DIAPH1
Description
The DIAPH1 (diaphanous related formin 1) is a protein-coding gene located on chromosome 5.
DIAPH1 is a protein encoded by the DIAPH1 gene in humans. It belongs to the formin protein family, characterized by the FH2 domain. DIAPH1 is a homolog of the Drosophila diaphanous gene and has been linked to autosomal dominant, fully penetrant, nonsyndromic low-frequency progressive sensorineural hearing loss. Actin polymerization involves proteins that interact with diaphanous protein in Drosophila and mouse, suggesting a role for DIAPH1 in regulating actin polymerization in hair cells of the inner ear. The gene has multiple transcript variants encoding distinct isoforms. DIAPH1 interacts with RHOA. Mutations in the DIAPH1 gene have been associated with macrothrombocytopenia, hearing loss, microcephaly, blindness, and early onset seizures. Its actions on platelet formation appear to occur in megakaryocytes, where it is involved in cytoskeleton formation.
DIAPH1 is an actin nucleation and elongation factor essential for the formation of F-actin structures like actin cables and stress fibers. It binds to the barbed end of actin filaments, slowing down both polymerization and depolymerization. DIAPH1 is crucial for cytokinesis and the transcriptional activation of the serum response factor. It also plays a role in coupling Rho and Src tyrosine kinases during signaling, regulating actin dynamics. DIAPH1 acts as a scaffold protein for MAPRE1 and APC, stabilizing microtubules and promoting cell migration. It has neurite outgrowth promoting activity and recruits PFY1 to the membrane in a Rho-dependent manner. In hair cells, DIAPH1 regulates actin polymerization. The MEMO1-RHOA-DIAPH1 signaling pathway stabilizes microtubules at the cell cortex in an ERBB2-dependent manner. DIAPH1 controls the localization of APC and CLASP2 to the cell membrane by regulating GSK3B activity. This leads to the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. DIAPH1 plays a role in cell morphology, cytoskeletal organization, and cell shape control. It is involved in brain development and also acts as an actin nucleation and elongation factor in the nucleus, promoting nuclear actin polymerization to drive serum-dependent SRF-MRTFA activity.
DIAPH1 is also known as DFNA1, DIA1, DRF1, LFHL1, SCBMS, hDIA1, mDia1.
Associated Diseases
- Seizures, cortical blindness, and microcephaly syndrome
- DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome
- Moyamoya disease
- Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
- Deafness, autosomal dominant 1
