Target Information
Target General Information | Top | |||||
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Target ID |
T29339
(Former ID: TTDI02051)
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Target Name |
Retinoic acid-inducible gene-1 (RIG-1)
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Synonyms |
Retinoic acidinducible gene I protein; Retinoic acidinducible gene 1 protein; Retinoic acid-inducible gene I protein; Retinoic acid-inducible gene 1 protein; RLR1; RLR-1; RIGIlike receptor 1; RIGI; RIG1; RIG-I-like receptor 1; RIG-I; Probable ATPdependent RNA helicase DDX58; Probable ATP-dependent RNA helicase DDX58; DEAD box protein 58
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Gene Name |
DDX58
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 4 Target-related Diseases | + | ||||
1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
2 | Melanoma [ICD-11: 2C30] | |||||
3 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
4 | Squamous cell carcinoma [ICD-11: 2B60-2D01] | |||||
Function |
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 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 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. 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.
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BioChemical Class |
Acid anhydride hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.6.4.13
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Sequence |
MTTEQRRSLQAFQDYIRKTLDPTYILSYMAPWFREEEVQYIQAEKNNKGPMEAATLFLKF
LLELQEEGWFRGFLDALDHAGYSGLYEAIESWDFKKIEKLEEYRLLLKRLQPEFKTRIIP TDIISDLSECLINQECEEILQICSTKGMMAGAEKLVECLLRSDKENWPKTLKLALEKERN KFSELWIVEKGIKDVETEDLEDKMETSDIQIFYQEDPECQNLSENSCPPSEVSDTNLYSP FKPRNYQLELALPAMKGKNTIICAPTGCGKTFVSLLICEHHLKKFPQGQKGKVVFFANQI PVYEQQKSVFSKYFERHGYRVTGISGATAENVPVEQIVENNDIIILTPQILVNNLKKGTI PSLSIFTLMIFDECHNTSKQHPYNMIMFNYLDQKLGGSSGPLPQVIGLTASVGVGDAKNT DEALDYICKLCASLDASVIATVKHNLEELEQVVYKPQKFFRKVESRISDKFKYIIAQLMR DTESLAKRICKDLENLSQIQNREFGTQKYEQWIVTVQKACMVFQMPDKDEESRICKALFL YTSHLRKYNDALIISEHARMKDALDYLKDFFSNVRAAGFDEIEQDLTQRFEEKLQELESV SRDPSNENPKLEDLCFILQEEYHLNPETITILFVKTRALVDALKNWIEGNPKLSFLKPGI LTGRGKTNQNTGMTLPAQKCILDAFKASGDHNILIATSVADEGIDIAQCNLVILYEYVGN VIKMIQTRGRGRARGSKCFLLTSNAGVIEKEQINMYKEKMMNDSILRLQTWDEAVFREKI LHIQTHEKFIRDSQEKPKPVPDKENKKLLCRKCKALACYTADVRVIEECHYTVLGDAFKE CFVSRPHPKPKQFSSFEKRAKIFCARQNCSHDWGIHVKYKTFEIPVIKIESFVVEDIATG VQTLYSKWKDFHFEKIPFDPAEMSK Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | SB-9200 | Drug Info | Phase 2 | Hepatitis B virus infection | [2] | |
2 | CV8102 | Drug Info | Phase 1 | Melanoma | [3] | |
3 | MK-4621 | Drug Info | Phase 1 | Solid tumour/cancer | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | SB-9200 | Drug Info | [1] | |||
Agonist | [+] 2 Agonist drugs | + | ||||
1 | CV8102 | Drug Info | [5] | |||
2 | MK-4621 | Drug Info | [6] |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 9 KEGG Pathways | + | ||||
1 | NF-kappa B signaling pathway | |||||
2 | RIG-I-like receptor signaling pathway | |||||
3 | Cytosolic DNA-sensing pathway | |||||
4 | Hepatitis C | |||||
5 | Hepatitis B | |||||
6 | Measles | |||||
7 | Influenza A | |||||
8 | Herpes simplex infection | |||||
9 | Epstein-Barr virus infection | |||||
Reactome | [+] 6 Reactome Pathways | + | ||||
1 | ISG15 antiviral mechanism | |||||
2 | TRAF3-dependent IRF activation pathway | |||||
3 | TRAF6 mediated IRF7 activation | |||||
4 | TRAF6 mediated NF-kB activation | |||||
5 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | |||||
6 | Negative regulators of RIG-I/MDA5 signaling | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways |
References | Top | |||||
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REF 1 | Company reprot (Spring Bank Pharmaceuticals) (drug: SB 9200) | |||||
REF 2 | ClinicalTrials.gov (NCT02751996) A Study Evaluating the Safety, Pharmacokinetics, and Antiviral Efficacy of SB 9200 in Subjects Infected With Chronic HBV (ACHIEVE). U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT03291002) Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT03739138) Intratumoral/Intralesional Administration of MK-4621/JetPEI With or Without Pembrolizumab in Participants With Advanced/Metastatic or Recurrent Solid Tumors (MK-4621-002). U.S. National Institutes of Health. | |||||
REF 5 | Clinical pipeline report, company report or official report of CureVac. | |||||
REF 6 | National Cancer Institute Drug Dictionary (drug name RGT100). |
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