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Q14653

- IRF3_HUMAN

UniProt

Q14653 - IRF3_HUMAN

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Protein

Interferon regulatory factor 3

Gene
IRF3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein 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.

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi5 – 111107IRF tryptophan pentad repeatAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: BHF-UCL
  2. identical protein binding Source: IntAct
  3. protein binding Source: UniProtKB
  4. protein homodimerization activity Source: BHF-UCL
  5. regulatory region DNA binding Source: InterPro
  6. sequence-specific DNA binding transcription factor activity Source: InterPro
  7. transcription cofactor activity Source: ProtInc
  8. transcription regulatory region DNA binding Source: Ensembl

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. cellular response to DNA damage stimulus Source: UniProtKB
  3. cellular response to dsRNA Source: Ensembl
  4. cytokine-mediated signaling pathway Source: Reactome
  5. defense response to virus Source: UniProtKB
  6. innate immune response Source: Reactome
  7. interferon-gamma-mediated signaling pathway Source: Reactome
  8. lipopolysaccharide-mediated signaling pathway Source: Ensembl
  9. macrophage apoptotic process Source: UniProtKB
  10. MDA-5 signaling pathway Source: UniProtKB
  11. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  12. negative regulation of defense response to virus by host Source: Ensembl
  13. negative regulation of interferon-beta biosynthetic process Source: Ensembl
  14. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  15. negative regulation of type I interferon production Source: Reactome
  16. positive regulation of cytokine secretion Source: Ensembl
  17. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  18. positive regulation of interferon-alpha production Source: UniProtKB
  19. positive regulation of interferon-beta production Source: UniProtKB
  20. positive regulation of type I interferon-mediated signaling pathway Source: Ensembl
  21. positive regulation of type I interferon production Source: Reactome
  22. response to exogenous dsRNA Source: Ensembl
  23. toll-like receptor 3 signaling pathway Source: Reactome
  24. toll-like receptor 4 signaling pathway Source: Reactome
  25. toll-like receptor signaling pathway Source: Reactome
  26. transcription from RNA polymerase II promoter Source: ProtInc
  27. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  28. type I interferon biosynthetic process Source: Ensembl
  29. type I interferon signaling pathway Source: Reactome
  30. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.
REACT_118811. IRF3 mediated activation of type 1 IFN.
REACT_163743. LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
REACT_163977. Regulation of innate immune responses to cytosolic DNA.
REACT_163993. IRF3-mediated induction of type I IFN.
REACT_24938. TRAF6 mediated IRF7 activation.
REACT_24970. Factors involved in megakaryocyte development and platelet production.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25078. Interferon gamma signaling.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25162. Interferon alpha/beta signaling.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 3
Short name:
IRF-3
Gene namesi
Name:IRF3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:6118. IRF3.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. cytosol Source: Reactome
  3. nucleoplasm Source: Reactome
  4. nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi77 – 782KR → NG: Abolishes nuclear localization. 1 Publication
Mutagenesisi86 – 872RK → LQ: No effect on subcellular localization. 1 Publication
Mutagenesisi139 – 1402IL → MM: Abolishes nuclear export. 1 Publication
Mutagenesisi193 – 1931K → R: Highly diminished ISGylation; when associated with R-360 and R-366. 2 Publications
Mutagenesisi360 – 3601K → R: Highly diminished ISGylation; when associated with R-193 and R-366. 2 Publications
Mutagenesisi366 – 3661K → R: Highly diminished ISGylation; when associated with R-193 and R-360. 2 Publications
Mutagenesisi385 – 3862SS → AA: Complete loss of viral infection induced phosphorylation. 2 Publications
Mutagenesisi385 – 3851S → A, D or E: Complete loss of viral infection induced phosphorylation. 2 Publications
Mutagenesisi386 – 3861S → A, D or E: Complete loss of viral infection induced phosphorylation. 2 Publications
Mutagenesisi386 – 3861S → A: Abolishes dimerization after phosphorylation.
Mutagenesisi396 – 40510SNSHPLSLTS → ANAHPLALAA: Complete loss of viral infection induced phosphorylation. 2 Publications
Mutagenesisi396 – 40510SNSHPLSLTS → DNDHPLDLDD: Acts as a constitutively activated IRF3. 2 Publications
Mutagenesisi396 – 3983SNS → ANA: Complete loss of viral infection induced phosphorylation. 1 Publication
Mutagenesisi402 – 4054SLTS → ALAA: Complete loss of viral infection induced phosphorylation. 1 Publication

