CSK_BOVIN
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 03-AUG-2022, entry version 124.
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 {ECO:0000250|UniProtKB:P32577, ECO:0000250|UniProtKB:P41240,
CC 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}.
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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.ENSBTAP00000028559; -.
DR PaxDb; Q0VBZ0; -.
DR PeptideAtlas; Q0VBZ0; -.
DR PRIDE; Q0VBZ0; -.
DR Ensembl; ENSBTAT00000028559; ENSBTAP00000028559; ENSBTAG00000021424.
DR Ensembl; ENSBTAT00000081272; ENSBTAP00000073137; ENSBTAG00000021424.
DR GeneID; 509246; -.
DR KEGG; bta:509246; -.
DR CTD; 1445; -.
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; QTMPWFH; -.
DR OrthoDB; 491765at2759; -.
DR TreeFam; TF351634; -.
DR Proteomes; UP000009136; Chromosome 21.
DR Bgee; ENSBTAG00000021424; Expressed in blood and 105 other 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:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
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:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IBA:GO_Central.
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 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
