FHOD3
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 (By similarity).
Function
Actin-organizing protein that may cause stress fiber formation together with cell elongation (By similarity). Isoform 4 may play a role in actin filament polymerization in cardiomyocytes.
Involvement in disease
Cardiomyopathy, familial hypertrophic, 28
CMH28
A form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH28 is an autosomal dominant form with incomplete penetrance.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Isoform 4
Phosphorylated on Thr-1474 and Thr-1476 by CK2.
Sequence Similarities
Belongs to the formin homology family.
Tissue Specificity
Expressed in the heart, kidney and brain. May be down-regulated in various types of heart diseases, including idiopathic dilated, ventricular dilated, familial dilated and perinatal dilated cardiomyopathies, as well as ischemic heart disease (at protein level).
Cellular localization
- Cytoplasm
- Cytoskeleton
- Main part of the protein localizes to actin fibers and the remaining part displays filamentous staining.
- Isoform 4
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
- Threonine phosphorylation in isoform 4-specific sequence TDTDEEEEVE is required for targeting to myofibrils in cardiomyocytes.
Alternative names
FHOS2, KIAA1695, FHOD3, FH1/FH2 domain-containing protein 3, Formactin-2, Formin homolog overexpressed in spleen 2, hFHOS2