STK10_HUMAN
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 03-AUG-2022, entry version 203.
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] {ECO:0007744|PDB:2J7T}
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 O94804; O94804: STK10; 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 variants 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};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; 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 PDB; 7QGP; X-ray; 1.90 A; A=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 PDBsum; 7QGP; -.
DR AlphaFoldDB; O94804; -.
DR SMR; O94804; -.
DR BioGRID; 112669; 31.
DR IntAct; O94804; 7.
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 MetOSite; 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 Antibodypedia; 28880; 287 antibodies from 32 providers.
DR DNASU; 6793; -.
DR Ensembl; ENST00000176763.10; ENSP00000176763.5; ENSG00000072786.13.
DR GeneID; 6793; -.
DR KEGG; hsa:6793; -.
DR MANE-Select; ENST00000176763.10; ENSP00000176763.5; NM_005990.4; NP_005981.3.
DR UCSC; uc003mbo.2; human.
DR CTD; 6793; -.
DR DisGeNET; 6793; -.
DR GeneCards; STK10; -.
DR HGNC; HGNC:11388; STK10.
DR HPA; ENSG00000072786; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; STK10; -.
DR MIM; 273300; phenotype.
DR MIM; 603919; gene.
DR neXtProt; NX_O94804; -.
DR OpenTargets; ENSG00000072786; -.
DR PharmGKB; PA36197; -.
DR VEuPathDB; HostDB:ENSG00000072786; -.
DR eggNOG; KOG0579; Eukaryota.
DR GeneTree; ENSGT00940000156818; -.
DR HOGENOM; CLU_001965_3_0_1; -.
DR InParanoid; O94804; -.
DR OMA; CHMLVEN; -.
DR OrthoDB; 851098at2759; -.
DR PhylomeDB; O94804; -.
DR TreeFam; TF351445; -.
DR PathwayCommons; O94804; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR SignaLink; O94804; -.
DR SIGNOR; O94804; -.
DR BioGRID-ORCS; 6793; 11 hits in 1112 CRISPR screens.
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 granulocyte and 176 other tissues.
DR ExpressionAtlas; O94804; baseline and differential.
DR Genevisible; O94804; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0071593; P:lymphocyte aggregation; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
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; Reference proteome;
KW 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 REGION 175..224
FT /note="Activation segment"
FT REGION 337..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 425..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 827..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 910..929
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 944..968
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 573..947
FT /evidence="ECO:0000255"
FT COMPBIAS 337..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..457
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 840..862
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|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:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 952
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|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:0007829|PDB:7QGP"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:6GTT"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:6EIM"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 131..150
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6EIM"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 180..187
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 201..207
FT /evidence="ECO:0007829|PDB:6EIM"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 217..232
FT /evidence="ECO:0007829|PDB:6EIM"
FT TURN 236..239
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 265..274
FT /evidence="ECO:0007829|PDB:6EIM"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:6EIM"
FT TURN 292..296
FT /evidence="ECO:0007829|PDB:6EIM"
FT HELIX 301..314
FT /evidence="ECO:0007829|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
