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Details on Person UniProt:Q8WXG1 RSAD2
| Class:Id | ReferenceGeneProduct:246567 |
|---|---|
| _chainChangeLog | chain:1-361 added on Fri February 6 2015 |
| _displayName | UniProt:Q8WXG1 RSAD2 |
| _timestamp | 2025-05-21 21:08:23 |
| chain | chain:1-361 |
| checksum | ED014743CE1568DF |
| comment | FUNCTION Interferon-inducible antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon (PubMed:31812350). Catalyzes the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-dependent radical mechanism (PubMed:29925952, PubMed:30872404). In turn, ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple viruses and directly inhibits viral replication (PubMed:29925952). Therefore, inhibits 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) (PubMed:29925952, PubMed:30587778, PubMed:30934824, PubMed:31921110). Also promotes TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating 'Lys-63'-linked ubiquitination of IRAK1 by TRAF6 (PubMed:30872404). 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.CATALYTIC ACTIVITY CTP + AH2 + S-adenosyl-L-methionine = 3'-deoxy-3',4'-didehydro-CTP + 5'-deoxyadenosine + L-methionine + A + H2O + H(+)COFACTOR Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.ACTIVITY REGULATION IRAK1 and TRAF6 synergistically activate RSAD2 increasing its activity with CTP as substrate about 10-fold.SUBUNIT Homodimer. Interacts with IRAK1 and TRAF6 (PubMed:30872404, PubMed:31921110). Interacts with FPPS (PubMed:18005724). Interacts with HADHB (PubMed:21527675). Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) (PubMed:21957124).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria.SUBUNIT (Microbial infection) Interacts (via N-terminus) with enterovirus A71 protein 2C; this interaction inhibits viral replication.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 glycoprotein D; this interaction inhibits HHV-1 replication by facilitating IRF7-mediated IFN-beta production.INTERACTION 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.INDUCTION By 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.DOMAIN The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.PTM Acetylated by HAT1. HAT1-mediated acetylation of Lys-197 in turn recruits UBE4A that stimulates RSAD2 polyubiquitination leading to proteasomal degradation.PTM 'Lys-6'-linked polyubiquitination at Lys-206 leads to RSAD2 protein degradation.MISCELLANEOUS Up-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.SIMILARITY Belongs to the radical SAM superfamily. RSAD2 family. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: fullName evidence="27"S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 shortName evidence="27"SAND ecNumber evidence="17 19"4.2.-.- alternativeName: fullName evidence="28"Cytomegalovirus-induced gene 5 protein alternativeName: fullName evidence="35"Radical S-adenosyl methionine domain-containing protein 2 alternativeName: fullName evidence="24"Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible shortName evidence="24 25 26"Viperin |
| geneName | RSAD2 CIG5 |
| identifier | Q8WXG1 |
| isSequenceChanged | FALSE |
| keyword | 4Fe-4S Acetylation Antiviral defense Atherosclerosis Endoplasmic reticulum Golgi apparatus Host-virus interaction Immunity Innate immunity Iron Iron-sulfur Isopeptide bond Lipid droplet Lyase Membrane Metal-binding Mitochondrion Mitochondrion inner membrane Mitochondrion outer membrane Proteomics identification Reference proteome S-adenosyl-L-methionine Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 |
| name | RSAD2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8992709] ENSEMBL:ENSG00000134321 RSAD2 [Homo sapiens] |
| secondaryIdentifier | RSAD2_HUMAN Q8WVI4 |
| sequenceLength | 361 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:5624199] RSAD2 [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:9981423] RSAD2 [lipid droplet] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q8WXG1 RSAD2 (246567)
