Serine incorporator 5 (SERINC5)

Serine incorporator 5 (SERINC5) is a multi-pass transmembrane protein that belongs to the SERINC family, characterized by ten to eleven transmembrane segments with a novel fold bisected by a long diagonal helix. SERINC5 is widely expressed in human tissues and is primarily localized at the plasma membrane, where it functions in the incorporation of serine into membranes, promoting the synthesis of serine-derived lipids such as phosphatidylserine and sphingolipids. Its most notable function is as an antiviral restriction factor, potently inhibiting the infectivity of HIV-1 and other viruses by interfering with viral entry mechanisms; it achieves this via direct inactivation of viral envelope glycoproteins, blocking membrane fusion during infection. SERINC5 is subject to downregulation and antagonism by the HIV-1 accessory protein Nef, a strategy that viruses use to evade SERINC5's restriction. In addition to its antiviral activity, SERINC5 can positively regulate type I interferon signaling by interacting with mitochondrial antiviral signaling protein (MAVS) and TRAF6 at the mitochondria, thus linking it to broader roles in innate immunity. It may also have a role in neural and psychiatric conditions, as suggested by genetic association studies. There are currently no approved drugs that directly target SERINC5 as a therapeutic, but its role in host-pathogen interactions makes it a molecule of interest in infectious disease and immune regulation research.

Other names

Serine incorporator 5SERINC5C5orf12TPO1

Incorporation into budding virions blocks virus–cell membrane fusion by inactivating viral envelope glycoproteins (notably HIV-1, also influenza, SARS-CoV-2); Interference with viral protein glycosylation (example: glycosylation of hepatitis B virus surface proteins, decreasing release); Drugs that alter viral membrane lipid order (e.g., amphotericin B) counteract SERINC5's inhibition of viral fusion