Membrane Associated Ring Finger Protein 4 (MARCH4)

MARCH4 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH4 reduces surface accumulation of several membrane glycoproteins by directing them to the endosomal compartment.

Following transfection into HeLa cells, MARCH4 downregulated the surface expression of cotransfected CD4 and endogenous MHC I. Mutation analysis revealed that the RING-CH domain of MARCH4 was required for downregulation of MHC I surface expression, and additional sequences in the MARCH4 N- and C-terminal ends contributed to internalization.