InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IRF1

Summary

InnateDB Protein

IDBP-42129.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

IRF1

Protein Name

interferon regulatory factor 1

Synonyms

IRF-1; MAR;

Species

Homo sapiens

Ensembl Protein

ENSP00000245414

InnateDB Gene

IDBG-42125 (IRF1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15226432, ECO:0000269PubMed:15509808, ECO:0000269PubMed:17516545, ECO:0000269PubMed:17942705, ECO:0000269PubMed:18084608, ECO:0000269PubMed:18497060, ECO:0000269PubMed:18641303, ECO:0000269PubMed:19404407, ECO:0000269PubMed:19851330, ECO:0000269PubMed:21389130, ECO:0000269PubMed:22200613, ECO:0000269PubMed:22367195}.

Subcellular Localization

Nucleus. Cytoplasm. Note=MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88- associated IRF1.

Disease Associations

Gastric cancer (GASC) [MIM:613659]: A 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. {ECO:0000269PubMed:10395927, ECO:0000269PubMed:9679752}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 206 experimentally validated interaction(s) in this database.
They are also associated with 45 interaction(s) predicted by orthology.

Experimentally validated
Total	206 [view]
Protein-Protein	70 [view]
Protein-DNA	135 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	45 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0002819	regulation of adaptive immune response
GO:0006366	transcription from RNA polymerase II promoter
GO:0006915	apoptotic process
GO:0007050	cell cycle arrest
GO:0007596	blood coagulation
GO:0008285	negative regulation of cell proliferation
GO:0010468	regulation of gene expression
GO:0019221	cytokine-mediated signaling pathway
GO:0032481	positive regulation of type I interferon production
GO:0032728	positive regulation of interferon-beta production
GO:0034124	regulation of MyD88-dependent toll-like receptor signaling pathway
GO:0035458	cellular response to interferon-beta
GO:0043374	CD8-positive, alpha-beta T cell differentiation
GO:0045084	positive regulation of interleukin-12 biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045088	regulation of innate immune response
GO:0045590	negative regulation of regulatory T cell differentiation
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051607	defense response to virus
GO:0051726	regulation of cell cycle
GO:0060333	interferon-gamma-mediated signaling pathway
GO:0060337	type I interferon signaling pathway
GO:0071260	cellular response to mechanical stimulus
GO:2000564	regulation of CD8-positive, alpha-beta T cell proliferation