Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • adherens junction organization Source: RGD
  • brain development Source: RGD
  • 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

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity
LigandATP-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
R-RNO-5674135 MAP2K and MAPK activation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi

Organism-specific databases

RGDi1308800 Csk

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

  • identical protein binding Source: Ensembl
  • proline-rich region binding Source: BHF-UCL
  • protein kinase A catalytic subunit binding Source: Ensembl
  • protein phosphatase binding Source: BHF-UCL
  • signaling receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi261119, 6 interactors
ELMiP32577
IntActiP32577, 2 interactors
MINTiP32577
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

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP32577
KOiK05728
OMAiWALNMKD
PhylomeDBiP32577
TreeFamiTF351634

Family and domain databases

CDDicd09937 SH2_csk_like, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035026 CSK
IPR035027 Csk-like_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PANTHERiPTHR24418:SF307 PTHR24418:SF307, 1 hit
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 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

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

Entry informationi

Entry nameiCSK_RAT
AccessioniPrimary (citable) accession number: P32577
Secondary accession number(s): Q4G003
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: May 23, 2018
This is version 179 of the entry and version 1 of the sequence. See 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

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health