Q8WXG1 · RSAD2_HUMAN
- ProteinS-adenosylmethionine-dependent nucleotide dehydratase RSAD2
- GeneRSAD2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids361 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
Promotes also 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
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).
Promotes also 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
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.
Catalytic activity
- AH2 + CTP + S-adenosyl-L-methionine = 3'-deoxy-3',4'-didehydro-CTP + 5'-deoxyadenosine + A + H+ + H2O + L-methionine
Cofactor
Note: 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.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Converts cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), via a SAM-dependent radical mechanism. Has antiviral activity by leading to premature chain termination during RNA virus replication.
Names & Taxonomy
Protein names
- Recommended nameS-adenosylmethionine-dependent nucleotide dehydratase RSAD2
- EC number
- Short namesSAND
- Alternative names
Gene names
- Community suggested namesViperin; RSAD2.
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8WXG1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
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.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_036980 | 42 | in dbSNP:rs17851586 | |||
Sequence: L → R | ||||||
Natural variant | VAR_053974 | 52 | in dbSNP:rs2305257 | |||
Sequence: V → I | ||||||
Mutagenesis | 83 | Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. | ||||
Sequence: C → A | ||||||
Mutagenesis | 87 | Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. | ||||
Sequence: C → A | ||||||
Mutagenesis | 90 | Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. | ||||
Sequence: C → A | ||||||
Mutagenesis | 197 | Loss of acetylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 206 | Loss of Lys-6-linked ubiquitination. | ||||
Sequence: K → R | ||||||
Mutagenesis | 358 | Complete loss of antiviral activity against Zika virus. | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 428 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000309583 | 1-361 | S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 | |||
Sequence: MWVLTPAAFAGKLLSVFRQPLSSLWRSLVPLFCWLRATFWLLATKRRKQQLVLRGPDETKEEEEDPPLPTTPTSVNYHFTRQCNYKCGFCFHTAKTSFVLPLEEAKRGLLLLKEAGMEKINFSGGEPFLQDRGEYLGKLVRFCKVELRLPSVSIVSNGSLIRERWFQNYGEYLDILAISCDSFDEEVNVLIGRGQGKKNHVENLQKLRRWCRDYRVAFKINSVINRFNVEEDMTEQIKALNPVRWKVFQCLLIEGENCGEDALREAERFVIGDEEFERFLERHKEVSCLVPESNQKMKDSYLILDEYMRFLNCRKGRKDPSKSILDVGVEEAIKFSGFDEKMFLKRGGKYIWSKADLKLDW | ||||||
Modified residue | 197 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 206 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
Post-translational modification
Acetylated by HAT1. HAT1-mediated acetylation of Lys-197 in turn recruits UBE4A that stimulates RSAD2 polyubiquitination leading to proteasomal degradation.
'Lys-6'-linked polyubiquitination at Lys-206 leads to RSAD2 protein degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
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).
Interacts with FPPS (PubMed:18005724).
Interacts with HADHB (PubMed:21527675).
Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) (PubMed:21957124).
(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.
(Microbial infection) Interacts (via N-terminus) with enterovirus A71 protein 2C; this interaction inhibits viral replication.
(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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8WXG1 | APOC1 P02654 | 3 | EBI-12736320, EBI-1220105 | |
BINARY | Q8WXG1 | APOC4 P55056 | 3 | EBI-12736320, EBI-18302142 | |
BINARY | Q8WXG1 | CIAO1 O76071 | 2 | EBI-12736320, EBI-725145 | |
BINARY | Q8WXG1 | RHBDD2 Q6NTF9-3 | 3 | EBI-12736320, EBI-17589229 | |
BINARY | Q8WXG1 | VAPA Q9P0L0 | 10 | EBI-12736320, EBI-1059156 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 69-289 | Radical SAM core | ||||
Sequence: PTTPTSVNYHFTRQCNYKCGFCFHTAKTSFVLPLEEAKRGLLLLKEAGMEKINFSGGEPFLQDRGEYLGKLVRFCKVELRLPSVSIVSNGSLIRERWFQNYGEYLDILAISCDSFDEEVNVLIGRGQGKKNHVENLQKLRRWCRDYRVAFKINSVINRFNVEEDMTEQIKALNPVRWKVFQCLLIEGENCGEDALREAERFVIGDEEFERFLERHKEVSCL |
Domain
The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.
Sequence similarities
Belongs to the radical SAM superfamily. RSAD2 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length361
- Mass (Da)42,170
- Last updated2002-03-01 v1
- ChecksumED014743CE1568DF
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J674 | C9J674_HUMAN | RSAD2 | 293 | ||
A0A7P0T918 | A0A7P0T918_HUMAN | RSAD2 | 60 | ||
A0A7P0TA11 | A0A7P0TA11_HUMAN | RSAD2 | 239 | ||
A0A7P0Z4E2 | A0A7P0Z4E2_HUMAN | RSAD2 | 72 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 13 | in Ref. 1; AF026941 | ||||
Sequence: L → F | ||||||
Sequence conflict | 216-217 | in Ref. 1; AF026941 | ||||
Sequence: VA → IP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF026941 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AF442151 EMBL· GenBank· DDBJ | AAL50053.1 EMBL· GenBank· DDBJ | mRNA | ||
AC017076 EMBL· GenBank· DDBJ | AAY14802.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX01034.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC017969 EMBL· GenBank· DDBJ | AAH17969.1 EMBL· GenBank· DDBJ | mRNA |