FRMPD1, FRMPD3, and FRMPD4 contain an N-terminal PDZ domain and a C-terminal FERM domain. The PDZ domain helps anchor transmembrane proteins to the cytoskeleton and hold together signaling complexes. The PDZ domain also binds to a short region of the C terminus of other specific proteins. The FERM domain is composed of three subdomains: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), which form a clover leaf fold. The C-lobe/F3 within the FERM domain is part of the PH domain superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, ].This entry represents the C-lobe of the FERM domain found in FRMPD1/3/4. FRMPD1 regulates the subcellular location of activator of G-protein signaling 3 and its interaction with G-proteins []. FRMPD4 has been shown to regulates dendritic spine morphogenesis []. The function of FRMPD3 is not clear.
