IFITM3

The protein encoded by this gene is an interferon-induced membrane protein that helps confer immunity to influenza A H1N1 virus, West Nile virus, and dengue virus. Two transcript variants, only one of them protein-coding, have been found for this gene. Another variant encoding an N-terminally truncated isoform has been reported, but the full-length nature of this variant has not been determined.

interferon induced transmembrane protein 3

IFN-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 coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV) (PubMed:26354436, PubMed:33270927, PubMed:33239446).

Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry (PubMed:33270927).

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. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation (PubMed:26354436).

IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome (PubMed:26354436).

Exerts opposing activities on SARS-CoV-2, including amphipathicity-dependent restriction of virus at endosomes and amphipathicity-independent enhancement of infection at the plasma membrane (PubMed:33270927).

Defense response to virus Source: UniProtKB
Immune response Source: ProtInc
Negative regulation of viral entry into host cell Source: UniProtKB
Negative regulation of viral genome replication Source: UniProtKB
Negative regulation of viral transcription Source: UniProtKB
Response to interferon-alpha Source: UniProtKB
Response to interferon-beta Source: UniProtKB
Response to interferon-gamma Source: UniProtKB
Response to virus Source: UniProtKB
Type I interferon signaling pathway Source: GO_Central

Lysosome membrane; Late endosome membrane; Early endosome membrane; Cell membrane; Perinuclear region. Co-localizes with BRI3 isoform 1 at the perinuclear region.

Cytoplasmic: 1-57
Helical: 58-78
Cytoplasmic: 79-107
Helical: 108-128
Extracellular: 129-133

Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus and hepatitis C virus (HCV). Has no effect on anti-SARS-CoV-2 activity.
Not glycosylated.
Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiquitination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site.
Phosphorylation at Tyr-20 is required for endosomal and lysosomal location.