This entry represents E3 ubiquitin-protein ligases MARCHF4, 9 and 11 predominantly found in chordates. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Members of this small protein family contain a RING-CH-type zinc finger domain and are integrated into the cellular membrane [, , ].MARCHF4 and 9 are closely related. These proteins reduce the surface expression of major histocompatibility complex class I (MHC I), and downregulate CD4. They promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. MARCHF4 appears to be mainly expressed in the brain. MARCHF9 controls the expression of the critical cell adhesion molecule ICAM-1 [, ].MARCHF11, identified later, is also involved in the regulation of the poly-ubiquitination of CD4. This protein seems to be specifically expressed in the early developmental stages of spermatids [].
