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Protein

Interferon regulatory factor 7

Gene

Irf7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. 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.4 Publications

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi9 – 126IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST118

GO - Molecular functioni

GO - Biological processi

  • immunoglobulin mediated immune response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • interferon-alpha production Source: UniProtKB
  • interferon-beta production Source: UniProtKB
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter 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 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
  • transcription, DNA-templated Source: UniProtKB-KW
  • type I interferon biosynthetic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-MMU-877300. Interferon gamma signaling.
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.
R-MMU-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 7
Short name:
IRF-7
Gene namesi
Name:Irf7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1859212. Irf7.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi425S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-426. 1 Publication1
Mutagenesisi425S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-426. 1 Publication1
Mutagenesisi426S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-425. 1 Publication1
Mutagenesisi426S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-425. 1 Publication1
Mutagenesisi427L → A: Strongly decreased transcriptional activation in response to viral infection. 1 Publication1
Mutagenesisi427L → D: No effect on transcriptional activation in response to viral infection. 1 Publication1
Mutagenesisi429S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-430 and A-431. 1 Publication1
Mutagenesisi429S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-430 and A-431. 1 Publication1
Mutagenesisi430S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-431. 1
Mutagenesisi430S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-431. 1
Mutagenesisi431S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-430. 1 Publication1
Mutagenesisi431S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-430. 1 Publication1
Mutagenesisi437S → A: Almost complete loss of transcriptional activation; when associated with A-438. 1 Publication1
Mutagenesisi437S → D: Increased transcriptional activation; when associated with D-438. 1 Publication1
Mutagenesisi438S → A: Almost complete loss of transcriptional activation; when associated with A-437. 1 Publication1
Mutagenesisi438S → D: Increased transcriptional activation; when associated with D-437. 1 Publication1
Mutagenesisi441S → A: Almost no effect on transcriptional activation in response to viral infection. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001545631 – 457Interferon regulatory factor 7Add BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei92N6-acetyllysine; by KAT2A and KAT2BBy similarity1
Cross-linki398Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki400Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei425Phosphoserine1 Publication1
Modified residuei426Phosphoserine1 Publication1
Modified residuei429Phosphoserine1 Publication1
Modified residuei431Phosphoserine; by TBK1 and IKKEBy similarity1
Modified residuei437Phosphoserine1 Publication1
Modified residuei438Phosphoserine1 Publication1
Modified residuei441Phosphoserine1 Publication1

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.1 Publication
Sumoylated by TRIM28, which inhibits its transactivation activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP70434.
PRIDEiP70434.

PTM databases

iPTMnetiP70434.
PhosphoSitePlusiP70434.

Expressioni

Inductioni

By type I interferon (IFN) and viruses.

Gene expression databases

BgeeiENSMUSG00000025498.
CleanExiMM_IRF7.
ExpressionAtlasiP70434. baseline and differential.
GenevisibleiP70434. MM.

Interactioni

Subunit structurei

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 TRAF6.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ChukQ606803EBI-997907,EBI-646245
Trim35Q8C0062EBI-997907,EBI-2536044

Protein-protein interaction databases

BioGridi207563. 9 interactors.
DIPiDIP-37903N.
IntActiP70434. 5 interactors.
STRINGi10090.ENSMUSP00000026571.

Structurei

Secondary structure

1457
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 22Combined sources11
Beta strandi29 – 32Combined sources4
Beta strandi37 – 41Combined sources5
Helixi52 – 55Combined sources4
Helixi56 – 64Combined sources9
Helixi77 – 85Combined sources9
Helixi88 – 100Combined sources13
Beta strandi105 – 111Combined sources7
Beta strandi119 – 124Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3QU3X-ray1.30A/B/C1-134[»]
ProteinModelPortaliP70434.
SMRiP70434.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation
Contains 1 IRF tryptophan pentad repeat DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IWNR. Eukaryota.
ENOG4111G85. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000111812.
HOVERGENiHBG105600.
InParanoidiP70434.
KOiK09447.
OMAiGWKTNFR.
OrthoDBiEOG091G067P.
PhylomeDBiP70434.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
SM01243. IRF-3. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P70434-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:457
Mass (Da):51,222
Last modified:February 1, 1997 - v1
Checksum:i30B102C668F56142
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73037 mRNA. Translation: AAB18626.1.
CCDSiCCDS22005.1.
RefSeqiNP_058546.1. NM_016850.3.
UniGeneiMm.3233.

Genome annotation databases

EnsembliENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
GeneIDi54123.
KEGGimmu:54123.
UCSCiuc009kkg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73037 mRNA. Translation: AAB18626.1.
CCDSiCCDS22005.1.
RefSeqiNP_058546.1. NM_016850.3.
UniGeneiMm.3233.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3QU3X-ray1.30A/B/C1-134[»]
ProteinModelPortaliP70434.
SMRiP70434.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207563. 9 interactors.
DIPiDIP-37903N.
IntActiP70434. 5 interactors.
STRINGi10090.ENSMUSP00000026571.

PTM databases

iPTMnetiP70434.
PhosphoSitePlusiP70434.

Proteomic databases

PaxDbiP70434.
PRIDEiP70434.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
GeneIDi54123.
KEGGimmu:54123.
UCSCiuc009kkg.2. mouse.

Organism-specific databases

CTDi3665.
MGIiMGI:1859212. Irf7.

Phylogenomic databases

eggNOGiENOG410IWNR. Eukaryota.
ENOG4111G85. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000111812.
HOVERGENiHBG105600.
InParanoidiP70434.
KOiK09447.
OMAiGWKTNFR.
OrthoDBiEOG091G067P.
PhylomeDBiP70434.
TreeFamiTF328512.

Enzyme and pathway databases

ReactomeiR-MMU-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-MMU-877300. Interferon gamma signaling.
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.
R-MMU-983231. Factors involved in megakaryocyte development and platelet production.

Miscellaneous databases

PROiP70434.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025498.
CleanExiMM_IRF7.
ExpressionAtlasiP70434. baseline and differential.
GenevisibleiP70434. MM.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
SM01243. IRF-3. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIRF7_MOUSE
AccessioniPrimary (citable) accession number: P70434
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.