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Aliases for IRF3 Gene

Aliases for IRF3 Gene

  • Interferon Regulatory Factor 3 2 3 5
  • IIAE7 3
  • IRF-3 4

External Ids for IRF3 Gene

Previous GeneCards Identifiers for IRF3 Gene

  • GC19M050821
  • GC19M050530
  • GC19M054838
  • GC19M054854
  • GC19M050162
  • GC19M046539

Summaries for IRF3 Gene

Entrez Gene Summary for IRF3 Gene

  • This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GeneCards Summary for IRF3 Gene

IRF3 (Interferon Regulatory Factor 3) is a Protein Coding gene. Diseases associated with IRF3 include Herpes Simplex Encephalitis 7 and Encephalitis. Among its related pathways are Interferon gamma signaling and Toll Comparative Pathway. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and identical protein binding. An important paralog of this gene is IRF7.

UniProtKB/Swiss-Prot for IRF3 Gene

  • 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.

Gene Wiki entry for IRF3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRF3 Gene

Genomics for IRF3 Gene

Regulatory Elements for IRF3 Gene

Enhancers for IRF3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19F049567 1.3 Ensembl ENCODE 11.4 +96.3 96310 4.6 PKNOX1 ARID4B FEZF1 ZNF2 ZNF121 ZNF143 ZNF263 MXD4 REST KAT8 PRR12 NOSIP PRRG2 ENSG00000268047 FCGRT MIR150 RPS11 SNORD35B RCN3 PTOV1-AS2
GH19F049662 0.5 ENCODE 11.2 +0.9 916 5.4 PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 YY1 ZNF143 SP3 SP5 MXD4 PRR12 TEAD2 PLEKHA4 ENSG00000268157 RPS11 RRAS ENSG00000197813 SNORD35A PIH1D1 IRF3
GH19F049655 0.2 ENCODE 10.7 +9.8 9770 1.5 ZNF121 ZNF316 RAD51 ZNF600 MNT EMSY MAFK IRF3 BCL2L12 SCAF1
GH19F049659 0.5 ENCODE 8.7 +6.0 5968 0.5 ATF1 ZNF76 DEAF1 ZNF2 ZBTB40 ZEB1 ETS1 GLIS2 ZNF143 KLF7 TEAD2 PLEKHA4 ENSG00000268157 RRAS ENSG00000197813 IRF3 BCL2L12 SCAF1
GH19F049675 0.2 ENCODE 8.3 -12.4 -12402 6.3 HDGF PKNOX1 ARNT CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 PRR12 AKT1S1 NUP62 TEAD2 POLD1 PLEKHA4 SNORD35A BCL2L12 ALDH16A1 ENSG00000268157
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around IRF3 on UCSC Golden Path with GeneCards custom track

Promoters for IRF3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000348232 475 2801 PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 YY1 ZNF143 SP3 SP5 MXD4

Genomic Location for IRF3 Gene

Chromosome:
19
Start:
49,659,569 bp from pter
End:
49,665,875 bp from pter
Size:
6,307 bases
Orientation:
Minus strand

Genomic View for IRF3 Gene

Genes around IRF3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRF3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IRF3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRF3 Gene

Proteins for IRF3 Gene

  • Protein details for IRF3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14653-IRF3_HUMAN
    Recommended name:
    Interferon regulatory factor 3
    Protein Accession:
    Q14653
    Secondary Accessions:
    • A8K7L2
    • B2RAZ3
    • Q5FBY1
    • Q5FBY2
    • Q5FBY4
    • Q7Z5G6

    Protein attributes for IRF3 Gene

    Size:
    427 amino acids
    Molecular mass:
    47219 Da
    Quaternary structure:
    • 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 (PubMed:26347139).
    • (Microbial infection) Interacts with rotavirus A NSP1 (via C-terminus); this interaction leads to the proteasome-dependent degradation of IRF3 (PubMed:12186937).
    • (Microbial infection) Interacts with herpes virus 8/HHV-8 protein VIRF1 (PubMed:11314014).

