neoplastic cell transformation and
CC cancer development (PubMed:15172994). Causes cell shrinkage and
CC disruption of actin stress fibers (PubMed:11042189).
CC {ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:15172994,
CC ECO:0000269|PubMed:15684425}.
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=2.7.11.25;
CC Evidence={ECO:0000269|PubMed:11836244};
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=2.7.11.25; Evidence={ECO:0000269|PubMed:11836244};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11836244};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation by PKN1 and
CC autophosphorylation on Thr-161 and Ser-165.
CC {ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:12761180,
CC ECO:0000269|PubMed:15342622}.
CC -!- SUBUNIT: Homodimer (PubMed:10924358, PubMed:26755636). Interacts with
CC PKN1 and ZNF33A (PubMed:12535642, PubMed:12761180). Component of a
CC signaling complex containing at least AKAP13, PKN1, MAPK14, MAP3K20 and
CC MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which
CC in turn recruits MAPK14, MAP2K3 and MAP3K20 (PubMed:21224381).
CC {ECO:0000269|PubMed:10924358, ECO:0000269|PubMed:12535642,
CC ECO:0000269|PubMed:12761180, ECO:0000269|PubMed:21224381,
CC ECO:0000269|PubMed:26755636}.
CC -!- INTERACTION:
CC Q9NYL2; O75582: RPS6KA5; NbExp=4; IntAct=EBI-602273, EBI-73869;
CC Q9NYL2; P63104: YWHAZ; NbExp=5; IntAct=EBI-602273, EBI-347088;
CC Q9NYL2; Q8N184: ZNF567; NbExp=3; IntAct=EBI-602273, EBI-749400;
CC Q9NYL2-1; Q16512: PKN1; NbExp=2; IntAct=EBI-687346, EBI-602382;
CC Q9NYL2-2; Q6P2D0: ZFP1; NbExp=4; IntAct=EBI-10255081, EBI-2555749;
CC Q9NYL2-2; Q6ZN57: ZFP2; NbExp=7; IntAct=EBI-10255081, EBI-7236323;
CC Q9NYL2-2; P13682: ZNF35; NbExp=3; IntAct=EBI-10255081, EBI-11041653;
CC Q9NYL2-2; Q8N184: ZNF567; NbExp=7; IntAct=EBI-10255081, EBI-749400;
CC Q9NYL2-2; Q6AZW8: ZNF660; NbExp=3; IntAct=EBI-10255081, EBI-12376497;
CC Q9NYL2-2; Q9NQZ8: ZNF71; NbExp=4; IntAct=EBI-10255081, EBI-7138235;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15684425}. Nucleus
CC {ECO:0000269|PubMed:15684425}. Note=Translocates to the nucleus upon
CC ultraviolet B irradiation. {ECO:0000269|PubMed:15684425}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:11042189}; Synonyms=Alpha;
CC IsoId=Q9NYL2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:11042189}; Synonyms=Beta;
CC IsoId=Q9NYL2-2; Sequence=VSP_051743, VSP_051744;
CC Name=3; Synonyms=HCCS-4;
CC IsoId=Q9NYL2-3; Sequence=VSP_051741, VSP_051742;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is the
CC predominant form in all tissues examined, except for liver, in which
CC isoform 1 is more highly expressed. {ECO:0000269|PubMed:10924358,
CC ECO:0000269|PubMed:11836244}.
CC -!- DISEASE: Split-foot malformation with mesoaxial polydactyly (SFMMP)
CC [MIM:616890]: An autosomal recessive disorder characterized by a split-
CC foot defect, mesoaxial polydactyly, nail abnormalities of the hands,
CC and sensorineural hearing loss. {ECO:0000269|PubMed:26755636}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myopathy, centronuclear, 6, with fiber-type disproportion
CC (CNM6) [MIM:617760]: A form of centronuclear myopathy, a congenital
CC muscle disorder characterized by progressive muscular weakness and
CC wasting involving mainly limb girdle, trunk, and neck muscles. It may
CC also affect distal muscles. Weakness may be present during childhood or
CC adolescence or may not become evident until the third decade of life.
