UniProtKB - P70434 (IRF7_MOUSE)
Protein
Interferon regulatory factor 7
Gene
Irf7
Organism
Mus musculus (Mouse)
Status
Functioni
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 (PubMed:27129230). 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. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (PubMed:27129230). 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.5 Publications
Activity regulationi
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.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 9 – 126 | IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST | 118 |
GO - Molecular functioni
- cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- sequence-specific double-stranded DNA binding Source: MGI
GO - Biological processi
- defense response to virus Source: UniProtKB
- immune system process Source: GO_Central
- immunoglobulin mediated immune response Source: MGI
- interferon-alpha production Source: UniProtKB
- interferon-beta production Source: UniProtKB
- positive regulation of interferon-alpha production Source: MGI
- positive regulation of interferon-beta production Source: MGI
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of type I interferon-mediated signaling pathway Source: MGI
- positive regulation of type I interferon production Source: MGI
- regulation of adaptive immune response Source: UniProtKB
- regulation of gene expression Source: MGI
- regulation of innate immune response Source: UniProtKB
- regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
- regulation of MyD88-independent toll-like receptor signaling pathway Source: UniProtKB
- type I interferon production Source: MGI
- type I interferon signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Immunity, Innate immunity, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-3134963, DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-MMU-9013973, TICAM1-dependent activation of IRF3/IRF7 R-MMU-918233, TRAF3-dependent IRF activation pathway R-MMU-933541, TRAF6 mediated IRF7 activation R-MMU-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-MMU-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Interferon regulatory factor 7Short name: IRF-7 |
Gene namesi | Name:Irf7 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1859212, Irf7 |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 425 | S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-426. 1 Publication | 1 | |
Mutagenesisi | 425 | S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-426. 1 Publication | 1 | |
Mutagenesisi | 426 | S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-425. 1 Publication | 1 | |
Mutagenesisi | 426 | S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-425. 1 Publication | 1 | |
Mutagenesisi | 427 | L → A: Strongly decreased transcriptional activation in response to viral infection. 1 Publication | 1 | |
Mutagenesisi | 427 | L → D: No effect on transcriptional activation in response to viral infection. 1 Publication | 1 | |
Mutagenesisi | 429 | S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-430 and A-431. 1 Publication | 1 | |
Mutagenesisi | 429 | S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-430 and A-431. 1 Publication | 1 | |
Mutagenesisi | 430 | S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-431. | 1 | |
Mutagenesisi | 430 | S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-431. | 1 | |
Mutagenesisi | 431 | S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-430. 1 Publication | 1 | |
Mutagenesisi | 431 | S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-430. 1 Publication | 1 | |
Mutagenesisi | 437 | S → A: Almost complete loss of transcriptional activation; when associated with A-438. 1 Publication | 1 | |
Mutagenesisi | 437 | S → D: Increased transcriptional activation; when associated with D-438. 1 Publication | 1 | |
Mutagenesisi | 438 | S → A: Almost complete loss of transcriptional activation; when associated with A-437. 1 Publication | 1 | |
Mutagenesisi | 438 | S → D: Increased transcriptional activation; when associated with D-437. 1 Publication | 1 | |
Mutagenesisi | 441 | S → A: Almost no effect on transcriptional activation in response to viral infection. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154563 | 1 – 457 | Interferon regulatory factor 7Add BLAST | 457 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 92 | N6-acetyllysine; by KAT2A and KAT2BBy similarity | 1 | |
Cross-linki | 398 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Cross-linki | 400 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Modified residuei | 425 | Phosphoserine1 Publication | 1 | |
Modified residuei | 426 | Phosphoserine1 Publication | 1 | |
Modified residuei | 429 | Phosphoserine1 Publication | 1 | |
Modified residuei | 431 | Phosphoserine; by TBK1 and IKKEBy similarity | 1 | |
Modified residuei | 437 | Phosphoserine1 Publication | 1 | |
Modified residuei | 438 | Phosphoserine1 Publication | 1 | |
Modified residuei | 441 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Acetylation inhibits its DNA-binding ability and activity.By similarity
In response to a viral infection, phosphorylated 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 (By similarity).By similarity
TRAF6-mediated ubiquitination is required for IRF7 activation (PubMed:15361868). TRIM35 mediates IRF7 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation (By similarity).By similarity1 Publication
Sumoylated by TRIM28, which inhibits its transactivation activity.By similarity
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P70434 |
PRIDEi | P70434 |
PTM databases
iPTMneti | P70434 |
PhosphoSitePlusi | P70434 |
Expressioni
Inductioni
Induced by lipopolysaccharide (LPS) (PubMed:27129230). Induced by type I interferon (IFN) and viruses (HIV-1 and SeV viruses) (PubMed:27129230).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000025498, Expressed in blood and 132 other tissues |
Genevisiblei | P70434, MM |
Interactioni
Subunit structurei
Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3.
Interacts with TICAM1 and TICAM2.
Interacts with MYD88 AND TRAF6.
