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Database: UniProt
Entry: O94804
LinkDB: O94804
Original site: O94804 
ID   STK10_HUMAN             Reviewed;         968 AA.
AC   O94804; A6ND35; B2R8F5; B3KMY1; Q6NSK0; Q9UIW4;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   11-DEC-2019, entry version 190.
DE   RecName: Full=Serine/threonine-protein kinase 10;
DE            EC=2.7.11.1;
DE   AltName: Full=Lymphocyte-oriented kinase;
GN   Name=STK10; Synonyms=LOK;
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].
RX   PubMed=10199912; DOI=10.1007/s002510050509;
RA   Kuramochi S., Matsuda Y., Okamoto M., Kitamura F., Yonekawa H.,
RA   Karasuyama H.;
RT   "Molecular cloning of the human gene STK10 encoding lymphocyte-oriented
RT   kinase, and comparative chromosomal mapping of the human, mouse, and rat
RT   homologues.";
RL   Immunogenetics 49:369-375(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Teratocarcinoma, and Testis;
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   [3]
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   [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 814-968.
RC   TISSUE=Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
RP   FUNCTION.
RX   PubMed=11903060; DOI=10.1042/0264-6021:3630175;
RA   Tao L., Wadsworth S., Mercer J., Mueller C., Lynn K., Siekierka J.,
RA   August A.;
RT   "Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the
RT   CD28 responsive element in T-cells.";
RL   Biochem. J. 363:175-182(2002).
RN   [8]
RP   FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-65.
RX   PubMed=12639966; DOI=10.1074/jbc.m212556200;
RA   Walter S.A., Cutler R.E. Jr., Martinez R., Gishizky M., Hill R.J.;
RT   "Stk10, a new member of the polo-like kinase kinase family highly expressed
RT   in hematopoietic tissue.";
RL   J. Biol. Chem. 278:18221-18228(2003).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=T-cell;
RX   PubMed=19367720; DOI=10.1021/pr800500r;
RA   Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT   "Phosphorylation analysis of primary human T lymphocytes using sequential
RT   IMAC and titanium oxide enrichment.";
RL   J. Proteome Res. 7:5167-5176(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191 AND SER-438, 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   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-191; SER-454 AND
RP   THR-952, AND 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   [14]
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   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191; SER-438 AND SER-549, 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   [16]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19255442; DOI=10.1073/pnas.0805963106;
RA   Belkina N.V., Liu Y., Hao J.J., Karasuyama H., Shaw S.;
RT   "LOK is a major ERM kinase in resting lymphocytes and regulates
RT   cytoskeletal rearrangement through ERM phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:4707-4712(2009).
RN   [17]
RP   IDENTIFICATION BY 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   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, 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   [19]
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   [20]
RP   ACTIVITY REGULATION.
RX   PubMed=21606217; DOI=10.1124/mol.110.070862;
RA   Yamamoto N., Honma M., Suzuki H.;
RT   "Off-target serine/threonine kinase 10 inhibition by erlotinib enhances
RT   lymphocytic activity leading to severe skin disorders.";
RL   Mol. Pharmacol. 80:466-475(2011).
RN   [21]
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   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-438; SER-450 AND
RP   SER-514, AND 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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485; SER-514 AND THR-952, AND
RP   IDENTIFICATION BY 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   [24]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 18-317 IN COMPLEX WITH
RP   PYRROLE-INDOLINONE INHIBITOR, ACTIVITY REGULATION, AUTOPHOSPHORYLATION,
RP   CATALYTIC ACTIVITY, AND SUBUNIT.
RX   PubMed=18239682; DOI=10.1038/emboj.2008.8;
RA   Pike A.C., Rellos P., Niesen F.H., Turnbull A., Oliver A.W., Parker S.A.,
RA   Turk B.E., Pearl L.H., Knapp S.;
RT   "Activation segment dimerization: a mechanism for kinase
RT   autophosphorylation of non-consensus sites.";
RL   EMBO J. 27:704-714(2008).
RN   [25]
RP   VARIANT TGCT GLU-277.
RX   PubMed=16175573; DOI=10.1002/gcc.20265;
RA   Bignell G., Smith R., Hunter C., Stephens P., Davies H., Greenman C.,
RA   Teague J., Butler A., Edkins S., Stevens C., O'meara S., Parker A.,
RA   Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J.,
RA   Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K.,
RA   Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R.,
RA   Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A.,
RA   Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S.,
RA   Yates A., Gillis A.J.M., Stoop H.J., van Gurp R.J.H.L.M., Oosterhuis J.W.,
RA   Looijenga L.H.J., Futreal P.A., Wooster R., Stratton M.R.;
RT   "Sequence analysis of the protein kinase gene family in human testicular
RT   germ-cell tumors of adolescents and adults.";
RL   Genes Chromosomes Cancer 45:42-46(2006).
