true1995-02-012024-03-27241CSK_HUMANCYL encodes a putative cytoplasmic tyrosine kinase lacking the conserved tyrosine autophosphorylation site (Y416src).Partanen J.Armstrong E.Bergman M.Maekelae T.P.Hirvonen H.Huebner K.Alitalo K.1991Oncogene62013-2018NUCLEOTIDE SEQUENCE [MRNA]PHOSPHORYLATION AT TYR-416Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase.Braeuninger A.Holtrich U.Strebhardt K.Ruebsamen-Waigmann H.doi:10.1073/pnas.88.23.104111991Proc. Natl. Acad. Sci. U.S.A.8810411-10415NUCLEOTIDE SEQUENCE [MRNA]LungIsolation and characterization of a human gene that encodes a new subclass of protein tyrosine kinases.Brauninger A.Holtrich U.Strebhardt K.Rubsamen-Waigmann H.doi:10.1016/0378-1119(92)90649-a1992Gene110205-211NUCLEOTIDE SEQUENCE [GENOMIC DNA]TISSUE SPECIFICITYCharacterization of the human CSK locus.Braeuninger A.Karn T.Strebhardt K.Ruebsamen-Waigmann H.1993Oncogene81365-1369NUCLEOTIDE SEQUENCE [GENOMIC DNA]Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).Halleck A.Ebert L.Mkoundinya M.Schick M.Eisenstein S.Neubert P.Kstrang K.Schatten R.Shen B.Henze S.Mar W.Korn B.Zuo D.Hu Y.LaBaer J.2004-06EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]NIEHS SNPs program2005-05EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [GENOMIC DNA]VARIANTS ASP-287; GLN-398 AND ARG-442The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]BrainUterusThe human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity.Bergman M.Mustelin T.Oetken C.Partanen J.Flint N.A.Amrein K.E.Autero M.Burn P.Alitalo K.doi:10.1002/j.1460-2075.1992.tb05361.x1992EMBO J.112919-2924FUNCTION IN PHOSPHORYLATION OF LCKCATALYTIC ACTIVITYCOFACTORRecombinant Csk expressed in Escherichia coli is autophosphorylated on tyrosine residue(s).Bougeret C.Rothhut B.Jullien P.Fischer S.Benarous R.1993Oncogene81241-1247AUTOPHOSPHORYLATIONCATALYTIC ACTIVITYExpression, purification, and initial characterization of human Yes protein tyrosine kinase from a bacterial expression system.Sun G.Budde R.J.doi:10.1006/abbi.1997.02361997Arch. Biochem. Biophys.345135-142FUNCTION IN PHOSPHORYLATION OF YES1CATALYTIC ACTIVITYCOFACTORIdentification of csk tyrosine phosphorylation sites and a tyrosine residue important for kinase domain structure.Joukov V.Vihinen M.Vainikka S.Sowadski J.M.Alitalo K.Bergman M.doi:10.1042/bj32209271997Biochem. J.322927-935PHOSPHORYLATION AT TYR-184 AND TYR-304MUTAGENESIS OF TYR-184 AND TYR-304Phosphorylation of Hic-5 at tyrosine 60 by CAKbeta and Fyn.Ishino M.Aoto H.Sasaski H.Suzuki R.Sasaki T.doi:10.1016/s0014-5793(00)01597-02000FEBS Lett.474179-183INTERACTION WITH TGFB1I1Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation.Brdicka T.Pavlistova D.Bruyns E.Leo A.Korinek V.Angelisova P.Scherer J.Shevchenko A.Shevchenko A.'Hilgert I.Cerny J.Drbal K.Kuramitsu Y.Horejsi V.Schraven B.doi:10.1084/jem.191.9.15912000J. Exp. Med.1911591-1604INTERACTION WITH PAG1Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein).Pfrepper K.