ARHGEF6

Description

The ARHGEF6 (Rac/Cdc42 guanine nucleotide exchange factor 6) is a protein-coding gene located on chromosome X.

ARHGEF6, also known as Alpha-Pix, is a protein encoded by the ARHGEF6 gene in humans. It is a multidomain protein that functions as both a signaling scaffold and an enzyme. It shares its domain structure and signaling function with the similar ARHGEF7/βPIX protein. ARHGEF6 contains a central DH/PH RhoGEF domain that acts as a guanine nucleotide exchange factor (GEF) for small GTPases of the Rho family, specifically Rac and Cdc42. It can promote both the release of GDP from an inactive small GTP-binding protein and the binding of GTP to activate it. As a signaling scaffold, ARHGEF6 binds to specific partners to facilitate signal transduction by organizing pathway elements and holding partner protein complexes in specific locations within the cell. Its SH3 domain binds to partner proteins with polyproline motifs, particularly group I p21-activated kinases (PAKs) (PAK1, PAK2, and PAK3). In the inactive state, PAK is bound to the αPIX SH3 domain. Activated Rac1 or Cdc42 binding to this PAK stimulates its protein kinase activity, leading to downstream target protein phosphorylation. This αPIX/PAK/Rac complex exemplifies a scaffolding function. Structurally, ARHGEF6 assembles as a trimer through its carboxyl-terminal coiled-coil domain and further interacts with dimers of GIT1 or GIT2 through a nearby GIT-binding domain to form oligomeric GIT-PIX complexes.

ARHGEF6 (Alpha-Pix) acts as a guanine nucleotide exchange factor (GEF) for RAC1, promoting its activation by facilitating the exchange of GDP for GTP.

ARHGEF6 is also known as COOL2, Cool-2, MRX46, PIXA, alpha-PIX, alphaPIX.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing