ID:DDX58_MOUSE DESCRIPTION: RecName: Full=Probable ATP-dependent RNA helicase DDX58; EC=3.6.4.13; AltName: Full=DEAD box protein 58; AltName: Full=RIG-I-like receptor 1; Short=RLR-1; AltName: Full=Retinoic acid-inducible gene 1 protein; Short=RIG-1; AltName: Full=Retinoic acid-inducible gene I protein; Short=RIG-I; FUNCTION: 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/IPS1) which activates the IKK- related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: newcastle disease virus (NDV) and Sendai virus (SeV), 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 orthoreovirus. 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. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. COFACTOR: Zinc (By similarity). SUBUNIT: Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS/IPS1. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING (By similarity). Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with CYLD. Interacts with RNF135 (By similarity). Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC (By similarity). Interacts with protein Z of Machupo virus and Junin arenavirus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction. Interacts with Rotavirus A non- structural protein 1 (NSP1) and this interaction induces down- regulation of DDX58/RIG-I (By similarity). Interacts with DDX60 (By similarity). Interacts with ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell projection, ruffle membrane (By similarity). Cytoplasm, cytoskeleton (By similarity). Cell junction, tight junction (By similarity). Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies (By similarity). Associated with the actin cytoskeleton at membrane ruffles (By similarity). INDUCTION: By interferon (IFN). DOMAIN: The helicase domain is responsible for dsRNA recognition (By similarity). Interacts with IFIT3 (via N-terminus) (By similarity). DOMAIN: The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton (By similarity). DOMAIN: The repressor domain controls homomultimerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions mediated by the repressor domain. Upon binding to viral RNA in the presence of ATP, the repressor domain induces a conformational change exposing the CARD domain and promotes dimerization and CARD interactions with the adapter protein MAVS/IPS1 leading to the induction of downstream signaling. DOMAIN: The second CARD domain is the primary site for 'Lys-63'- linked ubiquitination (By similarity). PTM: Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation (By similarity). PTM: Ubiquitinated. Undergoes 'Lys-63'-linked ubiquitination (By similarity). Lys-154 and Lys-164 are critical sites for RNF135- mediated ubiquitination. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains (By similarity). DISRUPTION PHENOTYPE: Death between E12.5 and E14 due to liver apoptosis. Those who are born alive show growth retardation and die within 3 weeks. SIMILARITY: Belongs to the helicase family. RLR subfamily. SIMILARITY: Contains 2 CARD domains. SIMILARITY: Contains 1 helicase ATP-binding domain. SIMILARITY: Contains 1 helicase C-terminal domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q6Q899
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002230 positive regulation of defense response to virus by host GO:0002376 immune system process GO:0009597 detection of virus GO:0009615 response to virus GO:0010628 positive regulation of gene expression GO:0030334 regulation of cell migration GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0032755 positive regulation of interleukin-6 production GO:0032757 positive regulation of interleukin-8 production GO:0035549 positive regulation of interferon-beta secretion GO:0039529 RIG-I signaling pathway GO:0043330 response to exogenous dsRNA GO:0045087 innate immune response GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051607 defense response to virus GO:0060760 positive regulation of response to cytokine stimulus GO:0071360 cellular response to exogenous dsRNA GO:1902741 positive regulation of interferon-alpha secretion GO:1904469 positive regulation of tumor necrosis factor secretion GO:2000778 positive regulation of interleukin-6 secretion
US Server
