CSK_HUMAN
ID CSK_HUMAN Reviewed; 450 AA.
AC P41240; Q2M3N2; Q6FGZ6;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Tyrosine-protein kinase CSK;
DE EC=2.7.10.2 {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:7683130, ECO:0000269|PubMed:9281320};
DE AltName: Full=C-Src kinase;
DE AltName: Full=Protein-tyrosine kinase CYL;
GN Name=CSK;
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], AND PHOSPHORYLATION AT TYR-416.
RX PubMed=1945408;
RA Partanen J., Armstrong E., Bergman M., Maekelae T.P., Hirvonen H.,
RA Huebner K., Alitalo K.;
RT "CYL encodes a putative cytoplasmic tyrosine kinase lacking the conserved
RT tyrosine autophosphorylation site (Y416src).";
RL Oncogene 6:2013-2018(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=1720539; DOI=10.1073/pnas.88.23.10411;
RA Braeuninger A., Holtrich U., Strebhardt K., Ruebsamen-Waigmann H.;
RT "Two additional protein-tyrosine kinases expressed in human lung: fourth
RT member of the fibroblast growth factor receptor family and an intracellular
RT protein-tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10411-10415(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=1371489; DOI=10.1016/0378-1119(92)90649-a;
RA Brauninger A., Holtrich U., Strebhardt K., Rubsamen-Waigmann H.;
RT "Isolation and characterization of a human gene that encodes a new subclass
RT of protein tyrosine kinases.";
RL Gene 110:205-211(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7683131;
RA Braeuninger A., Karn T., Strebhardt K., Ruebsamen-Waigmann H.;
RT "Characterization of the human CSK locus.";
RL Oncogene 8:1365-1369(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-287; GLN-398 AND
RP ARG-442.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Uterus;
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 FUNCTION IN PHOSPHORYLATION OF LCK, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=1639064; DOI=10.1002/j.1460-2075.1992.tb05361.x;
RA Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., Amrein K.E.,
RA Autero M., Burn P., Alitalo K.;
RT "The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down
RT regulates its catalytic activity.";
RL EMBO J. 11:2919-2924(1992).
RN [9]
RP AUTOPHOSPHORYLATION, AND CATALYTIC ACTIVITY.
RX PubMed=7683130;
RA Bougeret C., Rothhut B., Jullien P., Fischer S., Benarous R.;
RT "Recombinant Csk expressed in Escherichia coli is autophosphorylated on
RT tyrosine residue(s).";
RL Oncogene 8:1241-1247(1993).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF YES1, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=9281320; DOI=10.1006/abbi.1997.0236;
RA Sun G., Budde R.J.;
RT "Expression, purification, and initial characterization of human Yes
RT protein tyrosine kinase from a bacterial expression system.";
RL Arch. Biochem. Biophys. 345:135-142(1997).
RN [11]
RP PHOSPHORYLATION AT TYR-184 AND TYR-304, AND MUTAGENESIS OF TYR-184 AND
RP TYR-304.
RX PubMed=9148770; DOI=10.1042/bj3220927;
RA Joukov V., Vihinen M., Vainikka S., Sowadski J.M., Alitalo K., Bergman M.;
RT "Identification of csk tyrosine phosphorylation sites and a tyrosine
RT residue important for kinase domain structure.";
RL Biochem. J. 322:927-935(1997).
RN [12]
RP INTERACTION WITH TGFB1I1.
RX PubMed=10838081; DOI=10.1016/s0014-5793(00)01597-0;
RA Ishino M., Aoto H., Sasaski H., Suzuki R., Sasaki T.;
RT "Phosphorylation of Hic-5 at tyrosine 60 by CAKbeta and Fyn.";
RL FEBS Lett. 474:179-183(2000).
RN [13]
RP INTERACTION WITH PAG1.
RX PubMed=10790433; DOI=10.1084/jem.191.9.1591;
RA Brdicka T., Pavlistova D., Bruyns E., Leo A., Korinek V., Angelisova P.,
RA Scherer J., Shevchenko A., Shevchenko A., Hilgert I., Cerny J., Drbal K.,
RA Kuramitsu Y., Horejsi V., Schraven B.;
RT "Phosphoprotein associated with glycosphingolipid-enriched microdomains
RT (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds
RT the protein tyrosine kinase csk and is involved in regulation of T cell
RT activation.";
RL J. Exp. Med. 191:1591-1604(2000).
