Q5RCW8 · RSAD2_PONAB
- ProteinS-adenosylmethionine-dependent nucleotide dehydratase RSAD2
- GeneRSAD2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids361 (go to sequence)
- Protein existenceEvidence at transcript 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. Catalyzes the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-dependent radical mechanism. In turn, ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple viruses and directly inhibits viral replication. Therefore, inhibits a wide range of DNA and RNA viruses. 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. 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
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.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 83 | [4Fe-4S] cluster (UniProtKB | ChEBI); 4Fe-4S-S-AdoMet | |||
Binding site | 87 | [4Fe-4S] cluster (UniProtKB | ChEBI); 4Fe-4S-S-AdoMet | |||
Binding site | 90 | [4Fe-4S] cluster (UniProtKB | ChEBI); 4Fe-4S-S-AdoMet | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi apparatus | |
Cellular Component | lipid droplet | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial outer membrane | |
Molecular Function | 4 iron, 4 sulfur cluster binding | |
Molecular Function | lyase activity | |
Molecular Function | metal ion binding | |
Biological Process | CD4-positive, alpha-beta T cell activation | |
Biological Process | CD4-positive, alpha-beta T cell differentiation | |
Biological Process | defense response to virus | |
Biological Process | innate immune response | |
Biological Process | negative regulation of protein secretion | |
Biological Process | positive regulation of T-helper 2 cell cytokine production | |
Biological Process | positive regulation of toll-like receptor 7 signaling pathway | |
Biological Process | positive regulation of toll-like receptor 9 signaling pathway | |
Biological Process | response to virus |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameS-adenosylmethionine-dependent nucleotide dehydratase RSAD2
- EC number
- Short namesSAND
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Pongo
Accessions
- Primary accessionQ5RCW8
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000309585 | 1-361 | S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 | ||
Modified residue | 197 | N6-acetyllysine | |||
Cross-link | 206 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
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
Expression
Induction
By interferon type I, type II and LPS.
Interaction
Subunit
Homodimer. Interacts with IRAK1 and TRAF6. Interacts with FPPS. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 69-289 | Radical SAM core | |||
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)42,172
- Last updated2004-12-21 v1
- ChecksumBC6893B1319A16FA
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
CR858150 EMBL· GenBank· DDBJ | CAH90389.1 EMBL· GenBank· DDBJ | mRNA |