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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

The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II 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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei237 – 2371Proline switchBy similarity

GO - Molecular functioni

  • enzyme binding Source: RGD
  • protein binding, bridging Source: RGD
  • protein domain specific binding Source: RGD

GO - Biological processi

  • activation of JUN kinase activity Source: RGD
  • activation of MAPKK activity Source: Reactome
  • ephrin receptor signaling pathway Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cellular component movement Source: RGD
  • regulation of GTPase activity Source: UniProtKB
  • regulation of Rac protein signal transduction Source: RGD
Complete GO annotation...

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-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi2405. Crk.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi221 – 2211Y → F: No activation of Rac signaling. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 304303Adapter molecule crkPRO_0000079353Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei41 – 411PhosphoserineBy similarity
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei83 – 831PhosphoserineBy similarity
Modified residuei125 – 1251PhosphoserineBy similarity
Modified residuei221 – 2211Phosphotyrosine; by ABL11 Publication
Modified residuei239 – 2391PhosphotyrosineBy similarity

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.
PhosphoSiteiQ63768.

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

GenevisibleiQ63768. RN.

Interactioni

Subunit structurei

Interacts with ABL1, C3G, DOCK3, 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 a different organism.

GO - Molecular functioni

  • enzyme binding Source: RGD
  • protein binding, bridging Source: RGD
  • protein domain specific binding Source: RGD

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ63768.
SMRiQ63768. Positions 1-304.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 118106SH2PROSITE-ProRule annotationAdd
BLAST
Domaini132 – 19261SH3 1PROSITE-ProRule annotationAdd
BLAST
Domaini237 – 29660SH3 2PROSITE-ProRule annotationAdd
BLAST

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
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 2 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4792. Eukaryota.
ENOG4110574. LUCA.
GeneTreeiENSGT00820000127055.
HOGENOMiHOG000236288.
HOVERGENiHBG105616.
InParanoidiQ63768.
KOiK04438.
OMAiNQDSSHP.
OrthoDBiEOG7NW69P.
PhylomeDBiQ63768.
TreeFamiTF321436.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti244 – 2441Q → R in NRK-23 inactive mutant.
Natural varianti253 – 2531K → E in NRK-23 inactive mutant.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei205 – 304100Missing in isoform Crk-I. CuratedVSP_004175Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ63768.
SMRiQ63768. Positions 1-304.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ63768.
PhosphoSiteiQ63768.

Proteomic databases

PaxDbiQ63768.
PRIDEiQ63768.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1398.
RGDi2405. Crk.

Phylogenomic databases

eggNOGiKOG4792. Eukaryota.
ENOG4110574. LUCA.
GeneTreeiENSGT00820000127055.
HOGENOMiHOG000236288.
HOVERGENiHBG105616.
InParanoidiQ63768.
KOiK04438.
OMAiNQDSSHP.
OrthoDBiEOG7NW69P.
PhylomeDBiQ63768.
TreeFamiTF321436.

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-912631. Regulation of signaling by CBL.

Miscellaneous databases

PROiQ63768.

Gene expression databases

GenevisibleiQ63768. RN.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "CrkII signals from epidermal growth factor receptor to Ras."
    Kizaka-Kondoh S., Matsuda M., Okayama H.
    Proc. Natl. Acad. Sci. U.S.A. 93:12177-12182(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  2. "Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling."
    Abassi Y.A., Vuori K.
    EMBO J. 21:4571-4582(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-221, MUTAGENESIS OF TYR-221.
  3. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCRK_RAT
AccessioniPrimary (citable) accession number: Q63768
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 138 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

Complete proteome, Reference proteome

Documents

  1. 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.