Ifitm3
Developmental stage
At 7.25 dpc strong expression is found at the base of the incipient allantois and weak expression in the mesodermal portion of the posterior amnion, and, importantly, the expression did not extend to the allantois. Expression persisted until the late bud stage (7.5 dpc), but gradually faded around the early head fold stage (7.75 dpc). At an earlier stage, only weak expression is seen throughout the epiblast in 6.0 dpc. But around 6.25-6.5 dpc (before gastrulation), marked expression is evident within the most proximal layer of the epiblast that is in intimate contact with the extraembryonic ectoderm. Expression is indeed induced by extraembryonic ectoderm through signaling molecules. During germ cell formation, is expressed in putative PGC ancestors in embryos at 6.5-7.5 dpc. In migrating PGCs, expression is continuous. After the beginning of gastrulation, the expression migrates to the posterior end of the developing primitive streak at the early/mid streak stage and became very intense in the position where PGCs (Primordial germ cells) differentiate from late streak stage onward.
Function
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:33270927). 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. 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. 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.
Post-translational modifications
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.
Sequence Similarities
Belongs to the CD225/Dispanin family.
Tissue Specificity
Expressed in acinar cell. Predominantly expressed in nascent primordial germ cells, as well as in gonadal germ cells.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Late endosome membrane
- Single-pass type II membrane protein
- Early endosome membrane
- Single-pass type II membrane protein
- Lysosome membrane
- Single-pass type II membrane protein
- Cytoplasm
- Perinuclear region
- Co-localizes with BRI3 isoform 1 at the perinuclear region.
Alternative names
Interferon-induced transmembrane protein 3, Dispanin subfamily A member 2b, Fragilis protein, Interferon-inducible protein 15, Mouse ifitm-like protein 1, DSPA2b, Mil-1, Ifitm3