DIAPH3

DIAPH3 (diaphanous-related formin 3) is a human gene that encodes the DIAPH3 protein, a member of the diaphanous-related formin (DRF) subfamily of the formin superfamily. DRFs regulate actin filament nucleation and elongation and coordinate actin dynamics with microtubule behavior. DIAPH3 is widely expressed in human tissues, with higher levels in cells undergoing active cytoskeletal remodeling.

Function: DIAPH3 contains the core formin architecture, including an N-terminal GTPase-binding domain, a diaphanous inhibitory domain (DID), a dimerization region, and a C-terminal diaphanous autoregulatory domain (DAD), followed by FH1 and FH2 actin-polymerization domains. In the resting state the DAD binds DID, and activation by Rho-family GTPases relieves autoinhibition. The FH1 and FH2 domains nucleate and processively elongate unbranched actin filaments, typically in cooperation with profilin. DIAPH3 also influences microtubule stability and can coordinate cross-talk between actin and microtubules, contributing to processes such as cell polarity, migration, cytokinesis, vesicle trafficking, and ciliogenesis.

Regulation and interactions: DIAPH3 activity is controlled by Rho GTPases and by interactions with profilin and other actin-regulatory proteins. The protein localizes to membranes or cytoplasmic structures depending on context and participates in protein networks that organize the cytoskeleton and intracellular transport.

Clinical significance: Variants in DIAPH3 have been reported in some families with hereditary hearing loss, but the genetic and functional evidence remains under study and not yet conclusive. In general, DIAPH3 is studied for its role in cytoskeletal regulation and potential links to ciliopathy-like phenotypes.