Organism-specific databases

PharmGKBiPA29917.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 427427Interferon regulatory factor 3PRO_0000154553Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31Phosphothreonine
Modified residuei14 – 141Phosphoserine
Modified residuei75 – 751Phosphothreonine
Modified residuei97 – 971Phosphoserine
Modified residuei180 – 1801Phosphothreonine
Modified residuei188 – 1881Phosphoserine
Cross-linki193 – 193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei237 – 2371Phosphothreonine
Modified residuei244 – 2441Phosphothreonine
Modified residuei253 – 2531Phosphothreonine
Disulfide bondi267 ↔ 2892 Publications
Cross-linki360 – 360Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Cross-linki366 – 366Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei386 – 3861Phosphoserine; by TBK1
Modified residuei396 – 3961Phosphoserine; by IKKE1 Publication
Modified residuei398 – 3981Phosphoserine
Modified residuei404 – 4041Phosphothreonine
Modified residuei427 – 4271Phosphoserine

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-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.
Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation.2 Publications
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.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ14653.
PaxDbiQ14653.
PeptideAtlasiQ14653.
PRIDEiQ14653.

PTM databases

PhosphoSiteiQ14653.

Expressioni

Tissue specificityi

Expressed constitutively in a variety of tissues.

Gene expression databases

ArrayExpressiQ14653.
BgeeiQ14653.
CleanExiHS_IRF3.
GenevestigatoriQ14653.

Organism-specific databases

HPAiCAB013018.
HPA004895.

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 TRIM21. 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-1.11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself9EBI-2650369,EBI-2650369
CREBBPQ927934EBI-2650369,EBI-81215
GRIP1Q9Y3R02EBI-2650369,EBI-5349621
MAFBQ9Y5Q34EBI-2650369,EBI-3649340
RB1P064002EBI-2650369,EBI-491274
RBL1P287492EBI-2650369,EBI-971402
SGTAO437653EBI-2650369,EBI-347996
TBK1Q9UHD27EBI-2650369,EBI-356402

Protein-protein interaction databases

BioGridi109869. 45 interactions.
DIPiDIP-41448N.
IntActiQ14653. 20 interactions.
MINTiMINT-253351.
STRINGi9606.ENSP00000310127.

Structurei

Secondary structure

1
427
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi8 – 1811
Beta strandi25 – 273
Beta strandi28 – 314
Beta strandi33 – 375
Beta strandi41 – 455
Helixi49 – 513
Helixi53 – 608
Beta strandi66 – 694
Helixi73 – 8513
Beta strandi90 – 967
Beta strandi100 – 1023
Beta strandi104 – 1096
Helixi191 – 1955
Beta strandi202 – 2109
Beta strandi213 – 2219
Beta strandi226 – 2294
Beta strandi239 – 2446
Helixi248 – 2503
Helixi255 – 26713
Beta strandi272 – 2776
Beta strandi280 – 2856
Beta strandi287 – 2893
Beta strandi291 – 2966
Beta strandi308 – 3103
Beta strandi313 – 3153
Beta strandi317 – 3215
Helixi322 – 33312
Beta strandi343 – 3486
Beta strandi354 – 3563
Helixi357 – 3604
Beta strandi363 – 3697
Helixi370 – 38314
Beta strandi389 – 3913
Beta strandi401 – 4033
Helixi405 – 41612

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J2FX-ray2.30A/B175-427[»]
1QWTX-ray2.10A/B173-427[»]
1T2KX-ray3.00A/B1-112[»]
1ZOQX-ray2.37A/B196-386[»]
2O61X-ray2.80A9-111[»]
2O6GX-ray3.10E/F/G/H1-123[»]
2PI0X-ray2.31A/B/C/D1-113[»]
3A77X-ray1.80A/B/C/D189-427[»]
3QU6X-ray2.30A/B/C1-113[»]
ProteinModelPortaliQ14653.
SMRiQ14653. Positions 1-112, 189-427.

