Interferon-induced transmembrane protein 3 (IFITM3) (IFITM3)

Interferon-induced transmembrane protein 3 (IFITM3) is a small, palmitoylated protein that plays a pivotal role in the innate immune system's defense against viral pathogens (UniProt Consortium, 2023). It primarily localizes to the membranes of endosomes and lysosomes, where it acts as a potent restriction factor by preventing the fusion of viral and host cell membranes, effectively blocking the entry of viruses such as influenza A, SARS-CoV-2, and Ebola (Bailey et al., 2014). Beyond its antiviral properties, IFITM3 is involved in various cellular processes, including cell signaling and adhesion, and its dysregulation is linked to several diseases. In oncology, high IFITM3 expression is often associated with poor prognosis and tumor progression in cancers like colorectal and breast cancer (PubMed, 2022). Furthermore, IFITM3 has been identified as a modulator of gamma-secretase, contributing to the accumulation of amyloid-beta plaques in Alzheimer's disease (Hur et al., 2020). Therapeutic interest in IFITM3 spans from inducing its expression to provide broad-spectrum antiviral protection to inhibiting its function in cancer and neurodegenerative contexts.

Other names

FragilisIP151-8UCD225Dispanin subfamily A member 2bDSPA2b

IFITM3 restricts viral entry by altering the fluidity and curvature of host cell membranes, specifically at the site of viral fusion in endosomes, thereby preventing the release of the viral genome into the cytosol (Bailey et al., 2014). In Alzheimer's disease, it binds to and modulates gamma-secretase to increase the production of amyloid-beta (Hur et al., 2020).