    Three dimensional structures from OCA and Proteopedia for IRF3 Gene

    Alternative splice isoforms for IRF3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IRF3 Gene

Post-translational modifications for IRF3 Gene

  • (Microbial infection) Phosphorylation and subsequent activation of IRF3 is inhibited by vaccinia virus protein E3.
  • 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-396 by IKBKE upon ssRNA viral infection. Ser-385 and Ser-386 may be specifically phosphorylated in response to induction. Phosphorylation at Ser-386 by TBK1 results in oligomerization. An alternate model propose that the five serine/threonine residues between 396 and 405 are phosphorylated in response to a viral infection.
  • 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.
  • Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation.
  • Ubiquitination at Lys 70
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for IRF3 Gene

Domains & Families for IRF3 Gene

Graphical View of Domain Structure for InterPro Entry

Q14653

UniProtKB/Swiss-Prot:

IRF3_HUMAN :
  • Contains 1 IRF tryptophan pentad repeat DNA-binding domain.
  • Belongs to the IRF family.
Domain:
  • Contains 1 IRF tryptophan pentad repeat DNA-binding domain.
Family:
  • Belongs to the IRF family.
genes like me logo Genes that share domains with IRF3: view

No data available for Gene Families for IRF3 Gene

Function for IRF3 Gene

Molecular function for IRF3 Gene

GENATLAS Biochemistry:
interferon regulatory factor 3
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot Function:
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.

Gene Ontology (GO) - Molecular Function for IRF3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000975 regulatory region DNA binding IEA --
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IEA --
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding IEA --
GO:0003677 DNA binding NAS 12062447
GO:0003700 transcription factor activity, sequence-specific DNA binding IEA --
genes like me logo Genes that share ontologies with IRF3: view
genes like me logo Genes that share phenotypes with IRF3: view

Animal Models for IRF3 Gene

MGI Knock Outs for IRF3:

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for IRF3 Gene

Localization for IRF3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IRF3 Gene

Cytoplasm. Nucleus. 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.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IRF3 Gene COMPARTMENTS Subcellular localization image for IRF3 gene
Compartment Confidence
cytosol 5
nucleus 5
endosome 2
extracellular 2
mitochondrion 2
endoplasmic reticulum 1
plasma membrane 1
vacuole 1

Gene Ontology (GO) - Cellular Components for IRF3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 17079289
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA 17079289
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with IRF3: view

Pathways & Interactions for IRF3 Gene

SuperPathways for IRF3 Gene

SuperPathway Contained pathways
1 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
2 Activated TLR4 signalling
3 Cytosolic sensors of pathogen-associated DNA
4 Toll-like receptor signaling pathway
5 Toll-Like receptor Signaling Pathways
genes like me logo Genes that share pathways with IRF3: view

SIGNOR curated interactions for IRF3 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for IRF3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IEA --
GO:0002376 immune system process IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006366 transcription from RNA polymerase II promoter TAS 8524823
genes like me logo Genes that share ontologies with IRF3: view

Drugs & Compounds for IRF3 Gene

(6) Drugs for IRF3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) Additional Compounds for IRF3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IRF3: view

Transcripts for IRF3 Gene

Unigene Clusters for IRF3 Gene

Interferon regulatory factor 3:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for IRF3 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10a · 10b · 10c
SP1: - - - -
SP2: - - - - - -
SP3: -
SP4:
SP5: - -
SP6: -
SP7:

Relevant External Links for IRF3 Gene

GeneLoc Exon Structure for
IRF3
ECgene alternative splicing isoforms for
IRF3

Expression for IRF3 Gene

mRNA expression in normal human tissues for IRF3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IRF3 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (12.4) and Blymphocyte (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for IRF3 Gene



Protein tissue co-expression partners for IRF3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of IRF3 Gene:

IRF3

SOURCE GeneReport for Unigene cluster for IRF3 Gene:

Hs.75254

mRNA Expression by UniProt/SwissProt for IRF3 Gene:

Q14653-IRF3_HUMAN
Tissue specificity: Expressed constitutively in a variety of tissues.
genes like me logo Genes that share expression patterns with IRF3: view

Primer Products

No data available for mRNA differential expression in normal tissues for IRF3 Gene

