Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CSK (P41240) - Overview - Molecular Target Synopsis

Protein


CSK, Tyrosine-protein kinase CSK
Enzyme Classification 2.7.10.2
UniProt P41240

Also Known as CSK_HUMAN, CSK

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. 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 (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.

3EAC
CRYSTAL STRUCTURE OF SH2 DOMAIN OF HUMAN CSK (CARBOXYL-TERMINAL SRC KINASE), OXIDIZED FORM.
RCSB/PDB
Inspect Structure
See all 3D Structures for CSK

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CSK is active in the following subcellular-locations: cell membrane, cytoplasm.
GO terms: CSK is active in the following subcellular-locations: cell-cell junction, cytoplasm, cytosol, extracellular exosome, membrane raft, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CSK has gain in 1 cell-lines, loss in 2 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: COLO205, CCRF_CEM, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-LY-3, OCUM-1, HT

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, IMR-90

(see details)

RNA Interference


CSK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HUO3N1, PANC. (see details)

3D Structures


For CSK there are:
6 structures (10 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CSK has been screened with 1118 compounds (1824 bioactivities), 22 compounds have bioactivities that show binding affinity of <= 500nM (29 bioactivities). (see details)