Linked Life Data

O95786

Source:http://identifiers.org/uniprot/O95786

Statements in which the resource exists as a subject.
PredicateObject
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biopax3:comment
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: 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. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. COFACTOR: Zinc. 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. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 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/IPS1, 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/IPS1, impeding downstream IRF3 activation. Interacts with Rotavirus A non-structural protein 1 (NSP1) and this interaction induces down- regulation of DDX58/RIG-I. Interacts with DDX60. SUBCELLULAR LOCATION: Cytoplasm. Cell projection, ruffle membrane. Cytoplasm, cytoskeleton. Cell junction, tight junction. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O95786-1; Sequence=Displayed; Name=2; IsoId=O95786-2; Sequence=VSP_016054; Note=No experimental confirmation available; TISSUE SPECIFICITY: Present in vascular smooth cells (at protein level). INDUCTION: By bacterial lipopolysaccharides (LPS) in endothelial cells. By interferon (IFN). 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 helicase domain is responsible for dsRNA recognition. DOMAIN: The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton. DOMAIN: The second CARD domain is the primary site for 'Lys-63'- linked ubiquitination. PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854 and Ser- 855 results in inhibition of its activity while dephosphorylation at these sites results in its activation. PTM: Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. PTM: Ubiquitinated. Undergoes 'Lys-63'-linked ubiquitination. Lys- 172 is the critical site for TRIM25-mediated ubiquitination, for MAVS/IPS1 binding and to induce anti-viral signal transduction. Lys-154, Lys-164 and Lys-172 are critical sites for RNF135- mediated ubiquitination. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. 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. GENE SYNONYMS:DDX58. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 925 AA; 106600 MW; BF0D501C395BAE25 CRC64;
biopax3:xref
biopax3:displayName
DDX58_HUMAN
biopax3:name
3.6.4.13, DDX58, DEAD box protein 58, RIG-1, RIG-I, RIG-I-like receptor 1, RLR-1, Retinoic acid-inducible gene 1 protein, Retinoic acid-inducible gene I protein
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biopax3:sequence
MTTEQRRSLQAFQDYIRKTLDPTYILSYMAPWFREEEVQYIQAEKNNKGPMEAATLFLKFLLELQEEGWFRGFLDALDHAGYSGLYEAIESWDFKKIEKLEEYRLLLKRLQPEFKTRIIPTDIISDLSECLINQECEEILQICSTKGMMAGAEKLVECLLRSDKENWPKTLKLALEKERNKFSELWIVEKGIKDVETEDLEDKMETSDIQIFYQEDPECQNLSENSCPPSEVSDTNLYSPFKPRNYQLELALPAMKGKNTIICAPTGCGKTFVSLLICEHHLKKFPQGQKGKVVFFANQIPVYEQQKSVFSKYFERHGYRVTGISGATAENVPVEQIVENNDIIILTPQILVNNLKKGTIPSLSIFTLMIFDECHNTSKQHPYNMIMFNYLDQKLGGSSGPLPQVIGLTASVGVGDAKNTDEALDYICKLCASLDASVIATVKHNLEELEQVVYKPQKFFRKVESRISDKFKYIIAQLMRDTESLAKRICKDLENLSQIQNREFGTQKYEQWIVTVQKACMVFQMPDKDEESRICKALFLYTSHLRKYNDALIISEHARMKDALDYLKDFFSNVRAAGFDEIEQDLTQRFEEKLQELESVSRDPSNENPKLEDLCFILQEEYHLNPETITILFVKTRALVDALKNWIEGNPKLSFLKPGILTGRGKTNQNTGMTLPAQKCILDAFKASGDHNILIATSVADEGIDIAQCNLVILYEYVGNVIKMIQTRGRGRARGSKCFLLTSNAGVIEKEQINMYKEKMMNDSILRLQTWDEAVFREKILHIQTHEKFIRDSQEKPKPVPDKENKKLLCRKCKALACYTADVRVIEECHYTVLGDAFKECFVSRPHPKPKQFSSFEKRAKIFCARQNCSHDWGIHVKYKTFEIPVIKIESFVVEDIATGVQTLYSKWKDFHFEKIPFDPAEMSK
biopax3:standardName
Probable ATP-dependent RNA helicase DDX58