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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 vaccinia. Among its related pathways are Platelet activation, signaling and aggregation and Immune System. 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

Promoters for IRF3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around IRF3 on UCSC Golden Path with GeneCards custom track

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 rotavirus A NSP1 (via C-terminus); this interaction leads to the proteasome-dependent degradation of IRF3. Interacts with herpes virus 8/HHV-8 protein vIRF-1. Interacts with TRIM21 and ULK1, in the presence of TRIM21; this interaction leads to IRF3 degradation by autophagy (PubMed:26347139).

    Three dimensional structures from OCA and Proteopedia for IRF3 Gene

    Alternative splice isoforms for IRF3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IRF3 Gene

Proteomics data for IRF3 Gene at MOPED

Post-translational modifications for IRF3 Gene

  • 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. Phosphorylation, and subsequent activation of IRF3 is inhibited by vaccinia virus protein E3.
  • 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

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for IRF3 (IRF3)

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 --
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:

Inhibitory RNA Products

In Situ Assay 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:0005737 cytoplasm IDA 17079289
genes like me logo Genes that share ontologies with IRF3: view

Pathways & Interactions for IRF3 Gene

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:0002224 toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
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:

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, MOPED, and MaxQB for IRF3 Gene



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

Protein tissue co-expression partners for IRF3 Gene

- Elite partner

Primer Products

In Situ Assay 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
chimpanzee
(Pan troglodytes)
Mammalia IRF3 36
  • 62 (a)
OneToOne
cow
(Bos Taurus)
Mammalia IRF3 36
  • 63 (a)
OneToOne
IRF3 35
  • 82.49 (n)
  • 76.74 (a)
dog
(Canis familiaris)
Mammalia IRF3 36
  • 58 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Irf3 16
Irf3 36
  • 57 (a)
OneToOne
Irf3 35
  • 76.98 (n)
  • 72.42 (a)
oppossum
(Monodelphis domestica)
Mammalia mdo-mir-7306 36
  • 39 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Irf3 35
  • 77.46 (n)
  • 75 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100493780 35
  • 48.46 (n)
  • 38.78 (a)
zebrafish
(Danio rerio)
Actinopterygii irf3 35
  • 44.89 (n)
  • 35.2 (a)
irf3 36
  • 22 (a)
OneToOne
Species with no ortholog for IRF3:
  • 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

Paralogs for IRF3 Gene

genes like me logo Genes that share paralogs with IRF3: view

Variants for IRF3 Gene

Sequence variations from dbSNP and Humsavar for IRF3 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
VAR_011901 -
rs1049486 - 49,659,803(-) TGGTA(A/G)AAATG nc-transcript-variant, reference, missense
rs7251 - 49,659,652(-) GGAGA(C/G)CTGAG nc-transcript-variant, reference, missense
VAR_049643 -
rs1130611 -- 49,660,731(-) ACCAA(A/G)AGGCT nc-transcript-variant, reference, synonymous-codon, missense

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

Variant ID Type Subtype PubMed ID
nsv9739 CNV Gain+Loss 18304495
nsv833864 CNV Gain 17160897
nsv828578 CNV Loss 20364138
nsv469715 CNV Complex 16826518
nsv833865 CNV Gain+Loss 17160897
dgv3972n71 CNV Loss 21882294
nsv912269 CNV Loss 21882294
nsv817854 CNV Gain 17921354
nsv470150 CNV Gain 18288195
dgv3973n71 CNV Loss 21882294

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

HapMap Linkage Disequilibrium report
IRF3
Human Gene Mutation Database (HGMD)
IRF3

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

Disorders for IRF3 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
herpes simplex encephalitis 7
  • encephalopathy, acute, infection-induced, 7
vaccinia
hepatitis c
  • chronic hepatitis c
west nile virus
  • west nile virus, susceptibility to
severe acute respiratory syndrome
  • sars
- elite association - COSMIC cancer census association via MalaCards
Search IRF3 in MalaCards View complete list of genes associated with diseases

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 UniProtKB/Swiss-Prot and 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 23 67
  2. Viral induction of the zinc finger antiviral protein is IRF3-dependent but NF-kappaB-independent. (PMID: 20048147) Wang N. … Li K. (J. Biol. Chem. 2010) 3 23
  3. Essential role of mitochondrial antiviral signaling, IFN regulatory factor (IRF)3, and IRF7 in Chlamydophila pneumoniae-mediated IFN-beta response and control of bacterial replication in human endothelial cells. (PMID: 20154210) Buss C. … Eitel J. (J. Immunol. 2010) 3 23
  4. Synoviocyte innate immune responses: II. Pivotal role of IFN regulatory factor 3. (PMID: 20483755) Sweeney S.E. … Firestein G.S. (J. Immunol. 2010) 3 23
  5. Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7. (PMID: 19349300) GAcnin P. … Civas A. (Mol. Cell. Biol. 2009) 3 23

Products for IRF3 Gene

Sources for IRF3 Gene

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