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IRF3 interferon regulatory factor 3 [ Homo sapiens (human) ]

Gene ID: 3661, updated on 5-Jul-2020

Summary

Official Symbol
IRF3provided by HGNC
Official Full Name
interferon regulatory factor 3provided by HGNC
Primary source
HGNC:HGNC:6118
See related
Ensembl:ENSG00000126456 MIM:603734
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IIAE7
Summary
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. The protein plays an important in the innate immune response against DNA and RNA viruses. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2020]
Expression
Ubiquitous expression in spleen (RPKM 23.8), lymph node (RPKM 21.2) and 25 other tissues See more
Orthologs

Genomic context

See IRF3 in Genome Data Viewer
Location:
19q13.33
Exon count:
10
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (49659569..49665875, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (50162826..50169132, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene RAS related Neighboring gene SR-related CTD associated factor 1 Neighboring gene BCL2 like 12 Neighboring gene protein arginine methyltransferase 1 Neighboring gene microRNA 5088 Neighboring gene adrenomedullin 5 (putative) Neighboring gene carnitine palmitoyltransferase 1C

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 CN54 Env (gp120) induces phosphorylation of RELA (p65), IRF3, MAPK14 (p38), and MAPK1 (ERK1/2) through TLR4 induction in monocyte derived macrophages; anti-TLR4 antibodies could inhibit this activation PubMed
Nef nef HIV-1 Nef myristoylation is required for the activation of IRF-3, leading to the synthesis of IFNbeta in monocytes-derived-macrophages PubMed
nef The acidic cluster (residues 64-69) of HIV-1 Nef is required for IRF-3 activation and IFNbeta production PubMed
Tat tat HIV-1 Tat-mediated downregulation of TRAF3 increases levels of phosphorylation of IRF3 and IRF7 in human microglial cells PubMed
Vif vif HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu PubMed
vif Virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. Eleven lysine residues in the N-terminal domain of IRF-3 are important for the Vif and Vpr mediated degradation PubMed
Vpr vpr HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu PubMed
vpr HIV-1 Vpr-mediated suppression of IFN induction is caused by failure of IRF-3 nucleus translocation PubMed
vpr Virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. Eleven lysine residues in the N-terminal domain of IRF-3 are important for the Vif and Vpr mediated degradation PubMed
Vpu vpu HIV-1 Vpr and Vif proteins cooperate with HIV-1 Vpu to induce IRF3 cleavage, although their individual effects are weaker than those of Vpu PubMed
vpu Residue Asp121 is the primary site for Vpu-induced, caspase-mediated IRF3 cleavage, and the alternative site is residues Asp125 when Asp121 is mutated PubMed
vpu Caspase-8 and caspase-3 activity are required for HIV-1 Vpu-induced cleavage of IRF3 and HIV-1 infection also induces caspase-mediated IRF3 cleavage PubMed
vpu HIV-1 Vpu-induced cleavage of IRF3 is largely dependent on the ability of Vpu to interact with beta-TrCP, and mutation of the Vpu phosphorylation sites Ser52 and Ser56 greatly decreases the function of Vpu-induced IRF3 cleavage PubMed
vpu HIV-1 Vpu co-localizes with IRF3 during HIV protein expression PubMed
vpu Interaction of HIV-1 Vpu with IRF3 governs the innate immune response of the host cell to HIV-1 infection PubMed
vpu HIV-1 Vpu forms a stable and specific complex with IRF3 in HIV-1-infected cells, resulting in its specific sequestration within the endo-lysosomal compartment PubMed
capsid gag HIV-1 CA mutants N74D and P90A fail to bind to CPSF6 and cyclophilins (Nup358 and CypA), respectively, and trigger innate sensors, leading to nuclear translocation of NFkappaB and IRF3, production of type 1 IFN and induction of an antiviral state PubMed
reverse transcriptase gag-pol The reverse-transcribed viral DNA by HIV-1 RT is the trigger of IRF3 activation and IFN-beta production in HIV-1 infected human monocytic cell line THP1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
MDA-5 signaling pathway TAS
Traceable Author Statement
more info
PubMed 
TRIF-dependent toll-like receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
TRIF-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
cellular response to DNA damage stimulus TAS
Traceable Author Statement
more info
PubMed 
cellular response to exogenous dsRNA IEA
Inferred from Electronic Annotation
more info
 
defense response to virus ISS
Inferred from Sequence or Structural Similarity
more info
 
immune system process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
interferon-gamma-mediated signaling pathway TAS
Traceable Author Statement
more info
 
lipopolysaccharide-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
macrophage apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
negative regulation of type I interferon production TAS
Traceable Author Statement
more info
 
