Description: Homo sapiens interferon regulatory factor 1 (IRF1), mRNA. RefSeq Summary (NM_002198): The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]. Transcript (Including UTRs) Position: hg19 chr5:131,817,301-131,826,465 Size: 9,165 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr5:131,819,643-131,825,170 Size: 5,528 Coding Exon Count: 9
ID:IRF1_HUMAN DESCRIPTION: RecName: Full=Interferon regulatory factor 1; Short=IRF-1; 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. ENZYME REGULATION: Activated by MYD88 (By similarity). SUBUNIT: Monomer. Homodimer. Interacts with MYD88 and PIAS3 (By similarity). Interacts with EP300. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88- associated IRF1. INDUCTION: By viruses and interferon (IFN). PTM: Phosphorylated by CK2 and this positively regulates its activity. 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-275. Sumoylation is enhanced by PIAS3 (By similarity). Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites. PTM: Ubiquitinated. Appears to compete with sumoylation on C- terminal sites. DISEASE: Defects in IRF1 are a cause of gastric cancer (GASC) [MIM:613659]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is 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. MISCELLANEOUS: Deletion or rearrangement of IRF1 are found in preleukemic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). SIMILARITY: Belongs to the IRF family. SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/IRF1ID40990ch5q23.html";
asthma Nakao, F. et al. 2001, Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma, The Journal of allergy and clinical immunology. 2001 Mar;107(3):499-504.
[PubMed 11240951]
These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children.
asthma Wang, T. N. et al. 2006, Association of interferon-gamma and interferon regulatory factor 1 polymorphisms with asthma in a family-based association study in Taiwan, Clin Exp Allergy 2006 36(9) 1147-52.
[PubMed 16961714]
These findings provide strong evidence of which IFN-gamma CA repeat and IRF-1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.
C-Reactive Protein Abbas Dehghan et al. Circulation 2011, Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels., Circulation.
[PubMed 21300955]
We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P10914
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding
Biological Process: GO:0002376 immune system process GO:0002819 regulation of adaptive immune response GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated 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: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 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:0050776 regulation of immune response 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
US Server
