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Protein

Adapter molecule crk

Gene

Crk

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform Crk-II: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei237Proline switchBy similarity1

GO - Molecular functioni

  • cytoskeletal protein binding Source: RGD
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: Ensembl
  • insulin-like growth factor receptor binding Source: RGD
  • phosphotyrosine residue binding Source: Ensembl
  • protein binding, bridging Source: RGD
  • protein domain specific binding Source: RGD
  • protein self-association Source: Ensembl
  • protein tyrosine kinase binding Source: RGD
  • scaffold protein binding Source: RGD
  • SH2 domain binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: Ensembl
  • SH3 domain binding Source: Ensembl

GO - Biological processi

  • activation of JUN kinase activity Source: RGD
  • activation of MAPKK activity Source: Reactome
  • cellular response to endothelin Source: RGD
  • cellular response to insulin-like growth factor stimulus Source: RGD
  • cellular response to nerve growth factor stimulus Source: RGD
  • cellular response to nitric oxide Source: RGD
  • cellular response to transforming growth factor beta stimulus Source: RGD
  • ephrin receptor signaling pathway Source: UniProtKB
  • negative regulation of cell motility Source: Ensembl
  • negative regulation of natural killer cell mediated cytotoxicity Source: RGD
  • negative regulation of wound healing Source: Ensembl
  • positive regulation of smooth muscle cell migration Source: RGD
  • positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cell shape Source: Ensembl
  • regulation of cellular component movement Source: RGD
  • regulation of GTPase activity Source: UniProtKB
  • regulation of protein binding Source: Ensembl
  • regulation of Rac protein signal transduction Source: RGD
  • response to cholecystokinin Source: RGD
  • response to hepatocyte growth factor Source: RGD
  • response to hydrogen peroxide Source: RGD
  • response to peptide Source: RGD
  • response to yeast Source: RGD
  • SH2 domain-mediated complex assembly Source: Ensembl

Enzyme and pathway databases

ReactomeiR-RNO-170968. Frs2-mediated activation.
R-RNO-170984. ARMS-mediated activation.
R-RNO-186763. Downstream signal transduction.
R-RNO-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-RNO-372708. p130Cas linkage to MAPK signaling for integrins.
R-RNO-4420097. VEGFA-VEGFR2 Pathway.
R-RNO-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
R-RNO-8875555. MET activates RAP1 and RAC1.
R-RNO-8875656. MET receptor recycling.
R-RNO-912631. Regulation of signaling by CBL.

Names & Taxonomyi

Protein namesi
Recommended name:
Adapter molecule crk
Alternative name(s):
Proto-oncogene c-Crk
p38
Gene namesi
Name:Crk
Synonyms:Crko
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi2405. Crk.

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221Y → F: No activation of Rac signaling. 1 Publication1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000793532 – 304Adapter molecule crkAdd BLAST303

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei40PhosphoserineBy similarity1
Modified residuei41PhosphoserineBy similarity1
Modified residuei74PhosphoserineBy similarity1
Modified residuei83PhosphoserineBy similarity1
Modified residuei108PhosphotyrosineBy similarity1
Modified residuei125PhosphoserineBy similarity1
Modified residuei221Phosphotyrosine; by ABL11 Publication1
Modified residuei239PhosphotyrosineBy similarity1

Post-translational modificationi

Isoform Crk-II is phosphorylated by KIT (By similarity). Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway.By similarity1 Publication
Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ63768.
PRIDEiQ63768.

PTM databases

iPTMnetiQ63768.
PhosphoSitePlusiQ63768.

Expressioni

Tissue specificityi

CRK-II is expressed in all tissues and cells whereas CRK-I is expressed at lower level and in limited cell-types.

Gene expression databases

BgeeiENSRNOG00000025792.
GenevisibleiQ63768. RN.

Interactioni

Subunit structurei

Interacts with ABL1, C3G, DOCK3, DOCK5, MAP4K1, MAPK8 and SOS via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine-phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent. Interacts with EPHA3 (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated). Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with CBLC (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PTPN1P180312EBI-8423843,EBI-968788From Homo sapiens.

GO - Molecular functioni

  • cytoskeletal protein binding Source: RGD
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: Ensembl
  • insulin-like growth factor receptor binding Source: RGD
  • phosphotyrosine residue binding Source: Ensembl
  • protein binding, bridging Source: RGD
  • protein domain specific binding Source: RGD
  • protein self-association Source: Ensembl
  • protein tyrosine kinase binding Source: RGD
  • scaffold protein binding Source: RGD
  • SH2 domain binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: Ensembl
  • SH3 domain binding Source: Ensembl

Protein-protein interaction databases

BioGridi248468. 4 interactors.
IntActiQ63768. 2 interactors.
MINTiMINT-346964.
STRINGi10116.ENSRNOP00000006407.

Structurei

3D structure databases

ProteinModelPortaliQ63768.
SMRiQ63768.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 118SH2PROSITE-ProRule annotationAdd BLAST106
Domaini132 – 192SH3 1PROSITE-ProRule annotationAdd BLAST61
Domaini237 – 296SH3 2PROSITE-ProRule annotationAdd BLAST60

Domaini

The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation.By similarity
The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB (By similarity).By similarity

Sequence similaritiesi

Belongs to the CRK family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4792. Eukaryota.
ENOG4110574. LUCA.
GeneTreeiENSGT00820000127055.
HOGENOMiHOG000236288.
HOVERGENiHBG105616.
InParanoidiQ63768.
KOiK04438.
OMAiGSWYWGR.
OrthoDBiEOG091G0JPQ.
PhylomeDBiQ63768.
TreeFamiTF321436.

Family and domain databases

CDDicd11759. SH3_CRK_C. 1 hit.
cd11758. SH3_CRK_N. 1 hit.
Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR035458. CRK_SH3_C.
IPR035457. CRK_SH3_N.
IPR000980. SH2.
IPR036860. SH2_dom_sf.
IPR036028. SH3-like_dom.
IPR001452. SH3_domain.
PfamiView protein in Pfam
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
SUPFAMiSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 2 hits.
PROSITEiView protein in PROSITE
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Crk-II (identifier: Q63768-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS
60 70 80 90 100
VSENSRVSHY IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL
110 120 130 140 150
LEFYKIHYLD TTTLIEPVSR SRQGSGVILR QEEAEYVRAL FDFNGNDEED
160 170 180 190 200
LPFKKGDILR IRDKPEEQWW NAEDSEGKRG MIPVPYVEKY RPASASVSAL
210 220 230 240 250
IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA RVIQKRVPNA
260 270 280 290 300
YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPE

EDFS
Length:304
Mass (Da):33,845
Last modified:November 1, 1996 - v1
Checksum:i4CFBFB65BE72E265
GO
Isoform Crk-I (identifier: Q63768-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     205-304: Missing.

Show »
Length:204
Mass (Da):22,863
Checksum:iA485BF23887B6B80
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti244Q → R in NRK-23 inactive mutant. 1
Natural varianti253K → E in NRK-23 inactive mutant. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004175205 – 304Missing in isoform Crk-I. CuratedAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D44481 mRNA. Translation: BAA07924.1.
RefSeqiNP_062175.1. NM_019302.1. [Q63768-1]
UniGeneiRn.96136.

Genome annotation databases

EnsembliENSRNOT00000006407; ENSRNOP00000006407; ENSRNOG00000025792. [Q63768-1]
GeneIDi54245.
KEGGirno:54245.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCRK_RAT
AccessioniPrimary (citable) accession number: Q63768
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: October 25, 2017
This is version 149 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families