Q14653 (IRF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon regulatory factor 3
Short name=IRF-3

Gene names

Name:

IRF3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and 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, becomes 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 rotavirus A NSP1 (via C-terminus); this interaction leads to the proteasome-dependent degradation of IRF3. Interacts with RBCK1. Interacts with TRIM21. Interacts with HERC5. Ref.14 Ref.15 Ref.16 Ref.19 Ref.20 Ref.21 Ref.25 Ref.26 Ref.28
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. 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.18 Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation. Ref.25 Ref.26 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.28
Sequence similarities	Belongs to the IRF family. Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
Biological process	Antiviral defense Host-virus interaction Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Disulfide bond Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MDA-5 signaling pathway Traceable author statement Ref.23. Source: UniProtKB TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome induction of apoptosis Traceable author statement Ref.27. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome macrophage apoptotic process Traceable author statement Ref.22. Source: UniProtKB negative regulation of type I interferon production Traceable author statement. Source: Reactome 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 response to DNA damage stimulus Traceable author statement Ref.23. Source: UniProtKB toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Non-traceable author statement PubMed 12062447. Source: BHF-UCL regulatory region DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transcription cofactor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		9	EBI-2650369,EBI-2650369
CREBBP	Q92793	3	EBI-2650369,EBI-81215
MAFB	Q9Y5Q3	4	EBI-2650369,EBI-3649340
RB1	P06400	2	EBI-2650369,EBI-491274
RBL1	P28749	2	EBI-2650369,EBI-971402
SGTA	O43765	3	EBI-2650369,EBI-347996
TBK1	Q9UHD2	4	EBI-2650369,EBI-356402

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 427

427

Interferon regulatory factor 3

PRO_0000154553

Regions

DNA binding

5 – 111

107

IRF tryptophan pentad repeat

Region

200 – 360

161

Involved in HERC5 binding

Motif

139 – 149

11

Nuclear export signal

Compositional bias

151 – 191

41

Pro-rich

Amino acid modifications

Modified residue

123

1

Phosphoserine By similarity

Disulfide bond

267 ↔ 289

Ref.29 Ref.30

Cross-link

193

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.28

Cross-link

360

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.28

Cross-link

366

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.28

Natural variations

Alternative sequence

201 – 327

127

Missing in isoform 2.

VSP_043319

Natural variant

96

1

R → Q.
Corresponds to variant rs968457 [ dbSNP | Ensembl ].

VAR_011901

Natural variant

107

1

Y → F.
Corresponds to variant rs34745118 [ dbSNP | Ensembl ].

VAR_049643

Natural variant

377

1

E → K.
Corresponds to variant rs1049486 [ dbSNP | Ensembl ].

VAR_011902

Natural variant

427

1

S → T. Ref.3 Ref.5
Corresponds to variant rs7251 [ dbSNP | Ensembl ].

VAR_011903

Experimental info

Mutagenesis

77 – 78

2

KR → NG: Abolishes nuclear localization. Ref.10

Mutagenesis

86 – 87

2

RK → LQ: No effect on subcellular localization. Ref.10

Mutagenesis

139 – 140

2

IL → MM: Abolishes nuclear export. Ref.10

Mutagenesis

193

1

K → R: Highly diminished ISGylation; when associated with R-360 and R-366. Ref.10 Ref.28

Mutagenesis

360

1

K → R: Highly diminished ISGylation; when associated with R-193 and R-366. Ref.10 Ref.28

Mutagenesis

366

1

K → R: Highly diminished ISGylation; when associated with R-193 and R-360. Ref.10 Ref.28

Mutagenesis

385 – 386

2

SS → AA: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10

Mutagenesis

385

1

S → A, D or E: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10

Mutagenesis

386

1

S → A, D or E: Complete loss of viral infection induced phosphorylation. Ref.9 Ref.10

Mutagenesis

396 – 405

10

SNSHPLSLTS → ANAHPLALAA: Complete loss of viral infection induced phosphorylation. Ref.8 Ref.10

Mutagenesis

396 – 405

10

SNSHPLSLTS → DNDHPLDLDD: Acts as a constitutively activated IRF3. Ref.8 Ref.10

Mutagenesis

396 – 398

3

SNS → ANA: Complete loss of viral infection induced phosphorylation. Ref.10

Mutagenesis

402 – 405

4

SLTS → ALAA: Complete loss of viral infection induced phosphorylation. Ref.10

Secondary structure

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427

Helix Strand Turn

Details...

