Membrane-associated RING-CH-type finger protein 4 (MARCH4)

Membrane-associated RING-CH-type finger protein 4 (MARCH4) is a member of the MARCH family of E3 ubiquitin ligases characterized by the presence of a RING-CH finger domain and association with cellular membranes[1][2][3]. MARCH4 mediates the ubiquitination and subsequent lysosomal degradation of multiple cell surface proteins, including major histocompatibility complex class I (MHC I), tetraspanin CD81, hyaluronic acid receptor CD44, and others, thereby controlling their surface expression[2][3]. This regulatory function plays a substantial role in modulating immune responses, host-pathogen interactions, and protein trafficking. MARCH4 is structurally and functionally related to viral immune evasion proteins such as K3 and K5 from Kaposi’s sarcoma-associated herpesvirus, which also downregulate MHC I to evade immune detection[1][3]. MARCH4 is expressed predominantly in the brain, placenta, lungs, and pancreas[3]. Dysregulation of MARCH4 activity may contribute to immune system dysfunction or cancer progression due to altered expression of key surface receptors[1][3]. There are currently no known drugs directly targeting MARCH4.

Other names

Membrane-associated RING-CH 4MARCH-IVRNF174

E3 ubiquitin ligase activity: catalyzes ubiquitination of specific membrane proteins, targeting them for endocytosis and lysosomal degradation; Downregulation of immune surface receptors (such as MHC I, CD81, CD44, SX4, Mult1)