Miscellaneous databases

EvolutionaryTraceiQ14653.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni200 – 360161Involved in HERC5 bindingAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi139 – 14911Nuclear export signalAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi151 – 19141Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the IRF family.

Phylogenomic databases

eggNOGiNOG42868.
HOGENOMiHOG000033705.
HOVERGENiHBG105601.
KOiK05411.
OMAiCHTYWAV.
OrthoDBiEOG7CCBR1.
PhylomeDBiQ14653.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. 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.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q14653-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MGTPKPRILP WLVSQLDLGQ LEGVAWVNKS RTRFRIPWKH GLRQDAQQED    50
FGIFQAWAEA TGAYVPGRDK PDLPTWKRNF RSALNRKEGL RLAEDRSKDP 100
HDPHKIYEFV NSGVGDFSQP DTSPDTNGGG STSDTQEDIL DELLGNMVLA 150
PLPDPGPPSL AVAPEPCPQP LRSPSLDNPT PFPNLGPSEN PLKRLLVPGE 200
EWEFEVTAFY RGRQVFQQTI SCPEGLRLVG SEVGDRTLPG WPVTLPDPGM 250
SLTDRGVMSY VRHVLSCLGG GLALWRAGQW LWAQRLGHCH TYWAVSEELL 300
PNSGHGPDGE VPKDKEGGVF DLGPFIVDLI TFTEGSGRSP RYALWFCVGE 350
SWPQDQPWTK RLVMVKVVPT CLRALVEMAR VGGASSLENT VDLHISNSHP 400
LSLTSDQYKA YLQDLVEGMD FQGPGES 427
Length:427
Mass (Da):47,219
Last modified:November 1, 1997 - v1
Checksum:iF536676FA78B0110
GO
Isoform 2 (identifier: Q14653-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     201-327: Missing.

Show »
Length:300
Mass (Da):33,170
Checksum:i1195BFBBA65C2DCE
GO
Isoform 3 (identifier: Q14653-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-146: Missing.
     201-327: Missing.

Show »
Length:154
Mass (Da):16,730
Checksum:i7A327E1716F74231
GO
Isoform 4 (identifier: Q14653-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     328-427: DLITFTEGSG...GMDFQGPGES → GSWAPRSDYL...NPPVPHHLNQ

Note: No experimental confirmation available.

Show »
Length:452
Mass (Da):49,134
Checksum:i96B059A029751B64
GO
Isoform 5 (identifier: Q14653-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     56-104: AWAEATGAYV...DRSKDPHDPH → ELGTFPSQTP...SQIRDPQAWL
     105-427: Missing.

Show »
Length:104
Mass (Da):12,330
Checksum:i7DA489EFD316732D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961R → Q.
Corresponds to variant rs968457 [ dbSNP | Ensembl ].
VAR_011901
Natural varianti107 – 1071Y → F.
Corresponds to variant rs34745118 [ dbSNP | Ensembl ].
VAR_049643
Natural varianti377 – 3771E → K.
Corresponds to variant rs1049486 [ dbSNP | Ensembl ].
VAR_011902
Natural varianti427 – 4271S → T.2 Publications
Corresponds to variant rs7251 [ dbSNP | Ensembl ].
VAR_011903

