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Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Rattus norvegicus (Rat)
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 similarity2 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Cofactori

Mn2+1 Publication, Mg2+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: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • proline-rich region binding Source: BHF-UCL
  • protein phosphatase binding Source: BHF-UCL
  • protein tyrosine kinase activity Source: RGD
  • receptor binding Source: GO_Central

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • adherens junction organization Source: RGD
  • brain development Source: RGD
  • cell migration Source: GO_Central
  • cellular response to peptide hormone stimulus Source: RGD
  • innate immune response Source: GO_Central
  • negative regulation of bone resorption Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of ERK1 and ERK2 cascade Source: RGD
  • negative regulation of Golgi to plasma membrane protein transport Source: Ensembl
  • negative regulation of interleukin-6 production Source: RGD
  • negative regulation of kinase activity Source: RGD
  • negative regulation of low-density lipoprotein particle clearance Source: RGD
  • negative regulation of phagocytosis Source: RGD
  • oligodendrocyte differentiation Source: RGD
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • positive regulation of MAP kinase activity Source: RGD
  • protein autophosphorylation Source: RGD
  • protein phosphorylation Source: RGD
  • regulation of Fc receptor mediated stimulatory signaling pathway Source: RGD
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
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. 5301.
ReactomeiR-RNO-180292. GAB1 signalosome.
R-RNO-202427. Phosphorylation of CD3 and TCR zeta chains.
R-RNO-354192. Integrin alphaIIb beta3 signaling.
R-RNO-389948. PD-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase CSK (EC:2.7.10.21 Publication)
Alternative name(s):
C-Src kinase
Gene namesi
Name:Csk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi1308800. 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: RGD
  • extracellular exosome Source: Ensembl
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • membrane raft Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4365.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000880722 – 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

PaxDbiP32577.
PRIDEiP32577.

PTM databases

iPTMnetiP32577.
PhosphoSitePlusiP32577.

Expressioni

Tissue specificityi

Enriched in lymphoid tissues.

Gene expression databases

BgeeiENSRNOG00000019374.
GenevisibleiP32577. RN.

Interactioni

Subunit structurei

Homodimer (via SH3-domain). Interacts with PTPN22. 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. Interacts with SRCIN1. Interacts with RHOH. Interacts (via SH2 domain) with SCIMP (By similarity).By similarity

GO - Molecular functioni

  • proline-rich region binding Source: BHF-UCL
  • protein phosphatase binding Source: BHF-UCL
  • receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi261119. 4 interactors.
IntActiP32577. 2 interactors.
MINTiMINT-1535121.
STRINGi10116.ENSRNOP00000026358.

Chemistry databases

BindingDBiP32577.

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 strandi23 – 27Combined sources5
Beta strandi35 – 41Combined sources7
Beta strandi47 – 51Combined sources5
Beta strandi57 – 61Combined sources5
Helixi62 – 64Combined sources3
Beta strandi65 – 67Combined sources3
Beta strandi77 – 79Combined sources3
Helixi89 – 95Combined sources7
Beta strandi103 – 108Combined sources6
Beta strandi110 – 112Combined sources3
Beta strandi115 – 121Combined sources7
Beta strandi123 – 134Combined sources12
Beta strandi137 – 144Combined sources8
Beta strandi146 – 148Combined sources3
Helixi149 – 158Combined sources10
Beta strandi163 – 165Combined sources3
Helixi179 – 185Combined sources7
Helixi192 – 194Combined sources3
Beta strandi195 – 203Combined sources9
Beta strandi205 – 214Combined sources10
Beta strandi217 – 226Combined sources10
Helixi231 – 241Combined sources11
Beta strandi251 – 256Combined sources6
Beta strandi262 – 267Combined sources6
Helixi274 – 281Combined sources8
Turni283 – 285Combined sources3
Helixi288 – 307Combined sources20
Helixi317 – 319Combined sources3
Beta strandi320 – 322Combined sources3
Beta strandi328 – 330Combined sources3
Turni350 – 352Combined sources3
Helixi355 – 359Combined sources5
Helixi365 – 380Combined sources16
Turni381 – 383Combined sources3
Turni392 – 394Combined sources3
Helixi395 – 400Combined sources6
Helixi413 – 422Combined sources10
Helixi427 – 429Combined sources3
Helixi433 – 445Combined sources13
Turni446 – 449Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K9AX-ray2.50A/B/C/D/E/F1-450[»]
2RSYNMR-A80-173[»]
ProteinModelPortaliP32577.
SMRiP32577.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP32577.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 70SH3PROSITE-ProRule annotationAdd BLAST62
Domaini82 – 171SH2PROSITE-ProRule annotationAdd BLAST90
Domaini195 – 445Protein kinasePROSITE-ProRule annotationAdd BLAST251

