MGP Database

MGP006257

UniProt Annotations

Entry Information
Gene Nameradical S-adenosyl methionine domain containing 2
Protein EntryRSAD2_HUMAN
UniProt IDQ8WXG1
SpeciesHuman
Comments
Comment typeDescription
CofactorName=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000269|PubMed:20026307, ECO:0000269|PubMed:20176015, ECO:0000269|PubMed:22363738}; Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. {ECO:0000269|PubMed:20026307, ECO:0000269|PubMed:20176015, ECO:0000269|PubMed:22363738};
DomainThe N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.
FunctionInterferon-inducible iron-sulfur (4FE-4S) cluster- binding antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Can inhibit 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), and human immunodeficiency virus (HIV-1). Displays antiviral activity against influenza A virus by inhibiting the budding of the virus from the plasma membrane by disturbing the lipid rafts. This is accomplished, at least in part, through binding and inhibition of the enzyme farnesyl diphospate synthase (FPPS), which is essential for the biosynthesis of isoprenoid-derived lipids. Promotes TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating Lys-63'-linked ubiquitination of IRAK1. Plays a role in CD4+ T-cells activation and differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble proteins. {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16108059, ECO:0000269|PubMed:16982913, ECO:0000269|PubMed:17686841, ECO:0000269|PubMed:18005719, ECO:0000269|PubMed:19074433}.
InductionBy interferon type I, type II and bacterial lipopolysaccharides (LPS). Little or no induction by IFNG/IFN- gamma is observed in monocytic cell lines. Induced by infection with hepatitis C virus, yellow fever virus and Sendai virus, presumably through type I interferon pathway. Induction by infection with human cytomegalovirus (HCMV), stomatitis virus (VSV), chikungunya virus (CHIKV), Japanese encephalitis virus (JEV) occurs independent of the IFN pathway. {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16108059, ECO:0000269|PubMed:16150475, ECO:0000269|PubMed:16849320, ECO:0000269|PubMed:9391139}.
MiscellaneousUp-regulated in atherosclerosis. Latent viruses like HCMV may be involved in atherogenesis by initiating local inflammation. This may induce up-regulation of antiviral gene RSAD2, which modulates lipids synthesis, and thus could play a role in abnormal lipid accumulation leading to atherosclerosis.
SimilarityBelongs to the radical SAM superfamily. RSAD2 family. {ECO:0000305}.
Subcellular LocationEndoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16982913}. Endoplasmic reticulum {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16982913}. Lipid droplet {ECO:0000250}. Mitochondrion. Mitochondrion inner membrane. Mitochondrion outer membrane. Note=Infection with human cytomegalovirus (HCMV) causes relocation to the Golgi apparatus and to cytoplasmic vacuoles which also contain HCMV proteins glycoprotein B and pp28. Interaction with human cytomegalovirus/HHV-5 protein vMIA/UL37 results in its relocalization from the endoplasmic reticulum to the mitochondria.
SubunitHomodimer. Interacts with IRAK1 and TRAF6 (By similarity). Interacts with FPPS. Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) and inhibits its interaction with hepatitis virus C (HCV) protein NS5A. {ECO:0000250, ECO:0000269|PubMed:18005724, ECO:0000269|PubMed:19074433, ECO:0000269|PubMed:21527675, ECO:0000269|PubMed:21957124}.
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