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Q14653 (IRF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 3

Short name=IRF-3
Gene names
Name:IRF3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Enzyme regulation

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.

Subunit 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 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. Ref.13 Ref.15 Ref.16 Ref.17 Ref.20 Ref.21 Ref.22 Ref.26 Ref.27 Ref.30 Ref.31

Subcellular location

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. Ref.10

Tissue specificity

Expressed constitutively in a variety of tissues.

Post-translational modification

Constitutively phosphorylated on many serines 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. 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. Ref.11 Ref.12 Ref.19 Ref.28 Ref.31

Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation. Ref.26 Ref.27

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. Ref.30

Sequence similarities

Belongs to the IRF family.

Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
   Biological processAntiviral defense
Host-virus interaction
Immunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   Molecular functionActivator
   PTMDisulfide bond
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMDA-5 signaling pathway

Traceable author statement Ref.24. Source: UniProtKB

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement Ref.29. Source: UniProtKB

cellular response to DNA damage stimulus

Traceable author statement Ref.24. Source: UniProtKB

cellular response to dsRNA

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to virus

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

macrophage apoptotic process

Traceable author statement Ref.23. Source: UniProtKB

negative regulation of defense response to virus by host

Inferred from electronic annotation. Source: Ensembl

negative regulation of interferon-beta biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-alpha production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

type I interferon biosynthetic process

Inferred from electronic annotation. Source: Ensembl

type I interferon signaling pathway

Traceable author statement. Source: Reactome

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17079289PubMed 18818105. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 17079289PubMed 18818105. Source: BHF-UCL

   Molecular_functionDNA binding

Non-traceable author statement PubMed 12062447. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 15841462PubMed 16301520PubMed 19454348PubMed 20403326PubMed 20581830PubMed 21102435PubMed 21782231PubMed 22000020. Source: IntAct

protein homodimerization activity

Inferred from physical interaction PubMed 12062447. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription cofactor activity

Traceable author statement Ref.1. Source: ProtInc

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14653-1)

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.
Isoform 2 (identifier: Q14653-2)

The sequence of this isoform differs from the canonical sequence as follows:
     201-327: Missing.
Isoform 3 (identifier: Q14653-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-146: Missing.
     201-327: Missing.
Isoform 4 (identifier: Q14653-4)

The sequence of this isoform differs from the canonical sequence as follows:
     328-427: DLITFTEGSG...GMDFQGPGES → GSWAPRSDYL...NPPVPHHLNQ
Note: No experimental confirmation available.
Isoform 5 (identifier: Q14653-5)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427Interferon regulatory factor 3
PRO_0000154553

Regions

DNA binding5 – 111107IRF tryptophan pentad repeat
Region200 – 360161Involved in HERC5 binding
Motif139 – 14911Nuclear export signal
Compositional bias151 – 19141Pro-rich

Amino acid modifications

Modified residue3961Phosphoserine; by IKKE Ref.31
Disulfide bond267 ↔ 289 Ref.32 Ref.33
Cross-link193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.30
Cross-link360Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.30
Cross-link366Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.30

Natural variations

Alternative sequence1 – 146146Missing in isoform 3.
VSP_046911
Alternative sequence56 – 10449AWAEA…PHDPH → ELGTFPSQTPLRTPMVEAVL LIPRKTFWMSYWVTWCWPHS QIRDPQAWL in isoform 5.
VSP_047690
Alternative sequence105 – 427323Missing in isoform 5.
VSP_047691
Alternative sequence201 – 327127Missing in isoform 2 and isoform 3.
VSP_043319
Alternative sequence328 – 427100DLITF…GPGES → GSWAPRSDYLHGRKRTLTTL CPLVLCGGVMAPGPAVDQEA RDGQGCAHVPQGLGRNGPGR GCLLPGEYCGPAHFQQPPTL PHLRPVQGLPAGLGGGHGFP GPWGELSPRSSWCASNPPVP HHLNQ in isoform 4.
VSP_046912
Natural variant961R → Q.
Corresponds to variant rs968457 [ dbSNP | Ensembl ].
VAR_011901
Natural variant1071Y → F.
Corresponds to variant rs34745118 [ dbSNP | Ensembl ].
VAR_049643
Natural variant3771E → K.
Corresponds to variant rs1049486 [ dbSNP | Ensembl ].
VAR_011902
Natural variant4271S → T. Ref.3 Ref.5
Corresponds to variant rs7251 [ dbSNP | Ensembl ].
VAR_011903

Experimental info

Mutagenesis77 – 782KR → NG: Abolishes nuclear localization. Ref.10
Mutagenesis86 – 872RK → LQ: No effect on subcellular localization. Ref.10
Mutagenesis139 – 1402IL → MM: Abolishes nuclear export. Ref.10
Mutagenesis1931K → R: Highly diminished ISGylation; when associated with R-360 and R-366. Ref.10 Ref.30
Mutagenesis3601K → R: Highly diminished ISGylation; when associated with R-193 and R-366. Ref.10 Ref.30
Mutagenesis3661K → R: Highly diminished ISGylation; when associated with R-193 and R-360. Ref.10 Ref.30
Mutagenesis385 – 3862SS → AA: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10
Mutagenesis3851S → A, D or E: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10
Mutagenesis3861S → A, D or E: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10
Mutagenesis396 – 40510SNSHPLSLTS → ANAHPLALAA: Complete loss of viral infection induced phosphorylation. Ref.8 Ref.10
Mutagenesis396 – 40510SNSHPLSLTS → DNDHPLDLDD: Acts as a constitutively activated IRF3. Ref.8 Ref.10
Mutagenesis396 – 3983SNS → ANA: Complete loss of viral infection induced phosphorylation. Ref.10
Mutagenesis402 – 4054SLTS → ALAA: Complete loss of viral infection induced phosphorylation. Ref.10

