RSAD2

RSAD2 (Radical S-Adenosyl Methionine Domain Containing 2) is a Protein Coding gene. Diseases associated with RSAD2 include Yellow Fever and Influenza. Among its related pathways are Cytokine Signaling in Immune system and Innate Immune System. Gene Ontology (GO) annotations related to this gene include protein self-association and iron-sulfur cluster binding.

Full Name

Radical S-Adenosyl Methionine Domain Containing 2

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:31921110, PubMed:30934824).
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.

Biological Process

Biological Process CD4-positive, alpha-beta T cell activationISS:UniProtKB
Biological Process CD4-positive, alpha-beta T cell differentiationISS:UniProtKB
Biological Process defense response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process innate immune responseIEA:UniProtKB-KW
Biological Process negative regulation of protein secretionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of viral genome replicationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of immune responseManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of T-helper 2 cell cytokine productionISS:UniProtKB
Biological Process positive regulation of toll-like receptor 7 signaling pathwayISS:UniProtKB
Biological Process positive regulation of toll-like receptor 9 signaling pathwayISS:UniProtKB
Biological Process response to virusManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Endoplasmic reticulum membrane
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.

PTM

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.