Helix

8 – 18

11

Beta strand

25 – 27

3

Beta strand

28 – 31

4

Beta strand

33 – 37

5

Beta strand

41 – 45

5

Helix

49 – 51

3

Helix

53 – 60

8

Beta strand

66 – 69

4

Helix

73 – 85

13

Beta strand

90 – 96

7

Beta strand

100 – 102

3

Beta strand

104 – 109

6

Helix

191 – 195

5

Beta strand

202 – 210

9

Beta strand

213 – 221

9

Beta strand

226 – 229

4

Beta strand

239 – 244

6

Helix

248 – 250

3

Helix

255 – 267

13

Beta strand

272 – 277

6

Beta strand

280 – 285

6

Beta strand

287 – 289

3

Beta strand

291 – 296

6

Beta strand

308 – 310

3

Beta strand

313 – 315

3

Beta strand

317 – 321

5

Helix

322 – 333

12

Beta strand

343 – 348

6

Beta strand

354 – 356

3

Helix

357 – 360

4

Beta strand

363 – 369

7

Helix

370 – 383

14

Beta strand

389 – 391

3

Beta strand

401 – 403

3

Helix

405 – 416

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: F536676FA78B0110	FASTA	427	47,219
	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
	Isoform 2 [UniParc]. Checksum: 1195BFBBA65C2DCE	FASTA	300	33,170
	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 DLITFTEGSG RSPRYALWFC VGESWPQDQP WTKRLVMVKV 250 260 270 280 290 300 VPTCLRALVE MARVGGASSL ENTVDLHISN SHPLSLTSDQ YKAYLQDLVE GMDFQGPGES

References

	« Hide 'large scale' referencesShow '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 variant 3." 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] (ISOFORM 2).
[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]	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. , 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] (ISOFORM 1). Tissue: Eye.
[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]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	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)
[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]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.
[32]	"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.
AB102887 mRNA. Translation: BAD89416.1.
AK292027 mRNA. Translation: BAF84716.1.
AC011495 Genomic DNA. No translation available.
CH471177 Genomic DNA. Translation: EAW52510.1.
BC071721 mRNA. Translation: AAH71721.1.
U86636 Genomic DNA. Translation: AAC68818.1.

IPI

IPI00291901.

RefSeq

NP_001184053.1. NM_001197124.1.
NP_001562.1. NM_001571.5.

UniGene

Hs.289052.
Hs.731922.
Hs.75254.

3D structure databases

PDBe
RCSB PDB
PDBj

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	4-111	[»]
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	[»]

ProteinModelPortal

Q14653.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41448N.

IntAct

Q14653. 13 interactions.

MINT

MINT-253351.

STRING

9606.ENSP00000310127.

PTM databases

PhosphoSite

Q14653.

Polymorphism databases

DMDM

2497442.

Proteomic databases

PaxDb

Q14653.

PeptideAtlas

Q14653.

PRIDE

Q14653.

Protocols and materials databases

DNASU

3661.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309877; ENSP00000310127; ENSG00000126456.
ENST00000377135; ENSP00000366339; ENSG00000126456.
ENST00000377139; ENSP00000366344; ENSG00000126456.
ENST00000597198; ENSP00000469113; ENSG00000126456.
ENST00000599223; ENSP00000471358; ENSG00000126456.

GeneID

3661.

KEGG

hsa:3661.

UCSC

uc002pou.3. human.

Organism-specific databases

CTD

3661.

GeneCards

GC19M050162.

HGNC

HGNC:6118. IRF3.

HPA

CAB013018.
HPA004895.

MIM

603734. gene.

neXtProt

NX_Q14653.

PharmGKB

PA29917.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42868.

HOGENOM

HOG000033705.

HOVERGEN

HBG105601.

KO

K05411.

OMA

EGVAWLD.

PhylomeDB

Q14653.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q14653.

Bgee

Q14653.

CleanEx

HS_IRF3.

Genevestigator

Q14653.

GermOnline

ENSG00000126456. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
2.60.200.10. 1 hit.

InterPro

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]

Pfam

PF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]

PRINTS

PR00267. INTFRNREGFCT.

SMART

SM00348. IRF. 1 hit.
[Graphical view]

SUPFAM

SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

IRF3. human.

EvolutionaryTrace

Q14653.

GenomeRNAi

3661.

NextBio

14319.

SOURCE

Search...

Entry information

Entry name

IRF3_HUMAN

Accession

Primary (citable) accession number: Q14653
Secondary accession number(s): A8K7L2, Q5FBY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.