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Protein

Interferon regulatory factor 1

Gene

IRF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

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 proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA 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 by RNA polymerase II 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 by RNA polymerase II Source: ProtInc
  • type I interferon signaling pathway Source: Reactome

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processAntiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000125347.13
HGNCiHGNC:6116 IRF1
MIMi147575 gene
neXtProtiNX_P10914

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs121912469EnsemblClinVar.1
Natural variantiVAR_06513511W → R in GASC; the mutation abolishes DNA binding and transactivating activities. 1 PublicationCorresponds to variant dbSNP:rs121912470EnsemblClinVar.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

EPDiP10914
PaxDbiP10914
PeptideAtlasiP10914
PRIDEiP10914
ProteomicsDBi52676

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

Show more details

Protein-protein interaction databases

BioGridi109867, 34 interactors
DIPiDIP-40988N
IntActiP10914, 6 interactors
MINTiP10914
STRINGi9606.ENSP00000245414

Structurei

3D structure databases

ProteinModelPortaliP10914
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

CDDicd00103 IRF, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView 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
PANTHERiPTHR11949 PTHR11949, 1 hit
PTHR11949:SF3 PTHR11949:SF3, 1 hit
PfamiView protein in Pfam
PF00605 IRF, 1 hit
PIRSFiPIRSF038196 IFN_RF1/2, 1 hit
PRINTSiPR00267 INTFRNREGFCT
SMARTiView protein in SMART
SM00348 IRF, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00601 IRF_1, 1 hit
PS51507 IRF_2, 1 hit

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 dbSNP:rs121912469EnsemblClinVar.1
Natural variantiVAR_06513511W → 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
CCDSiCCDS4155.1
PIRiB31595
I52998
RefSeqiNP_002189.1, NM_002198.2
UniGeneiHs.436061

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiIRF1_HUMAN
AccessioniPrimary (citable) accession number: P10914
Secondary accession number(s): Q96GG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 16, 2002
Last modified: July 18, 2018
This is version 173 of the entry and version 2 of the sequence. See 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

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

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