FERM domain-containing protein 6 (FRMD6, also known as Willin) contains an N-terminal 4.1 Ezrin Radixin Moesin (FERM) domain that links the cytoskeleton with the plasma membrane. Association of Willin with the plasma membrane is induced by epidermal growth factor [].
This entry represents the C-lobe of FERM domain found in FRMD6. The Drosophilla FRMD6 homologue, Ex, is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, which plays a pivotal role in organ size control and is tumour suppression by restricting proliferation and promoting apoptosis []. However, human FRMD6 is thought to function independently of the Hippo pathway. Instead it may inhibit progression through the S phase of the cell cycle by upregulating p21(Cip1) and downregulating Cyclin A []. It has been implicated in the progression of Alzheimer disease []. FRMD6 contains asingle FERM domain which has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe is a member 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 [, ].
