P15314 (IRF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon regulatory factor 1
Short name=IRF-1

Gene names

Name:

Irf1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	329 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Antiviral defense Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CD8-positive, alpha-beta T cell differentiation Inferred from mutant phenotype PubMed 11359801. Source: MGI cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara defense response to virus Inferred from mutant phenotype PubMed 20451243. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. 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-dependent 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 protein acetylation Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara 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 innate immune response Traceable author statement Ref.14. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	regulatory region DNA binding Inferred from electronic annotation. Source: InterPro 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
KEAP1	Q14145	2	EBI-6115486,EBI-751001	From a different organism.
TRAF3	Q13114	2	EBI-6115486,EBI-357631	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 329

329

Interferon regulatory factor 1

PRO_0000154546

Regions

DNA binding

5 – 113

109

IRF tryptophan pentad repeat

Amino acid modifications

Modified residue

78

1

N6-acetyllysine By similarity

Cross-link

276

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

300

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Secondary structure

1

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329

Helix Strand Turn

Details...

Helix

12 – 20

9

Beta strand

21 – 25

5

Beta strand

29 – 34

6

Turn

48 – 50

3

Beta strand

51 – 53

3

Helix

54 – 61

8

Helix

74 – 87

14

Beta strand

89 – 93

5

Beta strand

100 – 102

3

Beta strand

107 – 109

3

Sequences

	Sequence		Length	Mass (Da)
	P15314 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 0E5DD23C0D977B34	FASTA	329	37,319
	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

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00129453.

PIR

A31595.

RefSeq

NP_001152868.1. NM_001159396.1.
NP_032416.1. NM_008390.2.

UniGene

Mm.105218.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IF1	X-ray	3.00	A/B	1-113	[»]

ProteinModelPortal

P15314.

SMR

P15314. Positions 7-111.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15314. 5 interactions.

PTM databases

PhosphoSite

P15314.

Proteomic databases

PRIDE

P15314.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000019043; ENSMUSP00000019043; ENSMUSG00000018899.
ENSMUST00000108920; ENSMUSP00000104548; ENSMUSG00000018899.

GeneID

16362.

KEGG

mmu:16362.

Organism-specific databases

CTD

3659.

MGI

MGI:96590. Irf1.

Phylogenomic databases

eggNOG

NOG42582.

HOGENOM

HOG000037937.

HOVERGEN

HBG003455.

InParanoid

P15314.

KO

K09444.

OMA

CKEEPEV.

OrthoDB

EOG4JWVDV.

Gene expression databases

ArrayExpress

P15314.

Bgee

P15314.

CleanEx

MM_IRF1.

Genevestigator

P15314.

GermOnline

ENSMUSG00000018899. Mus musculus.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR017431. Interferon_reg_fac-1/2.
IPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00605. IRF. 1 hit.
[Graphical view]

PIRSF

PIRSF038196. IFN_RF1/2. 1 hit.

PRINTS

PR00267. INTFRNREGFCT.

SMART

SM00348. IRF. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P15314.

NextBio

289466.

SOURCE

Search...

Entry information

Entry name

IRF1_MOUSE

Accession

Primary (citable) accession number: P15314

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program