RN   [26]
RP   VARIANTS [LARGE SCALE ANALYSIS] CYS-268; GLU-277; TRP-322; ILE-336;
RP   SER-467; THR-710; LEU-853; THR-905 AND TYR-947.
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 regulation of
CC       lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved
CC       in regulation of lymphocyte migration by mediating phosphorylation of
CC       ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1.
CC       May also act as a cell cycle regulator by acting as a polo kinase
CC       kinase: mediates phosphorylation of PLK1 in vitro; however such data
CC       require additional evidences in vivo. {ECO:0000269|PubMed:11903060,
CC       ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}.
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=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:18239682};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:18239682};
CC   -!- ACTIVITY REGULATION: Inhibited by the pyrrole-indolinone inhibitor
CC       SU11274 (K00593): intercalates between the ATP-binding Lys-65 and
CC       alpha-C glutamate (Glu-81), resulting in a partial disordering of the
CC       lysine side chain. Also specifically inhibited by erlotinib. Slightly
CC       inhibited by gefitinib. {ECO:0000269|PubMed:18239682,
CC       ECO:0000269|PubMed:21606217}.
CC   -!- SUBUNIT: Homodimer; homodimerization is required for activation segment
CC       autophosphorylation. {ECO:0000269|PubMed:18239682}.
CC   -!- INTERACTION:
CC       Self; NbExp=3; IntAct=EBI-3951541, EBI-3951541;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19255442};
CC       Peripheral membrane protein {ECO:0000269|PubMed:19255442}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in rapidly proliferating tissues
CC       (spleen, placenta, and peripheral blood leukocytes). Also expressed in
CC       brain, heart, skeletal muscle, colon, thymus, kidney, liver, small
CC       intestine and lung. {ECO:0000269|PubMed:12639966}.
CC   -!- PTM: Autophosphorylates following homodimerization, leading to
CC       activation of the protein.
CC   -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common
CC       malignancy in males representing 95% of all testicular neoplasms. TGCTs
CC       have various pathologic subtypes including: unclassified intratubular
CC       germ cell neoplasia, seminoma (including cases with
CC       syncytiotrophoblastic cells), spermatocytic seminoma, embryonal
CC       carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
CC       {ECO:0000269|PubMed:16175573}. Note=The disease may be caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: Inhibition by erlotinib, an orally administered EGFR
CC       tyrosine kinase inhibitor used for treatment, enhances STK10-dependent
CC       lymphocytic responses, possibly leading to the aggravation of skin
CC       inflammation observed upon treatment by erlotinib.
CC       {ECO:0000305|PubMed:21606217}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. STE20 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAG51143.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
DR   EMBL; AB015718; BAA35073.1; -; mRNA.
DR   EMBL; AK022960; BAG51143.1; ALT_INIT; mRNA.
DR   EMBL; AK313350; BAG36152.1; -; mRNA.
DR   EMBL; AC024561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471062; EAW61439.1; -; Genomic_DNA.
DR   EMBL; BC070077; AAH70077.1; -; mRNA.
DR   EMBL; AL133081; CAB61400.1; -; mRNA.
DR   CCDS; CCDS34290.1; -.
DR   PIR; T42687; T42687.
DR   RefSeq; NP_005981.3; NM_005990.3.
DR   PDB; 2J7T; X-ray; 2.00 A; A=18-317.
DR   PDB; 4AOT; X-ray; 2.33 A; A/B=18-317.
DR   PDB; 4BC6; X-ray; 2.20 A; A=24-316.
DR   PDB; 4EQU; X-ray; 2.00 A; A/B=18-317.
DR   PDB; 4USD; X-ray; 3.05 A; A/B=18-317.
DR   PDB; 4USE; X-ray; 2.65 A; A/B=18-317.
DR   PDB; 5AJQ; X-ray; 2.20 A; A/B=21-313.
DR   PDB; 5OWQ; X-ray; 2.70 A; A/B=18-317.
DR   PDB; 5OWR; X-ray; 2.30 A; A=18-317.
DR   PDB; 6EIM; X-ray; 1.43 A; A/B=18-317.
DR   PDB; 6GTT; X-ray; 2.25 A; A=18-317.
DR   PDB; 6HXF; X-ray; 2.09 A; A/B/C/D=18-317.
DR   PDB; 6I2Y; X-ray; 2.56 A; A/B=18-317.
DR   PDBsum; 2J7T; -.
DR   PDBsum; 4AOT; -.
DR   PDBsum; 4BC6; -.
DR   PDBsum; 4EQU; -.
DR   PDBsum; 4USD; -.
DR   PDBsum; 4USE; -.
DR   PDBsum; 5AJQ; -.
DR   PDBsum; 5OWQ; -.
DR   PDBsum; 5OWR; -.
