IRF3

Protein-coding gene in the species Homo sapiens
IRF3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

3QU6, 1J2F, 1QWT, 1T2K, 1ZOQ, 2O61, 2O6G, 2PI0, 3A77, 5JEO, 5JEK, 5JER, 5JEM, 5JEL, 5JEJ

Identifiers
AliasesIRF3, entrez:3661, IIAE7, interferon regulatory factor 3
External IDsOMIM: 603734 MGI: 1859179 HomoloGene: 1208 GeneCards: IRF3
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for IRF3
Genomic location for IRF3
Band19q13.33Start49,659,569 bp[1]
End49,665,875 bp[1]
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)[2]
Chromosome 7 (mouse)
Genomic location for IRF3
Genomic location for IRF3
Band7|7 B3Start44,647,072 bp[2]
End44,652,272 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • right uterine tube

  • spleen

  • right lobe of thyroid gland

  • canal of the cervix

  • left lobe of thyroid gland

  • anterior pituitary

  • lymph node

  • body of stomach

  • body of pancreas

  • left uterine tube
Top expressed in
  • spermatocyte

  • lip

  • thymus

  • yolk sac

  • crypt of lieberkuhn of small intestine

  • lacrimal gland

  • spleen

  • proximal tubule

  • esophagus

  • stomach
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • DNA binding
  • protein homodimerization activity
  • DNA-binding transcription factor activity
  • transcription coregulator activity
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
  • protein binding
  • protein domain specific binding
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • sequence-specific DNA binding
  • identical protein binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • cytoplasm
  • nucleoplasm
  • nucleus
  • cytosol
Biological process
  • apoptotic process
  • positive regulation of type I interferon-mediated signaling pathway
  • macrophage apoptotic process
  • regulation of transcription, DNA-templated
  • response to bacterium
  • response to exogenous dsRNA
  • positive regulation of interferon-alpha production
  • MDA-5 signaling pathway
  • interferon-gamma-mediated signaling pathway
  • immune system process
  • negative regulation of transcription by RNA polymerase II
  • transcription by RNA polymerase II
  • cellular response to dsRNA
  • transcription, DNA-templated
  • cellular response to DNA damage stimulus
  • TRIF-dependent toll-like receptor signaling pathway
  • response to lipopolysaccharide
  • defense response to virus
  • type I interferon signaling pathway
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • negative regulation of type I interferon production
  • programmed necrotic cell death
  • viral process
  • cellular response to lipopolysaccharide
  • positive regulation of type I interferon production
  • lipopolysaccharide-mediated signaling pathway
  • positive regulation of interferon-beta production
  • innate immune response
  • regulation of type I interferon production
  • positive regulation of transcription by RNA polymerase II
  • negative regulation of defense response to virus by host
  • regulation of gene expression
  • regulation of inflammatory response
  • cellular response to exogenous dsRNA
  • positive regulation of transcription, DNA-templated
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

3661

54131

Ensembl

ENSG00000126456

ENSMUSG00000003184

UniProt

Q14653

P70671

RefSeq (mRNA)
NM_001197122
NM_001197123
NM_001197124
NM_001197125
NM_001197126

NM_001197127
NM_001197128
NM_001571

NM_016849

RefSeq (protein)
NP_001184051
NP_001184052
NP_001184053
NP_001184054
NP_001184055

NP_001184056
NP_001184057
NP_001562
NP_001184053.1
NP_001184056.1
NP_001184057.1

NP_058545

Location (UCSC)Chr 19: 49.66 – 49.67 MbChr 7: 44.65 – 44.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.[5]

Function

IRF3 is a member of the interferon regulatory transcription factor (IRF) family.[5] IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites.[6] IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP.[7] The complex translocates into the nucleus for the transcriptional activation of interferons alpha and beta, and further interferon-induced genes.[8]

IRF3 plays an important role in the innate immune system's response to viral infection.[9] Aggregated MAVS have been found to activate IRF3 dimerization.[10] A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons.[11] Another study has shown that IRF3-/- knockouts protect from myocardial infarction.[12] The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-myocardial infarction cardioprotection.[12]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

IRF3 has been shown to interact with IRF7.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126456 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000003184 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). "Triggering the interferon response: the role of IRF-3 transcription factor". J. Interferon Cytokine Res. 19 (1): 1–13. doi:10.1089/107999099314360. PMID 10048763.
  6. ^ Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J (Feb 1999). "Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription". Mol Cell Biol. 19 (2): 959–66. doi:10.1128/MCB.19.2.959. PMC 116027. PMID 9891032.
  7. ^ Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
  8. ^ "Entrez Gene: IRF3 interferon regulatory factor 3".
  9. ^ Collins SE, Noyce RS, Mossman KL (Feb 2004). "Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication". J Virol. 78 (4): 1706–17. doi:10.1128/JVI.78.4.1706-1717.2004. PMC 369475. PMID 14747536.
  10. ^ Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). "MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response". Cell. 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231.
  11. ^ Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ (Mar 13, 2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation". Science. 347 (6227): aaa2630. doi:10.1126/science.aaa2630. PMID 25636800.
  12. ^ a b King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng Jr RP, Kohler RH, Arlauckas SP, Iwamoto Y, Savol A, Sadreyev RI, Kelly M, Fitzgibbons TP, Fitzgerald KA, Mitchison T, Libby P, Nahrendorf M, Weissleder R (Nov 6, 2017). "IRF3 and type I interferons fuel a fatal response to myocardial infarction". Nature Medicine. 23 (12): 1481–1487. doi:10.1038/nm.4428. PMC 6477926. PMID 29106401.
  13. ^ Au WC, Yeow WS, Pitha PM (Feb 2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology. 280 (2): 273–82. doi:10.1006/viro.2000.0782. PMID 11162841.