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 70Interaction with PTPN22By similarityAdd 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.
InParanoidiP32577.
KOiK05728.
OMAiTRDPNWY.
PhylomeDBiP32577.
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.

P32577-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAIQASWPS 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 CPPAVYDVMK NCWHLDAATR PTFLQLREQL EHIRTHELHL
Length:450
Mass (Da):50,746
Last modified:October 1, 1993 - v1
Checksum:i393DC8D737DAC67A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58631 mRNA. Translation: CAA41484.1.
BC098863 mRNA. Translation: AAH98863.1.
PIRiS15094.
RefSeqiNP_001025210.1. NM_001030039.1.
XP_006243225.1. XM_006243163.1.
XP_006243226.1. XM_006243164.3.
UniGeneiRn.2759.

Genome annotation databases

EnsembliENSRNOT00000026358; ENSRNOP00000026358; ENSRNOG00000019374.
ENSRNOT00000091223; ENSRNOP00000068638; ENSRNOG00000019374.
GeneIDi315707.
KEGGirno:315707.
UCSCiRGD:1308800. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58631 mRNA. Translation: CAA41484.1.
BC098863 mRNA. Translation: AAH98863.1.
PIRiS15094.
RefSeqiNP_001025210.1. NM_001030039.1.
XP_006243225.1. XM_006243163.1.
XP_006243226.1. XM_006243164.3.
UniGeneiRn.2759.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K9AX-ray2.50A/B/C/D/E/F1-450[»]
2RSYNMR-A80-173[»]
ProteinModelPortaliP32577.
SMRiP32577.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi261119. 4 interactors.
IntActiP32577. 2 interactors.
MINTiMINT-1535121.
STRINGi10116.ENSRNOP00000026358.

Chemistry databases

BindingDBiP32577.
ChEMBLiCHEMBL4365.

PTM databases

iPTMnetiP32577.
PhosphoSitePlusiP32577.

Proteomic databases

PaxDbiP32577.
PRIDEiP32577.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000026358; ENSRNOP00000026358; ENSRNOG00000019374.
ENSRNOT00000091223; ENSRNOP00000068638; ENSRNOG00000019374.
GeneIDi315707.
KEGGirno:315707.
UCSCiRGD:1308800. rat.

Organism-specific databases

CTDi1445.
RGDi1308800. Csk.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP32577.
KOiK05728.
OMAiTRDPNWY.
PhylomeDBiP32577.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiR-RNO-180292. GAB1 signalosome.
R-RNO-202427. Phosphorylation of CD3 and TCR zeta chains.
R-RNO-354192. Integrin alphaIIb beta3 signaling.
R-RNO-389948. PD-1 signaling.

Miscellaneous databases

EvolutionaryTraceiP32577.
PROiP32577.

Gene expression databases

BgeeiENSRNOG00000019374.
GenevisibleiP32577. RN.

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_RAT
AccessioniPrimary (citable) accession number: P32577
Secondary accession number(s): Q4G003
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: November 2, 2016
This is version 167 of the entry and version 1 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.