RSAD2
Description
The RSAD2 (radical S-adenosyl methionine domain containing 2) is a protein-coding gene located on chromosome 2.
Radical S-adenosyl methionine domain-containing protein 2 is a protein that in humans is encoded by the RSAD2 gene. RSAD2 is a multifunctional protein in viral processes that is an interferon stimulated gene. It has been reported that viperin could be induced by either IFN-dependent or IFN-independent pathways and certain viruses may use viperin to increase their infectivity. The protein was previously called Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin). The name viperin has been rectified due to inappropriate use of it to describe homologous prokaryotic enzymes producing nucleotide analogues. The enzymes across all domains of life are renamed SAM-dependent nucleotide dehydratase (SAND) using NC-IUBMB recommendations. Viperin is an interferon-stimulated gene whose expression inhibits many DNA and RNA viruses including CHIKV, HCMV, HCV, DENV, WNV, SINV, influenza, and HIV. Initially identified as an IFN-γ induced antiviral protein in human cytomegalovirus (HCMV) infected macrophages, it was reported that viperin could be induced by HCMV glycoprotein B in fibroblasts, but inhibits HCMV viral infection and down-regulates viral structural proteins. The reason why virus protein would induce viperin against itself is still not clear; however, the viral induced redistribution of viperin may reflect the mechanism of virus evading its antiviral activities. Viperin may also be induced and interact with HCMV viral proteins and relocate to mitochondria in HCMV viral infected cells to enhance viral infectivity by disrupting cellular metabolism. Viperin is a radical SAM enzyme which is capable of producing the chain terminator ddhCTP (3ʹ-deoxy-3′,4ʹdidehydro-CTP), which inhibits the viral RNA dependent RNA polymerase (RdRp).
RSAD2 (also known as viperin) is an interferon-inducible antiviral protein that plays a key role in the cellular antiviral response triggered by type I and type II interferons. It catalyzes the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) using a radical mechanism dependent on S-adenosylmethionine. DdhCTP acts as a chain terminator for RNA-dependent RNA polymerases from various viruses, directly inhibiting viral replication. This activity makes RSAD2 effective against a wide range of DNA and RNA viruses, including human cytomegalovirus (HCMV), hepatitis C virus (HCV), West Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, Sendai virus, vesicular stomatitis virus (VSV), Zika virus, and human immunodeficiency virus (HIV-1). Furthermore, RSAD2 promotes TLR7 and TLR9-dependent production of IFN-beta in plasmacytoid dendritic cells (pDCs) by facilitating Lys-63-linked ubiquitination of IRAK1 by TRAF6. It also contributes to CD4+ T-cell activation and differentiation, facilitating T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Additionally, RSAD2 can inhibit the secretion of soluble proteins.
RSAD2 is also known as SAND, cig33, cig5, vig1.