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 146146Missing in isoform 3. VSP_046911Add
BLAST
Alternative sequencei56 – 10449AWAEA…PHDPH → ELGTFPSQTPLRTPMVEAVL LIPRKTFWMSYWVTWCWPHS QIRDPQAWL in isoform 5. VSP_047690Add
BLAST
Alternative sequencei105 – 427323Missing in isoform 5. VSP_047691Add
BLAST
Alternative sequencei201 – 327127Missing in isoform 2 and isoform 3. VSP_043319Add
BLAST
Alternative sequencei328 – 427100DLITF…GPGES → GSWAPRSDYLHGRKRTLTTL CPLVLCGGVMAPGPAVDQEA RDGQGCAHVPQGLGRNGPGR GCLLPGEYCGPAHFQQPPTL PHLRPVQGLPAGLGGGHGFP GPWGELSPRSSWCASNPPVP HHLNQ in isoform 4. VSP_046912Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti196 – 1961L → F in BAG37040. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z56281 mRNA. Translation: CAA91227.1.
AB102884 mRNA. Translation: BAD89413.1.
AB102886 mRNA. Translation: BAD89415.1.
AB102887 mRNA. Translation: BAD89416.1.
AK292027 mRNA. Translation: BAF84716.1.
AK314421 mRNA. Translation: BAG37040.1.
AC011495 Genomic DNA. No translation available.
CH471177 Genomic DNA. Translation: EAW52510.1.
BC000660 mRNA. Translation: AAH00660.1.
BC071721 mRNA. Translation: AAH71721.1.
U86636 Genomic DNA. Translation: AAC68818.1.
CCDSiCCDS12775.1. [Q14653-1]
CCDS56099.1. [Q14653-2]
CCDS59407.1. [Q14653-3]
CCDS59409.1. [Q14653-4]
RefSeqiNP_001184051.1. NM_001197122.1. [Q14653-4]
NP_001184052.1. NM_001197123.1.
NP_001184053.1. NM_001197124.1. [Q14653-2]
NP_001184054.1. NM_001197125.1.
NP_001184055.1. NM_001197126.1.
NP_001184056.1. NM_001197127.1. [Q14653-3]
NP_001184057.1. NM_001197128.1. [Q14653-3]
NP_001562.1. NM_001571.5. [Q14653-1]
XP_006723260.1. XM_006723197.1. [Q14653-4]
XP_006723261.1. XM_006723198.1. [Q14653-4]
XP_006723262.1. XM_006723199.1. [Q14653-1]
UniGeneiHs.289052.
Hs.731922.
Hs.75254.

Genome annotation databases

EnsembliENST00000309877; ENSP00000310127; ENSG00000126456. [Q14653-1]
ENST00000377135; ENSP00000366339; ENSG00000126456. [Q14653-2]
ENST00000377139; ENSP00000366344; ENSG00000126456. [Q14653-1]
ENST00000442265; ENSP00000400378; ENSG00000126456. [Q14653-5]
ENST00000596765; ENSP00000470512; ENSG00000126456. [Q14653-3]
ENST00000597198; ENSP00000469113; ENSG00000126456. [Q14653-1]
ENST00000599223; ENSP00000471358; ENSG00000126456. [Q14653-2]
ENST00000600022; ENSP00000472700; ENSG00000126456. [Q14653-3]
ENST00000601291; ENSP00000471896; ENSG00000126456. [Q14653-4]
GeneIDi3661.
KEGGihsa:3661.
UCSCiuc002pot.2. human. [Q14653-2]
uc002pou.3. human. [Q14653-1]
uc002pow.3. human.

