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Protein

Interferon regulatory factor 1

Gene

Irf1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi5 – 113109IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

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

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cellular response to dsRNA Source: RGD
  • cellular response to interleukin-1 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 Stat1 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 from RNA polymerase II promoter 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
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2920. Irf1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL5927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 328328Interferon regulatory factor 1PRO_0000154547Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei78 – 781N6-acetyllysineBy similarity
Cross-linki276 – 276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki300 – 300Glycyl 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

PhosphoSiteiP23570.

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.
SMRiP23570. Positions 7-111.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation
Contains 1 IRF tryptophan pentad repeat DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IER3. Eukaryota.
ENOG4111HM7. LUCA.
HOGENOMiHOG000037937.
HOVERGENiHBG003455.
InParanoidiP23570.
KOiK09444.
PhylomeDBiP23570.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR031215. IRF1.
IPR017431. IRF1/IRF2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR11949:SF3. PTHR11949:SF3. 1 hit.
PfamiPF00605. IRF. 1 hit.
[Graphical view]
PIRSFiPIRSF038196. IFN_RF1/2. 1 hit.
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP23570.
SMRiP23570. Positions 7-111.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000010968.

Chemistry

ChEMBLiCHEMBL5927.

PTM databases

PhosphoSiteiP23570.

Proteomic databases

PaxDbiP23570.
PRIDEiP23570.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24508.
KEGGirno:24508.
UCSCiRGD:2920. rat.

Organism-specific databases

CTDi3659.
RGDi2920. Irf1.

Phylogenomic databases

eggNOGiENOG410IER3. Eukaryota.
ENOG4111HM7. LUCA.
HOGENOMiHOG000037937.
HOVERGENiHBG003455.
InParanoidiP23570.
KOiK09444.
PhylomeDBiP23570.

Miscellaneous databases

PROiP23570.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR031215. IRF1.
IPR017431. IRF1/IRF2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR11949:SF3. PTHR11949:SF3. 1 hit.
PfamiPF00605. IRF. 1 hit.
[Graphical view]
PIRSFiPIRSF038196. IFN_RF1/2. 1 hit.
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells."
    Yu-Lee L.Y., Hrachovy J.A., Stevens A.M., Schwarz L.A.
    Mol. Cell. Biol. 10:3087-3094(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiIRF1_RAT
AccessioniPrimary (citable) accession number: P23570
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 8, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.