DegronMD - Q14653(IRF3)

FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:25636800, PubMed:27302953). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.V261A	TCGA-A6-6780	COAD	TCGA	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.5825
p.L268M	TCGA-B5-A11H	UCEC	TCGA	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.5999
p.R276W	TCGA-BR-8487	STAD	TCGA	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.1389
p.P170S	TCGA-EY-A1GQ	UCEC	TCGA	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.1111
p.P170S	ACH-001346	Head and Neck Cancer	CCLE	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.1111
p.T253K	TCGA-GU-A767	BLCA	TCGA	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation blocking phosphorylation signal	0.5556
p.Y265S	DO51872	BLCA	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.712
p.G171E	DO2401	BRCA	ICGC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.0833
p.E271D	DO8858	COAD	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.2778
p.E151K	DO228927	COCA	ICGC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation altering degron motif	0.7022
p.D260E	DO50403	ESAD	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.3056
p.D260E	DO233726	GACA	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.3056
p.Q267K	DO229018	LICA	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.6944
p.H142N	DO229009	LICA	ICGC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.1389
p.F275L	DO23535	LIRI	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.1667
p.E271Q	DO232855	NACA	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.2778
p.P254Q	DO37896	SKCM	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.1389
p.F275Y	DO229248	THCA	ICGC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.1667
p.V149M	DO223286	UCEC	ICGC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation altering degron motif	0.7208
p.R172W	SIDM02021	Esophageal Carcinoma	GDSC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.0556
p.R276Q	SIDM01090	Colorectal Carcinoma	GDSC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.1389
p.P164S	SIDM00663	Melanoma	GDSC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.2778
p.P164S	ACH-000814	Skin Cancer	CCLE	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.2778
p.Q169R	SIDM00587	Biliary Tract Carcinoma	GDSC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.1389
p.Q169R	ACH-000778	Head and Neck Cancer	CCLE	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.1389
p.R262G	ACH-000982	Colon/Colorectal Cancer	CCLE	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.7568
p.R262G	ACH-001345	Colon/Colorectal Cancer	CCLE	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.7568
p.R262G	GP5d	large intestine	COSMIC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.7568
p.G278R	ACH-001172	Brain Cancer	CCLE	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation rewiring degron network	0.0833
p.A161P	ACH-002647	Gastric Cancer	CCLE	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation altering degron motif	0.6392
p.E164K	VAL	haematopoietic and lymphoid tissue	COSMIC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.2778
p.G172D	NCI-H2085	lung	COSMIC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.0556
p.E153K	NCI-H1355	lung	COSMIC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation altering degron motif	0.7022
p.R253Q	SN12C	kidney	COSMIC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation blocking phosphorylation signal	0.5556
p.R253Q	MCC13	skin	COSMIC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation blocking phosphorylation signal	0.5556
p.A148V	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	LAPLPDPGPPSLAV	DEG_ODPH_VHL_1	149:162	Mutation rewiring degron network	0.3056
p.T263A	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	VRHVLSCLG	DEG_APCC_DBOX_1	261:269	Mutation altering degron motif	0.7139

Kaplan plot for IRF3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IRF3

UniProt ID: Q14653

Entrez ID: 3661

Protein name: Interferon regulatory factor 3 (IRF-3)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IRF3 in