Adapter molecule crk phospho Y221
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.
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 (PubMed:31311869). 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 (PubMed:19004829). May regulate the EFNA5-EPHA3 signaling (By similarity).
Post-translational modifications
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:17515907). 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.
Sequence Similarities
Belongs to the CRK family.
Cellular localization
- Cytoplasm
- Cell membrane
- Translocated to the plasma membrane upon cell adhesion.
Alternative names
Adapter molecule crk, Proto-oncogene c-Crk, p38, CRK