-I.Marie-Cardine A.Simeoni L.Kuramitsu Y.Leo A.Spicka J.Hilgert I.Scherer J.Schraven B.doi:10.1002/1521-4141(200106)31:6<1825::aid-immu1825>3.0.co;2-v2001Eur. J. Immunol.311825-1836INTERACTION WITH SIT1Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor.Vang T.Torgersen K.M.Sundvold V.Saxena M.Levy F.O.Skalhegg B.S.Hansson V.Mustelin T.Tasken K.doi:10.1084/jem.193.4.4972001J. Exp. Med.193497-507PHOSPHORYLATION AT SER-364 BY PKAMUTAGENESIS OF SER-364LIME: a new membrane raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling.Brdickova N.Brdicka T.Angelisova P.Horvath O.Spicka J.Hilgert I.Paces J.Simeoni L.Kliche S.Merten C.Schraven B.Horejsi V.doi:10.1084/jem.200314842003J. Exp. Med.1981453-1462INTERACTION WITH LIME1A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.Begovich A.B.Carlton V.E.Honigberg L.A.Schrodi S.J.Chokkalingam A.P.Alexander H.C.Ardlie K.G.Huang Q.Smith A.M.Spoerke J.M.Conn M.T.Chang M.Chang S.Y.Saiki R.K.Catanese J.J.Leong D.U.Garcia V.E.McAllister L.B.Jeffery D.A.Lee A.T.Batliwalla F.Remmers E.Criswell L.A.Seldin M.F.Kastner D.L.Amos C.I.Sninsky J.J.Gregersen P.K.doi:10.1086/4228272004Am. J. Hum. Genet.75330-337INTERACTION WITH PTPN22C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) -- endogenous negative regulators of Src-family protein kinases.Chong Y.P.Mulhern T.D.Cheng H.C.doi:10.1080/089771905001788772005Growth Factors23233-244REVIEWp140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity.Di Stefano P.Damiano L.Cabodi S.Aramu S.Tordella L.Praduroux A.Piva R.Cavallo F.Forni G.Silengo L.Tarone G.Turco E.Defilippi P.doi:10.1038/sj.emboj.76017242007EMBO J.262843-2855INTERACTION WITH SRCIN1Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.Gauci S.Helbig A.O.Slijper M.Krijgsveld J.Heck A.J.Mohammed S.doi:10.1021/ac90043092009Anal. Chem.814493-4501ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]The tyrosine kinase Csk dimerizes through Its SH3 domain.Levinson N.M.Visperas P.R.Kuriyan J.doi:10.1371/journal.pone.00076832009PLoS ONE4E7683HOMODIMERIZATIONInitial characterization of the human central proteome.Burkard T.R.Planyavsky M.Kaupe I.Breitwieser F.P.Buerckstuemmer T.Bennett K.L.Superti-Furga G.Colinge J.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]RhoH modulates pre-TCR and TCR signalling by regulating LCK.Wang H.Zeng X.Fan Z.Lim B.doi:10.1016/j.cellsig.2010.09.0092011Cell. Signal.23249-258INTERACTION WITH RHOHSCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling.Draber P.Vonkova I.Stepanek O.Hrdinka M.Kucova M.Skopcova T.Otahal P.Angelisova P.Horejsi V.Yeung M.Weiss A.Brdicka T.doi:10.1128/mcb.05817-112011Mol. Cell. Biol.314550-4562INTERACTION WITH SCIMPTargeted disruption of leucine-rich repeat kinase 1 but not leucine-rich repeat kinase 2 in mice causes severe osteopetrosis.Xing W.Liu J.Cheng S.Vogel P.Mohan S.Brommage R.doi:10.1002/jbmr.19352013J. Bone Miner. Res.281962-1974INTERACTION WITH LRRK1The crystal structure of human CskSH3: structural diversity near the RT-Src and n-Src loop.Borchert T.V.Mathieu M.Zeelen J.P.Courtneidge S.A.Wierenga R.K.doi:10.1016/0014-5793(94)80244-01994FEBS Lett.34179-85X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-71Patterns of somatic mutation in human cancer genomes.Greenman C.Stephens P.Smith R.Dalgliesh G.L.Hunter C.Bignell G.Davies H.Teague J.Butler A.Stevens C.Edkins S.O'Meara S.Vastrik I.Schmidt E.E.Avis T.Barthorpe S.Bhamra G.Buck G.Choudhury B.Clements J.Cole J.Dicks E.Forbes S.Gray K.Halliday K.Harrison R.Hills K.Hinton J.Jenkinson A.Jones D.Menzies A.Mironenko T.Perry J.Raine K.Richardson D.Shepherd R.Small A.Tofts C.Varian J.Webb T.West S.Widaa S.Yates A.Cahill D.P.Louis D.N.Goldstraw P.Nicholson A.G.Brasseur F.Looijenga L.Weber B.L.Chiew Y.-E.DeFazio A.Greaves M.F.Green A.R.Campbell P.Birney E.Easton D.F.Chenevix-Trench G.Tan M.