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Protein

Tyrosine-protein kinase CSK

Gene

CSK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.3 Publications

Cofactori

Mg2+1 Publication, Mn2+1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei222 – 2221ATPPROSITE-ProRule annotation
Active sitei314 – 3141Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi201 – 2099ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • kinase activity Source: Reactome
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • protein C-terminus binding Source: ProtInc
  • protein kinase A catalytic subunit binding Source: UniProtKB
  • protein tyrosine kinase activity Source: Reactome
  • receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-180292. GAB1 signalosome.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-389948. PD-1 signaling.
R-HSA-5674135. MAP2K and MAPK activation.
SignaLinkiP41240.
SIGNORiP41240.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase CSK (EC:2.7.10.23 Publications)
Alternative name(s):
C-Src kinase
Protein-tyrosine kinase CYL
Gene namesi
Name:CSK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:2444. CSK.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity

  • Note: Mainly cytoplasmic, also present in lipid rafts.By similarity

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • membrane raft Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi184 – 1841Y → F: Abolishes phosphorylation. 1 Publication
Mutagenesisi304 – 3041Y → F: Decreases activity by two-thirds and alters conformation. 1 Publication
Mutagenesisi364 – 3641S → A: Strong decrease of phosphorylation by PRKACA (catalytic subunit of PKA). 1 Publication

Organism-specific databases

PharmGKBiPA26946.

Chemistry

ChEMBLiCHEMBL2634.
GuidetoPHARMACOLOGYi1994.

Polymorphism and mutation databases

BioMutaiCSK.
DMDMi729887.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 450449Tyrosine-protein kinase CSKPRO_0000088070Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources
Modified residuei184 – 1841Phosphotyrosine1 Publication
Modified residuei304 – 3041Phosphotyrosine1 Publication
Modified residuei364 – 3641Phosphoserine; by PKA1 Publication
Modified residuei416 – 4161Phosphotyrosine; by autocatalysis1 Publication

Post-translational modificationi

Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41240.
MaxQBiP41240.
PaxDbiP41240.
PeptideAtlasiP41240.
PRIDEiP41240.

2D gel databases

OGPiP41240.

PTM databases

iPTMnetiP41240.
PhosphoSiteiP41240.

Expressioni

Tissue specificityi

Expressed in lung and macrophages.1 Publication

Gene expression databases

BgeeiENSG00000103653.
CleanExiHS_CSK.
ExpressionAtlasiP41240. baseline and differential.
GenevisibleiP41240. HS.

Organism-specific databases

HPAiCAB011203.
HPA026488.
HPA028425.

Interactioni

Subunit structurei

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).8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-1380630,EBI-1380630
IGF1RP080695EBI-1380630,EBI-475981
PAG1Q9NWQ83EBI-1380630,EBI-2828115
PTPRCP085753EBI-1380630,EBI-1341
PXNP490232EBI-1380630,EBI-702209
SRCP005236EBI-1380630,EBI-848039From a different organism.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein C-terminus binding Source: ProtInc
  • protein kinase A catalytic subunit binding Source: UniProtKB
  • receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi107832. 54 interactions.
IntActiP41240. 37 interactions.
MINTiMINT-85878.
STRINGi9606.ENSP00000220003.

Chemistry

BindingDBiP41240.

Structurei

Secondary structure

1
450
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi12 – 187Combined sources
Beta strandi35 – 417Combined sources
Beta strandi47 – 515Combined sources
Beta strandi57 – 615Combined sources
Beta strandi64 – 663Combined sources
Helixi77 – 793Combined sources
Beta strandi83 – 864Combined sources
Helixi89 – 957Combined sources
Beta strandi103 – 1086Combined sources
Beta strandi116 – 1227Combined sources
Beta strandi125 – 1306Combined sources
Beta strandi132 – 1343Combined sources
Beta strandi137 – 1448Combined sources
Beta strandi146 – 1483Combined sources
Helixi149 – 15810Combined sources
Beta strandi163 – 1653Combined sources
Helixi192 – 1943Combined sources
Beta strandi195 – 2039Combined sources
Beta strandi208 – 2147Combined sources
Beta strandi217 – 2237Combined sources
Helixi231 – 2355Combined sources
Helixi237 – 2404Combined sources
Beta strandi251 – 2555Combined sources
Beta strandi263 – 2664Combined sources
Helixi274 – 28512Combined sources
Helixi288 – 30720Combined sources
Helixi317 – 3193Combined sources
Beta strandi320 – 3223Combined sources
Beta strandi328 – 3303Combined sources
Turni350 – 3523Combined sources
Helixi355 – 3606Combined sources
Helixi365 – 38016Combined sources
Helixi392 – 3943Combined sources
Helixi395 – 3995Combined sources
Turni400 – 4023Combined sources
Helixi413 – 42210Combined sources
Helixi427 – 4293Combined sources
Helixi433 – 44614Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BYGX-ray2.40A173-450[»]
1CSKX-ray2.50A/B/C/D1-71[»]
3D7TX-ray2.90A188-450[»]
3D7UX-ray4.11A/C188-450[»]
3EACX-ray1.37A73-178[»]
3EAZX-ray1.31A73-178[»]
ProteinModelPortaliP41240.
SMRiP41240. Positions 4-450.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41240.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 7062SH3PROSITE-ProRule annotationAdd
BLAST
Domaini82 – 17190SH2PROSITE-ProRule annotationAdd
BLAST
Domaini195 – 449255Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni9 – 7062Interaction with PTPN22By similarityAdd
BLAST

Domaini

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 similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP41240.
KOiK05728.
OMAiTRDPNWY.
OrthoDBiEOG091G05PB.
PhylomeDBiP41240.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P41240-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA
60 70 80 90 100
KNKVGREGII PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE
110 120 130 140 150
TGLFLVREST NYPGDYTLCV SCDGKVEHYR IMYHASKLSI DEEVYFENLM
160 170 180 190 200
QLVEHYTSDA DGLCTRLIKP KVMEGTVAAQ DEFYRSGWAL NMKELKLLQT
210 220 230 240 250
IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM TQLRHSNLVQ
260 270 280 290 300
LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
310 320 330 340 350
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV
360 370 380 390 400
KWTAPEALRE KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE
410 420 430 440 450
KGYKMDAPDG CPPAVYEVMK NCWHLDAAMR PSFLQLREQL EHIKTHELHL
Length:450
Mass (Da):50,704
Last modified:February 1, 1995 - v1
Checksum:i431023A88C54E00C
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti45 – 451P → L.1 Publication
VAR_041678
Natural varianti287 – 2871G → D.1 Publication
Corresponds to variant rs34866753 [ dbSNP | Ensembl ].
VAR_025203
Natural varianti398 – 3981R → Q.1 Publication
Corresponds to variant rs34616395 [ dbSNP | Ensembl ].
VAR_025204
Natural varianti442 – 4421H → R.1 Publication
Corresponds to variant rs35556162 [ dbSNP | Ensembl ].
VAR_025205

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60114 mRNA. Translation: CAA42713.1.
X59932 mRNA. Translation: CAA42556.1.
X74765 Genomic DNA. Translation: CAB58562.1.
CR541960 mRNA. Translation: CAG46758.1.
DQ075211 Genomic DNA. Translation: AAY57329.1.
BC104847 mRNA. Translation: AAI04848.1.
BC104875 mRNA. Translation: AAI04876.1.
BC106073 mRNA. Translation: AAI06074.1.
CCDSiCCDS10269.1.
PIRiJH0559.
RefSeqiNP_001120662.1. NM_001127190.1.
NP_004374.1. NM_004383.2.
XP_005254222.1. XM_005254165.4.
UniGeneiHs.77793.

Genome annotation databases

EnsembliENST00000220003; ENSP00000220003; ENSG00000103653.
ENST00000439220; ENSP00000414764; ENSG00000103653.
ENST00000567571; ENSP00000454906; ENSG00000103653.
GeneIDi1445.
KEGGihsa:1445.
UCSCiuc002ays.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60114 mRNA. Translation: CAA42713.1.
X59932 mRNA. Translation: CAA42556.1.
X74765 Genomic DNA. Translation: CAB58562.1.
CR541960 mRNA. Translation: CAG46758.1.
DQ075211 Genomic DNA. Translation: AAY57329.1.
BC104847 mRNA. Translation: AAI04848.1.
BC104875 mRNA. Translation: AAI04876.1.
BC106073 mRNA. Translation: AAI06074.1.
CCDSiCCDS10269.1.
PIRiJH0559.
RefSeqiNP_001120662.1. NM_001127190.1.
NP_004374.1. NM_004383.2.
XP_005254222.1. XM_005254165.4.
UniGeneiHs.77793.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BYGX-ray2.40A173-450[»]
1CSKX-ray2.50A/B/C/D1-71[»]
3D7TX-ray2.90A188-450[»]
3D7UX-ray4.11A/C188-450[»]
3EACX-ray1.37A73-178[»]
3EAZX-ray1.31A73-178[»]
ProteinModelPortaliP41240.
SMRiP41240. Positions 4-450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107832. 54 interactions.
IntActiP41240. 37 interactions.
MINTiMINT-85878.
STRINGi9606.ENSP00000220003.

Chemistry

BindingDBiP41240.
ChEMBLiCHEMBL2634.
GuidetoPHARMACOLOGYi1994.

PTM databases

iPTMnetiP41240.
PhosphoSiteiP41240.

Polymorphism and mutation databases

BioMutaiCSK.
DMDMi729887.

2D gel databases

OGPiP41240.

Proteomic databases

EPDiP41240.
MaxQBiP41240.
PaxDbiP41240.
PeptideAtlasiP41240.
PRIDEiP41240.

Protocols and materials databases

DNASUi1445.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220003; ENSP00000220003; ENSG00000103653.
ENST00000439220; ENSP00000414764; ENSG00000103653.
ENST00000567571; ENSP00000454906; ENSG00000103653.
GeneIDi1445.
KEGGihsa:1445.
UCSCiuc002ays.3. human.

Organism-specific databases

CTDi1445.
GeneCardsiCSK.
HGNCiHGNC:2444. CSK.
HPAiCAB011203.
HPA026488.
HPA028425.
MIMi124095. gene.
neXtProtiNX_P41240.
PharmGKBiPA26946.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP41240.
KOiK05728.
OMAiTRDPNWY.
OrthoDBiEOG091G05PB.
PhylomeDBiP41240.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-180292. GAB1 signalosome.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-389948. PD-1 signaling.
R-HSA-5674135. MAP2K and MAPK activation.
SignaLinkiP41240.
SIGNORiP41240.

Miscellaneous databases

EvolutionaryTraceiP41240.
GeneWikiiC-src_tyrosine_kinase.
GenomeRNAii1445.
PROiP41240.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103653.
CleanExiHS_CSK.
ExpressionAtlasiP41240. baseline and differential.
GenevisibleiP41240. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCSK_HUMAN
AccessioniPrimary (citable) accession number: P41240
Secondary accession number(s): Q2M3N2, Q6FGZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: September 7, 2016
This is version 190 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.