Orthologs for IRF3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for IRF3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia IRF3 34 35
  • 82.49 (n)
rat
(Rattus norvegicus)
Mammalia Irf3 34
  • 77.46 (n)
mouse
(Mus musculus)
Mammalia Irf3 34 16 35
  • 76.98 (n)
chimpanzee
(Pan troglodytes)
Mammalia IRF3 35
  • 62 (a)
OneToOne
dog
(Canis familiaris)
Mammalia IRF3 35
  • 58 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia mdo-mir-7306 35
  • 39 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100493780 34
  • 48.46 (n)
zebrafish
(Danio rerio)
Actinopterygii irf3 34 35
  • 44.89 (n)
Species where no ortholog for IRF3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for IRF3 Gene

ENSEMBL:
Gene Tree for IRF3 (if available)
TreeFam:
Gene Tree for IRF3 (if available)

Paralogs for IRF3 Gene

Variants for IRF3 Gene

Sequence variations from dbSNP and Humsavar for IRF3 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs750526659 Herpes simplex encephalitis 7 (HSE7) [MIM:616532], other 49,662,076(+) CCAGC(C/T)GCTGG intron-variant, nc-transcript-variant, reference, missense
rs10412713 -- 49,667,641(+) tgcta(A/G)cttga intron-variant, upstream-variant-2KB
rs10415576 -- 49,661,133(+) AGTCC(C/T)GTCTG intron-variant
rs1049486 -- 49,659,803(-) TGGTA(A/G)AAATG nc-transcript-variant, reference, missense
rs111859305 -- 49,665,688(+) AGCTC(C/T)GGGTA nc-transcript-variant, upstream-variant-2KB, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for IRF3 Gene

Variant ID Type Subtype PubMed ID
nsv1160655 CNV deletion 26073780
nsv469715 CNV gain+loss 16826518
nsv470150 CNV gain 18288195
nsv475216 CNV novel sequence insertion 20440878
nsv579908 CNV loss 21841781
nsv579909 CNV loss 21841781
nsv817854 CNV gain 17921354
nsv828578 CNV loss 20364138
nsv833864 CNV gain 17160897
nsv833865 CNV gain+loss 17160897
nsv953600 CNV deletion 24416366
nsv9739 CNV gain+loss 18304495

Variation tolerance for IRF3 Gene

Residual Variation Intolerance Score: 72.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.42; 81.88% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for IRF3 Gene

Human Gene Mutation Database (HGMD)
IRF3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IRF3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IRF3 Gene

Disorders for IRF3 Gene

MalaCards: The human disease database

(20) MalaCards diseases for IRF3 Gene - From: OMIM, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
herpes simplex encephalitis 7
  • encephalopathy, acute, infection-induced, 7
encephalitis
herpes simplex
  • herpesvirus hominis disease
viral infectious disease
  • arthropod-borne viruses
vaccinia
- elite association - COSMIC cancer census association via MalaCards
Search IRF3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

IRF3_HUMAN
  • Herpes simplex encephalitis 7 (HSE7) [MIM:616532]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269 PubMed:26216125}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Relevant External Links for IRF3

Genetic Association Database (GAD)
IRF3
Human Genome Epidemiology (HuGE) Navigator
IRF3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
IRF3
genes like me logo Genes that share disorders with IRF3: view

No data available for Genatlas for IRF3 Gene

Publications for IRF3 Gene

  1. Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. (PMID: 8524823) Au W.W.-C. … Pitha P.M. (Proc. Natl. Acad. Sci. U.S.A. 1995) 2 3 4 22 64
  2. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. (PMID: 18711448) Zhang M. … Shu H.B. (Cell Res. 2008) 3 4 22 64
  3. Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages. (PMID: 16846591) Solis M. … Hiscott J. (Biochem. Pharmacol. 2006) 3 4 22 64
  4. Crystal structure of IRF-3 in complex with CBP. (PMID: 16154084) Qin B.Y. … Lin K. (Structure 2005) 3 4 22 64
  5. [Relationship between polymorphism of IRF-3 gene codon 427 and esophageal cancer in Anyang population of China]. (PMID: 15303122) Zhang C.F. … Ke Y. (Beijing Da Xue Xue Bao 2004) 3 22 46 64

Products for IRF3 Gene

Sources for IRF3 Gene

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