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P15314 (IRF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 1

Short name=IRF-1
Gene names
Name:Irf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length329 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity are: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells. Ref.5 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14

Enzyme regulation

Activated by MYD88.

Subunit structure

Monomer. Homodimer. Interacts with EP300 By similarity. Interacts with MYD88 and PIAS3. Ref.5 Ref.9

Subcellular location

Nucleus. Cytoplasm. Note: MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1. Ref.9

Induction

By viruses and IFN-gamma.

Post-translational modification

Phosphorylated by CK2 and this positively regulates its activity By similarity.

Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation. Inactivates the tumor suppressor activity. Elevated levels in tumor cells. Major site is Lys-276. Sumoylation is enhanced by PIAS3. Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites By similarity. Ref.5 Ref.10

Ubiquitinated. Appears to compete with sumoylation on C-terminal sites By similarity. Ref.3

Sequence similarities

Belongs to the IRF family.

Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
   Biological processAntiviral defense
Immunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCD8-positive, alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 11359801. Source: MGI

apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to interferon-beta

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from mutant phenotype PubMed 20451243. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Inferred from mutant phenotype Ref.14. Source: UniProtKB

negative regulation of T-helper 2 cell differentiation

Traceable author statement Ref.4. Source: UniProtKB

negative regulation of regulatory T cell differentiation

Inferred from mutant phenotype Ref.11. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of T-helper 1 cell differentiation

Traceable author statement Ref.4. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-12 biosynthetic process

Inferred from direct assay PubMed 14568984. Source: MGI

positive regulation of natural killer cell differentiation

Traceable author statement Ref.4. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17159910. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of type I interferon production

Inferred from mutant phenotype Ref.9. Source: UniProtKB

regulation of CD8-positive, alpha-beta T cell proliferation

Inferred from mutant phenotype Ref.14. Source: UniProtKB

regulation of MyD88-dependent toll-like receptor signaling pathway

Inferred from mutant phenotype Ref.9. Source: UniProtKB

regulation of adaptive immune response

Traceable author statement Ref.14. Source: UniProtKB

regulation of gene expression

Inferred from mutant phenotype PubMed 11359801. Source: MGI

regulation of innate immune response

Traceable author statement Ref.14. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

nuclear chromatin

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay PubMed 14568984. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 17159910. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14568984PubMed 17159910. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KEAP1Q141452EBI-6115486,EBI-751001From a different organism.
TRAF3Q131142EBI-6115486,EBI-357631From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 329329Interferon regulatory factor 1
PRO_0000154546

Regions

DNA binding5 – 113109IRF tryptophan pentad repeat

Amino acid modifications

Modified residue781N6-acetyllysine By similarity
Cross-link276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Secondary structure

.................. 329
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P15314 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 0E5DD23C0D977B34

FASTA32937,319
        10         20         30         40         50         60 
MPITRMRMRP WLEMQINSNQ IPGLIWINKE EMIFQIPWKH AAKHGWDINK DACLFRSWAI 

        70         80         90        100        110        120 
HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN KGSSAVRVYR MLPPLTRNQR 

       130        140        150        160        170        180 
KERKSKSSRD TKSKTKRKLC GDVSPDTFSD GLSSSTLPDD HSSYTTQGYL GQDLDMERDI 

       190        200        210        220        230        240 
TPALSPCVVS SSLSEWHMQM DIIPDSTTDL YNLQVSPMPS TSEAATDEDE EGKIAEDLMK 

       250        260        270        280        290        300 
LFEQSEWQPT HIDGKGYLLN EPGTQLSSVY GDFSCKEEPE IDSPRGDIGI GIQHVFTEMK 

