Eps15 homology domain-containing protein 3 (EHD3)

Eps15 homology domain-containing protein 3 (EHD3) is a member of the EHD family, which are membrane remodeling proteins related to the Dynamin superfamily of large GTPases[1][2]. EHD3 is primarily involved in endocytic transport, controlling the transit of molecules from early endosomes to the recycling endosome compartment, as well as retrograde transport to the Golgi apparatus and rapid recycling to the plasma membrane[1][2][5]. It is an ATP- and membrane-binding protein that mediates membrane reorganization and tubulation upon ATP hydrolysis[5]. EHD3 is highly expressed in heart and brain, and more moderately in kidney, ovary, liver, and placenta[1]. Functional studies show roles in the control of endocytic trafficking, especially recycling of proteins such as the D1 dopamine receptor, integrin beta-3, and cardiac ion transporters, as well as general membrane protein localization[1][2][5]. EHD3 is a moonlighting protein, meaning it performs different functions depending on tissue context. Loss or dysfunction of EHD3 is associated with diseases such as heart failure, depressive disorders (notably with gender-specific genetic susceptibility), and acts as a tumor suppressor in glioma, where loss of EHD3 is an early oncogenic event. Mechanistically, it binds to GTP and nucleic acids, and interacts with proteins involved in vesicle trafficking such as Rab11-FIP2[1][2]. No drugs directly targeting EHD3 are known, and it is not currently a major therapeutic target[2][5].

Other names

PAST3PAST 3EH domain-containing protein 3EH-domain containing 3