Interferon Induced Helicase C Domain Containing Protein 1 (IFIH1)

Hlcd; IDDM19; MDA5; Helicard; Clinically amyopathic dermatomyositis autoantigen 140 kDa; Melanoma differentiation-associated protein 5; Murabutide down-regulated protein

SPN	M779
HGNC	18873
MGI	1918836
PubMed	19264985
RGD	1560496
UniProt	Q9BYX4
Wiki	IFIH1

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. IFIH1 encodes a DEAD box protein that is upregulated in response to treatment with beta-interferon (IFNB) and a protein kinase C-activating compound, mezerein (MEZ). Irreversible reprogramming of melanomas can be achieved by treatment with both these agents; treatment with either agent alone only achieves reversible differentiation.

Reference

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Proc. Natl. Acad. Sci. U.S.A. 99:637-642(2002) [PubMed] [Europe PMC] [Abstract]

"A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication."
J. Gen. Virol. 84:3215-3225(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation."
Curr. Biol. 12:838-843(2002) [PubMed] [Europe PMC] [Abstract]

Erratum
Curr. Biol. 12:1633-1633(2002)

"The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter."
Proc. Natl. Acad. Sci. U.S.A. 101:17264-17269(2004) [PubMed] [Europe PMC] [Abstract]

"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction."
Nat. Immunol. 6:981-988(2005) [PubMed] [Europe PMC] [Abstract]

"Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus."
Nature 437:1167-1172(2005) [PubMed] [Europe PMC] [Abstract]

"RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease."
Arthritis Rheum. 60:2193-2200(2009) [PubMed] [Europe PMC] [Abstract]

"Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2."
J. Biol. Chem. 284:9700-9712(2009) [PubMed] [Europe PMC] [Abstract]

"Activation of MDA5 requires higher-order RNA structures generated during virus infection."
J. Virol. 83:10761-10769(2009) [PubMed] [Europe PMC] [Abstract]

"PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4."
Nat. Immunol. 10:1300-1308(2009) [PubMed] [Europe PMC] [Abstract]

"NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways."
Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract]

"The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling."
Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract]

"The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody."
Rheumatology 49:433-440(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

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Immunity 34:680-692(2011) [PubMed] [Europe PMC] [Abstract]

"RIG-I-like receptors: cytoplasmic sensors for non-self RNA."
Immunol. Rev. 243:91-98(2011) [PubMed] [Europe PMC] [Abstract]

"Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules."
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"Retinoic acid-inducible gene-I-like receptors."
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"DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling."
Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract]

"MDA5 is SUMOylated by PIAS2? in the upregulation of type I interferon signaling."
Mol. Immunol. 48:415-422(2011) [PubMed] [Europe PMC] [Abstract]

"2 methylate or not 2 methylate: viral evasion of the type I interferon response."
Nat. Immunol. 12:114-115(2011) [PubMed] [Europe PMC] [Abstract]

"Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5."
Nat. Immunol. 12:137-143(2011) [PubMed] [Europe PMC] [Abstract]

"Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition."
Proc. Natl. Acad. Sci. U.S.A. 108:21010-21015(2011) [PubMed] [Europe PMC] [Abstract]

"Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5."
J. Virol. 86:3528-3540(2012) [PubMed] [Europe PMC] [Abstract]

"A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses."
FEBS Lett. 587:2137-2142(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region."
Nat. Genet. 38:617-619(2006) [PubMed] [Europe PMC] [Abstract]

"Aicardi-Goutieres syndrome is caused by IFIH1 mutations."
Am. J. Hum. Genet. 95:121-125(2014) [PubMed] [Europe PMC] [Abstract]

"Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling."
Nat. Genet. 46:503-509(2014) [PubMed] [Europe PMC] [Abstract]

"Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5."
Arch. Biochem. Biophys. 488:23-33(2009) [PubMed] [Europe PMC] [Abstract]

"Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors."
J. Biol. Chem. 284:17465-17474(2009) [PubMed] [Europe PMC] [Abstract]

"Human dech-box RNA helicase mda5 (melanoma differentiation-associated protein 5), dech-domain."
Submitted (FEB-2009) to the PDB data bank