Description: Homo sapiens interferon regulatory factor 7 (IRF7), transcript variant a, mRNA. RefSeq Summary (NM_001572): IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. Multiple IRF7 transcript variants have been identified, although the functional consequences of these have not yet been established. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr11:612,555-615,999 Size: 3,445 Total Exon Count: 11 Strand: - Coding Region Position: hg19 chr11:612,645-615,364 Size: 2,720 Coding Exon Count: 10
ID:IRF7_HUMAN DESCRIPTION: RecName: Full=Interferon regulatory factor 7; Short=IRF-7; FUNCTION: Key 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. ENZYME REGULATION: In 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. SUBUNIT: Monomer. 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. Interacts with MYD88 AND TRAF6. INTERACTION: O00170: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; P51617:IRAK1; NbExp=2; IntAct=EBI-968267, EBI-358664; O94822:LTN1; NbExp=2; IntAct=EBI-968267, EBI-1044684; Q9ULE6:PALD; NbExp=2; IntAct=EBI-968267, EBI-3957166; Q86UE8:TLK2; NbExp=2; IntAct=EBI-968267, EBI-1047967; Q9BVS5:TRMT61B; NbExp=2; IntAct=EBI-968267, EBI-3197877; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The phosphorylated and active form accumulates selectively in the nucleus. TISSUE SPECIFICITY: Expressed predominantly in spleen, thymus and peripheral blood leukocytes. INDUCTION: By type I interferon (IFN) and viruses. PTM: Acetylation inhibits its DNA-binding ability and activity. PTM: In 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. PTM: TRAF6-mediated ubiquitination is required for IRF7 activation (By similarity). PTM: Sumoylated by TRIM28, which inhibits its transactivation activity. SIMILARITY: Belongs to the IRF family. SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92985
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0044212 transcription regulatory region DNA binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0002376 immune system process GO:0002819 regulation of adaptive immune response GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006974 cellular response to DNA damage stimulus GO:0009615 response to virus GO:0016032 viral process GO:0016064 immunoglobulin mediated immune response GO:0019043 establishment of viral latency GO:0032479 regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032607 interferon-alpha production GO:0032608 interferon-beta production GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0034124 regulation of MyD88-dependent toll-like receptor signaling pathway GO:0034127 regulation of MyD88-independent toll-like receptor signaling pathway GO:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0039530 MDA-5 signaling pathway GO:0045087 innate immune response GO:0045351 type I interferon biosynthetic process GO:0045655 regulation of monocyte differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050776 regulation of immune response GO:0051607 defense response to virus GO:0060333 interferon-gamma-mediated signaling pathway GO:0060337 type I interferon signaling pathway GO:0060340 positive regulation of type I interferon-mediated signaling pathway GO:2000110 negative regulation of macrophage apoptotic process
BioCarta from NCI Cancer Genome Anatomy Project h_pcafpathway - The information-processing pathway at the IFN-beta enhancer
Reactome (by CSHL, EBI, and GO)
Protein Q92985 (Reactome details) participates in the following event(s):
R-HSA-933538 Recruitment of IRF7 to TRAF6 R-HSA-975188 TRAF6 interacts with IRF7 upon TLR7/8 or 9 activation R-HSA-933533 Dimerization of p-IRF7 R-HSA-933525 Phosphorylation and release of IRF7 R-HSA-975106 Phosphorylation and release of IRF7 upon TLR7/8 or 9 activation R-HSA-933536 p-IRF7 dimer interacts with coactivator CBP/p300 R-HSA-933531 Translocation of p-IRF7:p-IRF7 to nucleus R-HSA-1028816 Translocation of phosphorylated IRF3,IRF7 dimers into nucleus R-HSA-1028820 Formation of VAF (virus-activated factor) complex R-HSA-975118 TRAF6 ubiquitinqtes IRF7 in a K63-dependent manner following TLR7/8 or 9 stimulation R-HSA-166271 IRF3/IRF7 recruitment to p-TBK1/p-IKK epsilon bound to the activated TLR4 R-HSA-918232 Recruitment of IRF3,IRF7 R-HSA-9013979 IRF3/IRF7 recruitment to p-TBK1/p-IKK epsilon bound to the activated TLR3 R-HSA-1028821 Dimerization of Phospho IRF3 or phospho IRF7 R-HSA-168933 Dimerization of phosphorylated IRF3/IRF7 R-HSA-166245 Phosphorylation of IRF-3/IRF7 and their release from the activated TLR complex R-HSA-918229 Phosphorylation and release of IRF3/IRF7 R-HSA-9013978 Phosphorylation of IRF-3/IRF7 and their release from the activated TLR3 complex R-HSA-177671 Dimerized phospho-IRF3/IRF7 is transported to the nucleus R-HSA-1028819 VAF/pIRF7:CBP/p300 binds the promoters of type-I IFN genes R-HSA-933541 TRAF6 mediated IRF7 activation R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-HSA-918233 TRAF3-dependent IRF activation pathway R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 R-HSA-909733 Interferon alpha/beta signaling R-HSA-877300 Interferon gamma signaling R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-913531 Interferon Signaling R-HSA-168249 Innate Immune System R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
US Server
