Homo sapiens Gene: IFIH1
Summary
InnateDB Gene IDBG-109550.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol IFIH1
Gene Name interferon induced with helicase C domain 1
Synonyms AGS7; Hlcd; IDDM19; MDA-5; MDA5; RLR-2; SGMRT1
Species Homo sapiens
Ensembl Gene ENSG00000115267
Encoded Proteins
interferon induced with helicase C domain 1
interferon induced with helicase C domain 1
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IFIH1 (MDA5) recognizes distinct RNA viruses and plays a major role in the elimination of RNA viruses in vivo.
IFIH1 binds V proteins of paramyxoviruses and this inhibit its activation of the IFNB1 (IFN-beta) promoter.
IFIH1 is a double-stranded RNA-dependent ATPase that contains both a caspase recruitment domain and RNA helicase motifs. IFIH1 may also function as a mediator of interferon (IFN)-induced growth inhibition and/or apoptosis.
IFIH1 is indispensable for sustained expression of IFN in response to paramyxovirus infection and provide the first evidence of MDA5-dependent containment of in vivo infections caused by (-) sense RNA viruses.
IFIH1 is an RNA helicase and is a key component in activating the expression of type I IFN in response to viral infection. Viral mRNA with 5' cap and 3' poly(A) from parainfluenza virus 5 is able to activate IFN expression through RNASEL-IFIH1 signalling pathway.
IFIH1 (MDA5) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
IFIH1 deficiency results in a delayed type I IFN and attenuated type III IFN response to rhinovirus infection, leading to a transient increase in viral titer. Upon recognition of viral dsRNA, IFIH1 synergizes with TLR3 to induce pro-inflammatory signals leading to airways inflammation and hyper-responsiveness. (Demonstrated in murine model)
Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.
The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
IFIH1 recognizes hepatitis C virus (HCV) to initiate host interferon response during HCV infection.
DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Ifih1 is an RNA helicase and is a key component in activating the expression of type I IFN in response to viral infection. Viral mRNA with 5' cap and 3' poly(A) from parainfluenza virus 5 is able to activate IFN expression through Rnasel-Ifih1 signalling pathway.
[Mus musculus] Ifih1 (MDA5) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.
[Mus musculus] Ifih1 deficiency results in a delayed type I IFN and attenuated type III IFN response to rhinovirus infection, leading to a transient increase in viral titer. Upon recognition of viral dsRNA, Ifih1 synergizes with Tlr3 to induce pro-inflammatory signals leading to airways inflammation and hyper-responsiveness.
[Mus musculus] Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.
[Mus musculus] Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
[Mus musculus] Plasmodium RNA is a pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptors Ifih1 and Mavs, as well as via transcription factors Irf3 and Irf7.
[Mus musculus] Arl5b negatively regulates the antiviral innate immune response by binding to Ifih1 and prevents the subsequent interaction of Ifih1 to poly(I:C).
[Mus musculus] Ddx58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but Ifih1 is a significant contributor to the cellular defense against IAV.
[Mus musculus] Transgenic picornavirus RNA-dependent RNA polymerase (RdRP) expression in mice produces a quantitatively dramatic, sustained, effective antiviral interferon-stimulated genes (ISG) network, which requires the MDA5-MAVS pathway.
[Mus musculus] Transgenic picornavirus RNA-dependent RNA polymerase (RdRP) expression in mice produces a quantitatively dramatic, sustained, effective antiviral interferon-stimulated genes (ISG) network, which requires the MDA5-MAVS pathway.
Entrez Gene
Summary 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. This gene encodes a DEAD box protein that is upregulated in response to treatment with beta-interferon and a protein kinase C-activating compound, mezerein. Irreversible reprogramming of melanomas can be achieved by treatment with both these agents; treatment with either agent alone only achieves reversible differentiation. Genetic variation in this gene is associated with diabetes mellitus insulin-dependent type 19. [provided by RefSeq, Jul 2012]
Gene Information
Type Protein coding
Genomic Location Chromosome 2:162267079-162318703
Strand Reverse strand
Band q24.2
Transcripts
ENST00000263642 ENSP00000263642
ENST00000421365 ENSP00000408450
ENST00000464129
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 50 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
Experimentally validated
Total 50 [view]
Protein-Protein 23 [view]
Protein-DNA 27 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 6 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004386 helicase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0042802 identical protein binding
GO:0043021 ribonucleoprotein complex binding
GO:0046872 metal ion binding
Biological Process
GO:0002376 immune system process
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0016032 viral process
GO:0016579 protein deubiquitination
GO:0016925 protein sumoylation
GO:0032480 negative regulation of type I interferon production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0034344 regulation of type III interferon production
GO:0035549 positive regulation of interferon-beta secretion
GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0039530 MDA-5 signaling pathway
GO:0045087 innate immune response (InnateDB)
GO:0051607 defense response to virus
GO:0060760 positive regulation of response to cytokine stimulus
GO:0071360 cellular response to exogenous dsRNA
GO:1902741 positive regulation of interferon-alpha secretion
GO:1904469 positive regulation of tumor necrosis factor secretion
GO:2000778 positive regulation of interleukin-6 secretion
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
Orthologs
Species
Bos taurus
Mus musculus
Gene ID
Gene Order
Not yet available
Pathways
NETPATH
REACTOME
TRAF3-dependent IRF activation pathway pathway
Post-translational protein modification pathway
Ovarian tumor domain proteases pathway
Negative regulators of DDX58/IFIH1 signaling pathway
Ub-specific processing proteases pathway
Metabolism of proteins pathway
Immune System pathway
TRAF6 mediated NF-kB activation pathway
Innate Immune System pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
DDX58/IFIH1-mediated induction of interferon-alpha/beta pathway
Deubiquitination pathway
TRAF6 mediated IRF7 activation pathway
KEGG
RIG-I-like receptor signaling pathway pathway
Hepatitis B pathway
Measles pathway
Influenza A pathway
Herpes simplex infection pathway
INOH
PID NCI
Cross-References
SwissProt Q9BYX4
TrEMBL
UniProt Splice Variant
Entrez Gene 64135
UniGene
RefSeq NM_022168
HUGO HGNC:18873
OMIM 606951
CCDS CCDS2217
HPRD
IMGT
EMBL AF095844 AK056293 AY017378 BC046208 BC078180 BC111750
GenPept AAG34368 AAG54076 AAH46208 AAH78180 AAI11751 BAB71141
RNA Seq Atlas 64135