DegronMD - P10914(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). 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, DDX58/RIG-I, TNFSF10/TRAIL, ZBP1, 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; 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). {ECO:0000269|PubMed:15226432, ECO:0000269|PubMed:15509808, ECO:0000269|PubMed:17516545, ECO:0000269|PubMed:17942705, ECO:0000269|PubMed:18084608, ECO:0000269|PubMed:18497060, ECO:0000269|PubMed:18641303, ECO:0000269|PubMed:19404407, ECO:0000269|PubMed:19851330, ECO:0000269|PubMed:21389130, ECO:0000269|PubMed:22200613, ECO:0000269|PubMed:22367195, ECO:0000269|PubMed:32385160, ECO:0000303|PubMed:11244049, ECO:0000303|PubMed:11846971, ECO:0000303|PubMed:11846974, ECO:0000303|PubMed:16932750, ECO:0000303|PubMed:20049431}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E200D	TCGA-AB-2940	LAML	TCGA	AVSST	DEG_SPOP_SBC_1	187:191	Mutation rewiring degron network	0.0833
p.E200D	TCGA-AB-2940	LAML	TCGA	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.E200D	DO21773	LAML	ICGC	AVSST	DEG_SPOP_SBC_1	187:191	Mutation rewiring degron network	0.0833
p.E200D	DO21773	LAML	ICGC	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.D194V	TCGA-BR-7704	STAD	TCGA	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation rewiring degron network	0.0556
p.D194V	TCGA-BR-7704	STAD	TCGA	AVSST	DEG_SPOP_SBC_1	187:191	Mutation rewiring degron network	0.25
p.D194V	TCGA-BR-7704	STAD	TCGA	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.0833
p.D194V	DO38360	STAD	ICGC	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation rewiring degron network	0.0556
p.D194V	DO38360	STAD	ICGC	AVSST	DEG_SPOP_SBC_1	187:191	Mutation rewiring degron network	0.25
p.D194V	DO38360	STAD	ICGC	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.0833
p.L209V	TCGA-CF-A8HY	BLCA	TCGA	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.2778
p.L209V	DO218998	BLCA	ICGC	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.2778
p.S184L	TCGA-FI-A2D5	UCEC	TCGA	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation altering degron motif	0.8778
p.S184L	DO41331	UCEC	ICGC	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation altering degron motif	0.8778
p.QD171QN	DO220906	MELA	ICGC	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation rewiring degron network	0
p.D172N	DO220906	MELA	ICGC	LTPALS	DEG_SCF_FBW7_1	179:184	Mutation rewiring degron network	0.1389
p.Y210F	SIDM00737	Non-Small Cell Lung Carcinoma	GDSC	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.Y210F	ACH-000904	Lung Cancer	CCLE	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.Y210F	ACH-001362	Lung Cancer	CCLE	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.Y210F	NCI-H1770	lung	COSMIC	PDSTS	DEG_SPOP_SBC_1	203:207	Mutation rewiring degron network	0.25
p.G187R	HCT-15	large intestine	COSMIC	AVSST	DEG_SPOP_SBC_1	187:191	Mutation altering degron motif	0.7568

DegronMD: protein-targeted degradation, mutation and drug response to degrons

IRF1

UniProt ID: P10914

Entrez ID: 3659

Protein name: Interferon regulatory factor 1 (IRF-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IRF1 in