IFITM3
IFITM3 (interferon induced transmembrane protein 3, also known as 1-8U and DSPA2b) is an interferon-induced antiviral protein of the CD225/Dispanin family. It restricts the entry of many enveloped viruses into the host cell cytoplasm. Browse Assay Genie's current range of IFITM3 research reagents below, or read on for the biology behind the target.
IFITM3 is an interferon-induced antiviral protein that disrupts intracellular cholesterol homeostasis. It inhibits viral entry into the cytoplasm by preventing fusion of viral and host membranes with cholesterol-depleted endosomes, and it may also inactivate newly budding enveloped viruses by letting them leave the cell with a cholesterol-depleted membrane. The protein also contributes to the structural stability and function of vacuolar ATPase (v-ATPase). It makes physical contact with endosomal v-ATPase, which is critical for proper clathrin localisation and for lowering the pH of phagocytic endosomes, so establishing an antiviral state.
The IFITM3 protein is reported at the cell membrane and at early endosome, late endosome and lysosome membranes, as well as in the perinuclear cytoplasm. Its activity covers a broad range of viruses, including influenza A virus, SARS-CoV and SARS-CoV-2, Marburg virus, Ebola virus, Dengue virus, West Nile virus, HIV-1, hepatitis C virus and vesicular stomatitis virus. It can inhibit entry mediated by influenza haemagglutinin, Marburg and Ebola GP1,2, SARS coronavirus S protein and VSV G protein. In hepatocytes, IFITM proteins act together to restrict HCV by directing endocytosed virions to lysosomal degradation, with IFITM2 and IFITM3 complementing IFITM1 by acting on late stages of entry.
The IFITM3 gene belongs to a family of five interferon-induced transmembrane genes that includes IFITM1 and IFITM2, within the CD225 superfamily. Its previous HGNC name carried the designation 1-8U. For SARS-CoV-2, the protein has opposing effects: amphipathicity-dependent restriction of the virus at endosomes, and amphipathicity-independent enhancement of infection at the plasma membrane.
IFITM3 is an interferon-induced restriction factor that limits entry of diverse enveloped viruses, making it a central subject in innate antiviral defence.
The protein blocks fusion with cholesterol-depleted endosomes and inhibits entry mediated by influenza haemagglutinin, Ebola and Marburg GP1,2, and coronavirus S protein.
IFITM3 contacts endosomal v-ATPase, supporting clathrin localisation and endosomal acidification, which links it to the study of endolysosomal function.
IFITM3 restricts SARS-CoV-2 at endosomes yet can enhance infection at the plasma membrane, an opposing activity of interest in coronavirus research.
IFITM3 is an interferon-induced antiviral protein. It disrupts intracellular cholesterol homeostasis and prevents viral fusion with cholesterol-depleted endosomes, so blocking entry of viruses into the cytoplasm. It also contributes to v-ATPase stability and function, helping to establish an antiviral state in endosomes.
The gene is also known as 1-8U and DSPA2b, and its previous HGNC name was interferon induced transmembrane protein 3 (1-8U). It belongs to the interferon induced transmembrane protein family and the Dispanins, within the CD225 superfamily, alongside IFITM1 and IFITM2.
Mostly it restricts viruses, including influenza A, Ebola, Dengue and HIV-1. For SARS-CoV-2, however, it has opposing effects: it restricts the virus at endosomes but enhances infection at the plasma membrane. Mouse Ifitm3 and rat ifitm3 are the orthologues; check the datasheet of any product for its validated reactivity.
Other members of the IFITM family of interferon-induced antiviral proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q01628; product specifications from Assay Genie datasheets.