Dedicator of cytokinesis protein 1

DOCK1 (Dedicator of cytokinesis protein 1) is a guanine nucleotide exchange factor (GEF) that activates Rac small GTPases by exchanging bound GDP for free GTP (UniProt: Q14185). The protein functions in cytoskeletal rearrangements essential for phagocytosis of apoptotic cells and cell motility, and mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen. Its GEF activity may be enhanced by ELMO1.

DOCK1 is broadly expressed and plays roles in cellular processes requiring dynamic actin reorganization. No disease associations are documented in UniProt, though the protein's involvement in phagocytosis suggests potential relevance to neuroinflammatory and clearance mechanisms in the central nervous system.

In Alzheimer's disease, DOCK1 is significantly down-regulated in post-mortem AD brain compared to age-matched controls (mean log2 fold-change: −0.53; Chaparral AD proteomics). This reduction was observed across subcellular fractions in a TMT-labeled quantitative proteomics study, suggesting diminished cytoskeletal remodeling capacity may contribute to AD pathophysiology.