DIAPH3
Developmental stage
Increased expression in S phase and mitotic cells; levels decrease as cells enter in G0/G1 phase due to proteasomal degradation (at protein level).
Domain
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.
Function
Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers. Required for cytokinesis, stress fiber formation and transcriptional activation of the serum response factor. Binds to GTP-bound form of Rho and to profilin: acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity.
Involvement in disease
Auditory neuropathy, autosomal dominant 1
AUNA1
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination.
None
The disease is caused by variants affecting the gene represented in this entry. A disease-causing mutation in the conserved 5'-UTR leads to increased protein expression.
Post-translational modifications
Ubiquitinated.
Sequence Similarities
Belongs to the formin homology family. Diaphanous subfamily.
Cellular localization
- Cytoplasm
- Nucleus
- During mitosis, co-localizes with the actin-rich cleavage furrow and with the microtubule-rich central spindle during cytokinesis (PubMed:18755006, PubMed:19457867). Shuttles between the cytoplasm and the nucleus (By similarity).
Alternative names
DIAP3, DIAPH3, Protein diaphanous homolog 3, Diaphanous-related formin-3, MDia2, DRF3