The innate immune system detects viral infection by recognizing various viral components and triggers antiviral responses. Like the toll-like receptor 3 (TLR3), the cytoplasmic helicase retinoic acid inducible gene protein 1 (RIG1/DDX58) recognizes double-stranded (ds) RNA, a molecular pattern associated with viral infection. Unlike TLR3 however, RIG1/DDX58 activates the kinases TBK1 and IKKe through the adaptor protein IPS1. These kinases then phosphorylate the transcription factors IRF3 and IRF7 which are essential for the expression of type-I interferons. RIG1/DDX58 is required for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus, and Japanese encephalitis virus.
Function:
Involved in innate immune defense against viruses. Upon interaction with intracellular dsRNA produced during viral replication, triggers a transduction cascade involving MAVS/IPS1, which results in the activation of NF-kappa-B, IRF3 and IRF7 and the induction of the expression of antiviral cytokines such as IFN-beta and RANTES (CCL5). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). Essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza viruses, Japanese encephalitis virus and HCV.
Subunit:
Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS. 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 to DDX58. Interacts with SRC.
Subcellular Location:
Cytoplasm. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies.
Tissue Specificity:
Present in vascular smooth cells (at protein level).
Post-translational modifications:
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.
Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation.
Ubiquitinated. Undergoes 'Lys-48'- and '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. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'-and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor.
Similarity:
Belongs to the helicase family.
Contains 2 CARD domains.
Contains 1 helicase ATP-binding domain.
Contains 1 helicase SLCterminal domain.
SWISS:
O95786
Gene ID:
23586
Database links:
Entrez Gene: 23586 Human
Entrez Gene: 230073 Mouse
Entrez Gene: 297989 Rat
Omim: 609631 Human
SwissProt: O95786 Human
SwissProt: Q6Q899 Mouse
Unigene: 190622 Human
Unigene: 86382 Mouse
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Sample:
Raw264.7(Mouse) Cell Lysate at 30 ug
Primary: Anti- phospho-DDX58 (Thr170) (SL5300R) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 102 kD
Observed band size: 120 kD
Sample:
293T(Human) Cell Lysate at 30 ug
Primary: Anti- phospho-DDX58 (Thr170) (SL5300R) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 102 kD
Observed band size: 120 kD
Paraformaldehyde-fixed, paraffin embedded (human cervical carcinoma); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (phospho-DDX58 (Thr170)) Polyclonal Antibody, Unconjugated (SL5300R) at 1:200 overnight at 4°C, followed by operating according to SP Kit(Rabbit) (sp-0023) instructionsand DAB staining.
Paraformaldehyde-fixed, paraffin embedded (Human kidney); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (phospho-DDX58 (Thr170)) Polyclonal Antibody, Unconjugated (SL5300R) at 1:200 overnight at 4°C, followed by operating according to SP Kit(Rabbit) (sp-0023) instructionsand DAB staining.
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