ID CSK_BOVIN Reviewed; 450 AA. AC Q0VBZ0; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 1. DT 27-MAR-2024, entry version 133. DE RecName: Full=Tyrosine-protein kinase CSK; DE EC=2.7.10.2 {ECO:0000250|UniProtKB:P41240}; DE AltName: Full=C-Src kinase; GN Name=CSK; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Basal ganglia; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. 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 (By CC similarity). {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:0000250|UniProtKB:P41240, ECO:0000255|PROSITE- CC ProRule:PRU10028}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P41240}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P41240}; CC -!- SUBUNIT: Homodimer (via SH3-domain). Interacts with PTPN22. Interacts CC with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions CC serve to recruit CSK to the membrane where it can phosphorylate and CC inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH. CC Interacts (via SH2 domain) with SCIMP; this interaction is dependent on CC phosphorylation of a specific tyrosine on SCIMP (By similarity). CC Interacts (via SH2 domain) with PRAG1 (when phosphorylated); this CC interaction prevents translocation of CSK from the cytoplasm to the CC membrane leading to increased activity of CSK (By similarity). CC Interacts with LRRK1 (By similarity). {ECO:0000250|UniProtKB:P32577, CC ECO:0000250|UniProtKB:P41240, ECO:0000250|UniProtKB:P41241}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P41241}. Cell CC membrane {ECO:0000250|UniProtKB:P41241}. Note=Mainly cytoplasmic, also CC present in lipid rafts. {ECO:0000250|UniProtKB:P41241}. 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. {ECO:0000250}. CC -!- PTM: Phosphorylated at Ser-364 by PKA, leading to increased activity. CC Autophosphorylated (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSK subfamily. {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; BC120437; AAI20438.1; -; mRNA. DR RefSeq; NP_001068865.1; NM_001075397.1. DR AlphaFoldDB; Q0VBZ0; -. DR BMRB; Q0VBZ0; -. DR SMR; Q0VBZ0; -. DR STRING; 9913.ENSBTAP00000073137; -. DR PaxDb; 9913-ENSBTAP00000028559; -. DR PeptideAtlas; Q0VBZ0; -. DR Ensembl; ENSBTAT00000028559.5; ENSBTAP00000028559.4; ENSBTAG00000021424.5. DR Ensembl; ENSBTAT00000081272.1; ENSBTAP00000073137.1; ENSBTAG00000021424.5. DR GeneID; 509246; -. DR KEGG; bta:509246; -. DR VEuPathDB; HostDB:ENSBTAG00000021424; -. DR VGNC; VGNC:27761; CSK. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000157431; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; Q0VBZ0; -. DR OMA; PTMTTHS; -. DR OrthoDB; 1614410at2759; -. DR TreeFam; TF351634; -. DR Reactome; R-BTA-180292; GAB1 signalosome. DR Reactome; R-BTA-202427; Phosphorylation of CD3 and TCR zeta chains. DR Reactome; R-BTA-354192; Integrin signaling. DR Reactome; R-BTA-389948; PD-1 signaling. DR Reactome; R-BTA-5674135; MAP2K and MAPK activation. DR Reactome; R-BTA-9013407; RHOH GTPase cycle. DR Reactome; R-BTA-9706369; Negative regulation of FLT3. DR Proteomes; UP000009136; Chromosome 21. DR Bgee; ENSBTAG00000021424; Expressed in blood and 105 other cell types or tissues. DR ExpressionAtlas; Q0VBZ0; baseline and differential. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. 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:0034236; F:protein kinase A catalytic subunit 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:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; IEA:Ensembl. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IBA:GO_Central. DR CDD; cd05082; PTKc_Csk; 1. DR CDD; cd09937; SH2_csk_like; 1. DR CDD; cd11769; SH3_CSK; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF407; TYROSINE-PROTEIN KINASE CSK; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 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 2: Evidence at transcript level; KW Acetylation; Adaptive immunity; ATP-binding; Cell membrane; Cytoplasm; KW 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:0000250|UniProtKB:P41240" FT CHAIN 2..450 FT /note="Tyrosine-protein kinase CSK" FT /id="PRO_0000260260" 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:P41240" 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:0000250|UniProtKB:P41240" FT MOD_RES 304 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P41240" FT MOD_RES 364 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:P41240" FT MOD_RES 416 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P41240" SQ SEQUENCE 450 AA; 50633 MW; B42BD31C645783D0 CRC64; MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLCPPE TGLFLVREST NYPGDYTLCV SCDGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTSDA DGLCTRLIKP KVMEGTVAAQ DEFFRSGWAL NMKDLKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM TQLRHSNLVQ LLGVIVEEKS GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYEVMK NCWHLDAATR PSFLQLREQL ERIKTHELHL //