Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

AHR

contributors: mct/npt/pgu - updated : 19-06-2018

HGNC name	aryl hydrocarbon receptor
HGNC id	348

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	RP85 retinitis pigmentosa 85
Location	7p21.1      Physical location : 17.338.275 - 17.385.775
Synonym name	aromatic hydrocarbon receptor
	AH-receptor
Synonym symbol(s)	bHLHe76
EC.number	1.14.14.1

DNA

TYPE	functioning gene
STRUCTURE	47.47 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	involvement of Sp1 binding site in AHR gene regulation.

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001621 12 - 5827 96.1 848 - 2009 19592671

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Homo sapiens Lymphoid/Immune thymus       highly Nervous nerve       highly Reproductive male system male genital tract epididymis   highly Homo sapiens Skin/Tegument skin       highly Homo sapiens Urinary bladder       highly Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining retinal pigment epithelium (RPE)     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	basic helix-loop-helix (bHLH)
	a stretch of approximately 300 AA, termed the PAS (Per - ARNT - Sim) domain

HOMOLOGY

Homologene

FAMILY

basic helix-loop-helix/PER-ARNT-SIM family

CATEGORY

receptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	retained in cytoplasm in resting state in association with HSP90, and with AIP (AH receptor associated protein 9)
	released after exposure to xenobiotics
	ligand-activated transcription factor, mediating xenobiotic signaling to enhance the expression of target genes, including drug-metabolizing cytochrome P450s
	involved in xenobiotic induced regulation of the UGT1A3
	having a proproliferative, antiapoptotic function that likely plays a role in tumor progression
	mediates most, if not all, of the many toxicological effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo- p-dioxin [(TCDD) or dioxin
	its activation inhibits differentiation of human monocytes and Langerhans dendritic cells
	plays an essential role in the toxic response to environmental pollutants
	modulates expression of human MT2A via the glucocorticoid response element and protein-protein interactions with glucocorticoid receptor (GR)
	HSP90AA1 was co-localized with AHR after the nuclear translocation
	in osteoclast lineage cells are a negative regulator of bone mass
	regulatory role of AHR in not only adaptive but also innate lymphocytes including recently discovered innate lymphoid cells
	role of AHR signaling in the gene regulation of epidermal barrier proteins
	modulates the degradation of proteins involved in cell cycle control, consistent with previous reports demonstrating an essential role of the AHR in cell cycle regulation
	plays an important role in the pathogenesis of retinal diseases including age-related macular degeneration
	untimely expression of the Ahr gene needs to be repressed to maintain ES cell mitotic progression and prevent premature loss of pluripotency
	functional AHR expression is critical for skin barrier integrity and that AHR represents a molecular target for the development of therapeutic approaches for skin barrier diseases, including by dietary intervention
	is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut
	protective role of the AHR against carcinogenesis and oxidative stress because causal role of the AHR in the antioxidant response
	is required for optimal B-cell proliferation
	recognizes xenobiotics as well as natural compounds such as tryptophan metabolites, dietary components and microbiota-derived factors, and it is important for maintenance of homeostasis at mucosal surfaces
	AHR-induced inhibition that influences circadian rhythm amplitude
	ligand-activated transcription factor that is known as a mediator of toxic responses
	plays an important physiological role in hematopoiesis
	regulates early human hemato-lymphoid cell development and may be targeted to enhance production of specific cell populations derived from human pluripotent stem cells
	ligand-activated transcription factor whose activity is regulated by small molecules provided by the diet, the commensal flora, environmental pollutants and the metabolism
	potential role for the larger AHR pathway in melanoma risk

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	dimerizing with ARNT for inhibition of estrogen action and translocated to the nucleus interacting with pRB1 to induce G1 arrest
	AHR-ARNT dimer specifically associates with the enhancer regions of dioxin-responsive genes, leading to their increased transcription

INTERACTION

DNA

RNA

small molecule

protein	participated in SNAI2 induction, which, in turn, regulates cellular physiology including cell adhesion and migration
	interacting with NCOA4 (NCOA4-facilitation of AHR activity was abolished by overexpression of AR, suggesting a potential competition of AHR and AR for NCOA4)
	AHR paradoxically regulates IGFBP1 and LPL expressions in the liver
	binds to E2F1 and inhibits E2F1-induced apoptosis
	bound to MAF and promoted transactivation of the IL10 and IL21 promoters, which resulted in the generation of Type 1 regulatory T cells (TR1)
	expression of AIP in hepatocytes is essential to maintain high levels of functional cytosolic AHR protein in the mammalian liver, and expression of the AIP protein is essential for dioxin-induced hepatotoxicity
	VAV3, an activator of Rho/Rac GTPases, is an AHR transcriptional target in embryonic fibroblasts
	CCNG2 is an AHR target gene
	FOXA1, but not ESR1, is essential for AHR-dependent regulation of CCNG2, assigning a role for FOXA1 in AHR action
	STC2 gene expression is refractory to classic exogenous AHR agonists, but responds to cellular stress in an AHR-dependent mechanism consistent with a process promoting cell survival
	AHR was recruited to the glucocorticoid response element in the MT2A promoter
	LHCGR signaling in regulating the AHR message involves protein kinase A pathway and is attributable to decreased transcription rate
	critical link between AHR and IDO1 in the development of regulatory T cells and Th17 cells, which are key factors in a variety of human autoimmune diseases
	biphasic role of NCOA2 between AHR and hypoxic conditions, thus providing a novel mechanism underlying the cross talk between AHR and hypoxia that affects disease development and progression
	transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis
	DLX3 is a positive regulator of the aryl hydrocarbon receptor
	MAGED1 binds and positively regulates the transcriptional activity of family members SIM1, SIM2, NPAS4 and ARNT2, but does not interact with AHR, HIF1A and ARNT
	ARNT plays an important role in the modulation of the dual functions of the AHR
	cross-talk between NR1I2 and AHR plays a role in the regulation of CYP3A4 gene expression
	upon activation, AHR translocates to the nucleus and forms a complex with aryl hydrocarbon receptor nuclear translocator (ARNT), which binds to a DNA recognition sequence and initiates gene transcription

cell & other

REGULATION

activated by

is activated in response to a number of environmental factors, including dioxins and UVR

induced by

DLX3 (induces AHR promoter activity by binding to a regulatory region that resides ~5.5 kb upstream of the transcriptional start site)

repressed by

EGF (repression of aryl hydrocarbon receptor transcriptional activity by epidermal growth factor)

Other

regulated by NFE2L2 (directly modulates AHR signaling, highlighting bidirectional interactions of these pathways)

ASSOCIATED DISORDERS

corresponding disease(s)

RP85

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   of AHR mRNA and protein expression is associated with the pathogenesis of unexplained miscarriage constitutional       loss of function alters macrophage polarization when compared to WT macrophage

Susceptibility

to primary melanoma

Variant & Polymorphism other	rs117132860, located within a melanocyte enhancer and displays allele-specific cis-regulatory activity, and is associated with primary melanoma

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   manipulating AHR signaling could be beneficial in the resolution of excessive inflammatory responses cancer skin   importance of AHR antagonists as potential sensitizers for melanoma target therapy

ANIMAL & CELL MODELS

presence of sympathoexcitation and new cardiorespiratory defects in Ahr(-/-) mice