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 18-JUL-2018, entry version 179. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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- RT oriented kinase, and comparative chromosomal mapping of the human, RT mouse, and rat 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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 RT regulating the 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 RT expressed in hematopoietic tissue."; RL J. Biol. Chem. 278:18221-18228(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION RP BY 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 RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION RP BY 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 RT sequential 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 RP BY 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 RT the 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 RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [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., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191; SER-438 AND RP SER-549, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation 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., RA Buerckstuemmer T., 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 ENZYME 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 RT enhances 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome 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 RP 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 RP THR-952, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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, ENZYME 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., RA Parker S.A., 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., RA Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R., RA Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A., RA West S., Widaa S., Yates A., Gillis A.J.M., Stoop H.J., RA van Gurp R.J.H.L.M., Oosterhuis J.W., Looijenga L.H.J., Futreal P.A., RA Wooster R., Stratton M.R.; RT "Sequence analysis of the protein kinase gene family in human RT testicular 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 CC of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. CC Involved in regulation of lymphocyte migration by mediating CC phosphorylation of ERM proteins such as MSN. Acts as a negative CC regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator CC by acting as a polo kinase kinase: mediates phosphorylation of CC PLK1 in vitro; however such data require additional evidences in CC vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, CC ECO:0000269|PubMed:19255442}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC {ECO:0000269|PubMed:18239682}. CC -!- ENZYME 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 CC the lysine side chain. Also specifically inhibited by erlotinib. CC Slightly inhibited by gefitinib. {ECO:0000269|PubMed:18239682, CC ECO:0000269|PubMed:21606217}. CC -!- SUBUNIT: Homodimer; homodimerization is required for activation CC segment 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 CC tissues (spleen, placenta, and peripheral blood leukocytes). Also CC expressed in brain, heart, skeletal muscle, colon, thymus, kidney, CC liver, small 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. CC TGCTs have various pathologic subtypes including: unclassified CC intratubular 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 CC EGFR tyrosine kinase inhibitor used for treatment, enhances STK10- CC dependent lymphocytic responses, possibly leading to the CC aggravation of skin inflammation observed upon treatment by CC erlotinib. {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=Translation N-terminally extended.; 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 UniGene; Hs.744005; -. 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 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 ProteinModelPortal; O94804; -. DR SMR; O94804; -. DR BioGrid; 112669; 9. DR IntAct; O94804; 2. DR MINT; O94804; -. DR STRING; 9606.ENSP00000176763; -. DR BindingDB; O94804; -. DR ChEMBL; CHEMBL3981; -. DR GuidetoPHARMACOLOGY; 2211; -. DR iPTMnet; O94804; -. DR PhosphoSitePlus; O94804; -. DR BioMuta; STK10; -. DR EPD; 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; ENSGT00920000148966; -. DR HOGENOM; HOG000236268; -. DR HOVERGEN; HBG052712; -. DR InParanoid; O94804; -. DR KO; K08837; -. DR OMA; SEEAECP; -. DR OrthoDB; EOG091G01Y1; -. 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 PRO; PR:O94804; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000072786; -. DR CleanEx; HS_STK10; -. 