CC Ptosis is a frequent clinical feature. The most prominent
CC histopathologic features include high frequency of centrally located
CC nuclei in muscle fibers not secondary to regeneration, radial
CC arrangement of sarcoplasmic strands around the central nuclei, and
CC predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal
CC recessive, slowly progressive form with onset in infancy or early
CC childhood. {ECO:0000269|PubMed:27816943, ECO:0000269|PubMed:30237576}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92211.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF238255; AAF63490.1; -; mRNA.
DR EMBL; AB049733; BAB16444.1; -; mRNA.
DR EMBL; AB049734; BAB16445.1; -; mRNA.
DR EMBL; AF325454; AAK11615.1; -; mRNA.
DR EMBL; AF480461; AAL85891.1; -; mRNA.
DR EMBL; AF480462; AAL85892.1; -; mRNA.
DR EMBL; AB030034; BAB12040.1; -; mRNA.
DR EMBL; AF251441; AAF65822.1; -; mRNA.
DR EMBL; AF465843; AAO33376.1; -; mRNA.
DR EMBL; AK056310; BAG51674.1; -; mRNA.
DR EMBL; AB208974; BAD92211.1; ALT_INIT; mRNA.
DR EMBL; AC092573; AAX82002.1; -; Genomic_DNA.
DR EMBL; AC013461; AAX93067.1; -; Genomic_DNA.
DR EMBL; AC019046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11164.1; -; Genomic_DNA.
DR EMBL; BC001401; AAH01401.1; -; mRNA.
DR CCDS; CCDS2251.1; -. [Q9NYL2-2]
DR CCDS; CCDS42777.1; -. [Q9NYL2-1]
DR RefSeq; NP_057737.2; NM_016653.2. [Q9NYL2-1]
DR RefSeq; NP_598407.1; NM_133646.2. [Q9NYL2-2]
DR RefSeq; XP_005246697.1; XM_005246640.2. [Q9NYL2-1]
DR RefSeq; XP_016859812.1; XM_017004323.1. [Q9NYL2-2]
DR RefSeq; XP_016859813.1; XM_017004324.1. [Q9NYL2-2]
DR PDB; 5HES; X-ray; 2.14 A; A/B=5-309.
DR PDB; 5X5O; X-ray; 1.87 A; A=5-309.
DR PDB; 6JUT; X-ray; 2.10 A; A=5-309.
DR PDB; 6JUU; X-ray; 1.90 A; A=5-309.
DR PDBsum; 5HES; -.
DR PDBsum; 5X5O; -.
DR PDBsum; 6JUT; -.
DR PDBsum; 6JUU; -.
DR AlphaFoldDB; Q9NYL2; -.
DR SMR; Q9NYL2; -.
DR BioGRID; 119725; 88.
DR CORUM; Q9NYL2; -.
DR IntAct; Q9NYL2; 48.
DR MINT; Q9NYL2; -.
DR STRING; 9606.ENSP00000364361; -.
DR BindingDB; Q9NYL2; -.
DR ChEMBL; CHEMBL3886; -.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9NYL2; -.
DR GuidetoPHARMACOLOGY; 2289; -.
DR iPTMnet; Q9NYL2; -.
DR MetOSite; Q9NYL2; -.
DR PhosphoSitePlus; Q9NYL2; -.
DR BioMuta; MAP3K20; -.
DR DMDM; 313104215; -.
DR EPD; Q9NYL2; -.
DR jPOST; Q9NYL2; -.
DR MassIVE; Q9NYL2; -.
DR MaxQB; Q9NYL2; -.
DR PaxDb; Q9NYL2; -.
DR PeptideAtlas; Q9NYL2; -.
DR PRIDE; Q9NYL2; -.
DR ProteomicsDB; 83246; -. [Q9NYL2-1]
DR ProteomicsDB; 83248; -. [Q9NYL2-3]
DR Antibodypedia; 2065; 320 antibodies from 34 providers.
DR DNASU; 51776; -.
DR Ensembl; ENST00000338983.7; ENSP00000340257.3; ENSG00000091436.17. [Q9NYL2-2]
DR Ensembl; ENST00000375213.8; ENSP00000364361.3; ENSG00000091436.17. [Q9NYL2-1]
DR Ensembl; ENST00000409176.6; ENSP00000387259.2; ENSG00000091436.17. [Q9NYL2-1]
DR Ensembl; ENST00000539448.5; ENSP00000439414.1; ENSG00000091436.17. [Q9NYL2-2]
DR GeneID; 51776; -.
DR KEGG; hsa:51776; -.
DR MANE-Select; ENST00000375213.8; ENSP00000364361.3; NM_016653.3; NP_057737.2.
DR UCSC; uc002uhz.4; human. [Q9NYL2-1]
DR CTD; 51776; -.
DR DisGeNET; 51776; -.
DR GeneCards; MAP3K20; -.
DR HGNC; HGNC:17797; MAP3K20.
DR HPA; ENSG00000091436; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; MAP3K20; -.
DR MIM; 609479; gene.
DR MIM; 616890; phenotype.
DR MIM; 617760; phenotype.
DR neXtProt; NX_Q9NYL2; -.
DR OpenTargets; ENSG00000091436; -.
DR Orphanet; 2020; Congenital fiber-type disproportion myopathy.
DR Orphanet; 488232; Split-foot malformation-mesoaxial polydactyly syndrome.
DR VEuPathDB; HostDB:ENSG00000091436; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000161352; -.
DR HOGENOM; CLU_019131_1_0_1; -.
DR InParanoid; Q9NYL2; -.
DR OMA; QSNTPFF; -.
DR OrthoDB; 938929at2759; -.
DR PhylomeDB; Q9NYL2; -.
DR PathwayCommons; Q9NYL2; -.
DR SignaLink; Q9NYL2; -.
DR SIGNOR; Q9NYL2; -.
DR BioGRID-ORCS; 51776; 10 hits in 1062 CRISPR screens.
DR ChiTaRS; MAP3K20; human.
DR GeneWiki; ZAK; -.
DR GenomeRNAi; 51776; -.
DR Pharos; Q9NYL2; Tchem.
DR PRO; PR:Q9NYL2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NYL2; protein.
DR Bgee; ENSG00000091436; Expressed in heart right ventricle and 190 other tissues.
DR ExpressionAtlas; Q9NYL2; baseline and differential.
DR Genevisible; Q9NYL2; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB.
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:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0008219; P:cell death; NAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0038066; P:p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1904291; P:positive regulation of mitotic DNA damage checkpoint; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Cytoplasm; Disease variant; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..800
FT /note="Mitogen-activated protein kinase kinase kinase 20"
FT /id="PRO_0000086338"
FT DOMAIN 16..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 339..410
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 287..308
FT /note="Leucine-zipper"
FT REGION 652..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..668
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 680..707
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..800
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P80192,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 22..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P80192,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 45
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:11836244"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 161
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15342622"
FT MOD_RES 165
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15342622"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 628
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 285..312
FT /note="CEIEATLERLKKLERDLSFKEQELKERE -> WVAPTAGHSVWLSKTITRLN
FT EEVNQRSE (in isoform 3)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_051741"
FT VAR_SEQ 313..800
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_051742"
FT VAR_SEQ 332..455
FT /note="PSFEIGAWTEDDVYCWVQQLVRKGDSSAEMSVYASLFKENNITGKRLLLLEE
FT EDLKDMGIVSKGHIIHFKSAIEKLTHDYINLFHFPPLIKDSGGEPEENEEKIVNLELVF
FT GFHLKPGTGPQDC -> LPLAARMSEESYFESKTEESNSAEMSCQITATSNGEGHGMNP
FT SLQAMMLMGFGDIFSMNKAGAVMHSGMQINMQAKQNSSKTTSKRRGKKVNMALGFSDFD
FT LSEGDDDDDDDGEEEDNDMDNSE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042189,
FT ECO:0000303|PubMed:11549352, ECO:0000303|PubMed:11836244,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_051743"
FT VAR_SEQ 456..800
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042189,
FT ECO:0000303|PubMed:11549352, ECO:0000303|PubMed:11836244,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_051744"
FT VARIANT 95..800