RN [14]
RP INTERACTION WITH SIT1.
RX PubMed=11433379;
RX DOI=10.1002/1521-4141(200106)31:6<1825::aid-immu1825>3.0.co;2-v;
RA Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A.,
RA Spicka J., Hilgert I., Scherer J., Schraven B.;
RT "Structural and functional dissection of the cytoplasmic domain of the
RT transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor
RT protein).";
RL Eur. J. Immunol. 31:1825-1836(2001).
RN [15]
RP PHOSPHORYLATION AT SER-364 BY PKA, AND MUTAGENESIS OF SER-364.
RX PubMed=11181701; DOI=10.1084/jem.193.4.497;
RA Vang T., Torgersen K.M., Sundvold V., Saxena M., Levy F.O., Skalhegg B.S.,
RA Hansson V., Mustelin T., Tasken K.;
RT "Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein
RT kinase inhibits signaling through the T cell receptor.";
RL J. Exp. Med. 193:497-507(2001).
RN [16]
RP INTERACTION WITH LIME1.
RX PubMed=14610046; DOI=10.1084/jem.20031484;
RA Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., Hilgert I.,
RA Paces J., Simeoni L., Kliche S., Merten C., Schraven B., Horejsi V.;
RT "LIME: a new membrane raft-associated adaptor protein involved in CD4 and
RT CD8 coreceptor signaling.";
RL J. Exp. Med. 198:1453-1462(2003).
RN [17]
RP INTERACTION WITH PTPN22.
RX PubMed=15208781; DOI=10.1086/422827;
RA Begovich A.B., Carlton V.E., Honigberg L.A., Schrodi S.J.,
RA Chokkalingam A.P., Alexander H.C., Ardlie K.G., Huang Q., Smith A.M.,
RA Spoerke J.M., Conn M.T., Chang M., Chang S.Y., Saiki R.K., Catanese J.J.,
RA Leong D.U., Garcia V.E., McAllister L.B., Jeffery D.A., Lee A.T.,
RA Batliwalla F., Remmers E., Criswell L.A., Seldin M.F., Kastner D.L.,
RA Amos C.I., Sninsky J.J., Gregersen P.K.;
RT "A missense single-nucleotide polymorphism in a gene encoding a protein
RT tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.";
RL Am. J. Hum. Genet. 75:330-337(2004).
RN [18]
RP REVIEW.
RX PubMed=16243715; DOI=10.1080/08977190500178877;
RA Chong Y.P., Mulhern T.D., Cheng H.C.;
RT "C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) -- endogenous
RT negative regulators of Src-family protein kinases.";
RL Growth Factors 23:233-244(2005).
RN [19]
RP INTERACTION WITH SRCIN1.
RX PubMed=17525734; DOI=10.1038/sj.emboj.7601724;
RA Di Stefano P., Damiano L., Cabodi S., Aramu S., Tordella L., Praduroux A.,
RA Piva R., Cavallo F., Forni G., Silengo L., Tarone G., Turco E.,
RA Defilippi P.;
RT "p140Cap protein suppresses tumour cell properties, regulating Csk and Src
RT kinase activity.";
RL EMBO J. 26:2843-2855(2007).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [21]
RP HOMODIMERIZATION.
RX PubMed=19888460; DOI=10.1371/journal.pone.0007683;
RA Levinson N.M., Visperas P.R., Kuriyan J.;
RT "The tyrosine kinase Csk dimerizes through Its SH3 domain.";
RL PLoS ONE 4:E7683-E7683(2009).
RN [22]
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 [23]
RP INTERACTION WITH RHOH.
RX PubMed=20851766; DOI=10.1016/j.cellsig.2010.09.009;
RA Wang H., Zeng X., Fan Z., Lim B.;
RT "RhoH modulates pre-TCR and TCR signalling by regulating LCK.";
RL Cell. Signal. 23:249-258(2011).