       310        320 
NMDSIMWMDS LLGNSVRLPP SIQAIPCAP 

« Hide

References

« Hide 'large scale' references
[1]"Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements."
Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T.
Cell 54:903-913(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
Strain: FVB/N.
Tissue: Mammary gland.
[3]"Degradation of transcription factor IRF-1 by the ubiquitin-proteasome pathway. The C-terminal region governs the protein stability."
Nakagawa K., Yokosawa H.
Eur. J. Biochem. 267:1680-1686(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[4]"IRF family of transcription factors as regulators of host defense."
Taniguchi T., Ogasawara K., Takaoka A., Tanaka N.
Annu. Rev. Immunol. 19:623-655(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[5]"PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1."
Nakagawa K., Yokosawa H.
FEBS Lett. 530:204-208(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS3, SUMOYLATION, FUNCTION.
[6]"Activities of IRF-1."
Kroeger A., Koester M., Schroeder K., Hauser H., Mueller P.P.
J. Interferon Cytokine Res. 22:5-14(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[7]"IRF-1 as a negative regulator of cell proliferation."
Romeo G., Fiorucci G., Chiantore M.V., Percario Z.A., Vannucchi S., Affabris E.
J. Interferon Cytokine Res. 22:39-47(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[8]"IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors."
Honda K., Taniguchi T.
Nat. Rev. Immunol. 6:644-658(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[9]"Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program."
Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M., Takayanagi H., Ohba Y., Taniguchi T., Honda K.
Proc. Natl. Acad. Sci. U.S.A. 103:15136-15141(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYD88.
[10]"Ubc9-mediated sumoylation leads to transcriptional repression of IRF-1."
Kim E.-J., Park J.-S., Um S.-J.
Biochem. Biophys. Res. Commun. 377:952-956(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, FUNCTION.
[11]"IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression."
Fragale A., Gabriele L., Stellacci E., Borghi P., Perrotti E., Ilari R., Lanciotti A., Remoli A.L., Venditti M., Belardelli F., Battistini A.
J. Immunol. 181:1673-1682(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"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.
[13]"IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction."
Stirnweiss A., Ksienzyk A., Klages K., Rand U., Grashoff M., Hauser H., Kroeger A.
J. Immunol. 184:5179-5185(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection."
Brien J.D., Daffis S., Lazear H.M., Cho H., Suthar M.S., Gale M. Jr., Diamond M.S.
PLoS Pathog. 7:E1002230-E1002230(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Structure of IRF-1 with bound DNA reveals determinants of interferon regulation."
Escalante C.R., Yie J., Thanos D., Aggarwal A.K.
Nature 391:103-106(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 7-111.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M21065 mRNA. Translation: AAA39334.1.
BC003821 mRNA. Translation: AAH03821.1.
CCDSCCDS24686.1.
PIRA31595.
RefSeqNP_001152868.1. NM_001159396.1.
NP_032416.1. NM_008390.2.
UniGeneMm.105218.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IF1X-ray3.00A/B1-113[»]
ProteinModelPortalP15314.
SMRP15314. Positions 7-111.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200784. 5 interactions.
IntActP15314. 5 interactions.

PTM databases

PhosphoSiteP15314.

Proteomic databases

PRIDEP15314.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019043; ENSMUSP00000019043; ENSMUSG00000018899.
ENSMUST00000108920; ENSMUSP00000104548; ENSMUSG00000018899.
GeneID16362.
KEGGmmu:16362.
UCSCuc007iww.2. mouse.

Organism-specific databases

CTD3659.
MGIMGI:96590. Irf1.

Phylogenomic databases

eggNOGNOG42582.
HOGENOMHOG000037937.
HOVERGENHBG003455.
InParanoidP15314.
KOK09444.
OMACKEEPEV.
OrthoDBEOG72ZCFD.
PhylomeDBP15314.
TreeFamTF328512.

Gene expression databases

ArrayExpressP15314.
BgeeP15314.
CleanExMM_IRF1.
GenevestigatorP15314.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR017431. Interferon_reg_fac-1/2.
IPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00605. IRF. 1 hit.
[Graphical view]
PIRSFPIRSF038196. IFN_RF1/2. 1 hit.
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP15314.
NextBio289466.
PROP15314.
SOURCESearch...

Entry information

Entry nameIRF1_MOUSE
AccessionPrimary (citable) accession number: P15314
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot