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 14-DEC-2022, entry version 205. 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; 41. 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 ProteomicsDB; 50444; -. DR Antibodypedia; 28880; 284 antibodies from 31 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 AGR; HGNC:11388; -. 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; Protein kinase-like (PK-like); 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 //