FCH and mu domain containing endocytic adaptor 2 (FCHO2)

FCH and mu domain containing endocytic adaptor 2 (FCHO2) is a peripheral membrane protein that participates in the early steps of clathrin-mediated endocytosis, a central cellular process responsible for internalizing a wide array of nutrient and signaling receptors[1][3][5][7]. FCHO2 contains an F-BAR (Fes/CIP4 Homology-Bin-Amphiphysin-Rvs) domain, which binds to and shapes membrane curvature, and a C-terminal mu-homology domain (μHD), enabling it to bind endocytic proteins (e.g., Disabled-2, Eps15, AP2, and intersectin). FCHO2 is essential for the organization and size control of clathrin-coated structures (CCSs), regulating the nucleation and assembly of these structures at the plasma membrane[1][5][7]. FCHO2’s direct interaction with specific adaptor proteins (such as Dab2) is required for the internalization of cargoes such as the low-density lipoprotein receptor (LDLR) and transferrin receptor, especially under conditions where primary adaptors (like AP2) are depleted[1][5]. By promoting the clustering of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at endocytic sites, FCHO2 aids in the recruitment and organization of the early endocytic machinery and drives efficient vesicle budding[5][7]. To date, FCHO2 is not considered a direct therapeutic target, nor are there drugs known to modulate its activity in clinical use[3]. Mutations or dysregulation of FCHO2 are associated with certain diseases, including familial hypertrophic cardiomyopathy and infection susceptibility, but its specific disease roles are not well-established[3].

Other names

F-BAR domain only protein 2FCH domain only 2FCH domain only protein 2FCHO2