positive regulation of I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cytokine secretion IEA
Inferred from Electronic Annotation
more info
 
positive regulation of interferon-alpha production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interferon-beta production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interferon-beta production TAS
Traceable Author Statement
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of type I interferon production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of type I interferon production TAS
Traceable Author Statement
more info
 
positive regulation of type I interferon-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
programmed necrotic cell death IEA
Inferred from Electronic Annotation
more info
 
regulation of inflammatory response IEA
Inferred from Electronic Annotation
more info
 
regulation of type I interferon production TAS
Traceable Author Statement
more info
 
transcription by RNA polymerase II TAS
Traceable Author Statement
more info
PubMed 
type I interferon biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
type I interferon signaling pathway TAS
Traceable Author Statement
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IGI
Inferred from Genetic Interaction
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
nuclear chromatin ISA
Inferred from Sequence Alignment
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
interferon regulatory factor 3

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_031810.1 RefSeqGene

    Range
    5019..11304
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001197122.2NP_001184051.1  interferon regulatory factor 3 isoform 2

    See identical proteins and their annotated locations for NP_001184051.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a longer protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    BC000660, DA999381
    Consensus CDS
    CCDS59409.1
    UniProtKB/Swiss-Prot
    Q14653
    Related
    ENSP00000471896.1, ENST00000601291.5
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202326
    IRF-3; Interferon-regulatory factor 3
  2. NM_001197123.2NP_001184052.1  interferon regulatory factor 3 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as IRF3a) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    BC000660, BP347627, BU859806, DA999381, HM357932, HM357934
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM5, E2GIM7
    Conserved Domains (2) summary
    pfam10401
    Location:167345
    IRF-3; Interferon-regulatory factor 3
    cl00096
    Location:2175
    IRF; Interferon Regulatory Factor (IRF); also known as tryptophan pentad repeat. The family of IRF transcription factors is important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. The ...
  3. NM_001197124.2NP_001184053.1  interferon regulatory factor 3 isoform 4

    See identical proteins and their annotated locations for NP_001184053.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4, also known as IRF3e and IRF3-nirs3) lacks an in-frame exon in the coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.
    Source sequence(s)
    BC000660, BU859806, DA999381, HM357935, HM357936
    Consensus CDS
    CCDS56099.1
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM8, E2GIM9
    Related
    ENSP00000471358.1, ENST00000599223.5
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:200253
    IRF-3; Interferon-regulatory factor 3
  4. NM_001197125.1NP_001184054.1  interferon regulatory factor 3 isoform 5

    See identical proteins and their annotated locations for NP_001184054.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5, also known as IRF3f) lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (5) is shorter than isoform 1. Both variants 5 and 6 encode the same isoform (5).
    Source sequence(s)
    BC000660, BU859806, DA999381, HM357937
    Consensus CDS
    CCDS59408.1
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM7, M0QYT9
    Related
    ENSP00000366339.5, ENST00000377135.8
    Conserved Domains (1) summary
    pfam10401
    Location:56234
    IRF-3; Interferon-regulatory factor 3
  5. NM_001197126.2NP_001184055.1  interferon regulatory factor 3 isoform 5

    See identical proteins and their annotated locations for NP_001184055.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6, also known as IRF3c) lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (5) is shorter than isoform 1. Both variants 5 and 6 encode the same isoform (5).
    Source sequence(s)
    BC000660, BU859806, DA999381, HM357934
    Consensus CDS
    CCDS59408.1
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM7, M0QYT9
    Related
    ENSP00000470069.1, ENST00000599144.5
    Conserved Domains (1) summary
    pfam10401
    Location:56234
    IRF-3; Interferon-regulatory factor 3
  6. NM_001197127.2NP_001184056.1  interferon regulatory factor 3 isoform 6

    See identical proteins and their annotated locations for NP_001184056.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7, also known as IRF3d) lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. This variant also lacks an in-frame exon compared to variant 1. The encoded isoform (6) is shorter than isoform 1. Both variants 7 and 8 encode the same isoform (6).
    Source sequence(s)
    BC000660, BU859806, DA999381, HM357935
    Consensus CDS
    CCDS59407.1
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM8
    Related
    ENSP00000472700.1, ENST00000600022.5
    Conserved Domains (1) summary
    pfam10401
    Location:54107
    IRF-3; Interferon-regulatory factor 3
  7. NM_001197128.2NP_001184057.1  interferon regulatory factor 3 isoform 6

