IRF1_RAT
ID IRF1_RAT Reviewed; 328 AA.
AC P23570;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Interferon regulatory factor 1;
DE Short=IRF-1;
GN Name=Irf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2342469; DOI=10.1128/mcb.10.6.3087-3094.1990;
RA Yu-Lee L.Y., Hrachovy J.A., Stevens A.M., Schwarz L.A.;
RT "Interferon-regulatory factor 1 is an immediate-early gene under
RT transcriptional regulation by prolactin in Nb2 T cells.";
RL Mol. Cell. Biol. 10:3087-3094(1990).
CC -!- FUNCTION: Transcriptional regulator which displays a remarkable
CC functional diversity in the regulation of cellular responses (By
CC similarity). Regulates transcription of IFN and IFN-inducible genes,
CC host response to viral and bacterial infections, regulation of many
CC genes expressed during hematopoiesis, inflammation, immune responses
CC and cell proliferation and differentiation, regulation of the cell
CC cycle and induction of growth arrest and programmed cell death
CC following DNA damage (By similarity). Stimulates both innate and
CC acquired immune responses through the activation of specific target
CC genes and can act as a transcriptional activator and repressor
CC regulating target genes by binding to an interferon-stimulated response
CC element (ISRE) in their promoters (By similarity). Binds to a consensus
CC sequence in gene promoters (By similarity). Its target genes for
CC transcriptional activation activity include: genes involved in anti-
CC viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL,
CC ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial
CC response, such as NOS2/INOS; anti-proliferative response, such as
CC p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7
CC and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2
CC and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC
CC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B
CC and B2M and MHC class II expression, such as CIITA; metabolic enzymes,
CC such as ACOD1/IRG1 (By similarity). Represses genes involved in anti-
CC proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1,
CC CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and
CC TLR4 (By similarity). Stimulates p53/TP53-dependent transcription
CC through enhanced recruitment of EP300 leading to increased acetylation
CC of p53/TP53 (By similarity). Plays an important role in immune response
CC directly affecting NK maturation and activity, macrophage production of
CC IL12, Th1 development and maturation of CD8+ T-cells (By similarity).
CC Also implicated in the differentiation and maturation of dendritic
CC cells and in the suppression of regulatory T (Treg) cells development
CC (By similarity). Acts as a tumor suppressor and plays a role not only
CC in antagonism of tumor cell growth but also in stimulating an immune
CC response against tumor cells (By similarity).
CC {ECO:0000250|UniProtKB:P10914, ECO:0000250|UniProtKB:P15314}.
CC -!- ACTIVITY REGULATION: Activated by MYD88.
CC {ECO:0000250|UniProtKB:P15314}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (By similarity). Interacts
CC with EP300 (By similarity). Interacts with MYD88 (By similarity).
CC Interacts with PIAS3 (By similarity). {ECO:0000250|UniProtKB:P10914,
CC ECO:0000250|UniProtKB:P15314}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P15314}. Cytoplasm
CC {ECO:0000250|UniProtKB:P15314}. Note=MYD88-associated IRF1 migrates
CC into the nucleus more efficiently than non-MYD88-associated IRF1.
CC {ECO:0000250|UniProtKB:P15314}.
CC -!- PTM: Phosphorylated by CK2 and this positively regulates its activity.
CC {ECO:0000250|UniProtKB:P10914}.
CC -!- PTM: Sumoylation represses the transcriptional activity and displays
CC enhanced resistance to protein degradation (By similarity). Sumolyated
CC by UBE2I/UBC9 and SUMO1 (By similarity). Inactivates the tumor
CC suppressor activity (By similarity). Elevated levels in tumor cells (By
CC similarity). Major site is Lys-276 (By similarity). Sumoylation is
CC enhanced by PIAS3 (By similarity). Desumoylated by SENP1 in tumor cells
CC and appears to compete with ubiquitination on C-terminal sites (By
CC similarity). {ECO:0000250|UniProtKB:P10914,
CC ECO:0000250|UniProtKB:P15314}.
CC -!- PTM: Ubiquitinated. Appears to compete with sumoylation on C-terminal
CC sites (By similarity). {ECO:0000250|UniProtKB:P10914}.
CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC ProRule:PRU00840}.
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DR EMBL; M34253; AAA41450.1; -; mRNA.
DR PIR; A36330; A36330.
DR RefSeq; NP_036723.1; NM_012591.1.
DR AlphaFoldDB; P23570; -.
DR SMR; P23570; -.
DR STRING; 10116.ENSRNOP00000010968; -.
DR ChEMBL; CHEMBL5927; -.
DR PhosphoSitePlus; P23570; -.
DR PaxDb; P23570; -.
DR GeneID; 24508; -.
DR KEGG; rno:24508; -.
DR UCSC; RGD:2920; rat.
DR CTD; 3659; -.
DR RGD; 2920; Irf1.
DR eggNOG; ENOG502QVVN; Eukaryota.
DR InParanoid; P23570; -.
DR OrthoDB; 734108at2759; -.
DR PhylomeDB; P23570; -.
DR PRO; PR:P23570; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0043374; P:CD8-positive, alpha-beta T cell differentiation; ISO:RGD.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IEP:RGD.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IDA:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:RGD.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:RGD.
DR GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:InterPro.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; NAS:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:RGD.
DR GO; GO:0060416; P:response to growth hormone; IDA:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR CDD; cd00103; IRF; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR019817; Interferon_reg_fac_CS.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR031215; IRF1.
DR InterPro; IPR017431; IRF1/IRF2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11949:SF3; PTHR11949:SF3; 1.
DR Pfam; PF00605; IRF; 1.
DR PIRSF; PIRSF038196; IFN_RF1/2; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00601; IRF_1; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Antiviral defense; Cytoplasm; DNA-binding;
KW Immunity; Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..328
FT /note="Interferon regulatory factor 1"
FT /id="PRO_0000154547"
FT DNA_BIND 5..113
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 92..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 146..164
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 78
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10914"
FT CROSSLNK 276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 300
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 328 AA; 37065 MW; B94ADE14E975BBD9 CRC64;
MPITRMRMRP WLEMQINSNQ IPGLSWINKE EMIFQIPWKH AALHGWDINK DACLFRSWAI
HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN KGSSAVRVYR MLPPLTKNQR
KERKSKSSRD TKSKTKRKLC GDSSPDTLSD GLSSSTLPDD HSSYTAQGYL GQDLDMDRDI
TPALSPCVVS SSLSEWHMQM DIMPDSTTDL YNLQVSPMPS TSEAATDEDE EGKLPEDIMK
LFEQSEWQPT HVDGKGYLLN EPGAQLSTVY GDFSCKEEPE IDSPGGDIEI GIQRVFTEMK
NMDPVMWMDT LLGNSTRPPS IQAIPCAP