DR   PDBsum; 6EIM; -.
DR   PDBsum; 6GTT; -.
DR   PDBsum; 6HXF; -.
DR   PDBsum; 6I2Y; -.
DR   SMR; O94804; -.
DR   BioGrid; 112669; 14.
DR   IntAct; O94804; 4.
DR   MINT; O94804; -.
DR   STRING; 9606.ENSP00000176763; -.
DR   BindingDB; O94804; -.
DR   ChEMBL; CHEMBL3981; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; O94804; -.
DR   GuidetoPHARMACOLOGY; 2211; -.
DR   iPTMnet; O94804; -.
DR   PhosphoSitePlus; O94804; -.
DR   BioMuta; STK10; -.
DR   EPD; O94804; -.
DR   jPOST; O94804; -.
DR   MassIVE; O94804; -.
DR   MaxQB; O94804; -.
DR   PaxDb; O94804; -.
DR   PeptideAtlas; O94804; -.
DR   PRIDE; O94804; -.
DR   ProteomicsDB; 50444; -.
DR   DNASU; 6793; -.
DR   Ensembl; ENST00000176763; ENSP00000176763; ENSG00000072786.
DR   GeneID; 6793; -.
DR   KEGG; hsa:6793; -.
DR   UCSC; uc003mbo.2; human.
DR   CTD; 6793; -.
DR   DisGeNET; 6793; -.
DR   EuPathDB; HostDB:ENSG00000072786.12; -.
DR   GeneCards; STK10; -.
DR   HGNC; HGNC:11388; STK10.
DR   HPA; CAB020840; -.
DR   HPA; HPA015083; -.
DR   MalaCards; STK10; -.
DR   MIM; 273300; phenotype.
DR   MIM; 603919; gene.
DR   neXtProt; NX_O94804; -.
DR   OpenTargets; ENSG00000072786; -.
DR   PharmGKB; PA36197; -.
DR   eggNOG; KOG0579; Eukaryota.
DR   eggNOG; ENOG410XPQN; LUCA.
DR   GeneTree; ENSGT00940000156818; -.
DR   HOGENOM; HOG000236268; -.
DR   InParanoid; O94804; -.
DR   KO; K08837; -.
DR   OMA; SKWSLEF; -.
DR   OrthoDB; 851098at2759; -.
DR   PhylomeDB; O94804; -.
DR   TreeFam; TF351445; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; O94804; -.
DR   SIGNOR; O94804; -.
DR   ChiTaRS; STK10; human.
DR   EvolutionaryTrace; O94804; -.
DR   GeneWiki; STK10; -.
DR   GenomeRNAi; 6793; -.
DR   Pharos; O94804; Tchem.
DR   PRO; PR:O94804; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; O94804; protein.
DR   Bgee; ENSG00000072786; Expressed in 206 organ(s), highest expression level in blood.
DR   ExpressionAtlas; O94804; baseline and differential.
DR   Genevisible; O94804; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0071593; P:lymphocyte aggregation; IEA:Ensembl.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR   GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
DR   GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
DR   CDD; cd06644; STKc_STK10; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR022165; PKK.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR042743; STK10_STKc.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF12474; PKK; 2.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell cycle; Cell membrane; Coiled coil; Kinase;
KW   Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..968
FT                   /note="Serine/threonine-protein kinase 10"
FT                   /id="PRO_0000086697"
FT   DOMAIN          36..294
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         42..50
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          175..224
FT                   /note="Activation segment"
FT   COILED          573..947
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        750..884
FT                   /note="Gln-rich"
FT   ACT_SITE        157
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         65
FT                   /note="ATP"
FT                   /evidence="ECO:0000305"
FT   BINDING         111
FT                   /note="Inhibitor"
FT   BINDING         113
FT                   /note="Inhibitor"
FT   BINDING         117
FT                   /note="Inhibitor; via amide nitrogen"
FT   BINDING         175
FT                   /note="Inhibitor"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         20
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9PTG8"
FT   MOD_RES         191
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:19369195"
FT   MOD_RES         438
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:16964243,
FT                   ECO:0000244|PubMed:18088087, ECO:0000244|PubMed:18691976,
FT                   ECO:0000244|PubMed:19367720, ECO:0000244|PubMed:19369195,
FT                   ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163"
FT   MOD_RES         450
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         454
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         485
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:24275569"
FT   MOD_RES         514
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569"
FT   MOD_RES         549
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:19369195"
FT   MOD_RES         952
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:24275569"
FT   VARIANT         268
FT                   /note="R -> C (in dbSNP:rs35826078)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041131"
FT   VARIANT         277
FT                   /note="K -> E (in TGCT; somatic mutation;
FT                   dbSNP:rs757545210)"
FT                   /evidence="ECO:0000269|PubMed:16175573,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_023827"
FT   VARIANT         322
FT                   /note="R -> W (in dbSNP:rs56214442)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041132"
FT   VARIANT         336
