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MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. [5] MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2 , and functions as a pattern recognition receptor capable of detecting viruses .
Around 80% of people with DM test positive for ANA and around 30% of people have myositis-specific autoantibodies which include antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including antibodies against histidine—tRNA ligase ; antibodies to signal recognition particle (SRP); and anti-Mi-2 antibodies. [12]
In addition to the helicase core and CTD, RIG-I and MDA5 have two N-terminal CARD (caspase active recruitment domains) that are essential to the initiation of downstream signaling. LGP2 is dissimilar to both RIG-I and MDA5 as it lacks the CARD signaling domains and instead is implicated as a positive and negative regulator of RIG-I and MDA5.
RIG-I and Mda5-mediated signalling pathway. Three RLR helicases have so far been described: RIG-I and MDA5 (recognizing 5'triphosphate-RNA and dsRNA, respectively), which activate antiviral signaling, and LGP2, which appears to act as a dominant-negative inhibitor. RLRs initiate the release of inflammatory cytokines and type I interferon (IFN I).
At a resting state for the cell, a protein called mitofusin 2 (MFN2) is known to interact with MAVS, preventing MAVS from binding to the cytosolic proteins, such as RIG-I and MDA5. [ 7 ] [ 8 ] Upon recognition of the virus in the cytosol, mitochondria-associated ER membranes (MAM) and mitochondria will become physically tethered by MFN2 and RIG ...
Patients who had various antisyntetase antibodies had an estimated cumulative ten-year survival rate of 76.8%. [11] Respiratory complications, infectious diseases like pneumonia, cancer, [60] cardiovascular disorders, [63] severe myositis, and interstitial lung disease are the main causes of death amongst anti Jo-1-positive patients. [10]
The regulation of DAMP signaling can be a potential therapeutic target to reduce inflammation and treat diseases. For example, administration of neutralizing HMGB1 antibodies or truncated HMGB1-derived A-box protein ameliorated arthritis in collagen-induced arthritis rodent models. Clinical trials with HSP inhibitors have also been reported.
80861 Ensembl ENSG00000108771 ENSMUSG00000017830 UniProt Q96C10 Q99J87 RefSeq (mRNA) NM_024119 NM_030150 RefSeq (protein) NP_077024 NP_084426 Location (UCSC) Chr 17: 42.1 – 42.11 Mb Chr 11: 100.59 – 100.6 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Probable ATP-dependent RNA helicase DHX58 also known as RIG-I-like receptor 3 (RLR-3) or RIG-I-like receptor LGP2 (RLR) is a RIG ...
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