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Protein

Interferon regulatory factor 1

Gene

Irf1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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 include: 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 (By similarity).By similarity

Enzyme regulationi

Activated by MYD88.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi5 – 113IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST109

GO - Molecular functioni

  • DNA binding transcription factor activity Source: RGD
  • sequence-specific DNA binding Source: RGD
  • transcription regulatory region DNA binding Source: InterPro

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cellular response to dsRNA Source: RGD
  • cellular response to peptide hormone stimulus Source: RGD
  • cellular response to retinoic acid Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • defense response to virus Source: UniProtKB
  • female pregnancy Source: RGD
  • I-kappaB kinase/NF-kappaB signaling Source: RGD
  • interferon-gamma-mediated signaling pathway Source: UniProtKB
  • negative regulation of cell proliferation Source: InterPro
  • negative regulation of regulatory T cell differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of tyrosine phosphorylation of STAT protein Source: RGD
  • positive regulation of cell death Source: RGD
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: RGD
  • positive regulation of type I interferon production Source: UniProtKB
  • regulation of CD8-positive, alpha-beta T cell proliferation Source: UniProtKB
  • regulation of cell proliferation Source: RGD
  • regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
  • regulation of transcription, DNA-templated Source: RGD
  • response to growth hormone Source: RGD
  • response to heat Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processAntiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 1
Short name:
IRF-1
Gene namesi
Name:Irf1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2920 Irf1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5927

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001545471 – 328Interferon regulatory factor 1Add BLAST328

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78N6-acetyllysineBy similarity1
Cross-linki276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

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).By similarity
Ubiquitinated. Appears to compete with sumoylation on C-terminal sites (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP23570
PRIDEiP23570

PTM databases

PhosphoSitePlusiP23570

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with EP300, PIAS3 and MYD88 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000010968

Structurei

3D structure databases

ProteinModelPortaliP23570
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IER3 Eukaryota
ENOG4111HM7 LUCA
HOGENOMiHOG000037937
HOVERGENiHBG003455
InParanoidiP23570
KOiK09444
PhylomeDBiP23570

Family and domain databases

CDDicd00103 IRF, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR019817 Interferon_reg_fac_CS
IPR001346 Interferon_reg_fact_DNA-bd_dom
IPR031215 IRF1
IPR017431 IRF1/IRF2
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR11949 PTHR11949, 1 hit
PTHR11949:SF3 PTHR11949:SF3, 1 hit
PfamiView protein in Pfam
PF00605 IRF, 1 hit
PIRSFiPIRSF038196 IFN_RF1/2, 1 hit
PRINTSiPR00267 INTFRNREGFCT
SMARTiView protein in SMART
SM00348 IRF, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00601 IRF_1, 1 hit
PS51507 IRF_2, 1 hit

Sequencei

Sequence statusi: Complete.

P23570-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPITRMRMRP WLEMQINSNQ IPGLSWINKE EMIFQIPWKH AALHGWDINK
60 70 80 90 100
DACLFRSWAI HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN
110 120 130 140 150
KGSSAVRVYR MLPPLTKNQR KERKSKSSRD TKSKTKRKLC GDSSPDTLSD
160 170 180 190 200
GLSSSTLPDD HSSYTAQGYL GQDLDMDRDI TPALSPCVVS SSLSEWHMQM
210 220 230 240 250
DIMPDSTTDL YNLQVSPMPS TSEAATDEDE EGKLPEDIMK LFEQSEWQPT
260 270 280 290 300
HVDGKGYLLN EPGAQLSTVY GDFSCKEEPE IDSPGGDIEI GIQRVFTEMK
310 320
NMDPVMWMDT LLGNSTRPPS IQAIPCAP
Length:328
Mass (Da):37,065
Last modified:November 1, 1991 - v1
Checksum:iB94ADE14E975BBD9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34253 mRNA Translation: AAA41450.1
PIRiA36330
RefSeqiNP_036723.1, NM_012591.1
UniGeneiRn.6396

Genome annotation databases

GeneIDi24508
KEGGirno:24508
UCSCiRGD:2920 rat

Similar proteinsi

Entry informationi

Entry nameiIRF1_RAT
AccessioniPrimary (citable) accession number: P23570
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: May 23, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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