UniProtKB - P10914 (IRF1_HUMAN)
Interferon regulatory factor 1
IRF1
Functioni
Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195, PubMed:32385160).
Regulates transcription 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 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195).
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 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:21389130, PubMed:22367195).
Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters (PubMed:32385160).
Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, ZBP1, 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; metabolic enzymes, such as ACOD1/IRG1 (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195).
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 (PubMed:18641303, PubMed:22200613).
Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (PubMed:15509808, PubMed:18084608).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750).
Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750).
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 (PubMed:20049431).
5 Publications13 PublicationsMiscellaneous
Activity regulationi
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 5 – 113 | IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST | 109 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: ARUK-UCL
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB
- CD8-positive, alpha-beta T cell differentiation Source: Ensembl
- cellular response to interferon-beta Source: BHF-UCL
- cellular response to mechanical stimulus Source: UniProtKB
- defense response to virus Source: UniProtKB
- immune system process Source: GO_Central
- interferon-gamma-mediated signaling pathway Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of regulatory T cell differentiation Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of interferon-beta production Source: UniProtKB
- positive regulation of interleukin-12 production Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of type I interferon production Source: UniProtKB
- regulation of adaptive immune response Source: UniProtKB
- regulation of CD8-positive, alpha-beta T cell proliferation Source: UniProtKB
- regulation of cell cycle Source: UniProtKB
- regulation of innate immune response Source: UniProtKB
- regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P10914 |
Reactomei | R-HSA-5620971, Pyroptosis R-HSA-877300, Interferon gamma signaling R-HSA-909733, Interferon alpha/beta signaling R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SignaLinki | P10914 |
SIGNORi | P10914 |
Names & Taxonomyi
Protein namesi | Recommended name: Interferon regulatory factor 1Short name: IRF-1 |
Gene namesi | Name:IRF1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6116, IRF1 |
MIMi | 147575, gene |
neXtProti | NX_P10914 |
VEuPathDBi | HostDB:ENSG00000125347 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Other locations
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Gastric cancer (GASC)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065134 | 8 | M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. 1 PublicationCorresponds to variant dbSNP:rs121912469EnsemblClinVar. | 1 | |
Natural variantiVAR_065135 | 11 | W → R in GASC; the mutation abolishes DNA binding and transactivating activities. 1 PublicationCorresponds to variant dbSNP:rs121912470EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 78 | K → R: Loss of acetylation. Partial loss of DNA-binding and transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 275 | K → R: Some loss of sumoylation. Partial inhibition of acetylation and activity. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptotic activity; when associated with R-299. 1 Publication | 1 | |
Mutagenesisi | 299 | K → R: Large loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptotic activity; when associated with R-275. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Tumor suppressorOrganism-specific databases
DisGeNETi | 3659 |
MalaCardsi | IRF1 |
MIMi | 613659, phenotype |
OpenTargetsi | ENSG00000125347 |
PharmGKBi | PA29915 |
Miscellaneous databases
Pharosi | P10914, Tbio |
Genetic variation databases
BioMutai | IRF1 |
DMDMi | 20178295 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154545 | 1 – 325 | Interferon regulatory factor 1Add BLAST | 325 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 78 | N6-acetyllysine1 Publication | 1 | |
Cross-linki | 275 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||
Cross-linki | 299 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P10914 |
jPOSTi | P10914 |
MassIVEi | P10914 |
PaxDbi | P10914 |
PeptideAtlasi | P10914 |
PRIDEi | P10914 |
ProteomicsDBi | 52676 |
PTM databases
iPTMneti | P10914 |
PhosphoSitePlusi | P10914 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000125347, Expressed in granulocyte and 219 other tissues |
ExpressionAtlasi | P10914, baseline and differential |
Genevisiblei | P10914, HS |
Organism-specific databases
HPAi | ENSG00000125347, Tissue enhanced (bone) |
Interactioni
Subunit structurei
Monomer (By similarity). Homodimer (By similarity).
Interacts with EP300 (PubMed:15509808).
Interacts with MYD88 (By similarity).
Interacts with PIAS3 (By similarity).
