DegronMD - P35869(AHR)

FUNCTION: Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:30373764, PubMed:23275542, PubMed:7961644, PubMed:32818467). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:30373764, PubMed:23275542, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32866000, PubMed:32818467). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. 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.S440Y	TCGA-06-5416	GBM	TCGA	ATTST	DEG_SPOP_SBC_1	441:445	Mutation blocking phosphorylation signal	0.75
p.S440Y	DO10880	GBM	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation blocking phosphorylation signal	0.75
p.L451F	TCGA-33-A4WN	LUSC	TCGA	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.1667
p.L451F	DO219121	LUSC	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.1667
p.E725K	TCGA-33-AASI	LUSC	TCGA	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.1944
p.E725K	DO219129	LUSC	ICGC	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.1944
p.D737Y	TCGA-AG-A002	READ	TCGA	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.25
p.G437V	TCGA-C4-A0F0	BLCA	TCGA	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.2222
p.G437V	DO520	BLCA	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.2222
p.S733F	TCGA-EB-A1NK	SKCM	TCGA	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation altering degron motif	0.7982
p.S733F	DO228650	LICA	ICGC	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation altering degron motif	0.7982
p.S733F	DO37695	SKCM	ICGC	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation altering degron motif	0.7982
p.T445A	TCGA-F5-6814	READ	TCGA	ATTST	DEG_SPOP_SBC_1	441:445	Mutation altering degron motif	0.7139
p.T445A	DO36556	READ	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation altering degron motif	0.7139
p.G437A	TCGA-XF-AAN2	BLCA	TCGA	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.2222
p.G437A	DO219052	BLCA	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.2222
p.P726S	DO52511	EOPC	ICGC	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.2222
p.Y729H	DO234219	ESAD	ICGC	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.3056
p.N484K	DO45207	LIRI	ICGC	PASST	DEG_SPOP_SBC_1	471:475	Mutation rewiring degron network	0.0833
p.S477N	DO222527	MELA	ICGC	PASST	DEG_SPOP_SBC_1	471:475	Mutation rewiring degron network	0.2778
p.K448N	DO232761	PBCA	ICGC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation substituting flanking lysine	0.3611
p.S455F	SIDM00545	Melanoma	GDSC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.0556
p.S455F	ACH-000987	Skin Cancer	CCLE	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.0556
p.S455F	Mewo	skin	COSMIC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation rewiring degron network	0.0556
p.F485L	SIDM00875	Breast Carcinoma	GDSC	PASST	DEG_SPOP_SBC_1	471:475	Mutation rewiring degron network	0.0556
p.P471A	SIDM00006	Other Solid Cancers	GDSC	PASST	DEG_SPOP_SBC_1	471:475	Mutation altering degron motif	0.6392
p.P471A	ACH-001552	Skin Cancer	CCLE	PASST	DEG_SPOP_SBC_1	471:475	Mutation altering degron motif	0.6392
p.P471A	MCC26	skin	COSMIC	PASST	DEG_SPOP_SBC_1	471:475	Mutation altering degron motif	0.6392
p.K432T	SIDM01588	Endometrial Carcinoma	GDSC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation substituting flanking lysine	0.1944
p.K432T	ACH-000993	Endometrial/Uterine Cancer	CCLE	ATTST	DEG_SPOP_SBC_1	441:445	Mutation substituting flanking lysine	0.1944
p.Y470C	SIDM01442	Glioma	GDSC	PASST	DEG_SPOP_SBC_1	471:475	Mutation rewiring degron network	0.3056
p.F485S	ACH-000937	Leukemia	CCLE	PASST	DEG_SPOP_SBC_1	471:475	Mutation rewiring degron network	0.0556
p.V739F	ACH-001674	Neuroblastoma	CCLE	PTTSS	DEG_SPOP_SBC_1	730:734	Mutation rewiring degron network	0.1944
p.S440F	Mewo	skin	COSMIC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation blocking phosphorylation signal	0.75
p.E473K	SNU-81	large intestine	COSMIC	PASST	DEG_SPOP_SBC_1	471:475	Mutation altering degron motif	0.7022
p.L441F	DBTRG-05MG	central nervous system	COSMIC	ATTST	DEG_SPOP_SBC_1	441:445	Mutation altering degron motif	0.6981

Kaplan plot for AHR in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

AHR

UniProt ID: P35869

Entrez ID: 196

Protein name: Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for AHR in