Polymorphism databases

DMDMi2497442.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z56281 mRNA. Translation: CAA91227.1 .
AB102884 mRNA. Translation: BAD89413.1 .
AB102886 mRNA. Translation: BAD89415.1 .
AB102887 mRNA. Translation: BAD89416.1 .
AK292027 mRNA. Translation: BAF84716.1 .
AK314421 mRNA. Translation: BAG37040.1 .
AC011495 Genomic DNA. No translation available.
CH471177 Genomic DNA. Translation: EAW52510.1 .
BC000660 mRNA. Translation: AAH00660.1 .
BC071721 mRNA. Translation: AAH71721.1 .
U86636 Genomic DNA. Translation: AAC68818.1 .
CCDSi CCDS12775.1. [Q14653-1 ]
CCDS56099.1. [Q14653-2 ]
CCDS59407.1. [Q14653-3 ]
CCDS59409.1. [Q14653-4 ]
RefSeqi NP_001184051.1. NM_001197122.1. [Q14653-4 ]
NP_001184052.1. NM_001197123.1.
NP_001184053.1. NM_001197124.1. [Q14653-2 ]
NP_001184054.1. NM_001197125.1.
NP_001184055.1. NM_001197126.1.
NP_001184056.1. NM_001197127.1. [Q14653-3 ]
NP_001184057.1. NM_001197128.1. [Q14653-3 ]
NP_001562.1. NM_001571.5. [Q14653-1 ]
XP_006723260.1. XM_006723197.1. [Q14653-4 ]
XP_006723261.1. XM_006723198.1. [Q14653-4 ]
XP_006723262.1. XM_006723199.1. [Q14653-1 ]
UniGenei Hs.289052.
Hs.731922.
Hs.75254.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1J2F X-ray 2.30 A/B 175-427 [» ]
1QWT X-ray 2.10 A/B 173-427 [» ]
1T2K X-ray 3.00 A/B 1-112 [» ]
1ZOQ X-ray 2.37 A/B 196-386 [» ]
2O61 X-ray 2.80 A 9-111 [» ]
2O6G X-ray 3.10 E/F/G/H 1-123 [» ]
2PI0 X-ray 2.31 A/B/C/D 1-113 [» ]
3A77 X-ray 1.80 A/B/C/D 189-427 [» ]
3QU6 X-ray 2.30 A/B/C 1-113 [» ]
ProteinModelPortali Q14653.
SMRi Q14653. Positions 1-112, 189-427.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109869. 45 interactions.
DIPi DIP-41448N.
IntActi Q14653. 20 interactions.
MINTi MINT-253351.
STRINGi 9606.ENSP00000310127.

PTM databases

PhosphoSitei Q14653.

Polymorphism databases

DMDMi 2497442.

Proteomic databases

MaxQBi Q14653.
PaxDbi Q14653.
PeptideAtlasi Q14653.
PRIDEi Q14653.

Protocols and materials databases

DNASUi 3661.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000309877 ; ENSP00000310127 ; ENSG00000126456 . [Q14653-1 ]
ENST00000377135 ; ENSP00000366339 ; ENSG00000126456 . [Q14653-2 ]
ENST00000377139 ; ENSP00000366344 ; ENSG00000126456 . [Q14653-1 ]
ENST00000442265 ; ENSP00000400378 ; ENSG00000126456 . [Q14653-5 ]
ENST00000596765 ; ENSP00000470512 ; ENSG00000126456 . [Q14653-3 ]
ENST00000597198 ; ENSP00000469113 ; ENSG00000126456 . [Q14653-1 ]
ENST00000599223 ; ENSP00000471358 ; ENSG00000126456 . [Q14653-2 ]
ENST00000600022 ; ENSP00000472700 ; ENSG00000126456 . [Q14653-3 ]
ENST00000601291 ; ENSP00000471896 ; ENSG00000126456 . [Q14653-4 ]
GeneIDi 3661.
KEGGi hsa:3661.
UCSCi uc002pot.2. human. [Q14653-2 ]
uc002pou.3. human. [Q14653-1 ]
uc002pow.3. human.

Organism-specific databases

CTDi 3661.
GeneCardsi GC19M050162.
HGNCi HGNC:6118. IRF3.
HPAi CAB013018.
HPA004895.
MIMi 603734. gene.
neXtProti NX_Q14653.
PharmGKBi PA29917.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG42868.
HOGENOMi HOG000033705.
HOVERGENi HBG105601.
KOi K05411.
OMAi CHTYWAV.
OrthoDBi EOG7CCBR1.
PhylomeDBi Q14653.
TreeFami TF328512.

