Mus musculus Gene: Ifih1
Summary
InnateDB Gene IDBG-174129.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Ifih1
Gene Name interferon induced with helicase C domain 1
Synonyms 9130009C22Rik; Helicard; Hlcd; MDA5; RLR-2;
Species Mus musculus
Ensembl Gene ENSMUSG00000026896
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 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.
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.
Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.
Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
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.
Arl5b negatively regulates the antiviral innate immune response by binding to Ifih1 and prevents the subsequent interaction of Ifih1 to poly(I:C).
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.
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.
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.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] IFIH1 (MDA5) recognizes distinct RNA viruses and plays a major role in the elimination of RNA viruses in vivo.
[Homo sapiens] IFIH1 binds V proteins of paramyxoviruses and this inhibit its activation of the IFNB1 (IFN-beta) promoter.
[Homo sapiens] 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.
[Homo sapiens] 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.
[Homo sapiens] 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.
[Homo sapiens] 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)
[Homo sapiens] 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)
[Homo sapiens] Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.
[Homo sapiens] The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
[Homo sapiens] IFIH1 recognizes hepatitis C virus (HCV) to initiate host interferon response during HCV infection.
[Homo sapiens] 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.
[Homo sapiens] EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000115267:
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 2:62595798-62646255
Strand Reverse strand
Band C1.3
Transcripts
ENSMUST00000028259 ENSMUSP00000028259
ENSMUST00000112459 ENSMUSP00000108078
ENSMUST00000176431
ENSMUST00000176388
ENSMUST00000175964
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.
Experimentally validated
Total 7 [view]
Protein-Protein 3 [view]
Protein-DNA 4 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 23 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003676 nucleic acid binding
GO:0003677 DNA 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:0016817 hydrolase activity, acting on acid anhydrides
GO:0043021 ribonucleoprotein complex binding
Biological Process
GO:0009615 response to virus
GO:0016925 protein sumoylation
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0042981 regulation of apoptotic process
GO:0045087 innate immune response (InnateDB)
GO:0051607 defense response to virus
Cellular Component
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
TRAF6 mediated NF-kB activation pathway
Innate Immune System pathway
Negative regulators of RIG-I/MDA5 signaling pathway
Immune System pathway
TRAF6 mediated IRF7 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
TRAF3-dependent IRF activation pathway pathway
KEGG
RIG-I-like receptor signaling pathway pathway
INOH
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
REACTOME
Innate Immune System pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
Immune System pathway
TRAF3-dependent IRF activation pathway pathway
Negative regulators of RIG-I/MDA5 signaling pathway
KEGG
RIG-I-like receptor signaling pathway pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt Q8R5F7
TrEMBL Q3U605
UniProt Splice Variant
Entrez Gene 71586
UniGene Mm.136224
RefSeq NM_001164477 NM_027835
OMIM
CCDS CCDS50594 CCDS16068
HPRD
IMGT
MGI ID MGI:1918836
MGI Symbol Ifih1
EMBL AF374384 AK018602 AK037057 AK040519 AK153018 AK153344 AL929246 AY075132 BC004031 BC019605 BC025508 BC080200
GenPept AAH04031 AAH19605 AAH25508 AAH80200 AAL77205 AAM21359 BAB31303 BAC29687 BAC30614 BAE31652 BAE31920 CAM21790
RNA Seq Atlas 71586