ATP-dependent RNA helicase DDX58; DEAD box protein 58; retinoic acid-inducible gene 1 protein; RIG-1 (DDX58)

Function: 1) innate immune defense against viruses 2) interacts with intracellular dsRNA produced during viral replication, triggers a cascade involving - MAVS, NF-kappa-B, IRF3, IRF7, IFN-beta, RANTES 3) detects dsRNA produced from non-self dsDNA by RNA polymerase 3, such as Epstein-Barr virus-encoded RNAs 4) essential for production of interferons in response to RNA viruses including paramyxoviruses, influenza viruses, Japanese encephalitis virus & HCV (putative) 5) isgylated: conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation 6) ubiquitinated a) undergoes Lys-63-linked ubiquitination b) Lys-172 is the critical site for TRIM25-mediated ubiquitination, for MAVS binding & to induce anti-viral signal transduction c) Lys-154, Lys-164 & Lys-172 are critical sites for RNF135-mediated ubiquitination 6) deubiquitinated by CYLD, a protease that selectively cleaves Lys-63-linked ubiquitin chains 7) monomer in an autoinhibited state 8) upon viral dsRNA binding & conformation shift, homomultimerizes & interacts with MAVS 9) interacts with DHX58/LGP2, IKBKE, TBK1 & TMEM173/STING 10) interacts (via CARD domain) with TRIM25 (via SPRY domain) 11) interacts with RNF135 12) interacts with CYLD 13) interacts with NLRC5 - interaction inhibits interaction of MAVS with DDX58 14) interacts with SRC Cofactor: Zn⁺² Structure: - repressor domain controls homomultimerization & interaction with MAVS (probable) - helicase domain is responsible for dsRNA recognition - 2 CARD domains are responsible for interaction with & signaling through MAVS - second CARD domain is the primary site for Lys-63-linked ubiquitination - belongs to the helicase family - contains 2 CARD domains - contains 1 helicase ATP-binding domain - contains 1 helicase C-terminal domain Compartment: - cytoplasm - colocalized with TRIM25 at cytoplasmic perinuclear bodies Alternative splicing: named isoforms=2 Expression: - present in vascular smooth cells - induced by a) bacterial lipopolysaccharide (LPS) in endothelial cells b) IFN-alpha, IFN-beta, IFN-gamma

Properties

SIZE: entity length = 925 aa MW = 107 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: CARD domain {1-87} CARD domain {92-172} helicase NAME: helicase SITE: 251-430 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 264-271 DECH box {372-375} DNA-binding motif active site MOTIF: P-loop FOR-BINDING-OF: adenosine triphosphate Helicase C-terminal {610-776} Repressor {735-925} MOTIF: Zn+2-binding site SITE: 810-810 Zn+2-binding site SITE: 813-813 Zn+2-binding site SITE: 864-864 Zn+2-binding site SITE: 869-869

Database Correlations

OMIM 609631 UniProt O95786 PFAM correlations Entrez Gene 23586 Kegg hsa:23586 ENZYME 3.6.4.13

References

UniProt :accession O95786