    See identical proteins and their annotated locations for NP_001184057.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8, also known as IRF3b) lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. This variant also lacks an in-frame exon compared to variant 1. The encoded isoform (6) is shorter than isoform 1. Both variants 7 and 8 encode the same isoform (6).
    Source sequence(s)
    BC000660, BU859806, DA999381, HM357933, HM357935
    Consensus CDS
    CCDS59407.1
    UniProtKB/Swiss-Prot
    Q14653
    UniProtKB/TrEMBL
    E2GIM6, E2GIM8
    Related
    ENSP00000470512.1, ENST00000596765.5
    Conserved Domains (1) summary
    pfam10401
    Location:54107
    IRF-3; Interferon-regulatory factor 3
  8. NM_001571.6NP_001562.1  interferon regulatory factor 3 isoform 1

    See identical proteins and their annotated locations for NP_001562.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AC011495, DA999381, Z56281
    Consensus CDS
    CCDS12775.1
    UniProtKB/Swiss-Prot
    Q14653
    Related
    ENSP00000366344.3, ENST00000377139.8
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202380
    IRF-3; Interferon-regulatory factor 3

RNA

  1. NR_045568.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AA568913, AK292027, DA938709

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

    Range
    49659569..49665875 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017026767.2XP_016882256.1  interferon regulatory factor 3 isoform X4

    UniProtKB/Swiss-Prot
    Q14653
    Related
    ENSP00000310127.6, ENST00000309877.11
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202380
    IRF-3; Interferon-regulatory factor 3
  2. XM_006723198.2XP_006723261.1  interferon regulatory factor 3 isoform X3

    See identical proteins and their annotated locations for XP_006723261.1

    UniProtKB/Swiss-Prot
    Q14653
    Related
    ENSP00000470431.1, ENST00000600911.5
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202326
    IRF-3; Interferon-regulatory factor 3
  3. XM_017026766.2XP_016882255.1  interferon regulatory factor 3 isoform X4

    UniProtKB/Swiss-Prot
    Q14653
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202380
    IRF-3; Interferon-regulatory factor 3
  4. XM_006723197.1XP_006723260.1  interferon regulatory factor 3 isoform X3

    See identical proteins and their annotated locations for XP_006723260.1

    UniProtKB/Swiss-Prot
    Q14653
    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:202326
    IRF-3; Interferon-regulatory factor 3
  5. XM_024451497.1XP_024307265.1  interferon regulatory factor 3 isoform X7

    Conserved Domains (1) summary
    pfam10401
    Location:56234
    IRF-3; Interferon-regulatory factor 3
  6. XM_024451498.1XP_024307266.1  interferon regulatory factor 3 isoform X7

    Conserved Domains (1) summary
    pfam10401
    Location:56234
    IRF-3; Interferon-regulatory factor 3
  7. XM_024451495.1XP_024307263.1  interferon regulatory factor 3 isoform X6

    Conserved Domains (1) summary
    pfam10401
    Location:56180
    IRF-3; Interferon-regulatory factor 3
  8. XM_024451494.1XP_024307262.1  interferon regulatory factor 3 isoform X6

    Conserved Domains (1) summary
    pfam10401
    Location:56180
    IRF-3; Interferon-regulatory factor 3
  9. XM_006723201.1XP_006723264.1  interferon regulatory factor 3 isoform X6

    See identical proteins and their annotated locations for XP_006723264.1

    Conserved Domains (1) summary
    pfam10401
    Location:56180
    IRF-3; Interferon-regulatory factor 3
  10. XM_024451496.1XP_024307264.1  interferon regulatory factor 3 isoform X7

    Related
    ENSP00000472582.1, ENST00000598808.5
    Conserved Domains (1) summary
    pfam10401
    Location:56234
    IRF-3; Interferon-regulatory factor 3
  11. XM_024451493.1XP_024307261.1  interferon regulatory factor 3 isoform X2

    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:230408
    IRF-3; Interferon-regulatory factor 3
  12. XM_024451492.1XP_024307260.1  interferon regulatory factor 3 isoform X1

    Conserved Domains (2) summary
    pfam00605
    Location:7110
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:230354
    IRF-3; Interferon-regulatory factor 3
  13. XM_006723200.1XP_006723263.1  interferon regulatory factor 3 isoform X5

    Conserved Domains (2) summary
    pfam10401
    Location:167291
    IRF-3; Interferon-regulatory factor 3
    cl00096
    Location:2175
    IRF; Interferon Regulatory Factor (IRF); also known as tryptophan pentad repeat. The family of IRF transcription factors is important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. The ...

RNA

  1. XR_001753678.1 RNA Sequence

  2. XR_002958310.1 RNA Sequence

  3. XR_002958311.1 RNA Sequence

  4. XR_002958312.1 RNA Sequence

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