Enzyme and pathway databases

Reactomei REACT_115831. ISG15 antiviral mechanism.
REACT_118811. IRF3 mediated activation of type 1 IFN.
REACT_163743. LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
REACT_163977. Regulation of innate immune responses to cytosolic DNA.
REACT_163993. IRF3-mediated induction of type I IFN.
REACT_24938. TRAF6 mediated IRF7 activation.
REACT_24970. Factors involved in megakaryocyte development and platelet production.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25078. Interferon gamma signaling.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25162. Interferon alpha/beta signaling.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

ChiTaRSi IRF3. human.
EvolutionaryTracei Q14653.
GeneWikii IRF3.
GenomeRNAii 3661.
NextBioi 14319.
PROi Q14653.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q14653.
Bgeei Q14653.
CleanExi HS_IRF3.
Genevestigatori Q14653.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProi IPR019817. Interferon_reg_fac_CS.
IPR001346. 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 ]
Pfami PF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view ]
PRINTSi PR00267. INTFRNREGFCT.
SMARTi SM00348. IRF. 1 hit.
[Graphical view ]
SUPFAMi SSF49879. SSF49879. 1 hit.
PROSITEi PS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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."
    Au W.W.-C., Moore P.P.A., Lowther W.W., Juang Y.-T., Pitha P.M.
    Proc. Natl. Acad. Sci. U.S.A. 92:11657-11661(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Retina.
  2. "IRF3 mRNA, nirs splice variants."
    Tabata Y., Sameshima E., Hayashi A., Iida K., Mitsuyama M., Kanai S., Furuya T., Saito T.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 5).
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-427.
    Tissue: Spleen.
  4. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-427.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
    Tissue: Eye and Kidney.
  7. "Mapping of human interferon regulatory factor 3 (IRF3) to chromosome 19q13.3-13.4 by an intragenic polymorphic marker."
    Bellingham J., Gregory-Evans K., Gregory-Evans C.Y.
    Ann. Hum. Genet. 62:231-234(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 323-413.
  8. "Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation."
    Lin R., Heylbroeck C., Pitha P.M., Hiscott J.
    Mol. Cell. Biol. 18:2986-2996(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF 385-SER-SER-386 AND 396-SER--SER-405.
  9. "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300."
    Suhara W., Yoneyama M., Iwamura T., Yoshimura S., Tamura K., Namiki H., Aimoto S., Fujita T.
    J. Biochem. 128:301-307(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-385 AND SER-386.
  10. "Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1."
    Kumar K.P., McBride K.M., Weaver B.K., Dingwall C., Reich N.C.
    Mol. Cell. Biol. 20:4159-4168(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 77-LYS-ARG-78; 86-ARG-LYS-87 AND 139-ILE-LEU-140.
  11. "Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3."
    Servant M.J., ten Oever B., LePage C., Conti L., Gessani S., Julkunen I., Lin R., Hiscott J.
    J. Biol. Chem. 276:355-363(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  12. "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."
    Smith E.J., Marie I.J., Prakash A., Garcia-Sastre A., Levy D.E.
    J. Biol. Chem. 276:8951-8957(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION OF PHOSPHORYLATION BY VACCINIA VIRUS PROTEIN E3.
  13. "HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators."
    Lin R., Genin P., Mamane Y., Sgarbanti M., Battistini A., Harrington W.J. Jr., Barber G.N., Hiscott J.
    Oncogene 20:800-811(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HHV-8 PROTEIN VIRF1.
  14. Cited for: REVIEW.
  15. "A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling."
    Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., Akira S.
    J. Immunol. 169:6668-6672(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TICAM1.
  16. "Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1."
    Graff J.W., Mitzel D.N., Weisend C.M., Flenniken M.L., Hardy M.E.
    J. Virol. 76:9545-9550(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ROTAVIRUS A NSP1.
  17. "LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF."
    Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A., Latz E., Monks B., Pitha P.M., Golenbock D.T.