By similarity1 PublicationBinary interactionsi
P10914
With | #Exp. | IntAct |
---|---|---|
IRF3 [Q14653] | 5 | EBI-1055781,EBI-2650369 |
NFE2L2 [Q16236] | 3 | EBI-1055781,EBI-2007911 |
SUMO1 [P63165] | 2 | EBI-1055781,EBI-80140 |
E7 [P03129] from Human papillomavirus type 16. | 3 | EBI-1055781,EBI-866453 |
Protein-protein interaction databases
BioGRIDi | 109867, 47 interactors |
DIPi | DIP-40988N |
IntActi | P10914, 32 interactors |
MINTi | P10914 |
STRINGi | 9606.ENSP00000245414 |
Miscellaneous databases
RNActi | P10914, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 92 – 165 | DisorderedSequence analysisAdd BLAST | 74 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 116 – 143 | Basic and acidic residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 144 – 162 | Polar residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QVVN, Eukaryota |
GeneTreei | ENSGT00940000156288 |
HOGENOMi | CLU_056386_1_0_1 |
InParanoidi | P10914 |
OMAi | PGLVWIN |
OrthoDBi | 734108at2759 |
PhylomeDBi | P10914 |
TreeFami | TF328512 |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11949, PTHR11949, 1 hit PTHR11949:SF3, PTHR11949:SF3, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit |
PIRSFi | PIRSF038196, IFN_RF1/2, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 25 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MPITRMRMRP WLEMQINSNQ IPGLIWINKE EMIFQIPWKH AAKHGWDINK
60 70 80 90 100
DACLFRSWAI HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN
110 120 130 140 150
KGSSAVRVYR MLPPLTKNQR KERKSKSSRD AKSKAKRKSC GDSSPDTFSD
160 170 180 190 200
GLSSSTLPDD HSSYTVPGYM QDLEVEQALT PALSPCAVSS TLPDWHIPVE
210 220 230 240 250
VVPDSTSDLY NFQVSPMPST SEATTDEDEE GKLPEDIMKL LEQSEWQPTN
260 270 280 290 300
VDGKGYLLNE PGVQPTSVYG DFSCKEEPEI DSPGGDIGLS LQRVFTDLKN
310 320
MDATWLDSLL TPVRLPSIQA IPCAP
Computationally mapped potential isoform sequencesi
There are 25 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketX5D3F6 | X5D3F6_HUMAN | Interferon regulatory factor | IRF1 IRF-1 | 284 | Annotation score: | ||
A0A7P0TAL6 | A0A7P0TAL6_HUMAN | Interferon regulatory factor | IRF1 | 263 | Annotation score: | ||
C9J9C5 | C9J9C5_HUMAN | Interferon regulatory factor 1 | IRF1 | 189 | Annotation score: | ||
C9JD95 | C9JD95_HUMAN | Interferon regulatory factor 1 | IRF1 | 192 | Annotation score: | ||
V9P921 | V9P921_HUMAN | Interferon regulatory factor 1 | IRF1 | 201 | Annotation score: | ||
A0A7P0T7Z4 | A0A7P0T7Z4_HUMAN | Interferon regulatory factor 1 | IRF1 | 205 | Annotation score: | ||
B4DQF0 | B4DQF0_HUMAN | Interferon regulatory factor 1 | IRF1 | 112 | Annotation score: | ||
A0A7P0T9W2 | A0A7P0T9W2_HUMAN | Interferon regulatory factor 1 | IRF1 | 141 | Annotation score: | ||
R4GNI0 | R4GNI0_HUMAN | Interferon regulatory factor 1 | IRF1 | 118 | Annotation score: | ||
F8WCM1 | F8WCM1_HUMAN | Interferon regulatory factor 1 | IRF1 | 51 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 5 | R → W no nucleotide entry (PubMed:2726461).Curated | 1 | |
Sequence conflicti | 5 | R → W no nucleotide entry (PubMed:3409321).Curated | 1 | |
Sequence conflicti | 34 – 35 | FQ → LE no nucleotide entry (PubMed:2726461).Curated | 2 | |
Sequence conflicti | 34 – 35 | FQ → LE no nucleotide entry (PubMed:3409321).Curated | 2 | |
Sequence conflicti | 220 | T → I no nucleotide entry (PubMed:2726461).Curated | 1 | |
Sequence conflicti | 220 | T → I no nucleotide entry (PubMed:3409321).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_065134 | 8 | M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. 1 PublicationCorresponds to variant dbSNP:rs121912469EnsemblClinVar. | 1 | |
