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UniProt functional annotation for P41240 | ||
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| UniProt code: P41240. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Non-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. {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:9281320}. |
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| Catalytic activity: | |
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:7683130, ECO:0000269|PubMed:9281320}; |
| Cofactor: | |
Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:9281320}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:1639064}; |
| Subunit: | |
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). {ECO:0000250|UniProtKB:P32577, ECO:0000269|PubMed:10790433, ECO:0000269|PubMed:10838081, ECO:0000269|PubMed:11433379, ECO:0000269|PubMed:14610046, ECO:0000269|PubMed:15208781, ECO:0000269|PubMed:17525734, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21930792}. |
| Subcellular location: | |
Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Mainly cytoplasmic, also present in lipid rafts. {ECO:0000250}. |
| Tissue specificity: | |
Expressed in lung and macrophages. {ECO:0000269|PubMed:1371489}. |
| Domain: | |
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. |
| Ptm: | |
Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated. {ECO:0000269|PubMed:11181701, ECO:0000269|PubMed:9148770}. |
| Similarity: | |
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. |
Annotations taken from UniProtKB at the EBI.