FT /note="Missing (in CNM6; decrease of protein abundance)"
FT /evidence="ECO:0000269|PubMed:27816943"
FT /id="VAR_080563"
FT VARIANT 172..800
FT /note="Missing (in CNM6; decrease of protein abundance)"
FT /evidence="ECO:0000269|PubMed:27816943"
FT /id="VAR_080564"
FT VARIANT 250
FT /note="R -> W (in CNM6; unknown pathological significance;
FT dbSNP:rs763481300)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082158"
FT VARIANT 267
FT /note="T -> M (in dbSNP:rs6758025)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040806"
FT VARIANT 281
FT /note="A -> T (in an ovarian endometrioid sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040807"
FT VARIANT 281
FT /note="A -> V (in dbSNP:rs34683477)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040808"
FT VARIANT 368
FT /note="F -> C (in SFMMP; produces protein aggregation;
FT dbSNP:rs863225437)"
FT /evidence="ECO:0000269|PubMed:26755636"
FT /id="VAR_076448"
FT VARIANT 531
FT /note="S -> L (in dbSNP:rs3769148)"
FT /evidence="ECO:0000269|PubMed:10924358,
FT ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:11836244,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.6"
FT /id="VAR_022827"
FT VARIANT 580
FT /note="R -> W (in dbSNP:rs7593622)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040809"
FT VARIANT 740
FT /note="P -> T (in dbSNP:rs56202258)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040810"
FT VARIANT 773
FT /note="Y -> H (in dbSNP:rs35608243)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040811"
FT VARIANT 784
FT /note="K -> T (in dbSNP:rs55830025)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.9"
FT /id="VAR_040812"
FT MUTAGEN 45
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:11836244"
FT MUTAGEN 161
FT /note="T->A: Loss of autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:15342622"
FT MUTAGEN 162
FT /note="T->A: Slight loss of autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:15342622"
FT MUTAGEN 165
FT /note="S->A: Loss of autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:15342622"
FT CONFLICT 346
FT /note="C -> W (in Ref. 1; AAF63490)"
FT /evidence="ECO:0000305"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 16..20
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6JUT"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:5X5O"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 90..94
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 97..101
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 104..123
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:5X5O"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:6JUT"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 186..201
FT /evidence="ECO:0007829|PDB:5X5O"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 211..220
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 253..264
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 269..277
FT /evidence="ECO:0007829|PDB:5X5O"
FT HELIX 280..298
FT /evidence="ECO:0007829|PDB:5X5O"
FT MOD_RES Q9NYL2-2:339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q9NYL2-2:429
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11042189"
FT MOD_RES Q9NYL2-2:434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q9NYL2-2:454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
SQ SEQUENCE 800 AA; 91155 MW; B2814509EC54B07A CRC64;
MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL
SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMDHIMTW ATDVAKGMHY
LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS
LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH
QCWEADAKKR PSFKQIISIL ESMSNDTSLP DKCNSFLHNK AEWRCEIEAT LERLKKLERD
LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LPSFEIGAWT EDDVYCWVQQ LVRKGDSSAE
MSVYASLFKE NNITGKRLLL LEEEDLKDMG IVSKGHIIHF KSAIEKLTHD YINLFHFPPL
IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT GPQDCKWKMY MEMDGDEIAI TYIKDVTFNT
NLPDAEILKM TKPPFVMEKW IVGIAKSQTV ECTVTYESDV RTPKSTKHVH SIQWSRTKPQ
DEVKAVQLAI QTLFTNSDGN PGSRSDSSAD CQWLDTLRMR QIASNTSLQR SQSNPILGSP
FFSHFDGQDS YAAAVRRPQV PIKYQQITPV NQSRSSSPTQ YGLTKNFSSL HLNSRDSGFS
SGNTDTSSER GRYSDRSRNK YGRGSISLNS SPRGRYSGKS QHSTPSRGRY PGKFYRVSQS
ALNPHQSPDF KRSPRDLHQP NTIPGMPLHP ETDSRASEED SKVSEGGWTK VEYRKKPHRP
SPAKTNKERA RGDHRGWRNF
