ID STYK1_HUMAN Reviewed; 422 AA. AC Q6J9G0; B2R9T2; Q52LR3; Q9BXY2; Q9NSH1; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 27-MAR-2024, entry version 165. DE RecName: Full=Tyrosine-protein kinase STYK1; DE EC=2.7.10.2; DE AltName: Full=Novel oncogene with kinase domain; DE AltName: Full=Protein PK-unique; DE AltName: Full=Serine/threonine/tyrosine kinase 1; GN Name=STYK1; Synonyms=NOK; 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], TISSUE SPECIFICITY, AND VARIANT GLY-204. RC TISSUE=Fetal brain; RX PubMed=12841579; DOI=10.1023/a:1023934017174; RA Ye X., Ji C., Huang Q., Cheng C., Tang R., Xu J., Zeng L., Dai J., Wu Q., RA Gu S., Xie Y., Mao Y.; RT "Isolation and characterization of a human putative receptor protein kinase RT cDNA STYK1."; RL Mol. Biol. Rep. 30:91-96(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Amygdala; RX PubMed=15150103; DOI=10.1158/0008-5472.can-03-2106; RA Liu L., Yu X.-Z., Li T.-S., Song L.-X., Chen P.-L., Suo T.-L., Li Y.-H., RA Wang S.-D., Chen Y., Ren Y.-M., Zhang S.-P., Chang Z.-J., Fu X.-Y.; RT "A novel protein tyrosine kinase NOK that shares homology with platelet- RT derived growth factor/fibroblast growth factor receptors induces RT tumorigenesis and metastasis in nude mice."; RL Cancer Res. 64:3491-3499(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-204. RC TISSUE=Hippocampus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-204. RC TISSUE=Amygdala; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-204. 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-204. RC TISSUE=Brain; 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 [8] RP TISSUE SPECIFICITY. RX PubMed=17298854; DOI=10.1016/j.lungcan.2007.01.002; RA Amachika T., Kobayashi D., Moriai R., Tsuji N., Watanabe N.; RT "Diagnostic relevance of overexpressed mRNA of novel oncogene with kinase- RT domain (NOK) in lung cancers."; RL Lung Cancer 56:337-340(2007). RN [9] RP VARIANTS [LARGE SCALE ANALYSIS] GLY-204; TRP-210; SER-237; HIS-379; ILE-395 RP AND LEU-400. 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: Probable tyrosine protein-kinase, which has strong CC transforming capabilities on a variety of cell lines. When CC overexpressed, it can also induce tumor cell invasion as well as CC metastasis in distant organs. May act by activating both MAP kinase and CC phosphatidylinositol 3'-kinases (PI3K) pathways (By similarity). CC {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- INTERACTION: CC Q6J9G0; P49841: GSK3B; NbExp=2; IntAct=EBI-6424915, EBI-373586; CC Q6J9G0; P08238: HSP90AB1; NbExp=3; IntAct=EBI-6424915, EBI-352572; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane CC protein {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in brain, CC placenta and prostate. Expressed in tumor cells such as hepatoma cells CC L-02, cervix carcinoma cells HeLa, ovary cancer cells Ho8910 and CC chronic myelogenous leukemia cells K-562, but not in other tumor cells CC such as epidermoid carcinoma (A-431). Undetectable in most normal lung CC tissues, widely expressed in lung cancers. CC {ECO:0000269|PubMed:12841579, ECO:0000269|PubMed:15150103, CC ECO:0000269|PubMed:17298854}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. 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; AF251059; AAK34949.1; -; mRNA. DR EMBL; AY563054; AAT01226.1; -; mRNA. DR EMBL; AK313906; BAG36629.1; -; mRNA. DR EMBL; AL353940; CAB89250.1; -; mRNA. DR EMBL; AC021049; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471094; EAW96200.1; -; Genomic_DNA. DR EMBL; BC093822; AAH93822.1; -; mRNA. DR EMBL; BC093824; AAH93824.1; -; mRNA. DR CCDS; CCDS8629.1; -. DR PIR; T48680; T48680. DR RefSeq; NP_060893.2; NM_018423.2. DR RefSeq; XP_005253474.1; XM_005253417.2. DR RefSeq; XP_011519038.1; XM_011520736.1. DR RefSeq; XP_011519039.1; XM_011520737.2. DR RefSeq; XP_011519040.1; XM_011520738.2. DR AlphaFoldDB; Q6J9G0; -. DR SMR; Q6J9G0; -. DR BioGRID; 120638; 165. DR IntAct; Q6J9G0; 140. DR MINT; Q6J9G0; -. DR STRING; 9606.ENSP00000075503; -. DR