Dedicator of cytokinesis protein 9

Protein_DOCK9_PDB_1wg7

Dedicator of cytokinesis protein 9

Dedicator of cytokinesis protein 9 (DOCK9) is a protein that in humans is encoded by the DOCK9 gene. DOCK9 is a member of the DOCK180-related family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. It plays a crucial role in regulating cell migration, cytoskeletal dynamics, and cell adhesion.

Structure

DOCK9 contains multiple domains, including the DHR-1 (Dock Homology Region 1) domain, the DHR-2 domain, and the SH3 (Src Homology 3) domain. These domains are involved in mediating protein-protein interactions and GEF activity towards Rho GTPases.

Function

As a GEF for Rho GTPases, DOCK9 activates Rho GTPases by promoting the exchange of GDP for GTP, leading to downstream signaling cascades that regulate actin cytoskeleton dynamics and cell migration. DOCK9 is also implicated in the regulation of cell polarity and cell adhesion through its interactions with various signaling molecules.

Clinical significance

Mutations in the DOCK9 gene have been associated with various human diseases, including cancer and neurodevelopmental disorders. Dysregulation of DOCK9 expression or activity can lead to aberrant cell migration and invasion, contributing to tumor progression and metastasis.

Interactions

DOCK9 interacts with several proteins involved in cytoskeletal organization and cell signaling pathways, such as Rac1, Cdc42, and Nck. These interactions modulate the spatial and temporal activation of Rho GTPases, coordinating cellular processes essential for normal cell function.