PMID:11756476

Citation	Coscoy, L, Sanchez, DJ and Ganem, D (2001) A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition. J. Cell Biol. 155:1265-73
Abstract	Kaposi's sarcoma-associated herpesvirus encodes two transmembrane proteins (modulator of immune recognition [MIR]1 and MIR2) that downregulate cell surface molecules (MHC-I, B7.2, and ICAM-1) involved in the immune recognition of infected cells. This downregulation results from enhanced endocytosis and subsequent endolysosomal degradation of the target proteins. Here, we show that expression of MIR1 and MIR2 leads to ubiquitination of the cytosolic tail of their target proteins and that ubiquitination is essential for their removal from the cell surface. MIR1 and MIR2 both contain cytosolic zinc fingers of the PHD subfamily, and these structures are required for this activity. In vitro, addition of a MIR2-glutathione S-transferase (GST) fusion protein to purified E1 and E2 enzymes leads to transfer of ubiquitin (Ub) to GST-containing targets in an ATP- and E2-dependent fashion; this reaction is abolished by mutation of the Zn-coordinating residues of the PHD domain. Thus, MIR2 defines a novel class of membrane-bound E3 Ub ligases that modulates the trafficking of host cell membrane proteins.
Links	PubMed PMC2199318 Online version:10.1083/jcb.200111010
Keywords	Amino Acid Sequence; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Chimera; Endocytosis/physiology; Flow Cytometry; Gene Expression Regulation; Glutathione Transferase/metabolism; HLA-B7 Antigen/genetics; HLA-B7 Antigen/immunology; HeLa Cells; Herpesviridae/immunology; Humans; Intracellular Membranes/metabolism; Isoenzymes/metabolism; Ligases/metabolism; Major Histocompatibility Complex/genetics; Mitochondrial Proteins; Molecular Sequence Data; Phosphate Transport Proteins; Recombinant Proteins/metabolism; Saccharomyces cerevisiae Proteins; Sequence Alignment; Transfection; Ubiquitin-Protein Ligases
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HHV8P:MIR1		GO:0016567: protein ubiquitination	ECO:0000314:		P		Fig 4 Ubiquitination of human B7.2 molecules and MHC-I molecules	complete

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