iPTMnet; Q6J9G0; -. DR PhosphoSitePlus; Q6J9G0; -. DR BioMuta; STYK1; -. DR DMDM; 317373546; -. DR CPTAC; CPTAC-3013; -. DR CPTAC; CPTAC-3014; -. DR jPOST; Q6J9G0; -. DR MassIVE; Q6J9G0; -. DR PaxDb; 9606-ENSP00000075503; -. DR PeptideAtlas; Q6J9G0; -. DR ProteomicsDB; 66510; -. DR TopDownProteomics; Q6J9G0; -. DR Antibodypedia; 23371; 357 antibodies from 34 providers. DR DNASU; 55359; -. DR Ensembl; ENST00000075503.8; ENSP00000075503.3; ENSG00000060140.9. DR GeneID; 55359; -. DR KEGG; hsa:55359; -. DR MANE-Select; ENST00000075503.8; ENSP00000075503.3; NM_018423.3; NP_060893.2. DR UCSC; uc001qys.2; human. DR AGR; HGNC:18889; -. DR CTD; 55359; -. DR DisGeNET; 55359; -. DR GeneCards; STYK1; -. DR HGNC; HGNC:18889; STYK1. DR HPA; ENSG00000060140; Tissue enhanced (intestine, stomach). DR MIM; 611433; gene. DR neXtProt; NX_Q6J9G0; -. DR OpenTargets; ENSG00000060140; -. DR PharmGKB; PA134976821; -. DR VEuPathDB; HostDB:ENSG00000060140; -. DR eggNOG; KOG0200; Eukaryota. DR GeneTree; ENSGT00940000157871; -. DR HOGENOM; CLU_000288_7_7_1; -. DR InParanoid; Q6J9G0; -. DR OMA; SCCQWKE; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q6J9G0; -. DR TreeFam; TF316675; -. DR PathwayCommons; Q6J9G0; -. DR SignaLink; Q6J9G0; -. DR SIGNOR; Q6J9G0; -. DR BioGRID-ORCS; 55359; 13 hits in 1180 CRISPR screens. DR GeneWiki; STYK1; -. DR GenomeRNAi; 55359; -. DR Pharos; Q6J9G0; Tbio. DR PRO; PR:Q6J9G0; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q6J9G0; Protein. DR Bgee; ENSG00000060140; Expressed in endothelial cell and 156 other cell types or tissues. DR ExpressionAtlas; Q6J9G0; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR PANTHER; PTHR24416:SF592; SERINE_THREONINE_TYROSINE KINASE 1; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PRINTS; PR00109; TYRKINASE. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR Genevisible; Q6J9G0; HS. PE 1: Evidence at protein level; KW ATP-binding; Kinase; Membrane; Nucleotide-binding; Proto-oncogene; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase. FT CHAIN 1..422 FT /note="Tyrosine-protein kinase STYK1" FT /id="PRO_0000088163" FT TRANSMEM 26..46 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 114..384 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 251 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 120..128 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 147 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT VARIANT 71 FT /note="R -> G (in dbSNP:rs6650202)" FT /id="VAR_030766" FT VARIANT 204 FT /note="S -> G (in dbSNP:rs3759259)" FT /evidence="ECO:0000269|PubMed:12841579, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:17974005, FT ECO:0000269|Ref.6" FT /id="VAR_022245" FT VARIANT 210 FT /note="R -> W (in dbSNP:rs34981955)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041841" FT VARIANT 237 FT /note="L -> S (in dbSNP:rs55877878)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041842" FT VARIANT 379 FT /note="R -> H (in dbSNP:rs34638573)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041843" FT VARIANT 395 FT /note="V -> I (in a glioblastoma multiforme sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041844" FT VARIANT 400 FT /note="V -> L (in dbSNP:rs55766125)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041845" FT CONFLICT 192 FT /note="M -> V (in Ref. 1; AAK34949 and 2; AAT01226)" FT /evidence="ECO:0000305" FT CONFLICT 304 FT /note="S -> R (in Ref. 1; AAK34949 and 2; AAT01226)" FT /evidence="ECO:0000305" SQ SEQUENCE 422 AA; 47577 MW; AAD45F481BD61C73 CRC64; MGMTRMLLEC SLSDKLCVIQ EKQYEVIIVP TLLVTIFLIL LGVILWLFIR EQRTQQQRSG PQGIAPVPPP RDLSWEAGHG GNVALPLKET SVENFLGATT PALAKLQVPR EQLSEVLEQI CSGSCGPIFR ANMNTGDPSK PKSVILKALK EPAGLHEVQD FLGRIQFHQY LGKHKNLVQL EGCCTEKLPL YMVLEDVAQG DLLSFLWTCR RDVMTMDGLL YDLTEKQVYH IGKQVLLALE FLQEKHLFHG DVAARNILMQ SDLTAKLCGL GLAYEVYTRG AISSTQTIPL KWLAPERLLL RPASIRADVW SFGILLYEMV TLGAPPYPEV PPTSILEHLQ RRKIMKRPSS CTHTMYSIMK SCWRWREADR PSPRELRLRL EAAIKTADDE AVLQVPELVV PELYAAVAGI RVESLFYNYS ML //