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Details on Person UniProt:P41240 CSK

Class:IdReferenceGeneProduct:52852
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-450 added on Sat February 7 2015;initiator methionine:1 for 52852 removed on Fri Nov 03 2023;initiator methionine: for 52852 added on Fri Nov 03 2023;initiator methionine: for 52852 removed on Fri Aug 15 2025;initiator methionine:1 for 52852 added on Fri Aug 15 2025
_displayNameUniProt:P41240 CSK
_timestamp2026-02-20 22:31:12
chaininitiator methionine:1
chain:2-450
checksum431023A88C54E00C
commentFUNCTION 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. May act as a negative regulator of EGFR and STAT3 signaling pathways (PubMed:26918609).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)COFACTOR 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:10790433, PubMed:10838081, PubMed:11433379, PubMed:14610046). 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).INTERACTION Mainly cytoplasmic, also present in lipid rafts.TISSUE SPECIFICITY Expressed in lung and macrophages.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.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.
descriptionrecommendedName: Tyrosine-protein kinase CSK ecNumber evidence="14 22 24"2.7.10.2 alternativeName: C-Src kinase alternativeName: Protein-tyrosine kinase CYL
geneNameCSK
identifierP41240
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Adaptive immunity
ATP-binding
Cell membrane
Cytoplasm
Immunity
Kinase
Magnesium
Manganese
Membrane
Metal-binding
Nucleotide-binding
Phosphoprotein
Proteomics identification
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameCSK
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8991793] ENSEMBL:ENSG00000103653 CSK [Homo sapiens]
secondaryIdentifierCSK_HUMAN
Q2M3N2
Q6FGZ6
sequenceLength450
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:180499] CSK [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:203776] CSK [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P41240 CSK (52852)