Version 5.4
| Homo sapiens Gene: IFIH1 | |||||||||||||||||||||||||||
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| Summary | |||||||||||||||||||||||||||
| InnateDB Gene | IDBG-73750.6 | ||||||||||||||||||||||||||
| Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||
| Gene Symbol | IFIH1 | ||||||||||||||||||||||||||
| Gene Name | interferon induced with helicase C domain 1 | ||||||||||||||||||||||||||
| Synonyms | |||||||||||||||||||||||||||
| Species | Homo sapiens | ||||||||||||||||||||||||||
| Ensembl Gene | ENSG00000115267 | ||||||||||||||||||||||||||
| Encoded Proteins |
interferon induced with helicase C domain 1
interferon induced with helicase C domain 1
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| 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.
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| 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.
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| 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] |
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| Gene Information | |||||||||||||||||||||||||||
| Type | Protein coding | ||||||||||||||||||||||||||
| Genomic Location | Chromosome 2:162267079-162318703 | ||||||||||||||||||||||||||
| Strand | Reverse strand | ||||||||||||||||||||||||||
| Band | q24.2 | ||||||||||||||||||||||||||
| Transcripts |
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| Interactions | |||||||||||||||||||||||||||
| Number of Interactions |
This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
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| Gene Ontology | |||||||||||||||||||||||||||
Molecular Function |
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| Biological Process |
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| Cellular Component |
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| Orthologs | |||||||||||||||||||||||||||
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Species
Mus musculus
Bos taurus
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Gene ID
Gene Order
Not yet available
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| Pathways | |||||||||||||||||||||||||||
| NETPATH | |||||||||||||||||||||||||||
| REACTOME |
TRAF6 mediated IRF7 activation pathway
Negative regulators of RIG-I/MDA5 signaling pathway
TRAF3-dependent IRF activation pathway pathway
TRAF6 mediated NF-kB activation pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Innate Immune System pathway
Immune System pathway
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| KEGG |
RIG-I-like receptor signaling pathway pathway
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| INOH | |||||||||||||||||||||||||||
| PID NCI | |||||||||||||||||||||||||||
| Cross-References | |||||||||||||||||||||||||||
| SwissProt | |||||||||||||||||||||||||||
| TrEMBL | |||||||||||||||||||||||||||
| UniProt Splice Variant | |||||||||||||||||||||||||||
| Entrez Gene | |||||||||||||||||||||||||||
| UniGene | Hs.163173 | ||||||||||||||||||||||||||
| RefSeq | NM_022168 | ||||||||||||||||||||||||||
| HUGO | |||||||||||||||||||||||||||
| OMIM | |||||||||||||||||||||||||||
| CCDS | CCDS2217 | ||||||||||||||||||||||||||
| HPRD | 09507 | ||||||||||||||||||||||||||
| IMGT | |||||||||||||||||||||||||||
| EMBL | |||||||||||||||||||||||||||
| GenPept | |||||||||||||||||||||||||||
| RNA Seq Atlas | |||||||||||||||||||||||||||