RN [24]
RP INTERACTION WITH SCIMP.
RX PubMed=21930792; DOI=10.1128/mcb.05817-11;
RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T.,
RA Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.;
RT "SCIMP, a transmembrane adapter protein involved in major
RT histocompatibility complex class II signaling.";
RL Mol. Cell. Biol. 31:4550-4562(2011).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-71.
RX PubMed=7511113; DOI=10.1016/0014-5793(94)80244-0;
RA Borchert T.V., Mathieu M., Zeelen J.P., Courtneidge S.A., Wierenga R.K.;
RT "The crystal structure of human CskSH3: structural diversity near the RT-
RT Src and n-Src loop.";
RL FEBS Lett. 341:79-85(1994).
RN [26]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-45.
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: Non-receptor tyrosine-protein kinase that plays an important
CC role in the regulation of cell growth, differentiation, migration and
CC immune response. Phosphorylates tyrosine residues located in the C-
CC terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK,
CC FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members
CC engage in intramolecular interactions between the phosphotyrosine tail
CC and the SH2 domain that result in an inactive conformation. To inhibit
CC SFKs, CSK is recruited to the plasma membrane via binding to
CC transmembrane proteins or adapter proteins located near the plasma
CC membrane. Suppresses signaling by various surface receptors, including
CC T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and
CC maintaining inactive several positive effectors such as FYN or LCK.
CC {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:9281320}.
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:0000269|PubMed:1639064, ECO:0000269|PubMed:7683130,
CC ECO:0000269|PubMed:9281320};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9281320};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:1639064};
CC -!- SUBUNIT: Homodimer (via SH3-domain) (PubMed:19888460). Interacts with
CC PTPN22 (PubMed:15208781). Interacts with phosphorylated SIT1, PAG1,
CC LIME1 and TGFB1I1; these interactions serve to recruit CSK to the
CC membrane where it can phosphorylate and inhibit Src-family kinases
CC (PubMed:11433379, PubMed:10790433, PubMed:14610046, PubMed:10838081).
CC Interacts with SRCIN1 (PubMed:17525734). Interacts with RHOH
CC (PubMed:20851766). Interacts (via SH2 domain) with SCIMP; this
CC interaction is dependent on phosphorylation of SCIMP 'Tyr-107'
CC (PubMed:21930792). Interacts (via SH2 domain) with PRAG1 (when
CC phosphorylated at 'Tyr-391'); this interaction prevents translocation
CC of CSK from the cytoplasm to the membrane leading to increased activity
CC of CSK (By similarity). {ECO:0000250|UniProtKB:P32577,
CC ECO:0000269|PubMed:10790433, ECO:0000269|PubMed:10838081,
CC ECO:0000269|PubMed:11433379, ECO:0000269|PubMed:14610046,
CC ECO:0000269|PubMed:15208781, ECO:0000269|PubMed:17525734,
CC ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21930792}.
CC -!- INTERACTION:
CC P41240; P41240: CSK; NbExp=7; IntAct=EBI-1380630, EBI-1380630;
CC P41240; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-1380630, EBI-742054;
CC P41240; P08069: IGF1R; NbExp=5; IntAct=EBI-1380630, EBI-475981;
CC P41240; Q5T7N3: KANK4; NbExp=3; IntAct=EBI-1380630, EBI-9355810;
CC P41240; Q9NWQ8: PAG1; NbExp=5; IntAct=EBI-1380630, EBI-2828115;
CC P41240; P08575: PTPRC; NbExp=3; IntAct=EBI-1380630, EBI-1341;
CC P41240; P49023: PXN; NbExp=4; IntAct=EBI-1380630, EBI-702209;
CC P41240; Q6UWF3: SCIMP; NbExp=3; IntAct=EBI-1380630, EBI-2872510;
CC P41240; Q7VLE8: lspA1; Xeno; NbExp=4; IntAct=EBI-1380630, EBI-26445163;
CC P41240; P00523: SRC; Xeno; NbExp=7; IntAct=EBI-1380630, EBI-848039;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Mainly cytoplasmic, also present in lipid rafts.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lung and macrophages.
