CSK (C-terminal Src kinase)

Gene

• Entrez ID: 1445
• Gene name: C-terminal Src kinase
• Gene symbol: CSK
• Synonyms: -
• Chromosome: 15
• Chromosome location: 15q24.1
• Summary: The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003960	hsa-miR-140-5p	Microarray	17875710
MIRT030606	hsa-miR-24-3p	Microarray	19748357
MIRT035928	hsa-miR-1180-3p	CLASH	23622248
MIRT736232	hsa-miR-1233-5p	PAR-CLIP	26701625
MIRT738318	hsa-miR-1908-5p	PAR-CLIP	26701625
MIRT740242	hsa-miR-3148	PAR-CLIP	26701625
MIRT740345	hsa-miR-3151-5p	PAR-CLIP	26701625
MIRT740771	hsa-miR-3180-3p	PAR-CLIP	26701625
MIRT740811	hsa-miR-3180	PAR-CLIP	26701625
MIRT741055	hsa-miR-3194-5p	PAR-CLIP	26701625
MIRT741068	hsa-miR-3196	PAR-CLIP	26701625
MIRT743451	hsa-miR-4258	PAR-CLIP	26701625
MIRT745516	hsa-miR-4505	PAR-CLIP	26701625
MIRT747350	hsa-miR-4707-3p	PAR-CLIP	26701625
MIRT748217	hsa-miR-4747-3p	PAR-CLIP	26701625
MIRT750363	hsa-miR-541-3p	PAR-CLIP	26701625
MIRT751466	hsa-miR-5787	PAR-CLIP	26701625
MIRT753196	hsa-miR-6511b-5p	PAR-CLIP	26701625
MIRT753434	hsa-miR-654-5p	PAR-CLIP	26701625
MIRT753578	hsa-miR-663a	PAR-CLIP	26701625
MIRT753702	hsa-miR-671-5p	PAR-CLIP	26701625
MIRT755146	hsa-miR-6768-3p	PAR-CLIP	26701625
MIRT755179	hsa-miR-6769a-5p	PAR-CLIP	26701625
MIRT755225	hsa-miR-6769b-5p	PAR-CLIP	26701625
MIRT755939	hsa-miR-6787-5p	PAR-CLIP	26701625
MIRT756683	hsa-miR-6811-5p	PAR-CLIP	26701625
MIRT756797	hsa-miR-6816-5p	PAR-CLIP	26701625
MIRT759102	hsa-miR-7113-5p	PAR-CLIP	26701625
MIRT760306	hsa-miR-873-5p	PAR-CLIP	26701625
MIRT760547	hsa-miR-92a-2-5p	PAR-CLIP	26701625
MIRT760665	hsa-miR-92b-5p	PAR-CLIP	26701625
MIRT760878	hsa-miR-9500	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	TAS
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	7507203, 10026153, 10790433, 14665621, 15683240, 17911601, 18070987, 18614016, 19167335, 21930792, 28514442, 31980649, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005737	Component	Cytoplasm	TAS	8890164
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IPI	10790433
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0006468	Process	Protein phosphorylation	TAS	1945408
GO:0007420	Process	Brain development	IEA
GO:0008022	Function	Protein C-terminus binding	TAS	8890164
GO:0008285	Process	Negative regulation of cell population proliferation	IEA
GO:0010989	Process	Negative regulation of low-density lipoprotein particle clearance	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IEA
GO:0019903	Function	Protein phosphatase binding	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0032715	Process	Negative regulation of interleukin-6 production	IEA
GO:0033673	Process	Negative regulation of kinase activity	IEA
GO:0034236	Function	Protein kinase A catalytic subunit binding	IPI	17911601
GO:0034332	Process	Adherens junction organization	IBA	21873635
GO:0042802	Function	Identical protein binding	IPI	19888460
GO:0042997	Process	Negative regulation of Golgi to plasma membrane protein transport	IDA	20605918
GO:0043406	Process	Positive regulation of MAP kinase activity	IEA
GO:0045121	Component	Membrane raft	IEA
GO:0045779	Process	Negative regulation of bone resorption	IEA
GO:0046777	Process	Protein autophosphorylation	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048709	Process	Oligodendrocyte differentiation	IEA
GO:0050765	Process	Negative regulation of phagocytosis	IEA
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0060368	Process	Regulation of Fc receptor mediated stimulatory signaling pathway	IBA	21873635
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0070064	Function	Proline-rich region binding	IEA
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IEA
GO:0071375	Process	Cellular response to peptide hormone stimulus	IEA

Other IDs

• MIM: 124095
• HGNC: 2444
• e!Ensembl: ENSG00000103653

Protein

• UniProt ID: P41240
• Protein name: Tyrosine-protein kinase CSK (EC 2.7.10.2) (C-Src kinase) (Protein-tyrosine kinase CYL)
• Protein 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.
• PDB: 1BYG, 1CSK, 3D7T, 3D7U, 3EAC, 3EAZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	15 → 62	SH3 domain	Domain
  PF00017	SH2	82 → 156	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	195 → 440	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MSAIQAAWPSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGII
  PANYVQKREGVKAGTKLSLMPWFHGKITREQAERLLYPPETGLFLVRESTNYPGDYTLCV
  SCDGKVEHYRIMYHASKLSIDEEVYFENLMQLVEHYTSDADGLCTRLIKPKVMEGTVAAQ
  DEFYRSGWALNMKELKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKNDATAQAFLAEASVM
  TQLRHSNLVQLLGVIVEEKGGLYIVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCE
  AMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVKWTAPEALRE
  KKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYEVMK
  NCWHLDAAMRPSFLQLREQLEHIKTHELHL

• Sequence length: 450

Pathways

KEGG:

Epithelial cell signaling in Helicobacter pylori infection

Reactome:

GAB1 signalosome
Phosphorylation of CD3 and TCR zeta chains
Integrin signaling
PD-1 signaling
MAP2K and MAPK activation
Signaling by moderate kinase activity BRAF mutants
Signaling by high-kinase activity BRAF mutants
Signaling by BRAF and RAF fusions
Paradoxical activation of RAF signaling by kinase inactive BRAF
Signaling downstream of RAS mutants

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	30525989
Coronary heart disease	Coronary heart disease	rs-1	21347282
Lung carcinoma	Carcinoma of lung	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs-1, rs1584238193	28604730

Unknown
Disease name	Disease term	dbSNP ID	References
Lupus erythematosus	Lupus Erythematosus, Systemic		23042117
Nonbacterial verrucal endocardiosis	Libman-Sacks Disease		23042117
Scleroderma	Systemic Scleroderma		31672989