Target General Infomation
Target ID
T29339
Former ID
TTDI02051
Target Name
Retinoic acid-inducible gene-1 (RIG-1)
Gene Name
DDX58
Synonyms
DEAD box protein 58; Probable ATPdependent RNA helicase DDX58; RIG1; RIGI; RIGIlike receptor 1; RLR1; Retinoic acidinducible gene 1 protein; Retinoic acidinducible gene I protein; DDX58
Target Type
Clinical Trial
Disease HBV infection [ICD9: 070.2-070.3; ICD10: B16, B18.0, B18.1]
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 the5'-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 syncytial 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 andreovirus. 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.
BioChemical Class
Acid anhydrides hydrolase
UniProt ID
EC Number
EC 3.6.4.13
Sequence
MTTEQRRSLQAFQDYIRKTLDPTYILSYMAPWFREEEVQYIQAEKNNKGPMEAATLFLKF
LLELQEEGWFRGFLDALDHAGYSGLYEAIESWDFKKIEKLEEYRLLLKRLQPEFKTRIIP
TDIISDLSECLINQECEEILQICSTKGMMAGAEKLVECLLRSDKENWPKTLKLALEKERN
KFSELWIVEKGIKDVETEDLEDKMETSDIQIFYQEDPECQNLSENSCPPSEVSDTNLYSP
FKPRNYQLELALPAMKGKNTIICAPTGCGKTFVSLLICEHHLKKFPQGQKGKVVFFANQI
PVYEQQKSVFSKYFERHGYRVTGISGATAENVPVEQIVENNDIIILTPQILVNNLKKGTI
PSLSIFTLMIFDECHNTSKQHPYNMIMFNYLDQKLGGSSGPLPQVIGLTASVGVGDAKNT
DEALDYICKLCASLDASVIATVKHNLEELEQVVYKPQKFFRKVESRISDKFKYIIAQLMR
DTESLAKRICKDLENLSQIQNREFGTQKYEQWIVTVQKACMVFQMPDKDEESRICKALFL
YTSHLRKYNDALIISEHARMKDALDYLKDFFSNVRAAGFDEIEQDLTQRFEEKLQELESV
SRDPSNENPKLEDLCFILQEEYHLNPETITILFVKTRALVDALKNWIEGNPKLSFLKPGI
LTGRGKTNQNTGMTLPAQKCILDAFKASGDHNILIATSVADEGIDIAQCNLVILYEYVGN
VIKMIQTRGRGRARGSKCFLLTSNAGVIEKEQINMYKEKMMNDSILRLQTWDEAVFREKI
LHIQTHEKFIRDSQEKPKPVPDKENKKLLCRKCKALACYTADVRVIEECHYTVLGDAFKE
CFVSRPHPKPKQFSSFEKRAKIFCARQNCSHDWGIHVKYKTFEIPVIKIESFVVEDIATG
VQTLYSKWKDFHFEKIPFDPAEMSK
Drugs and Mode of Action
Drug(s) SB-9200 Drug Info Phase 1 HBV infection [524226]
Modulator SB-9200 Drug Info
Pathways
KEGG Pathway NF-kappa B signaling pathway
RIG-I-like receptor signaling pathway
Cytosolic DNA-sensing pathway
Hepatitis C
Hepatitis B
Measles
Influenza A
Herpes simplex infection
Epstein-Barr virus infection
Reactome ISG15 antiviral mechanism
TRAF3-dependent IRF activation pathway
TRAF6 mediated IRF7 activation
TRAF6 mediated NF-kB activation
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
Negative regulators of RIG-I/MDA5 signaling
WikiPathways RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
References
Ref 524226ClinicalTrials.gov (NCT01803308) A Multiple Ascending Dose Phase I Study of SB 9200 in Treatment Naive Adults With Chronic Hepatitis C Infection. U.S. National Institutes of Health.

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