F-BAR proteins been identified as important coordinators for membrane curvatures, which regulate cellular processes such as endocytosis, phagocytosis, adhesion and migration []. They bind to cell membrane via a N-terminal F-BAR domain, which associates with membrane phospholipids []. FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. FCHSD1 is expressed in cochlear sensory hair cells, and has been shown to bind via its F-BAR domain to the SH3 domain of Sorting Nexin 9, a BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization [].
This entry represents the first SH3 domain found in the F-BAR and double SH3 domains proteins, including FCHSD1 and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains []. FCHSD1 and FCHSD2 are expressed in cochlear sensory hair cells. FCHSD2 interacts with WASP and N-WASP, and stimulates F-actin assembly in vitro. FCHSD1 does not bind to WASP, but binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9, a BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization []. FCHSD2 has been implicated in receptor endocytosis and transport []. The insect protein nervous wreck, which acts as a regulator of synaptic growth signaling [], also contains this domain.
