RSAD2
Domain
The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.
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.
Post-translational modifications
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.
Sequence Similarities
Belongs to the radical SAM superfamily. RSAD2 family.
Cellular localization
- Endoplasmic reticulum membrane
- Peripheral membrane protein
- Cytoplasmic side
- Golgi apparatus
- Endoplasmic reticulum
- Lipid droplet
- Mitochondrion
- Mitochondrion inner membrane
- Mitochondrion outer membrane
- 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.
Alternative names
CIG5, RSAD2, S-adenosylmethionine-dependent nucleotide dehydratase RSAD2, SAND, Cytomegalovirus-induced gene 5 protein, Radical S-adenosyl methionine domain-containing protein 2, Viperin