1 PublicationBinary interactionsi
Hide detailsProtein-protein interaction databases
BioGRIDi | 207563, 9 interactors |
DIPi | DIP-37903N |
IntActi | P70434, 6 interactors |
MINTi | P70434 |
STRINGi | 10090.ENSMUSP00000026571 |
Miscellaneous databases
RNActi | P70434, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P70434 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the IRF family.PROSITE-ProRule annotation
Phylogenomic databases
eggNOGi | ENOG502R2I9, Eukaryota |
GeneTreei | ENSGT00940000160931 |
InParanoidi | P70434 |
OrthoDBi | 648909at2759 |
PhylomeDBi | P70434 |
TreeFami | TF328512 |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.200.10, 1 hit |
InterProi | View protein in InterPro IPR019817, Interferon_reg_fac_CS IPR001346, Interferon_reg_fact_DNA-bd_dom IPR019471, Interferon_reg_factor-3 IPR017855, SMAD-like_dom_sf IPR008984, SMAD_FHA_dom_sf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11949, PTHR11949, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit PF10401, IRF-3, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit SM01243, IRF-3, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
P70434-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL
60 70 80 90 100
DEEDAQIFKA WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH
110 120 130 140 150
STGRFILRQD NSGDPVDPHK VYELSRELGS TVGPATENRE EVSLSNALPT
160 170 180 190 200
QGVSPGSFLA RENAGLQTPS PLLSSDAGDL LLQVLQYSHI LESESGADPV
210 220 230 240 250
PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL GFLDVTIMYK
260 270 280 290 300
GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT
310 320 330 340 350
ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL
360 370 380 390 400
ERNRHTPIFD FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK
410 420 430 440 450
TLILVKLEPW VCKAYLEGVQ REGVSSLDSS SLGLCLSSTN SLYEDIEHFL
MDLGQWP
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1B0GRH7 | A0A1B0GRH7_MOUSE | Interferon regulatory factor 7 | Irf7 | 237 | Annotation score: | ||
D3Z4U9 | D3Z4U9_MOUSE | Interferon regulatory factor 7 | Irf7 | 425 | Annotation score: | ||
Q3TW14 | Q3TW14_MOUSE | Interferon regulatory factor 7 | Irf7 | 426 | Annotation score: | ||
F6TQ89 | F6TQ89_MOUSE | Interferon regulatory factor 7 | Irf7 | 251 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U73037 mRNA Translation: AAB18626.1 |
CCDSi | CCDS22005.1 |
RefSeqi | NP_058546.1, NM_016850.3 |
Genome annotation databases
Ensembli | ENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498 |
GeneIDi | 54123 |
KEGGi | mmu:54123 |
UCSCi | uc009kkg.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U73037 mRNA Translation: AAB18626.1 |
CCDSi | CCDS22005.1 |
RefSeqi | NP_058546.1, NM_016850.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3QU3 | X-ray | 1.30 | A/B/C | 1-134 | [»] | |
SMRi | P70434 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 207563, 9 interactors |
DIPi | DIP-37903N |
IntActi | P70434, 6 interactors |
MINTi | P70434 |
STRINGi | 10090.ENSMUSP00000026571 |
PTM databases
iPTMneti | P70434 |
PhosphoSitePlusi | P70434 |
Proteomic databases
PaxDbi | P70434 |
PRIDEi | P70434 |
Protocols and materials databases
Antibodypediai | 4325, 591 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498 |
GeneIDi | 54123 |
KEGGi | mmu:54123 |
UCSCi | uc009kkg.2, mouse |
Organism-specific databases
CTDi | 3665 |
MGIi | MGI:1859212, Irf7 |
Phylogenomic databases
eggNOGi | ENOG502R2I9, Eukaryota |
GeneTreei | ENSGT00940000160931 |
InParanoidi | P70434 |
OrthoDBi | 648909at2759 |
PhylomeDBi | P70434 |
TreeFami | TF328512 |
Enzyme and pathway databases
Reactomei | R-MMU-3134963, DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-MMU-9013973, TICAM1-dependent activation of IRF3/IRF7 R-MMU-918233, TRAF3-dependent IRF activation pathway R-MMU-933541, TRAF6 mediated IRF7 activation R-MMU-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-MMU-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling |
Miscellaneous databases
BioGRID-ORCSi | 54123, 1 hit in 19 CRISPR screens |
PROi | PR:P70434 |
RNActi | P70434, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000025498, Expressed in blood and 132 other tissues |
Genevisiblei | P70434, MM |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.200.10, 1 hit |
InterProi | View protein in InterPro IPR019817, Interferon_reg_fac_CS IPR001346, Interferon_reg_fact_DNA-bd_dom IPR019471, Interferon_reg_factor-3 IPR017855, SMAD-like_dom_sf IPR008984, SMAD_FHA_dom_sf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11949, PTHR11949, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit PF10401, IRF-3, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit SM01243, IRF-3, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IRF7_MOUSE | |
Accessioni | P70434Primary (citable) accession number: P70434 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | February 1, 1997 | |
Last modified: | February 10, 2021 | |
This is version 166 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families