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Interferon regulatory factor 1 (IRF-1)

 IRF1_RAT                Reviewed;         328 AA.
P23570;
01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
01-NOV-1991, sequence version 1.
05-DEC-2018, entry version 124.
RecName: Full=Interferon regulatory factor 1;
Short=IRF-1;
Name=Irf1;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2342469; DOI=10.1128/MCB.10.6.3087;
Yu-Lee L.Y., Hrachovy J.A., Stevens A.M., Schwarz L.A.;
"Interferon-regulatory factor 1 is an immediate-early gene under
transcriptional regulation by prolactin in Nb2 T cells.";
Mol. Cell. Biol. 10:3087-3094(1990).
-!- 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 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). {ECO:0000250}.
-!- ACTIVITY REGULATION: Activated by MYD88. {ECO:0000250}.
-!- SUBUNIT: Monomer. Homodimer. Interacts with EP300, PIAS3 and MYD88
(By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm
{ECO:0000250}. Note=MYD88-associated IRF1 migrates into the
nucleus more efficiently than non-MYD88-associated IRF1.
{ECO:0000250}.
-!- PTM: Phosphorylated by CK2 and this positively regulates its
activity. {ECO:0000250}.
-!- PTM: 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). {ECO:0000250}.
-!- PTM: Ubiquitinated. Appears to compete with sumoylation on C-
terminal sites (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
ProRule:PRU00840}.
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EMBL; M34253; AAA41450.1; -; mRNA.
PIR; A36330; A36330.
RefSeq; NP_036723.1; NM_012591.1.
UniGene; Rn.6396; -.
ProteinModelPortal; P23570; -.
STRING; 10116.ENSRNOP00000010968; -.
ChEMBL; CHEMBL5927; -.
PhosphoSitePlus; P23570; -.
PaxDb; P23570; -.
PRIDE; P23570; -.
GeneID; 24508; -.
KEGG; rno:24508; -.
UCSC; RGD:2920; rat.
CTD; 3659; -.
RGD; 2920; Irf1.
eggNOG; ENOG410IER3; Eukaryota.
eggNOG; ENOG4111HM7; LUCA.
HOGENOM; HOG000037937; -.
HOVERGEN; HBG003455; -.
InParanoid; P23570; -.
KO; K09444; -.
PhylomeDB; P23570; -.
PRO; PR:P23570; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:RGD.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:InterPro.
GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
GO; GO:0007050; P:cell cycle arrest; ISS:UniProtKB.
GO; GO:0071360; P:cellular response to exogenous dsRNA; IEP:RGD.
GO; GO:0071375; P:cellular response to peptide hormone stimulus; IDA:RGD.
GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:RGD.
GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
GO; GO:0007565; P:female pregnancy; IEP:RGD.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:RGD.
GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IEA:InterPro.
GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:RGD.
GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
GO; GO:0042127; P:regulation of cell proliferation; NAS:RGD.
GO; GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:RGD.
GO; GO:0060416; P:response to growth hormone; IDA:RGD.
GO; GO:0009408; P:response to heat; IEP:RGD.
CDD; cd00103; IRF; 1.
Gene3D; 1.10.10.10; -; 1.
InterPro; IPR019817; Interferon_reg_fac_CS.
InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
InterPro; IPR031215; IRF1.
InterPro; IPR017431; IRF1/IRF2.
InterPro; IPR036388; WH-like_DNA-bd_sf.
InterPro; IPR036390; WH_DNA-bd_sf.
PANTHER; PTHR11949; PTHR11949; 1.
PANTHER; PTHR11949:SF3; PTHR11949:SF3; 1.
Pfam; PF00605; IRF; 1.
PIRSF; PIRSF038196; IFN_RF1/2; 1.
PRINTS; PR00267; INTFRNREGFCT.
SMART; SM00348; IRF; 1.
SUPFAM; SSF46785; SSF46785; 1.
PROSITE; PS00601; IRF_1; 1.
PROSITE; PS51507; IRF_2; 1.
2: Evidence at transcript level;
Acetylation; Activator; Antiviral defense; Complete proteome;
Cytoplasm; DNA-binding; Immunity; Innate immunity; Isopeptide bond;
Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
Transcription regulation; Ubl conjugation.
CHAIN 1 328 Interferon regulatory factor 1.
/FTId=PRO_0000154547.
DNA_BIND 5 113 IRF tryptophan pentad repeat.
{ECO:0000255|PROSITE-ProRule:PRU00840}.
MOD_RES 78 78 N6-acetyllysine.
{ECO:0000250|UniProtKB:P10914}.
CROSSLNK 276 276 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
{ECO:0000250}.
CROSSLNK 300 300 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
{ECO:0000250}.
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


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