DIAPH1
Developmental stage
Strongly expressed in ventricular and subventricular zone progenitor cells of the neocortical wall at 12 weeks post-conception.
Domain
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain (By similarity). This autoinhibition is released upon competitive binding of an activated GTPase (By similarity). The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).
Function
Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). 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 (By similarity).
Involvement in disease
Deafness, autosomal dominant 1, with or without thrombocytopenia
DFNA1
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Patients may have mild thrombocytopenia and enlarged platelets, although most of DFNA1 affected individuals do not have significant bleeding tendencies.
None
The disease is caused by variants affecting the gene represented in this entry.
Seizures, cortical blindness, and microcephaly syndrome
SCBMS
A severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, short stature, and cortical blindness.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Thr-768 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement.
Sequence Similarities
Belongs to the formin homology family. Diaphanous subfamily.
Tissue Specificity
Expressed in brain, heart, placenta, lung, kidney, pancreas, liver, skeletal muscle and cochlea. Expressed in platelets (PubMed:26912466).
Cellular localization
- Cell membrane
- Cell projection
- Ruffle membrane
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Cytoskeleton
- Spindle
- Cytoplasm
- Nucleus
- Membrane ruffles, especially at the tip of ruffles, of motile cells.
Alternative names
DIAP1, DIAPH1, Protein diaphanous homolog 1, Diaphanous-related formin-1, DRF1