    J. Exp. Med. 198:1043-1055(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TICAM2.
  18. "Triggering the interferon antiviral response through an IKK-related pathway."
    Sharma S., tenOever B.R., Grandvaux N., Zhou G.-P., Lin R., Hiscott J.
    Science 300:1148-1151(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  19. "Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways."
    Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.
    J. Biol. Chem. 279:15652-15661(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TICAM1.
  20. "SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."
    Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.
    EMBO J. 24:4018-4028(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IKBKE AND TBK1.
  21. "VISA is an adapter protein required for virus-triggered IFN-beta Signaling."
    Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B.
    Mol. Cell 19:727-740(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAVS.
  22. "Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages."
    Solis M., Goubau D., Romieu-Mourez R., Genin P., Civas A., Hiscott J.
    Biochem. Pharmacol. 72:1469-1476(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  23. "Type I interferon gene induction by the interferon regulatory factor family of transcription factors."
    Honda K., Takaoka A., Taniguchi T.
    Immunity 25:349-360(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  24. Erratum
    Honda K., Takaoka A., Taniguchi T.
    Immunity 25:849-849(2006)
  25. "Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3."
    Zhang M., Tian Y., Wang R.P., Gao D., Zhang Y., Diao F.C., Chen D.Y., Zhai Z.H., Shu H.B.
    Cell Res. 18:1096-1104(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, INTERACTION WITH RBCK1.
  26. "The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3."
    Higgs R., Ni Gabhann J., Ben Larbi N., Breen E.P., Fitzgerald K.A., Jefferies C.A.
    J. Immunol. 181:1780-1786(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TRIM21, POLYUBIQUITINATION.
  27. "Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1."
    Prins K.C., Cardenas W.B., Basler C.F.
    J. Virol. 83:3069-3077(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY IKBKE AND TBK1.
  28. "Regulation of immunity and oncogenesis by the IRF transcription factor family."
    Savitsky D., Tamura T., Yanai H., Taniguchi T.
    Cancer Immunol. Immunother. 59:489-510(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  29. "Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification."
    Shi H.X., Yang K., Liu X., Liu X.Y., Wei B., Shan Y.F., Zhu L.H., Wang C.
    Mol. Cell. Biol. 30:2424-2436(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ISGYLATION AT LYS-193; LYS-360 AND LYS-366, MUTAGENESIS OF LYS-193; LYS-360 AND LYS-366, INTERACTION WITH HERC5.
  30. "Human DEAD box helicase 3 couples IkappaB kinase epsilon to interferon regulatory factor 3 activation."
    Gu L., Fullam A., Brennan R., Schroder M.
    Mol. Cell. Biol. 33:2004-2015(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DDX3X AND IKBKE, PHOSPHORYLATION AT SER-396.
  31. "Structural insights into the functions of TBK1 in innate antimicrobial immunity."
    Shu C., Sankaran B., Chaton C.T., Herr A.B., Mishra A., Peng J., Li P.
    Structure 21:1137-1148(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-3; SER-14; THR-75; SER-97; THR-180; SER-188; THR-237; THR-244; THR-253; SER-398; THR-404 AND SER-427, PHOSPHORYLATION AT SER-386 BY TBK1, MUTAGENESIS OF SER-386.
  32. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 175-427, DISULFIDE BOND.
  33. "Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation."
    Qin B.Y., Liu C., Lam S.S., Srinath H., Delston R., Correia J.J., Derynck R., Lin K.
    Nat. Struct. Biol. 10:913-921(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 173-427, DISULFIDE BOND.
  34. "Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer."
    Panne D., Maniatis T., Harrison S.C.
    EMBO J. 23:4384-4393(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-112.
  35. Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 173-394.

Entry informationi

Entry nameiIRF3_HUMAN
AccessioniPrimary (citable) accession number: Q14653
Secondary accession number(s): A8K7L2
, B2RAZ3, Q5FBY1, Q5FBY2, Q5FBY4, Q7Z5G6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: September 3, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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