CC {ECO:0000269|PubMed:1371489}.
CC -!- DOMAIN: The architecture of this protein is similar to that of Src-
CC family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain,
CC and a C-terminal kinase domain.
CC -!- PTM: Phosphorylated at Ser-364 by PKA, leading to increased activity.
CC Autophosphorylated. {ECO:0000269|PubMed:11181701,
CC ECO:0000269|PubMed:9148770}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/csk/";
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DR EMBL; X60114; CAA42713.1; -; mRNA.
DR EMBL; X59932; CAA42556.1; -; mRNA.
DR EMBL; X74765; CAB58562.1; -; Genomic_DNA.
DR EMBL; CR541960; CAG46758.1; -; mRNA.
DR EMBL; DQ075211; AAY57329.1; -; Genomic_DNA.
DR EMBL; BC104847; AAI04848.1; -; mRNA.
DR EMBL; BC104875; AAI04876.1; -; mRNA.
DR EMBL; BC106073; AAI06074.1; -; mRNA.
DR CCDS; CCDS10269.1; -.
DR PIR; JH0559; JH0559.
DR RefSeq; NP_001120662.1; NM_001127190.1.
DR RefSeq; NP_004374.1; NM_004383.2.
DR RefSeq; XP_005254222.1; XM_005254165.4.
DR RefSeq; XP_016877414.1; XM_017021925.1.
DR PDB; 1BYG; X-ray; 2.40 A; A=173-450.
DR PDB; 1CSK; X-ray; 2.50 A; A/B/C/D=1-71.
DR PDB; 3D7T; X-ray; 2.90 A; A=188-450.
DR PDB; 3D7U; X-ray; 4.11 A; A/C=188-450.
DR PDB; 3EAC; X-ray; 1.37 A; A=73-178.
DR PDB; 3EAZ; X-ray; 1.31 A; A=73-178.
DR PDBsum; 1BYG; -.
DR PDBsum; 1CSK; -.
DR PDBsum; 3D7T; -.
DR PDBsum; 3D7U; -.
DR PDBsum; 3EAC; -.
DR PDBsum; 3EAZ; -.
DR AlphaFoldDB; P41240; -.
DR BMRB; P41240; -.
DR SMR; P41240; -.
DR BioGRID; 107832; 824.
DR ELM; P41240; -.
DR IntAct; P41240; 90.
DR MINT; P41240; -.
DR STRING; 9606.ENSP00000220003; -.
DR BindingDB; P41240; -.
DR ChEMBL; CHEMBL2634; -.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB02010; Staurosporine.
DR DrugBank; DB05075; TG-100801.
DR DrugCentral; P41240; -.
DR GuidetoPHARMACOLOGY; 1994; -.
DR GlyGen; P41240; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P41240; -.
DR MetOSite; P41240; -.
DR PhosphoSitePlus; P41240; -.
DR BioMuta; CSK; -.
DR DMDM; 729887; -.
DR OGP; P41240; -.
DR EPD; P41240; -.
DR jPOST; P41240; -.
DR MassIVE; P41240; -.
DR MaxQB; P41240; -.
DR PaxDb; P41240; -.
DR PeptideAtlas; P41240; -.
DR PRIDE; P41240; -.
DR ProteomicsDB; 55450; -.
DR Antibodypedia; 4405; 794 antibodies from 42 providers.
DR DNASU; 1445; -.
DR Ensembl; ENST00000220003.14; ENSP00000220003.9; ENSG00000103653.17.
DR Ensembl; ENST00000439220.6; ENSP00000414764.2; ENSG00000103653.17.
DR Ensembl; ENST00000567571.5; ENSP00000454906.1; ENSG00000103653.17.
DR GeneID; 1445; -.
DR KEGG; hsa:1445; -.
DR MANE-Select; ENST00000220003.14; ENSP00000220003.9; NM_004383.3; NP_004374.1.
DR UCSC; uc002ays.3; human.
DR CTD; 1445; -.
DR DisGeNET; 1445; -.
DR GeneCards; CSK; -.
DR HGNC; HGNC:2444; CSK.
