Membrane-associated ring finger (C3HC4) 1, E3 ubiquitin protein ligase (MARCH1)

MARCH1 (Membrane-associated ring finger (C3HC4) 1, E3 ubiquitin protein ligase), commonly abbreviated as MARCHF1 or MARCH1, is a membrane-bound E3 ubiquitin ligase that facilitates the conjugation of ubiquitin to lysine residues of substrate membrane proteins. This post-translational modification signals for vesicular trafficking and degradation, most notably downregulating the surface expression of MHC class II molecules and other glycoproteins by targeting them for lysosomal degradation. MARCH1 also regulates the surface levels of various immune receptors (e.g., CD86, FAS, transferrin receptor), impacting immune responses, pathogen interactions, and processes including insulin sensitivity through insulin receptor turnover. It has been implicated in cancer promotion, viral infection (e.g., cytomegalovirus), immunodeficiency, and modulation of neuronal GABAB receptor trafficking. The broad involvement in cellular homeostasis and disease highlights MARCH1 as a potential therapeutic target, but it is not currently the focus of direct pharmacological interventions.

Other names

MARCHF1MARCH-IRNF171E3 ubiquitin-protein ligase MARCHF1Membrane Associated Ring-CH-Type Finger 1Membrane-Associated RING Finger Protein 1RING-type E3 Ubiquitin Transferase MARCHF1

Not applicable; no approved drugs target MARCH1 directly. Mechanistically, inhibition or modulation of ubiquitin ligase activity would alter degradation or trafficking of the protein’s substrates.