CSK (C-Terminal Src Kinase)

A key negative regulator of Src family tyrosine kinases, involved in cell growth, differentiation, and immune signaling.

Gene Information Card

Symbol CSK
Full Name C-terminal Src kinase
Gene Type protein-coding
Chromosomal Location 15q24.1
NCBI Gene ID 1445 ncbi.nlm.nih.gov/gene/1445
Ensembl ID ENSG00000103653
UniProt ID P41240
OMIM ID 190090
HGNC ID 2444
Aliases CSK, C-Src kinase, CSK tyrosine kinase

Description

The CSK gene encodes C-terminal Src kinase, a cytoplasmic tyrosine kinase that negatively regulates Src family kinases (SFKs) by phosphorylating their C-terminal inhibitory tyrosine residue. CSK plays a critical role in controlling cell proliferation, adhesion, migration, and immune receptor signaling. Dysregulation of CSK is implicated in various cancers and immune disorders.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Hepatocellular carcinoma Reduced CSK expression leads to increased SFK activity, promoting cell proliferation and invasion. PMID: 23455478
Colorectal cancer CSK downregulation correlates with Src activation and poor prognosis. PMID: 17157791
Breast cancer Loss of CSK expression enhances Src-dependent signaling and metastasis. PMID: 18413744
T-cell immunodeficiency Mutations in CSK impair T-cell receptor signaling and immune response. PMID: 25642768

Expression Profile

Tissue Expression
Tissue nTPM level
Lymph node 12.5 Medium
Spleen 11.8 Medium
Bone marrow 10.2 Medium
Brain 8.5 Low
Liver 7.3 Low
Cell Line Expression
Cell Line nTPM Notes
K-562 (leukemia) 14.2 High expression
HeLa (cervical) 9.8 Moderate
A549 (lung) 8.1 Moderate
MCF7 (breast) 6.5 Low
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.791G>A (p.Arg264His) Missense <0.01% Reduced kinase activity; associated with T-cell immunodeficiency.
c.1123C>T (p.Arg375*) Nonsense <0.01% Loss of function; truncation of protein.
c.1A>G (p.Met1Val) Start loss <0.01% Loss of translation initiation; likely loss of function.
Mutation functional classification

Loss of Function (LOF)

Missense and nonsense mutations that reduce or abolish CSK kinase activity, leading to increased SFK signaling.

Gain of Function (GOF)

No well-characterized gain-of-function mutations reported in CSK.

Dominant Negative (DN)

No dominant-negative mutations described for CSK.

Pathways

• Regulation of Src family kinases (Reactome: R-HSA-8848021)
• Signaling by Src-family kinases (Reactome: R-HSA-177929)
• T-cell receptor signaling pathway (KEGG: hsa04660)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)

Protein Summary

CSK is a 50 kDa cytoplasmic tyrosine kinase composed of an N-terminal SH2 domain, a central SH3 domain, and a C-terminal kinase domain. It specifically phosphorylates the C-terminal tyrosine (Tyr530 in Src) of Src family kinases, inducing an intramolecular inhibitory conformation. CSK is ubiquitously expressed but enriched in hematopoietic tissues. Its activity is essential for maintaining low basal SFK activity and regulating immune receptor signaling.

Related Products

Product name Cat.No. Species Gene ID
CSK Knockout HEK293 Cell Line EDJ-KQ4363 Human 1445 Details Get a Quote
CSKMT Knockout HEK293 Cell Line EDJ-KQ13016 Human 751071 Details Get a Quote
CSK Knockout A-549 Cell Line EDJ-KQ25589 Human 1445 Details Get a Quote
CSK Knockout HCT 116 Cell Line EDJ-KQ26872 Human 1445 Details Get a Quote
CSK Knockout HeLa Cell Line EDJ-KQ26873 Human 1445 Details Get a Quote
CSKMT Knockout A-549 Cell Line EDJ-KQ42276 Human 751071 Details Get a Quote
CSKMT Knockout HCT 116 Cell Line EDJ-KQ42277 Human 751071 Details Get a Quote
CSKMT Knockout HeLa Cell Line EDJ-KQ42278 Human 751071 Details Get a Quote
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