P41240 · CSK_HUMAN
- ProteinTyrosine-protein kinase CSK
- GeneCSK
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids450 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein kinase CSK
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP41240
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly cytoplasmic, also present in lipid rafts.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041678 | 45 | ||||
Sequence: P → L | ||||||
Mutagenesis | 184 | Abolishes phosphorylation. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_025203 | 287 | in dbSNP:rs34866753 | |||
Sequence: G → D | ||||||
Mutagenesis | 304 | Decreases activity by two-thirds and alters conformation. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 364 | Strong decrease of phosphorylation by PRKACA (catalytic subunit of PKA). | ||||
Sequence: S → A | ||||||
Natural variant | VAR_025204 | 398 | in dbSNP:rs34616395 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_025205 | 442 | in dbSNP:rs35556162 | |||
Sequence: H → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 367 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylserine | ||||
Sequence: S | |||||||
Chain | PRO_0000088070 | 2-450 | UniProt | Tyrosine-protein kinase CSK | |||
Sequence: SAIQAAWPSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGIIPANYVQKREGVKAGTKLSLMPWFHGKITREQAERLLYPPETGLFLVRESTNYPGDYTLCVSCDGKVEHYRIMYHASKLSIDEEVYFENLMQLVEHYTSDADGLCTRLIKPKVMEGTVAAQDEFYRSGWALNMKELKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKNDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKGGLYIVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYEVMKNCWHLDAAMRPSFLQLREQLEHIKTHELHL | |||||||
Modified residue (large scale data) | 23 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 97 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 184 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 184 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 304 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 364 | UniProt | Phosphoserine; by PKA | ||||
Sequence: S | |||||||
Modified residue | 416 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y |
Post-translational modification
Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Expressed in lung and macrophages.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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:10790433, PubMed:10838081, PubMed:11433379, PubMed:14610046).
Interacts with SRCIN1 (PubMed:17525734).
Interacts with RHOH (PubMed:20851766).
Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-107' (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 (By similarity).
Interacts with LRRK1 (PubMed:23526378).
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:10790433, PubMed:10838081, PubMed:11433379, PubMed:14610046).
Interacts with SRCIN1 (PubMed:17525734).
Interacts with RHOH (PubMed:20851766).
Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-107' (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 (By similarity).
Interacts with LRRK1 (PubMed:23526378).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P41240 | CSK P41240 | 7 | EBI-1380630, EBI-1380630 | |
BINARY | P41240 | DDIT4L Q96D03 | 3 | EBI-1380630, EBI-742054 | |
BINARY | P41240 | IGF1R P08069 | 5 | EBI-1380630, EBI-475981 | |
BINARY | P41240 | KANK4 Q5T7N3 | 3 | EBI-1380630, EBI-9355810 | |
XENO | P41240 | lspA1 Q7VLE8 | 4 | EBI-1380630, EBI-26445163 | |
BINARY | P41240 | PAG1 Q9NWQ8 | 6 | EBI-1380630, EBI-2828115 | |
BINARY | P41240 | PTPRC P08575 | 3 | EBI-1380630, EBI-1341 | |
BINARY | P41240 | PXN P49023 | 4 | EBI-1380630, EBI-702209 | |
BINARY | P41240 | SCIMP Q6UWF3 | 3 | EBI-1380630, EBI-2872510 | |
XENO | P41240 | SRC P00523 | 7 | EBI-1380630, EBI-848039 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 9-70 | SH3 | ||||
Sequence: PSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGIIPANYVQKREG | ||||||
Region | 9-70 | Interaction with PTPN22 | ||||
Sequence: PSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGIIPANYVQKREG | ||||||
Domain | 82-171 | SH2 | ||||
Sequence: WFHGKITREQAERLLYPPETGLFLVRESTNYPGDYTLCVSCDGKVEHYRIMYHASKLSIDEEVYFENLMQLVEHYTSDADGLCTRLIKPK | ||||||
Domain | 195-449 | Protein kinase | ||||
Sequence: LKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKNDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKGGLYIVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYEVMKNCWHLDAAMRPSFLQLREQLEHIKTHELH |
Domain
The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length450
- Mass (Da)50,704
- Last updated1995-02-01 v1
- Checksum431023A88C54E00C
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X60114 EMBL· GenBank· DDBJ | CAA42713.1 EMBL· GenBank· DDBJ | mRNA | ||
X59932 EMBL· GenBank· DDBJ | CAA42556.1 EMBL· GenBank· DDBJ | mRNA | ||
X74765 EMBL· GenBank· DDBJ | CAB58562.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CR541960 EMBL· GenBank· DDBJ | CAG46758.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ075211 EMBL· GenBank· DDBJ | AAY57329.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC104847 EMBL· GenBank· DDBJ | AAI04848.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104875 EMBL· GenBank· DDBJ | AAI04876.1 EMBL· GenBank· DDBJ | mRNA | ||
BC106073 EMBL· GenBank· DDBJ | AAI06074.1 EMBL· GenBank· DDBJ | mRNA |