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MGP004229

UniProt Annotations

Entry Information
Gene Nameinterferon induced transmembrane protein 3
Protein EntryIFM3_HUMAN
UniProt IDQ01628
SpeciesHuman
Comments
Comment typeDescription
FunctionIFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endosomes. May inactivate new enveloped viruses which buds out of the infected cell, by letting them go out with a cholesterol depleted membrane. Active against multiple viruses, including influenza A virus, SARS coronavirus (SARS-CoV), Marburg virus (MARV) and Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2- mediated viral entry, SARS-CoV S protein-mediated viral entry and VSV G protein-mediated viral entry. Plays a critical role in the structural stability and function of vacuolar ATPase (v-ATPase). Establishes physical contact with the v-ATPase of endosomes which is critical for proper clathrin localization and is also required for the function of the v-ATPase to lower the pH in phagocytic endosomes thus establishing an antiviral state. {ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20534863, ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:22046135, ECO:0000269|PubMed:22479637, ECO:0000269|PubMed:23601107}.
InductionBy IFN-alpha and IFNG/IFN-gamma.
InteractionP43490:NAMPT; NbExp=3; IntAct=EBI-7932862, EBI-2829310;
PolymorphismGenetic variations in IFITM3 are responsible for susceptibility to severe influenza virus infection [MIM:614680].
PtmNot glycosylated.
PtmPalmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus. {ECO:0000269|PubMed:20601941, ECO:0000269|PubMed:22511783}.
PtmPolyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiqutination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site. {ECO:0000269|PubMed:22511783}.
SimilarityBelongs to the CD225/Dispanin family. {ECO:0000305}.
Subcellular LocationCell membrane; Single-pass type II membrane protein. Late endosome membrane; Single-pass type II membrane protein. Lysosome membrane; Single-pass type II membrane protein.
SubunitInteracts with ATP6V0B and CD81 (By similarity). Interacts with SPP1; the interaction reduces OPN expression. Interacts with VAPA. {ECO:0000250, ECO:0000269|PubMed:19901966, ECO:0000269|PubMed:23601107}.
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