FT                   /note="T -> I (in dbSNP:rs55972616)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041133"
FT   VARIANT         467
FT                   /note="N -> S (in dbSNP:rs56063773)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041134"
FT   VARIANT         480
FT                   /note="P -> L (in dbSNP:rs34505340)"
FT                   /id="VAR_051671"
FT   VARIANT         520
FT                   /note="P -> L (in dbSNP:rs17074311)"
FT                   /id="VAR_051672"
FT   VARIANT         710
FT                   /note="M -> T (in dbSNP:rs34936670)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041135"
FT   VARIANT         853
FT                   /note="S -> L (in dbSNP:rs56066852)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041136"
FT   VARIANT         905
FT                   /note="S -> T (in dbSNP:rs55791916)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041137"
FT   VARIANT         942
FT                   /note="S -> N (in dbSNP:rs1128204)"
FT                   /id="VAR_051673"
FT   VARIANT         947
FT                   /note="C -> Y (in dbSNP:rs56355550)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041138"
FT   MUTAGEN         65
FT                   /note="K->I: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:12639966"
FT   CONFLICT        62
FT                   /note="A -> V (in Ref. 5; AAH70077)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        136
FT                   /note="V -> E (in Ref. 5; AAH70077)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        317
FT                   /note="E -> G (in Ref. 5; AAH70077)"
FT                   /evidence="ECO:0000305"
FT   STRAND          27..30
FT                   /evidence="ECO:0000244|PDB:2J7T"
FT   HELIX           32..34
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          36..41
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          45..47
FT                   /evidence="ECO:0000244|PDB:6GTT"
FT   STRAND          50..55
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   TURN            56..58
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          61..68
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           72..87
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          96..102
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          105..111
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           118..125
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           131..150
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           160..162
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          163..165
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   STRAND          171..173
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           180..187
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           196..198
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           201..207
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   TURN            208..211
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           213..216
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           217..232
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   TURN            236..239
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           242..251
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           260..262
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           265..274
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   TURN            279..281
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           285..288
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   TURN            292..296
FT                   /evidence="ECO:0000244|PDB:6EIM"
FT   HELIX           301..314
FT                   /evidence="ECO:0000244|PDB:6EIM"
SQ   SEQUENCE   968 AA;  112135 MW;  15E245193ECC553D CRC64;
     MAFANFRRIL RLSTFEKRKS REYEHVRRDL DPNEVWEIVG ELGDGAFGKV YKAKNKETGA
     LAAAKVIETK SEEELEDYIV EIEILATCDH PYIVKLLGAY YHDGKLWIMI EFCPGGAVDA
     IMLELDRGLT EPQIQVVCRQ MLEALNFLHS KRIIHRDLKA GNVLMTLEGD IRLADFGVSA
     KNLKTLQKRD SFIGTPYWMA PEVVMCETMK DTPYDYKADI WSLGITLIEM AQIEPPHHEL
     NPMRVLLKIA KSDPPTLLTP SKWSVEFRDF LKIALDKNPE TRPSAAQLLE HPFVSSITSN
     KALRELVAEA KAEVMEEIED GRDEGEEEDA VDAASTLENH TQNSSEVSPP SLNADKPLEE
     SPSTPLAPSQ SQDSVNEPCS QPSGDRSLQT TSPPVVAPGN ENGLAVPVPL RKSRPVSMDA
     RIQVAQEKQV AEQGGDLSPA ANRSQKASQS RPNSSALETL GGEKLANGSL EPPAQAAPGP
     SKRDSDCSSL CTSESMDYGT NLSTDLSLNK EMGSLSIKDP KLYKKTLKRT RKFVVDGVEV
     SITTSKIISE DEKKDEEMRF LRRQELRELR LLQKEEHRNQ TQLSNKHELQ LEQMHKRFEQ
     EINAKKKFFD TELENLERQQ KQQVEKMEQD HAVRRREEAR RIRLEQDRDY TRFQEQLKLM
     KKEVKNEVEK LPRQQRKESM KQKMEEHTQK KQLLDRDFVA KQKEDLELAM KRLTTDNRRE
     ICDKERECLM KKQELLRDRE AALWEMEEHQ LQERHQLVKQ QLKDQYFLQR HELLRKHEKE
     REQMQRYNQR MIEQLKVRQQ QEKARLPKIQ RSEGKTRMAM YKKSLHINGG GSAAEQREKI
     KQFSQQEEKR QKSERLQQQQ KHENQMRDML AQCESNMSEL QQLQNEKCHL LVEHETQKLK
     ALDESHNQNL KEWRDKLRPR KKALEEDLNQ KKREQEMFFK LSEEAECPNP STPSKAAKFF
     PYSSADAS
//
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