InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-174131

interferon induced with helicase C domain 1

IDBP-255962

interferon induced with helicase C domain 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21245317

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.

PMID 19936053

Ifih1 (MDA5) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.

PMID 21637773

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.

PMID 23328395

Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.

PMID 23966395

Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.

PMID 24362933

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.

PMID 25451939

Arl5b negatively regulates the antiviral innate immune response by binding to Ifih1 and prevents the subsequent interaction of Ifih1 to poly(I:C).

PMID 26074083

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.

PMID 26633895

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.

PMID 26633895

InnateDB Annotation from Orthologs

Summary

PMID 16785313

[Homo sapiens] IFIH1 (MDA5) recognizes distinct RNA viruses and plays a major role in the elimination of RNA viruses in vivo.

PMID 15563593

[Homo sapiens] IFIH1 binds V proteins of paramyxoviruses and this inhibit its activation of the IFNB1 (IFN-beta) promoter.

PMID 11805321

[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.

PMID 20107606

[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.

PMID 21245317

[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.

PMID 19936053

[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)

PMID 21637773

[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)

PMID 23328395

[Homo sapiens] Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.

PMID 24550253

[Homo sapiens] The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.

PMID 25463548

[Homo sapiens] IFIH1 recognizes hepatitis C virus (HCV) to initiate host interferon response during HCV infection.

PMID 26074083

[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.

PMID 25878102

[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