ATP-dependent RNA helicase DDX58; DEAD box protein 58; retinoic acid-inducible gene 1 protein; RIG-1 (DDX58)
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Function
- innate immune defense against viruses
- interacts with intracellular dsRNA produced during viral replication, triggers a cascade involving
- detects dsRNA produced from non-self dsDNA by RNA polymerase 3, such as Epstein-Barr virus-encoded RNAs
- essential for production of interferons in response to RNA viruses including paramyxoviruses, influenza viruses, Japanese encephalitis virus & HCV (putative)
- isgylated: conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation
- ubiquitinated
- undergoes Lys-63-linked ubiquitination
- Lys-172 is the critical site for TRIM25-mediated ubiquitination, for MAVS binding & to induce anti-viral signal transduction
- Lys-154, Lys-164 & Lys-172 are critical sites for RNF135-mediated ubiquitination
- deubiquitinated by CYLD, a protease that selectively cleaves Lys-63-linked ubiquitin chains
- monomer in an autoinhibited state
- upon viral dsRNA binding & conformation shift, homomultimerizes & interacts with MAVS
- interacts with DHX58/LGP2, IKBKE, TBK1 & TMEM173/STING
- interacts (via CARD domain) with TRIM25 (via SPRY domain)
- interacts with RNF135
- interacts with CYLD
- interacts with NLRC5
- interaction inhibits interaction of MAVS with DDX58
- interacts with SRC
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