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Protein / target

Tyrosine-protein kinase CSK

Encoded byCSKP41240Homo sapiensSwiss-Prot
UniProt: P41240Ensembl: ENSG00000103653HGNC: HGNC:2444NCBI Gene: 1445
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Hypertension

Via encoding gene CSK · Genetic evidence · score 0.45

Research activity

Emerging research

1 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response.

View complete UniProt function annotation

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)

Subcellular location

CytoplasmCell membrane
Domains and Gene Ontology detail (35)

Domains & features

SH3SH2Protein kinase

Gene Ontology

  • Ccell-cell junction
  • Ccytoplasm
  • Ccytosol
  • Cextracellular exosome
  • Cplasma membrane
  • FATP binding
  • Fidentical protein binding
  • Fmetal ion binding
  • Fnon-membrane spanning protein tyrosine kinase activity
  • Fproline-rich region binding
  • Fprotein kinase A catalytic subunit binding
  • Fprotein phosphatase binding

450 aa · 51 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOLipid & lipoprotein metabolismGOKinase signallingUniProt · GOImmune signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Lipid & lipoprotein metabolism

  • ·negative regulation of low-density lipoprotein particle clearance

Kinase signalling

  • ·Non-receptor tyrosine-protein kinase that plays an important role in the regulation of c…
  • ·non-membrane spanning protein tyrosine kinase activity
  • ·protein kinase A catalytic subunit binding
  • ·protein tyrosine kinase activity

Immune signalling

  • ·Non-receptor tyrosine-protein kinase that plays an important role in the regulation of c…
  • ·adaptive immune response
  • ·negative regulation of interleukin-6 production
  • ·negative regulation of T cell activation

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CSK

Gene-level evidence surfaced through the gene CSKthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hypertension
0.49Limited support

Genetic evidence dominant · Open Targets 0.29

Neoplasms
0.46Preliminary

Pathway evidence dominant · Open Targets 0.61 · no direct causal or clinical evidence

Essential Hypertension
0.38Limited support

Genetic evidence dominant · Open Targets 0.23

Neurodegenerative Diseases
0.36Preliminary

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

Noonan syndrome
0.35Preliminary

Pathway evidence dominant · Open Targets 0.53 · no direct causal or clinical evidence

View evidence synthesis (5)
HypertensionLimited support
0.49
agreement 0.35–0.63
Genetic87%Literature14%

Open Targets aggregate 0.29 · 2 independent evidence families

NeoplasmsPreliminary
0.46
agreement 0.28–0.63
Pathway77%Literature23%

Open Targets aggregate 0.61 · 2 independent evidence families · no direct causal or clinical evidence

Essential HypertensionLimited support
0.38
agreement 0.26–0.50
Genetic100%

Open Targets aggregate 0.23 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary
0.36
agreement 0.13–0.59
Pathway100%

Open Targets aggregate 0.55 · 1 independent evidence family · no direct causal or clinical evidence

Noonan syndromePreliminary
0.35
agreement 0.12–0.57
Pathway100%

Open Targets aggregate 0.53 · 1 independent evidence family · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neoplasms0.61
Neurodegenerative Diseases0.55
Noonan syndrome0.53
Costello syndrome0.50
Cardiomyopathy, Hypertrophic0.50
Cardiofaciocutaneous syndrome0.37
Hypertension0.29
Autoimmune disorder of central nervous system0.24
Essential Hypertension0.23

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (10)
SM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and antitumor immunity through eNOS/Src.38 cites

Sjöberg E · The Journal of clinical investigation · 2023

Recent

Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and antitumor immunity through eNOS/Src.

Sjöberg E · The Journal of clinical investigation · 2023

Europe PMC papers linked directly to this protein.