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Background: MARCH8 is an E3 ubiquitin-protein ligase that may regulate immune responses by promoting ubiquitination of MHC-II and CD86, which leads to their subsequent endocytosis and lysosomal degradation. May also promote ubiquitination and endocytosis of TFRC and FAS. 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.