Probable ATP-Dependent RNA Helicase DDX58 (DDX58) Human Recombinant Protein

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of immune response. [provided by RefSeq, Jul 2008]

DDX58: an innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'- triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein MAVS which activates the IKK- related kinases TBK1 and IKBKE which phosphorylate interferon regulatory factors IRF3 and IRF7, in turn activating transcription of antiviral immunological genes, including IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory synctial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. Maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS. Interacts with DHX58, IKBKE, TBK1 and STING. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS to DDX58. Interacts with SRC. Interacts with protein Z of Guanarito virus, Machupo virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction. Interacts (via CARD domain) with Human respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with MAVS, impeding downstream IRF3 activation. Present in vascular smooth cells. Belongs to the helicase family. RLR subfamily. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: EC 3.6.4.13; Hydrolase

Chromosomal Location of Human Ortholog: 9p12

Cellular Component: actin cytoskeleton; cytoplasm; cytosol; tight junction

Molecular Function: double-stranded RNA binding; identical protein binding; protein binding; single-stranded RNA binding; zinc ion binding

Biological Process: detection of virus; innate immune response; negative regulation of interferon type I production; positive regulation of defense response to virus by host; positive regulation of granulocyte macrophage colony-stimulating factor production; positive regulation of interferon-alpha production; positive regulation of interferon-beta production; positive regulation of interleukin-6 production; positive regulation of interleukin-8 production; positive regulation of transcription factor activity; positive regulation of transcription factor import into nucleus; positive regulation of transcription from RNA polymerase II promoter; regulation of cell migration; response to virus

Disease: Singleton-merten Syndrome 2