JavaScript is disabled in your browser. Please enable JavaScript to view this website.

IRF1

Function

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). Has an essentail role in IFNG-dependent immunity to mycobacteria (PubMed:36736301). 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, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as GBP2, GBP5 and 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).

Involvement in disease

Gastric cancer

GASC

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Immunodeficiency 117

IMD117

An autosomal recessive immunologic disorder characterized by increased susceptibility to disseminated mycobacterial infection apparent in early childhood, after exposure to weakly virulent mycobacteria. Affected individuals develop mycobacterial disease after BCG (bacille Calmette-Guerin) vaccination. Immunologic workup shows impaired development of myeloid and lymphoid cell subsets that secrete and respond to gamma-interferon.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated by CK2 and this positively regulates its activity.

Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation (PubMed:17942705). Sumoylated by UBE2I/UBC9 and SUMO1 (By similarity). Inactivates the tumor suppressor activity (PubMed:17942705). Elevated levels in tumor cells (PubMed:17942705). Major site is Lys-275 (PubMed:17942705). Sumoylation is enhanced by PIAS3 (By similarity). Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (PubMed:17942705).

Ubiquitinated in a SPOP-depedent manner (PubMed:37622993). Appears to compete with sumoylation on C-terminal sites.

Sequence Similarities

Belongs to the IRF family.

Cellular localization

Alternative names

Interferon regulatory factor 1, IRF-1, IRF1

swissprot:P10914 omim:147575 entrezGene:3659

Other research areas