Q64010 · CRK_MOUSE
- ProteinAdapter molecule crk
- GeneCrk
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids304 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1.
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 (By similarity).
May regulate the EFNA5-EPHA3 signaling (PubMed:11870224).
May regulate the EFNA5-EPHA3 signaling (PubMed:11870224).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 237 | Proline switch | ||||
Sequence: P |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAdapter molecule crk
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ64010
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Translocated to the plasma membrane upon cell adhesion.
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 14 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000079352 | 2-304 | Adapter molecule crk | |||
Sequence: AGNFDSEERSSWYWGRLSRQEAVALLQGQRHGVFLVRDSSTSPGDYVLSVSENSRVSHYIINSSGPRPPVPPSPAQPPPGVSPSRLRIGDQEFDSLPALLEFYKIHYLDTTTLIEPVARSRQGSGVILRQEEAEYVRALFDFNGNDEEDLPFKKGDILRIRDKPEEQWWNAEDSEGKRGMIPVPYVEKYRPASASVSALIGGNQEGSHPQPLGGPEPGPYAQPSVNTPLPNLQNGPIYARVIQKRVPNAYDKTALALEVGELVKVTKINVSGQWEGECNGKRGHFPFTHVRLLDQQNPDEDFS | ||||||
Modified residue | 40 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 41 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 74 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 83 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 108 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 125 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 221 | Phosphotyrosine; by ABL1 | ||||
Sequence: Y | ||||||
Modified residue | 239 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
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 (PubMed:12878163, PubMed:8194526).
Isoform Crk-II: Phosphorylated by KIT (By similarity).
Isoform Crk-II: Phosphorylated by KIT (By similarity).
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK (By similarity).
Within the complex, interacts with SH2D3C (via C-terminus), and BCAR1/CAS (By similarity).
Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity).
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. Interacts with FLT4 (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).
Within the complex, interacts with SH2D3C (via C-terminus), and BCAR1/CAS (By similarity).
Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity).
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. Interacts with FLT4 (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).
Isoform Crk-II
Interacts (via SH2 domain) with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated) (By similarity).
Interacts with EPHA3 (phosphorylated); upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent and mediates EFNA5-EPHA3 signaling through RHOA GTPase activation (PubMed:11870224).
Interacts with KIT (PubMed:12878163).
Interacts with PEAK3; the interaction requires PEAK3 homodimerization (By similarity).
Interacts with EPHA3 (phosphorylated); upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent and mediates EFNA5-EPHA3 signaling through RHOA GTPase activation (PubMed:11870224).
Interacts with KIT (PubMed:12878163).
Interacts with PEAK3; the interaction requires PEAK3 homodimerization (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q64010 | IGF1R P08069 | 3 | EBI-2906540, EBI-475981 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 13-118 | SH2 | ||||
Sequence: WYWGRLSRQEAVALLQGQRHGVFLVRDSSTSPGDYVLSVSENSRVSHYIINSSGPRPPVPPSPAQPPPGVSPSRLRIGDQEFDSLPALLEFYKIHYLDTTTLIEPV | ||||||
Region | 60-85 | Disordered | ||||
Sequence: YIINSSGPRPPVPPSPAQPPPGVSPS | ||||||
Compositional bias | 66-82 | Pro residues | ||||
Sequence: GPRPPVPPSPAQPPPGV | ||||||
Domain | 132-192 | SH3 1 | ||||
Sequence: EEAEYVRALFDFNGNDEEDLPFKKGDILRIRDKPEEQWWNAEDSEGKRGMIPVPYVEKYRP | ||||||
Region | 201-229 | Disordered | ||||
Sequence: IGGNQEGSHPQPLGGPEPGPYAQPSVNTP | ||||||
Domain | 235-296 | SH3 2 | ||||
Sequence: NGPIYARVIQKRVPNAYDKTALALEVGELVKVTKINVSGQWEGECNGKRGHFPFTHVRLLDQ |
Domain
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.
The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB.
Sequence similarities
Belongs to the CRK family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q64010-1
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.
- NameCrk-II
- Length304
- Mass (Da)33,815
- Last updated1996-11-01 v1
- Checksum5491896FC7A89065
Q64010-2
- NameCrk-I
- Differences from canonical
- 205-304: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 66-82 | Pro residues | ||||
Sequence: GPRPPVPPSPAQPPPGV | ||||||
Alternative sequence | VSP_004174 | 205-304 | in isoform Crk-I | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S72408 EMBL· GenBank· DDBJ | AAB30755.1 EMBL· GenBank· DDBJ | mRNA | ||
AK028488 EMBL· GenBank· DDBJ | BAC25976.1 EMBL· GenBank· DDBJ | mRNA |