Secondary structure

................................................................... 427
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: F536676FA78B0110

FASTA42747,219
        10         20         30         40         50         60 
MGTPKPRILP WLVSQLDLGQ LEGVAWVNKS RTRFRIPWKH GLRQDAQQED FGIFQAWAEA 

        70         80         90        100        110        120 
TGAYVPGRDK PDLPTWKRNF RSALNRKEGL RLAEDRSKDP HDPHKIYEFV NSGVGDFSQP 

       130        140        150        160        170        180 
DTSPDTNGGG STSDTQEDIL DELLGNMVLA PLPDPGPPSL AVAPEPCPQP LRSPSLDNPT 

       190        200        210        220        230        240 
PFPNLGPSEN PLKRLLVPGE EWEFEVTAFY RGRQVFQQTI SCPEGLRLVG SEVGDRTLPG 

       250        260        270        280        290        300 
WPVTLPDPGM SLTDRGVMSY VRHVLSCLGG GLALWRAGQW LWAQRLGHCH TYWAVSEELL 

       310        320        330        340        350        360 
PNSGHGPDGE VPKDKEGGVF DLGPFIVDLI TFTEGSGRSP RYALWFCVGE SWPQDQPWTK 

       370        380        390        400        410        420 
RLVMVKVVPT CLRALVEMAR VGGASSLENT VDLHISNSHP LSLTSDQYKA YLQDLVEGMD 


FQGPGES 

« Hide

Isoform 2 [UniParc].

Checksum: 1195BFBBA65C2DCE
Show »

FASTA30033,170
Isoform 3 [UniParc].

Checksum: 7A327E1716F74231
Show »

FASTA15416,730
Isoform 4 [UniParc].

Checksum: 96B059A029751B64
Show »

FASTA45249,134
Isoform 5 [UniParc].

Checksum: 7DA489EFD316732D
Show »

FASTA10412,330

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"Control of IRF-3 activation by phosphorylation."
Yoneyama M., Suhara W., Fujita T.
J. Interferon Cytokine Res. 22:73-76(2002) [PubMed] [Europe PMC] [Abstract]
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]Erratum
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. 198:1451-1451(2003)
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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.
[24]"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.
[25]Erratum
Honda K., Takaoka A., Taniguchi T.
Immunity 25:849-849(2006)
[26]"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.
[27]"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.
[28]"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.
[29]"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.
[30]"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.
[31]"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.
[32]"X-ray crystal structure of IRF-3 and its functional implications."
Takahasi K., Suzuki N.N., Horiuchi M., Mori M., Suhara W., Okabe Y., Fukuhara Y., Terasawa H., Akira S., Fujita T., Inagaki F.
Nat. Struct. Biol. 10:922-927(2003) [PubMed] [Europe PMC] [Abstract]
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]"Crystal structure of IRF-3 in complex with CBP."
Qin B.Y., Liu C., Srinath H., Lam S.S., Correia J.J., Derynck R., Lin K.
Structure 13:1269-1277(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 173-394.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
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.
RefSeqNP_001184051.1. NM_001197122.1.
NP_001184052.1. NM_001197123.1.
NP_001184053.1. NM_001197124.1.
NP_001184054.1. NM_001197125.1.
NP_001184055.1. NM_001197126.1.
NP_001184056.1. NM_001197127.1.
NP_001184057.1. NM_001197128.1.
NP_001562.1. NM_001571.5.
UniGeneHs.289052.
Hs.731922.
Hs.75254.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J2FX-ray2.30A/B175-427[»]
1QWTX-ray2.10A/B173-427[»]
1T2KX-ray3.00A/B1-112[»]
1ZOQX-ray2.37A/B196-386[»]
2O61X-ray2.80A4-111[»]
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[»]
ProteinModelPortalQ14653.
SMRQ14653. Positions 1-112, 189-427.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109869. 44 interactions.
DIPDIP-41448N.
IntActQ14653. 19 interactions.
MINTMINT-253351.
STRING9606.ENSP00000310127.

PTM databases

PhosphoSiteQ14653.

Polymorphism databases

DMDM2497442.

Proteomic databases

PaxDbQ14653.
PeptideAtlasQ14653.
PRIDEQ14653.

Protocols and materials databases

DNASU3661.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309877; 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]
GeneID3661.
KEGGhsa:3661.
UCSCuc002pot.2. human. [Q14653-2]
uc002pou.3. human. [Q14653-1]
uc002pow.3. human.

Organism-specific databases

CTD3661.
GeneCardsGC19M050162.
HGNCHGNC:6118. IRF3.
HPACAB013018.
HPA004895.
MIM603734. gene.
neXtProtNX_Q14653.
PharmGKBPA29917.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42868.
HOGENOMHOG000033705.
HOVERGENHBG105601.
KOK05411.
OMACHTYWAV.
OrthoDBEOG7CCBR1.
PhylomeDBQ14653.
TreeFamTF328512.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ14653.
BgeeQ14653.
CleanExHS_IRF3.
GenevestigatorQ14653.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProIPR019817. 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]
PfamPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIRF3. human.
EvolutionaryTraceQ14653.
GeneWikiIRF3.
GenomeRNAi3661.
NextBio14319.
PROQ14653.
SOURCESearch...

Entry information

Entry nameIRF3_HUMAN
AccessionPrimary (citable) accession number: Q14653
Secondary accession number(s): A8K7L2 expand/collapse secondary AC list , Q5FBY1, Q5FBY2, Q5FBY4, Q7Z5G6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM