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Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotationBy similarity

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei222ATPPROSITE-ProRule annotation1
Active sitei314Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi201 – 209ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • identical protein binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • protein kinase A catalytic subunit binding Source: MGI
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: GO_Central
  • transferase activity Source: HGNC

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. 3474.
ReactomeiR-MMU-180292. GAB1 signalosome.
R-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.
R-MMU-354192. Integrin alphaIIb beta3 signaling.
R-MMU-389948. PD-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase CSK (EC:2.7.10.2By similarity)
Alternative name(s):
C-Src kinase
Protein-tyrosine kinase MPK-2
p50CSK
Gene namesi
Name:Csk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:88537. Csk.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice die between day 9 and day 10 of gestation with several defects including a non-functional neural tube. SRC and FYN kinases show increased activity when CSK is missing.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000880712 – 450Tyrosine-protein kinase CSKAdd BLAST449

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei184PhosphotyrosineBy similarity1
Modified residuei304PhosphotyrosineBy similarity1
Modified residuei364Phosphoserine; by PKABy similarity1
Modified residuei416Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41241.
MaxQBiP41241.
PaxDbiP41241.
PeptideAtlasiP41241.
PRIDEiP41241.

PTM databases

iPTMnetiP41241.
PhosphoSitePlusiP41241.

Expressioni

Tissue specificityi

Ubiquitous, but most abundant in thymus and spleen, as well as in neonatal brain.

Gene expression databases

BgeeiENSMUSG00000032312.
CleanExiMM_CSK.
GenevisibleiP41241. MM.

Interactioni

Subunit structurei

Homodimer (via SH3-domain) (By similarity). Interacts with PTPN22 (PubMed:8890164). 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:9858471, PubMed:12218089, PubMed:12612075, PubMed:16166631). Interacts with SRCIN1 (By similarity). Interacts with RHOH (By similarity). Interacts (via SH2 domain) with SCIMP (By similarity).By similarity5 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198936. 33 interactors.
IntActiP41241. 30 interactors.
MINTiMINT-1345201.
STRINGi10090.ENSMUSP00000034863.

Structurei

Secondary structure

1450
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 18Combined sources6
Beta strandi35 – 41Combined sources7
Beta strandi43 – 51Combined sources9
Beta strandi57 – 61Combined sources5
Helixi62 – 64Combined sources3
Beta strandi65 – 67Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-A1-83[»]
ProteinModelPortaliP41241.
SMRiP41241.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41241.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 70SH3PROSITE-ProRule annotationAdd BLAST62
Domaini82 – 171SH2PROSITE-ProRule annotationAdd BLAST90
Domaini195 – 449Protein kinasePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 70Interaction with PTPN221 PublicationAdd BLAST62

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.By similarity

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.
InParanoidiP41241.
KOiK05728.
OMAiTRDPNWY.
OrthoDBiEOG091G05PB.
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.

P41241-1 [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 SCEGKVEHYR IMYHASKLSI DEEVYFENLM
160 170 180 190 200
QLVEHYTTDA 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 NCWHLDAATR PTFLQLREQL EHIKTHELHL
Length:450
Mass (Da):50,716
Last modified:July 27, 2011 - v2
Checksum:iE8D3EC9357B86277
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti299C → L in AAA18766 (PubMed:7511815).Curated1
Sequence conflicti417E → D in AAA18766 (PubMed:7511815).Curated1
Sequence conflicti423W → S in AAA18766 (PubMed:7511815).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05247 mRNA. Translation: AAA18766.1.
AY902339 Genomic DNA. Translation: AAX90624.1.
AK156058 mRNA. Translation: BAE33565.1.
AK170815 mRNA. Translation: BAE42047.1.
BC018394 mRNA. Translation: AAH18394.1.
BC052006 mRNA. Translation: AAH52006.2.
X57242 mRNA. Translation: CAA40518.1.
CCDSiCCDS23228.1.
PIRiI48929.
RefSeqiNP_001291690.1. NM_001304761.1.
NP_031809.2. NM_007783.3.
XP_006510864.1. XM_006510801.3.
XP_006510865.1. XM_006510802.3.
UniGeneiMm.21974.

Genome annotation databases

EnsembliENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312.
GeneIDi12988.
KEGGimmu:12988.
UCSCiuc009pvk.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05247 mRNA. Translation: AAA18766.1.
AY902339 Genomic DNA. Translation: AAX90624.1.
AK156058 mRNA. Translation: BAE33565.1.
AK170815 mRNA. Translation: BAE42047.1.
BC018394 mRNA. Translation: AAH18394.1.
BC052006 mRNA. Translation: AAH52006.2.
X57242 mRNA. Translation: CAA40518.1.
CCDSiCCDS23228.1.
PIRiI48929.
RefSeqiNP_001291690.1. NM_001304761.1.
NP_031809.2. NM_007783.3.
XP_006510864.1. XM_006510801.3.
XP_006510865.1. XM_006510802.3.
UniGeneiMm.21974.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-A1-83[»]
ProteinModelPortaliP41241.
SMRiP41241.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198936. 33 interactors.
IntActiP41241. 30 interactors.
MINTiMINT-1345201.
STRINGi10090.ENSMUSP00000034863.

PTM databases

iPTMnetiP41241.
PhosphoSitePlusiP41241.

Proteomic databases

EPDiP41241.
MaxQBiP41241.
PaxDbiP41241.
PeptideAtlasiP41241.
PRIDEiP41241.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312.
GeneIDi12988.
KEGGimmu:12988.
UCSCiuc009pvk.2. mouse.

Organism-specific databases

CTDi1445.
MGIiMGI:88537. Csk.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP41241.
KOiK05728.
OMAiTRDPNWY.
OrthoDBiEOG091G05PB.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-180292. GAB1 signalosome.
R-MMU-202427. Phosphorylation of CD3 and TCR zeta chains.
R-MMU-354192. Integrin alphaIIb beta3 signaling.
R-MMU-389948. PD-1 signaling.

Miscellaneous databases

EvolutionaryTraceiP41241.
PROiP41241.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032312.
CleanExiMM_CSK.
GenevisibleiP41241. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P41241
Secondary accession number(s): Q03143, Q80WU4, Q8VCW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 172 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. 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.