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Beschreibung

Interferon-induced helicase C domain-containing protein 1 (UniProt: Q9BYX4, also known as EC: 3.6.4.13, Clinically amyopathic dermatomyositis autoantigen 140 kDa, CADM-140 autoantigen, Helicase with 2 CARD domains, Helicard, Interferon-induced with helicase C domain protein 1, Melanoma differentiation-associated protein 5, MDA-5, Murabutide down-regulated protein, RIG-I-like receptor 2, RLR-2, RNA helicase-DEAD box protein 116) is encoded by the IFIH1 (also known as MDA5, RH116) gene (Gene ID: 64135) in human. MDA-5 is an innate immune receptor that 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 pro-inflammatory cytokines. MDA-5 is widely expressed, but at low levels. Expression is detected at slightly higher levels in placenta, pancreas and spleen. Its ligands include mRNA lacking 2&prime,-O-methylation at their 5&prime, cap and long-dsRNA. In the absence of ligands it is monomeric and homodimerizes in the presence of dsRNA ligands. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1), which activates the IKK-related kinases TBK1 and IKBKE that phosphorylate interferon regulatory factors IRF3 and IRF7. These factors activate transcription of antiviral immunological genes, including interferons alpha and beta. MDA-5 also plays an important role in enhancing natural killer cell function and is believed to be involved in growth inhibition and apoptosis in several tumor cell lines. MDA-5 contains 2 CARD domains, 1 helicase ATP-binding domain, 1 helicase C-terminal domain, and 1 RLR C-terminal regulatory domain.