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MGP001655

UniProt Annotations

Entry Information
Gene Nameinterferon regulatory factor 7
Protein EntryIRF7_HUMAN
UniProt IDQ92985
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=A; IsoId=Q92985-1; Sequence=Displayed; Name=B; Synonyms=Beta; IsoId=Q92985-2; Sequence=VSP_002760; Name=C; Synonyms=Gamma; IsoId=Q92985-3; Sequence=VSP_002758, VSP_002759; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=D; Synonyms=H; IsoId=Q92985-4; Sequence=VSP_002757;
Enzyme RegulationIn the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA- binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.
FunctionKey transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88- independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:17404045}.
InductionBy type I interferon (IFN) and viruses.
InteractionO00170:AIP; NbExp=2; IntAct=EBI-968267, EBI-704197; P10398:ARAF; NbExp=2; IntAct=EBI-968267, EBI-365961; Q96A33:CCDC47; NbExp=2; IntAct=EBI-968267, EBI-720151; O15111:CHUK; NbExp=4; IntAct=EBI-968267, EBI-81249; P51617:IRAK1; NbExp=2; IntAct=EBI-968267, EBI-358664; O94822:LTN1; NbExp=2; IntAct=EBI-968267, EBI-1044684; F5HDE4:ORF45 (xeno); NbExp=3; IntAct=EBI-968267, EBI-8843990; Q77M19:P (xeno); NbExp=3; IntAct=EBI-968267, EBI-6149376; Q9ULE6:PALD1; NbExp=2; IntAct=EBI-968267, EBI-3957166; Q9UHD2:TBK1; NbExp=2; IntAct=EBI-968267, EBI-356402; Q86UE8:TLK2; NbExp=2; IntAct=EBI-968267, EBI-1047967; Q9BVS5:TRMT61B; NbExp=2; IntAct=EBI-968267, EBI-3197877;
PtmAcetylation inhibits its DNA-binding ability and activity. {ECO:0000269|PubMed:12374802}.
PtmIn response to a viral infection, phosphorylated on Ser-477 and Ser-479 by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1. {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15767370}.
PtmSumoylated by TRIM28, which inhibits its transactivation activity. {ECO:0000269|PubMed:21940674}.
PtmTRAF6-mediated ubiquitination is required for IRF7 activation. {ECO:0000250}.
SimilarityBelongs to the IRF family. {ECO:0000255|PROSITE- ProRule:PRU00840}.
SimilarityContains 1 IRF tryptophan pentad repeat DNA-binding domain. {ECO:0000255|PROSITE-ProRule:PRU00840}.
Subcellular LocationNucleus. Cytoplasm. Note=The phosphorylated and active form accumulates selectively in the nucleus.
SubunitMonomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with rotavirus A NSP1; this interaction leads to the proteasome- dependent degradation of IRF7. Interacts with Epstein-Barr virus LF2 and human herpes virus 8/HHV-8 proteins ORF45 and vIRF-1. Interacts with MYD88 AND TRAF6. {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:11314014, ECO:0000269|PubMed:11943871, ECO:0000269|PubMed:14517278, ECO:0000269|PubMed:14739303, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:15492225, ECO:0000269|PubMed:17301153, ECO:0000269|PubMed:18987133}.
Tissue SpecificityExpressed predominantly in spleen, thymus and peripheral blood leukocytes.
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