UniProt Accession

 CSK_HUMAN; P41240; Q2M3N2; Q6FGZ6 

Genbank Protein ID

 X60114; X59932; X74765; CR541960; DQ075211; BC104847; BC104875; BC106073 

Genbank Nucleotide ID

 CAA42713.1; CAA42556.1; CAB58562.1; CAG46758.1; AAY57329.1; AAI04848.1; AAI04876.1; AAI06074.1 

Protein Name

 Tyrosine-protein kinase CSK 

Protein Synonyms/Alias

 C-Src kinase; Protein-tyrosine kinase CYL 

Gene Name

 CSK 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
76	EGVKAGTKLSLMPWF	ubiquitination	[1, 2]
86	LMPWFHGKITREQAE	ubiquitination	[2]
169	GLCTRLIKPKVMEGT	ubiquitination	[2]
171	CTRLIKPKVMEGTVA	ubiquitination	[2]
193	SGWALNMKELKLLQT	ubiquitination	[2]
196	ALNMKELKLLQTIGK	ubiquitination	[2, 3, 4]
222	RGNKVAVKCIKNDAT	ubiquitination	[2]
329	VSEDNVAKVSDFGLT	ubiquitination	[2]
337	VSDFGLTKEASSTQD	ubiquitination	[2]
347	SSTQDTGKLPVKWTA	ubiquitination	[2]
351	DTGKLPVKWTAPEAL	ubiquitination	[2]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 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 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. 

Sequence Annotation

 DOMAIN 9 70 SH3.
 DOMAIN 82 171 SH2.
 DOMAIN 195 449 Protein kinase.
 NP_BIND 201 209 ATP (By similarity).
 REGION 9 70 Interaction with PTPN8 (By similarity).
 ACT_SITE 314 314 Proton acceptor (By similarity).
 BINDING 222 222 ATP (By similarity).
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 184 184 Phosphotyrosine.
 MOD_RES 304 304 Phosphotyrosine.
 MOD_RES 364 364 Phosphoserine; by PKA.
 MOD_RES 416 416 Phosphotyrosine.  

Keyword

 3D-structure; Acetylation; Adaptive immunity; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 450 AA 

Protein Sequence

Gene Ontology

 GO:0005911; C:cell-cell junction; IEA:Compara.
 GO:0005813; C:centrosome; IDA:HPA.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005886; C:plasma membrane; IPI:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0008022; F:protein C-terminus binding; TAS:ProtInc.
 GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
 GO:0034332; P:adherens junction organization; IEA:Compara.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045779; P:negative regulation of bone resorption; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
 GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Compara.
 GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; IDA:UniProtKB.
 GO:0032715; P:negative regulation of interleukin-6 production; IEA:Compara.
 GO:0033673; P:negative regulation of kinase activity; IEA:Compara.
 GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Compara.
 GO:0050765; P:negative regulation of phagocytosis; IEA:Compara.
 GO:0048709; P:oligodendrocyte differentiation; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0043406; P:positive regulation of MAP kinase activity; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 

Pfam

 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 

SMART

 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 

PRINTS

 PR00401; SH2DOMAIN.
 PR00109; TYRKINASE.