Natural variantiVAR_065135 | 11 | W → R in GASC; the mutation abolishes DNA binding and transactivating activities. 1 PublicationCorresponds to variant dbSNP:rs121912470EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X14454 mRNA Translation: CAA32624.1 L05072 Genomic DNA Translation: AAA36043.1 BT019756 mRNA Translation: AAV38561.1 BC009483 mRNA Translation: AAH09483.1 |
CCDSi | CCDS4155.1 |
PIRi | B31595 I52998 |
RefSeqi | NP_002189.1, NM_002198.2 |
Genome annotation databases
Ensembli | ENST00000245414.9; ENSP00000245414.4; ENSG00000125347.15 ENST00000405885.6; ENSP00000384406.1; ENSG00000125347.15 |
GeneIDi | 3659 |
KEGGi | hsa:3659 |
MANE-Selecti | ENST00000245414.9; ENSP00000245414.4; NM_002198.3; NP_002189.1 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X14454 mRNA Translation: CAA32624.1 L05072 Genomic DNA Translation: AAA36043.1 BT019756 mRNA Translation: AAV38561.1 BC009483 mRNA Translation: AAH09483.1 |
CCDSi | CCDS4155.1 |
PIRi | B31595 I52998 |
RefSeqi | NP_002189.1, NM_002198.2 |
3D structure databases
AlphaFoldDBi | P10914 |
SMRi | P10914 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109867, 47 interactors |
DIPi | DIP-40988N |
IntActi | P10914, 32 interactors |
MINTi | P10914 |
STRINGi | 9606.ENSP00000245414 |
PTM databases
iPTMneti | P10914 |
PhosphoSitePlusi | P10914 |
Genetic variation databases
BioMutai | IRF1 |
DMDMi | 20178295 |
Proteomic databases
EPDi | P10914 |
jPOSTi | P10914 |
MassIVEi | P10914 |
PaxDbi | P10914 |
PeptideAtlasi | P10914 |
PRIDEi | P10914 |
ProteomicsDBi | 52676 |
Protocols and materials databases
Antibodypediai | 3180, 490 antibodies from 37 providers |
DNASUi | 3659 |
Genome annotation databases
Ensembli | ENST00000245414.9; ENSP00000245414.4; ENSG00000125347.15 ENST00000405885.6; ENSP00000384406.1; ENSG00000125347.15 |
GeneIDi | 3659 |
KEGGi | hsa:3659 |
MANE-Selecti | ENST00000245414.9; ENSP00000245414.4; NM_002198.3; NP_002189.1 |
Organism-specific databases
CTDi | 3659 |
DisGeNETi | 3659 |
GeneCardsi | IRF1 |
HGNCi | HGNC:6116, IRF1 |
HPAi | ENSG00000125347, Tissue enhanced (bone) |
MalaCardsi | IRF1 |
MIMi | 147575, gene 613659, phenotype |
neXtProti | NX_P10914 |
OpenTargetsi | ENSG00000125347 |
PharmGKBi | PA29915 |
VEuPathDBi | HostDB:ENSG00000125347 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QVVN, Eukaryota |
GeneTreei | ENSGT00940000156288 |
HOGENOMi | CLU_056386_1_0_1 |
InParanoidi | P10914 |
OMAi | PGLVWIN |
OrthoDBi | 734108at2759 |
PhylomeDBi | P10914 |
TreeFami | TF328512 |
Enzyme and pathway databases
PathwayCommonsi | P10914 |
Reactomei | R-HSA-5620971, Pyroptosis R-HSA-877300, Interferon gamma signaling R-HSA-909733, Interferon alpha/beta signaling R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SignaLinki | P10914 |
SIGNORi | P10914 |
Miscellaneous databases
BioGRID-ORCSi | 3659, 18 hits in 1098 CRISPR screens |
ChiTaRSi | IRF1, human |
GeneWikii | IRF1 |
GenomeRNAii | 3659 |
Pharosi | P10914, Tbio |
PROi | PR:P10914 |
RNActi | P10914, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125347, Expressed in granulocyte and 219 other tissues |
ExpressionAtlasi | P10914, baseline and differential |
Genevisiblei | P10914, HS |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11949, PTHR11949, 1 hit PTHR11949:SF3, PTHR11949:SF3, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit |
PIRSFi | PIRSF038196, IFN_RF1/2, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IRF1_HUMAN | |
Accessioni | P10914Primary (citable) accession number: P10914 Secondary accession number(s): Q96GG7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | April 16, 2002 | |
Last modified: | May 25, 2022 | |
This is version 195 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families