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Protein

Interferon regulatory factor 1

Gene

IRF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.12 Publications

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 Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • blood coagulation Source: Reactome
  • CD8-positive, alpha-beta T cell differentiation Source: Ensembl
  • cell cycle arrest Source: UniProtKB
  • cellular response to interferon-beta Source: BHF-UCL
  • cellular response to mechanical stimulus Source: UniProtKB
  • defense response to virus Source: UniProtKB
  • interferon-gamma-mediated signaling pathway Source: UniProtKB
  • negative regulation of cell 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 biosynthetic process Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • 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
  • transcription from RNA polymerase II promoter Source: ProtInc
  • type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

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

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125347-MONOMER.
ReactomeiR-HSA-877300. Interferon gamma signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiP10914.
SIGNORiP10914.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 1
Short name:
IRF-1
Gene namesi
Name:IRF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6116. IRF1.

Subcellular locationi

  • Nucleus
  • Cytoplasm

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

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Gastric cancer (GASC)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
See also OMIM:613659
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0651348M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. 1 PublicationCorresponds to variant rs121912469dbSNPEnsembl.1
Natural variantiVAR_06513511W → R in GASC; the mutation abolishes DNA binding and transactivating activities. 1 PublicationCorresponds to variant rs121912470dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78K → R: Loss of acetylation. Partial loss of DNA-binding and transcriptional activity. 1 Publication1
Mutagenesisi275K → 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 Publication1
Mutagenesisi299K → R: Large loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptotic activity; when associated with R-275. 1 Publication1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi3659.
MalaCardsiIRF1.
MIMi613659. phenotype.
OpenTargetsiENSG00000125347.
PharmGKBiPA29915.

Polymorphism and mutation databases

BioMutaiIRF1.
DMDMi20178295.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001545451 – 325Interferon regulatory factor 1Add BLAST325

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78N6-acetyllysine1 Publication1
Cross-linki275Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Cross-linki299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Post-translational modificationi

Phosphorylated by CK2 and this positively regulates its activity.1 Publication
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-275. Sumoylation is enhanced by PIAS3 (By similarity). Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites.By similarity1 Publication
Ubiquitinated. Appears to compete with sumoylation on C-terminal sites.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP10914.
PeptideAtlasiP10914.
PRIDEiP10914.

PTM databases

iPTMnetiP10914.
PhosphoSitePlusiP10914.

Expressioni

Inductioni

By viruses and interferon (IFN).

Gene expression databases

BgeeiENSG00000125347.
CleanExiHS_IRF1.
ExpressionAtlasiP10914. baseline and differential.
GenevisibleiP10914. HS.

Organism-specific databases

HPAiCAB011662.
HPA063131.

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with MYD88 and PIAS3 (By similarity). Interacts with EP300.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
E7P031293EBI-1055781,EBI-866453From a different organism.

Protein-protein interaction databases

BioGridi109867. 34 interactors.
DIPiDIP-40988N.
IntActiP10914. 4 interactors.
MINTiMINT-123145.
STRINGi9606.ENSP00000245414.

Structurei

3D structure databases

ProteinModelPortaliP10914.
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.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000037937.
HOVERGENiHBG003455.
InParanoidiP10914.
KOiK09444.
OMAiCKEEPEV.
OrthoDBiEOG091G0CB8.
PhylomeDBiP10914.
TreeFamiTF328512.

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.

P10914-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:325
Mass (Da):36,502
Last modified:April 16, 2002 - v2
Checksum:i2E06245A212D1541
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5R → W no nucleotide entry (PubMed:2726461).Curated1
Sequence conflicti5R → W no nucleotide entry (PubMed:3409321).Curated1
Sequence conflicti34 – 35FQ → LE no nucleotide entry (PubMed:2726461).Curated2
Sequence conflicti34 – 35FQ → LE no nucleotide entry (PubMed:3409321).Curated2
Sequence conflicti220T → I no nucleotide entry (PubMed:2726461).Curated1
Sequence conflicti220T → I no nucleotide entry (PubMed:3409321).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0651348M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. 1 PublicationCorresponds to variant rs121912469dbSNPEnsembl.1
Natural variantiVAR_06513511W → R in GASC; the mutation abolishes DNA binding and transactivating activities. 1 PublicationCorresponds to variant rs121912470dbSNPEnsembl.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.
CCDSiCCDS4155.1.
PIRiB31595.
I52998.
RefSeqiNP_002189.1. NM_002198.2.
UniGeneiHs.436061.

Genome annotation databases

EnsembliENST00000245414; ENSP00000245414; ENSG00000125347.
ENST00000405885; ENSP00000384406; ENSG00000125347.
GeneIDi3659.
KEGGihsa:3659.

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.
CCDSiCCDS4155.1.
PIRiB31595.
I52998.
RefSeqiNP_002189.1. NM_002198.2.
UniGeneiHs.436061.

3D structure databases

ProteinModelPortaliP10914.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109867. 34 interactors.
DIPiDIP-40988N.
IntActiP10914. 4 interactors.
MINTiMINT-123145.
STRINGi9606.ENSP00000245414.

PTM databases

iPTMnetiP10914.
PhosphoSitePlusiP10914.

Polymorphism and mutation databases

BioMutaiIRF1.
DMDMi20178295.

Proteomic databases

PaxDbiP10914.
PeptideAtlasiP10914.
PRIDEiP10914.

Protocols and materials databases

DNASUi3659.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245414; ENSP00000245414; ENSG00000125347.
ENST00000405885; ENSP00000384406; ENSG00000125347.
GeneIDi3659.
KEGGihsa:3659.

Organism-specific databases

CTDi3659.
DisGeNETi3659.
GeneCardsiIRF1.
H-InvDBHIX0200727.
HGNCiHGNC:6116. IRF1.
HPAiCAB011662.
HPA063131.
MalaCardsiIRF1.
MIMi147575. gene.
613659. phenotype.
neXtProtiNX_P10914.
OpenTargetsiENSG00000125347.
PharmGKBiPA29915.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IER3. Eukaryota.
ENOG4111HM7. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000037937.
HOVERGENiHBG003455.
InParanoidiP10914.
KOiK09444.
OMAiCKEEPEV.
OrthoDBiEOG091G0CB8.
PhylomeDBiP10914.
TreeFamiTF328512.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125347-MONOMER.
ReactomeiR-HSA-877300. Interferon gamma signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiP10914.
SIGNORiP10914.

Miscellaneous databases

GeneWikiiIRF1.
GenomeRNAii3659.
PROiP10914.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125347.
CleanExiHS_IRF1.
ExpressionAtlasiP10914. baseline and differential.
GenevisibleiP10914. HS.

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...

Entry informationi

Entry nameiIRF1_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

Deletion or rearrangement of IRF1 are found in preleukemic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.