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MGP005746

UniProt Annotations

Entry Information
Gene Nameinterferon induced with helicase C domain 1
Protein EntryIFIH1_HUMAN
UniProt IDQ9BYX4
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9BYX4-1; Sequence=Displayed; Name=2; IsoId=Q9BYX4-2; Sequence=VSP_013337, VSP_013338; Note=No experimental confirmation available.;
Catalytic ActivityATP + H(2)O = ADP + phosphate.
CofactorName=Zn(2+); Xref=ChEBI:CHEBI:29105;
DiseaseAicardi-Goutieres syndrome 7 (AGS7) [MIM:615846]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:24686847, ECO:0000269|PubMed:24995871}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDiabetes 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.
DiseaseNote=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).
FunctionInnate 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:0000269|PubMed:14645903, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19656871, ECO:0000269|PubMed:21217758, ECO:0000269|PubMed:21742966}.
InductionBy interferon (IFN) and TNF. {ECO:0000269|PubMed:11805321}.
InteractionQ7Z434:MAVS; NbExp=5; IntAct=EBI-6115771, EBI-995373; P11207:P/V (xeno); NbExp=2; IntAct=EBI-6115771, EBI-6148694; P30927:P/V (xeno); NbExp=2; IntAct=EBI-6115771, EBI-6599165; Q9EMA9:P/V (xeno); NbExp=2; IntAct=EBI-6115771, EBI-6598728; P04487:US11 (xeno); NbExp=4; IntAct=EBI-6115771, EBI-6150681;
MiscellaneousIn HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein.
PtmDuring apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation (By similarity). {ECO:0000250}.
PtmSumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta. {ECO:0000269|PubMed:21156324}.
PtmUbiquitinated. USP17/UPS17L2-dependent deubiquitination positively regulates the receptor. {ECO:0000269|PubMed:20368735}.
Sequence CautionSequence=AAH78180.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB71141.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the helicase family. RLR subfamily. {ECO:0000305}.
SimilarityContains 1 helicase ATP-binding domain. {ECO:0000255|PROSITE-ProRule:PRU00541}.
SimilarityContains 1 helicase C-terminal domain. {ECO:0000255|PROSITE-ProRule:PRU00542}.
SimilarityContains 2 CARD domains. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:11805321, ECO:0000269|PubMed:14645903}. Nucleus {ECO:0000305}. Note=May be found in the nucleus, during apoptosis.
SubunitMonomer in the absence of ligands and homodimerizes in the presence of dsRNA ligands. Can assemble into helical or linear polymeric filaments on long dsRNA. Interacts with MAVS/IPS1. Interacts with V protein of Simian virus 5, Human parainfluenza virus 2, Mumps virus, Sendai virus and Hendra virus. Binding to paramyxoviruses V proteins prevents IFN-beta induction, and the further establishment of an antiviral state. Interacts with PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with DDX60. Interacts with ANKRD17. {ECO:0000269|PubMed:15563593, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19380577, ECO:0000269|PubMed:19531363, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:21156324, ECO:0000269|PubMed:21791617, ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:23711367}.
Tissue SpecificityWidely 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:0000269|PubMed:11805321, ECO:0000269|PubMed:12015121, ECO:0000269|PubMed:14645903}.
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