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:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB. DR GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central. DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central. 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 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; KW Complete proteome; Kinase; Membrane; Nucleotide-binding; KW Phosphoprotein; Polymorphism; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 968 Serine/threonine-protein kinase 10. FT /FTId=PRO_0000086697. FT DOMAIN 36 294 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 42 50 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 175 224 Activation segment. FT COILED 573 947 {ECO:0000255}. FT COMPBIAS 750 884 Gln-rich. FT ACT_SITE 157 157 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 65 65 ATP. {ECO:0000305}. FT BINDING 111 111 Inhibitor. FT BINDING 113 113 Inhibitor. FT BINDING 117 117 Inhibitor; via amide nitrogen. FT BINDING 175 175 Inhibitor. FT MOD_RES 13 13 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 20 20 Phosphoserine. FT {ECO:0000250|UniProtKB:E9PTG8}. FT MOD_RES 191 191 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195}. FT MOD_RES 438 438 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18088087, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19367720, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 450 450 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 454 454 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 485 485 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 514 514 Phosphoserine. FT {ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 549 549 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 952 952 Phosphothreonine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT VARIANT 268 268 R -> C (in dbSNP:rs35826078). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041131. FT VARIANT 277 277 K -> E (in TGCT; somatic mutation; FT dbSNP:rs757545210). FT {ECO:0000269|PubMed:16175573, FT ECO:0000269|PubMed:17344846}. FT /FTId=VAR_023827. FT VARIANT 322 322 R -> W (in dbSNP:rs56214442). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041132. FT VARIANT 336 336 T -> I (in dbSNP:rs55972616). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041133. FT VARIANT 467 467 N -> S (in dbSNP:rs56063773). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041134. FT VARIANT 480 480 P -> L (in dbSNP:rs34505340). FT /FTId=VAR_051671. FT VARIANT 520 520 P -> L (in dbSNP:rs17074311). FT /FTId=VAR_051672. FT VARIANT 710 710 M -> T (in dbSNP:rs34936670). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041135. FT VARIANT 853 853 S -> L (in dbSNP:rs56066852). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041136. FT VARIANT 905 905 S -> T (in dbSNP:rs55791916). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041137. FT VARIANT 942 942 S -> N (in dbSNP:rs1128204). FT /FTId=VAR_051673. FT VARIANT 947 947 C -> Y (in dbSNP:rs56355550). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041138. FT MUTAGEN 65 65 K->I: Loss of kinase activity. FT {ECO:0000269|PubMed:12639966}. FT CONFLICT 62 62 A -> V (in Ref. 5; AAH70077). FT {ECO:0000305}. FT CONFLICT 136 136 V -> E (in Ref. 5; AAH70077). FT {ECO:0000305}. FT CONFLICT 317 317 E -> G (in Ref. 5; AAH70077). FT {ECO:0000305}. FT STRAND 27 30 {ECO:0000244|PDB:2J7T}. FT HELIX 32 34 {ECO:0000244|PDB:6EIM}. FT STRAND 36 41 {ECO:0000244|PDB:6EIM}. FT STRAND 45 47 {ECO:0000244|PDB:4USE}. FT STRAND 50 55 {ECO:0000244|PDB:6EIM}. FT TURN 56 58 {ECO:0000244|PDB:6EIM}. FT STRAND 61 68 {ECO:0000244|PDB:6EIM}. FT HELIX 72 87 {ECO:0000244|PDB:6EIM}. FT STRAND 96 102 {ECO:0000244|PDB:6EIM}. FT STRAND 105 111 {ECO:0000244|PDB:6EIM}. FT HELIX 118 125 {ECO:0000244|PDB:6EIM}. FT HELIX 131 150 {ECO:0000244|PDB:6EIM}. FT HELIX 160 162 {ECO:0000244|PDB:6EIM}. FT STRAND 163 165 {ECO:0000244|PDB:6EIM}. FT STRAND 171 173 {ECO:0000244|PDB:6EIM}. FT HELIX 180 187 {ECO:0000244|PDB:6EIM}. FT HELIX 196 198 {ECO:0000244|PDB:6EIM}. FT HELIX 201 207 {ECO:0000244|PDB:6EIM}. FT TURN 208 211 {ECO:0000244|PDB:6EIM}. FT HELIX 213 216 {ECO:0000244|PDB:6EIM}. FT HELIX 217 232 {ECO:0000244|PDB:6EIM}. FT TURN 236 239 {ECO:0000244|PDB:6EIM}. FT HELIX 242 251 {ECO:0000244|PDB:6EIM}. FT HELIX 260 262 {ECO:0000244|PDB:6EIM}. FT HELIX 265 274 {ECO:0000244|PDB:6EIM}. FT TURN 279 281 {ECO:0000244|PDB:6EIM}. FT HELIX 285 288 {ECO:0000244|PDB:6EIM}. FT TURN 292 296 {ECO:0000244|PDB:6EIM}. FT HELIX 301 314 {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 //