DOCK1
Description
The DOCK1 (dedicator of cytokinesis 1) is a protein-coding gene located on chromosome 10.
DOCK1, also known as DOCK180, is a large (~180 kDa) protein encoded by the DOCK1 gene in humans. It participates in intracellular signaling networks and is the mammalian counterpart of the C. elegans protein CED-5. DOCK1 belongs to the DOCK family of guanine nucleotide exchange factors (GEFs). DOCK180 was discovered as a binding partner of the adaptor protein Crk, capable of inducing morphological changes in 3T3 fibroblasts. It was later found to activate the small GTP-binding protein (G protein) Rac1, through its GEF activity. DOCK180 belongs to a large class of proteins (GEFs) that activate small G proteins by facilitating the exchange of GDP for GTP. Unlike other GEFs, DOCK180 lacks the typical tandem DH-PH domains, instead possessing a DHR2 domain that stabilizes Rac in its nucleotide-free state for activation. DOCK180 also contains a DHR1 domain, which binds phospholipids in vitro and may be involved in interactions with cellular membranes. Additional structural features include an N-terminal SH3 domain that binds to ELMO proteins and a C-terminal proline-rich region that binds DCrk in Drosophila.
DOCK1 plays a crucial role in cytoskeletal reorganization, which is essential for the engulfment of dying cells (phagocytosis) and cell movement. Together with DOCK1, it regulates the spreading and migration of epithelial and endothelial cells on type IV collagen, a process controlled by the CRK/CRKL signaling pathway. DOCK1 acts as a guanine nucleotide exchange factor (GEF), activating Rac Rho GTPases by replacing GDP with GTP. ELMO1 can further enhance this GEF activity.
DOCK1 is also known as DOCK180, ced5.