Further reading

  • Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA (1999). "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie. 80 (8–9): 651–8. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
  • Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
  • Au WC, Moore PA, Lowther W, Juang YT, Pitha PM (1996). "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". Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11657–61. doi:10.1073/pnas.92.25.11657. PMC 40461. PMID 8524823.
  • Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T (1998). "Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300". EMBO J. 17 (4): 1087–95. doi:10.1093/emboj/17.4.1087. PMC 1170457. PMID 9463386.
  • Weaver BK, Kumar KP, Reich NC (1998). "Interferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1". Mol. Cell. Biol. 18 (3): 1359–68. doi:10.1128/MCB.18.3.1359. PMC 108849. PMID 9488451.
  • Lin R, Heylbroeck C, Pitha PM, Hiscott J (1998). "Virus-Dependent Phosphorylation of the IRF-3 Transcription Factor Regulates Nuclear Translocation, Transactivation Potential, and Proteasome-Mediated Degradation". Mol. Cell. Biol. 18 (5): 2986–96. doi:10.1128/MCB.18.5.2986. PMC 110678. PMID 9566918.
  • Ronco LV, Karpova AY, Vidal M, Howley PM (1998). "Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity". Genes Dev. 12 (13): 2061–72. doi:10.1101/gad.12.13.2061. PMC 316980. PMID 9649509.
  • Bellingham J, Gregory-Evans K, Gregory-Evans CY (1999). "Mapping of human interferon regulatory factor 3 (IRF3) to chromosome 19q13.3-13.4 by an intragenic polymorphic marker". Annals of Human Genetics. 62 (Pt 3): 231–4. doi:10.1046/j.1469-1809.1998.6230231.x. PMID 9803267. S2CID 46070705.
  • Lowther WJ, Moore PA, Carter KC, Pitha PM (1999). "Cloning and functional analysis of the human IRF-3 promoter". DNA Cell Biol. 18 (9): 685–92. doi:10.1089/104454999314962. PMID 10492399.
  • Kim T, Kim TY, Song YH, Min IM, Yim J, Kim TK (1999). "Activation of interferon regulatory factor 3 in response to DNA-damaging agents". J. Biol. Chem. 274 (43): 30686–9. doi:10.1074/jbc.274.43.30686. PMID 10521456.
  • Kumar KP, McBride KM, Weaver BK, Dingwall C, Reich NC (2000). "Regulated Nuclear-Cytoplasmic Localization of Interferon Regulatory Factor 3, a Subunit of Double-Stranded RNA-Activated Factor 1". Mol. Cell. Biol. 20 (11): 4159–68. doi:10.1128/MCB.20.11.4159-4168.2000. PMC 85785. PMID 10805757.
  • Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, Aimoto S, Fujita T (2000). "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7. doi:10.1093/oxfordjournals.jbchem.a022753. PMID 10920266.
  • Servant MJ, ten Oever B, LePage C, Conti L, Gessani S, Julkunen I, Lin R, Hiscott J (2001). "Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3". J. Biol. Chem. 276 (1): 355–63. doi:10.1074/jbc.M007790200. PMID 11035028.
  • Smith EJ, Marié I, Prakash A, García-Sastre A, Levy DE (2001). "IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein". J. Biol. Chem. 276 (12): 8951–7. doi:10.1074/jbc.M008717200. PMID 11124948.
  • Au WC, Yeow WS, Pitha PM (2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology. 280 (2): 273–82. doi:10.1006/viro.2000.0782. PMID 11162841.
  • Barnes BJ, Moore PA, Pitha PM (2001). "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes". J. Biol. Chem. 276 (26): 23382–90. doi:10.1074/jbc.M101216200. PMID 11303025.
  • Mach CM, Hargrove BW, Kunkel GR (2002). "The Small RNA gene activator protein, SphI postoctamer homology-binding factor/selenocysteine tRNA gene transcription activating factor, stimulates transcription of the human interferon regulatory factor-3 gene". J. Biol. Chem. 277 (7): 4853–8. doi:10.1074/jbc.M108308200. PMID 11724783.
  • Morin P, Bragança J, Bandu MT, Lin R, Hiscott J, Doly J, Civas A (2002). "Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription". J. Mol. Biol. 316 (5): 1009–22. doi:10.1006/jmbi.2001.5401. PMID 11884139.
  • Dang O, Navarro L, Anderson K, David M (2004). "Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3 by lipopolysaccharide". Journal of Immunology. 172 (2): 747–51. doi:10.4049/jimmunol.172.2.747. PMID 14707042.

External links

Wikimedia Commons has media related to Interferon regulatory factor 3, IRF-3.
  • v
  • t
  • e
  • 1j2f: X-ray crystal structure of IRF-3 and its functional implications
    1j2f: X-ray crystal structure of IRF-3 and its functional implications
  • 1qwt: Auto-inhibitory interferon regulation factor-3 (IRF3) transactivation domain
    1qwt: Auto-inhibitory interferon regulation factor-3 (IRF3) transactivation domain
  • 1t2k: Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA
    1t2k: Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA
  • 1zoq: IRF3-CBP complex
    1zoq: IRF3-CBP complex
  • v
  • t
  • e
JAK-STAT
  • see JAK-STAT signaling pathway
Growth factor receptor-bound protein
Other
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies
  • v
  • t
  • e
Signaling pathway: TLR signaling pathway
TLRs
Other receptors
Downstream signalling
  • v
  • t
  • e
Ligand
Cytokine receptor
Janus kinase
Adaptor proteins
STAT
PIAS
SOCS
IRF