Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Interferon regulatory factor 3

Gene

IRF3

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which 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. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages.By similarity

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.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi5 – 111IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST107

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-BTA-1169408. ISG15 antiviral mechanism.
R-BTA-1606341. IRF3 mediated activation of type 1 IFN.
R-BTA-3134973. LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
R-BTA-3270619. IRF3-mediated induction of type I IFN.
R-BTA-877300. Interferon gamma signaling.
R-BTA-918233. TRAF3-dependent IRF activation pathway.
R-BTA-933541. TRAF6 mediated IRF7 activation.
R-BTA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-BTA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 3
Short name:
IRF-3
Gene namesi
Name:IRF3
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 18

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002236751 – 417Interferon regulatory factor 3Add BLAST417

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphothreonineBy similarity1
Modified residuei14PhosphoserineBy similarity1
Modified residuei75PhosphothreonineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei123PhosphoserineBy similarity1
Modified residuei184PhosphoserineBy similarity1
Cross-linki189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Modified residuei249PhosphothreonineBy similarity1
Cross-linki356Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Cross-linki362Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Modified residuei382Phosphoserine; by TBK1By similarity1
Modified residuei392Phosphoserine; by IKKEBy similarity1
Modified residuei394PhosphoserineBy similarity1
Modified residuei400PhosphothreonineBy similarity1

Post-translational modificationi

Constitutively phosphorylated on many Ser/Thr residues. C-terminal serine/threonine cluster is phosphorylated in response of induction by IKBKE and TBK1. Phosphorylated at Ser-392 by IKBKE upon ssRNA viral infection. Phosphorylation at Ser-382 by TBK1 results in oligomerization (By similarity).By similarity
Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation.By similarity
ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ4JF28.
PRIDEiQ4JF28.

Expressioni

Gene expression databases

BgeeiENSBTAG00000006633.

Interactioni

Subunit structurei

Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF7. Interacts with CREBBP. May interact with MAVS. Interacts with IKBKE and TBK1. Interacts with TICAM1 and TICAM2. Interacts with RBCK1. Interacts with HERC5. Interacts with DDX3X (phosphorylated at 'Ser-102'); the interaction allows the phosphorylation and activation of IRF3 by IKBKE. Interacts with TRIM21 and ULK1, in the presence of TRIM21; this interaction leads to IRF3 degradation by autophagy.By similarity

Protein-protein interaction databases

IntActiQ4JF28. 1 interactor.
STRINGi9913.ENSBTAP00000031815.

Structurei

3D structure databases

ProteinModelPortaliQ4JF28.
SMRiQ4JF28.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni196 – 356Involved in HERC5 bindingBy similarityAdd BLAST161

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IXD8. Eukaryota.
ENOG410YA4B. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000033705.
HOVERGENiHBG105601.
InParanoidiQ4JF28.
KOiK05411.
OMAiCHTYWAV.
OrthoDBiEOG091G067P.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR001346. 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.
PROSITEiPS51507. IRF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q4JF28-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTQKPRILP WLISQLDRGE LEGVAWLGES RTRFRIPWKH GLRQDAQQED
60 70 80 90 100
FGIFQAWAVA SGAYTPGKDK PDLPTWKRNF RSALNRKEVL RLAEDHSKDS
110 120 130 140 150
QDPHKIYEFV NSGVRDIPEP DTSQDNGRHN TSDTQEDTLE KLLSDMDLSP
160 170 180 190 200
GGPSNLTMAS EKPPQFLQSP DSDIPALCPN SGLSENPLKQ LLANEEDWEF
210 220 230 240 250
EVTAFYRGCQ VFQQTVFCPG GLRLVGSEAG DRMLPGQPIR LPDPATSLTD
260 270 280 290 300
KSVTDYVQRV LSCLGGGLAL WRAGQWLCAQ RLGHCHVYWA IGEELLPSCG
310 320 330 340 350
HKPDGEVPKD REGGVFNLGP FITDLITFIE GSRRSPLYTL WFCVGQSWPQ
360 370 380 390 400
DQPWIKRLVM VKVVPMCLRV LVDIARQGGA SSLENTVDLH ISNSDPLSLT
410
PDQYMACLQD LAEDMDF
Length:417
Mass (Da):46,646
Last modified:August 2, 2005 - v1
Checksum:i06ADC5BCCD4D6389
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti56 – 59AWAV → VRAE in AAZ38325 (Ref. 2) Curated4
Sequence conflicti100 – 101SQ → PH in AAZ38325 (Ref. 2) Curated2
Sequence conflicti115 – 117RDI → GDF in AAZ38325 (Ref. 2) Curated3
Sequence conflicti130N → S in AAZ38325 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ879589 mRNA. Translation: CAI53672.1.
DQ103889 mRNA. Translation: AAZ38325.1.
EU194377 mRNA. Translation: ABW74073.1.
BC102119 mRNA. Translation: AAI02120.1.
RefSeqiNP_001025016.1. NM_001029845.3.
UniGeneiBt.45332.

Genome annotation databases

EnsembliENSBTAT00000031869; ENSBTAP00000031815; ENSBTAG00000006633.
GeneIDi516979.
KEGGibta:516979.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ879589 mRNA. Translation: CAI53672.1.
DQ103889 mRNA. Translation: AAZ38325.1.
EU194377 mRNA. Translation: ABW74073.1.
BC102119 mRNA. Translation: AAI02120.1.
RefSeqiNP_001025016.1. NM_001029845.3.
UniGeneiBt.45332.

3D structure databases

ProteinModelPortaliQ4JF28.
SMRiQ4JF28.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4JF28. 1 interactor.
STRINGi9913.ENSBTAP00000031815.

Proteomic databases

PaxDbiQ4JF28.
PRIDEiQ4JF28.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000031869; ENSBTAP00000031815; ENSBTAG00000006633.
GeneIDi516979.
KEGGibta:516979.

Organism-specific databases

CTDi3661.

Phylogenomic databases

eggNOGiENOG410IXD8. Eukaryota.
ENOG410YA4B. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000033705.
HOVERGENiHBG105601.
InParanoidiQ4JF28.
KOiK05411.
OMAiCHTYWAV.
OrthoDBiEOG091G067P.
TreeFamiTF328512.

Enzyme and pathway databases

ReactomeiR-BTA-1169408. ISG15 antiviral mechanism.
R-BTA-1606341. IRF3 mediated activation of type 1 IFN.
R-BTA-3134973. LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
R-BTA-3270619. IRF3-mediated induction of type I IFN.
R-BTA-877300. Interferon gamma signaling.
R-BTA-918233. TRAF3-dependent IRF activation pathway.
R-BTA-933541. TRAF6 mediated IRF7 activation.
R-BTA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-BTA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.

Gene expression databases

BgeeiENSBTAG00000006633.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR001346. 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.
PROSITEiPS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIRF3_BOVIN
AccessioniPrimary (citable) accession number: Q4JF28
Secondary accession number(s): A8W7A8, Q45VM9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: August 2, 2005
Last modified: November 30, 2016
This is version 99 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

Complete proteome, Reference proteome

Documents

  1. 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.