DR HPA; ENSG00000103653; Tissue enhanced (lymphoid).
DR MIM; 124095; gene.
DR neXtProt; NX_P41240; -.
DR OpenTargets; ENSG00000103653; -.
DR PharmGKB; PA26946; -.
DR VEuPathDB; HostDB:ENSG00000103653; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000157431; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P41240; -.
DR OMA; QTMPWFH; -.
DR PhylomeDB; P41240; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P41240; -.
DR Reactome; R-HSA-180292; GAB1 signalosome.
DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-9706369; Negative regulation of FLT3.
DR SignaLink; P41240; -.
DR SIGNOR; P41240; -.
DR BioGRID-ORCS; 1445; 80 hits in 1121 CRISPR screens.
DR ChiTaRS; CSK; human.
DR EvolutionaryTrace; P41240; -.
DR GeneWiki; C-src_tyrosine_kinase; -.
DR GenomeRNAi; 1445; -.
DR Pharos; P41240; Tchem.
DR PRO; PR:P41240; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P41240; protein.
DR Bgee; ENSG00000103653; Expressed in granulocyte and 187 other tissues.
DR ExpressionAtlas; P41240; baseline and differential.
DR Genevisible; P41240; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IPI:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0070064; F:proline-rich region binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; TAS:ProtInc.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0045779; P:negative regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; IDA:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IEA:Ensembl.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IBA:GO_Central.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR CDD; cd09937; SH2_csk_like; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035027; Csk-like_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Adaptive immunity; ATP-binding; Cell membrane;
KW Cytoplasm; Immunity; Kinase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; SH2 domain;
KW SH3 domain; Transferase; Tyrosine-protein kinase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..450
FT /note="Tyrosine-protein kinase CSK"
FT /id="PRO_0000088070"
FT DOMAIN 9..70
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 82..171
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 195..449
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 9..70
FT /note="Interaction with PTPN22"
FT /evidence="ECO:0000250|UniProtKB:P41241"
FT ACT_SITE 314
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 201..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 184
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9148770"
FT MOD_RES 304
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9148770"
FT MOD_RES 364
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:11181701"
FT MOD_RES 416
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:1945408"
FT VARIANT 45
FT /note="P -> L"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041678"
FT VARIANT 287
FT /note="G -> D (in dbSNP:rs34866753)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025203"
FT VARIANT 398
FT /note="R -> Q (in dbSNP:rs34616395)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025204"
FT VARIANT 442
FT /note="H -> R (in dbSNP:rs35556162)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025205"
FT MUTAGEN 184
FT /note="Y->F: Abolishes phosphorylation."
FT /evidence="ECO:0000269|PubMed:9148770"
FT MUTAGEN 304
FT /note="Y->F: Decreases activity by two-thirds and alters
FT conformation."
FT /evidence="ECO:0000269|PubMed:9148770"
FT MUTAGEN 364
FT /note="S->A: Strong decrease of phosphorylation by PRKACA
FT (catalytic subunit of PKA)."
FT /evidence="ECO:0000269|PubMed:11181701"
FT STRAND 12..18
FT /evidence="ECO:0007829|PDB:1CSK"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:1CSK"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:1CSK"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:1CSK"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1CSK"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:3EAC"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 116..122
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 137..144
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:3EAZ"
FT HELIX 149..158
FT /evidence="ECO:0007829|PDB:3EAZ"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3EAZ"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 195..203
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 231..235
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 274..285
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 288..307
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:1BYG"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:1BYG"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 355..360
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 365..380
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 395..399
FT /evidence="ECO:0007829|PDB:1BYG"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 413..422
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:1BYG"
FT HELIX 433..446
FT /evidence="ECO:0007829|PDB:1BYG"
SQ SEQUENCE 450 AA; 50704 MW; 431023A88C54E00C CRC64;
MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII
PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE TGLFLVREST NYPGDYTLCV
SCDGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTSDA DGLCTRLIKP KVMEGTVAAQ
DEFYRSGWAL NMKELKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM
TQLRHSNLVQ LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE
KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYEVMK
NCWHLDAAMR PSFLQLREQL EHIKTHELHL