-H.Khoo S.K.Teh B.T.Yuen S.T.Leung S.Y.Wooster R.Futreal P.A.Stratton M.R.doi:10.1038/nature056102007Nature446153-158VARIANT [LARGE SCALE ANALYSIS] LEU-45NIEHS-SNPs2.40A=173-4502.50A/B/C/D=1-712.90A=188-4504.11A/C=188-4501.37A=73-1781.31A=73-17884893DasatinibFostamatinibStaurosporineTG-1008011 site, 1 O-linked glycan (1 site)882 antibodies from 42 providershumanCSKTissue enhanced (lymphoid)geneEukaryota2681GAB1 signalosomePhosphorylation of CD3 and TCR zeta chainsIntegrin signalingPD-1 signalingMAP2K and MAPK activationSignaling by moderate kinase activity BRAF mutantsSignaling by high-kinase activity BRAF mutantsSignaling by BRAF and RAF1 fusionsParadoxical activation of RAF signaling by kinase inactive BRAFRHOH GTPase cycleSignaling downstream of RAS mutantsSignaling by RAF1 mutantsNegative regulation of FLT385 hits in 1203 CRISPR screenshumanTchemProteinExpressed in granulocyte and 189 other cell types or tissuesbaseline and differentialPTKc_CskSH2_csk_likeSH3_CSKSH2 domainSH3 DomainsTransferase(Phosphotransferase) domain 1Csk-like_SH2Kinase-like_dom_sfProt_kinase_domProtein_kinase_ATP_BSSer-Thr/Tyr_kinase_cat_domSH2SH2_dom_sfSH3-like_dom_sfSH3_domainTyr_kinase_ASTyr_kinase_cat_domTYROSINE-PROTEIN KINASETYROSINE-PROTEIN KINASE CSKPK_Tyr_Ser-ThrSH2SH3_1SH2DOMAINTYRKINASESH2SH3TyrKcProtein kinase-like (PK-like)SH2 domainSH3-domainPROTEIN_KINASE_ATPPROTEIN_KINASE_DOMPROTEIN_KINASE_TYRSH2SH3HSTyrosine-protein kinase CSK2.7.10.2C-Src kinaseProtein-tyrosine kinase CYLCSKNon-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK.Homodimer (via SH3-domain) (PubMed:19888460). Interacts with PTPN22 (PubMed:15208781). Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases (PubMed:11433379, PubMed:10790433, PubMed:14610046, PubMed:10838081). Interacts with SRCIN1 (PubMed:17525734). Interacts with RHOH (PubMed:20851766). Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-107' (PubMed:21930792). Interacts (via SH2 domain) with PRAG1 (when phosphorylated at 'Tyr-391'); this interaction prevents translocation of CSK from the cytoplasm to the membrane leading to increased activity of CSK (By similarity). Interacts with LRRK1 (PubMed:23526378).Mainly cytoplasmic, also present in lipid rafts.Expressed in lung and macrophages.The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated.Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.Removed1Tyrosine-protein kinase CSK505732450SH3970SH282171Protein kinase195449Interaction with PTPN22Proton acceptor314201209222N-acetylserinePhosphotyrosine184Phosphotyrosine304Phosphoserine; by PKA364Phosphotyrosine; by autocatalysis416L45D287Q398R442Abolishes phosphorylation.FDecreases activity by two-thirds and alters conformation.FStrong decrease of phosphorylation by PRKACA (catalytic subunit of PKA).A12183541475157616466777983868995103108116122125130132134137144146148149158163165192194203208214217223231235237240251255263266274285288307317319320322328330350352355360365380392394395399400402413422427429433446false7false3false5false3false5false3false4false3true4true7CSKDDIT4LIGF1RKANK4PAG1PTPRCPXNSCIMPlspA1SRC1995-02-0115070464016a73cb830d06c4225bede18f3ee5MSAIQAAWPSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGIIPANYVQKREGVKAGTKLSLMPWFHGKITREQAERLLYPPETGLFLVRESTNYPGDYTLCVSCDGKVEHYRIMYHASKLSIDEEVYFENLMQLVEHYTSDADGLCTRLIKPKVMEGTVAAQDEFYRSGWALNMKELKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKNDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKGGLYIVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYEVMKNCWHLDAAMRPSFLQLREQLEHIKTHELHLtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue