Homo sapiens Protein: IFIH1
InnateDB Protein IDBP-387033.5
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IFIH1
Protein Name interferon induced with helicase C domain 1
Species Homo sapiens
Ensembl Protein ENSP00000408450
InnateDB Gene IDBG-73750 (IFIH1)
Protein Structure
UniProt Annotation
Function Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O- methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV) and mengo encephalomyocarditis virus (ENMG). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. {ECO:0000269PubMed:14645903, ECO:0000269PubMed:19211564, ECO:0000269PubMed:19656871, ECO:0000269PubMed:21217758, ECO:0000269PubMed:21742966}.
Subcellular Localization Cytoplasm {ECO:0000269PubMed:11805321, ECO:0000269PubMed:14645903}. Nucleus {ECO:0000305}. Note=May be found in the nucleus, during apoptosis.
Disease Associations Diabetes mellitus, insulin-dependent, 19 (IDDM19) [MIM:610155]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.Note=IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).
Tissue Specificity Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung. {ECO:0000269PubMed:11805321, ECO:0000269PubMed:12015121, ECO:0000269PubMed:14645903}.
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.
Experimentally validated
Total 44 [view]
Protein-Protein 42 [view]
Protein-DNA 2 [view]
Protein-RNA 0
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
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:0043021 ribonucleoprotein complex binding
Biological Process
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0016032 viral process
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:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0042981 regulation of apoptotic process
GO:0045087 innate immune response (InnateDB)
Cellular Component
GO:0005634 nucleus
GO:0005829 cytosol
Protein Structure and Domains
InterPro IPR001315 CARD domain
IPR011029 Death-like domain
PFAM PF00619
Post-translational Modifications
SwissProt Q9BYX4
PhosphoSite PhosphoSite-Q9BYX4
UniProt Splice Variant
Entrez Gene 64135
UniGene Hs.163173
OMIM 606951
HPRD 09507
EMBL AF095844 AK056293 AY017378 BC046208 BC078180 BC111750
GenPept AAG34368 AAG54076 AAH46208 AAH78180 AAI11751 BAB71141