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FLASH GENE

Symbol

EDNRB

contributors: shn/pgu - updated : 23-02-2010

HGNC name	endothelin receptor type B
HGNC id	3180

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ABCD albinism, black lock, cell migration disorder of the neurocytes of the gut and deafness HSCR2 Hirschsprung disease 2 WS4A Waardenburg syndrome, type 4A
Location	13q22.3      Physical location : 78.469.615 - 78.549.664
Synonym name	endothelin receptor non- selective type B
Synonym symbol(s)	ETBR, ETRB, HSCR, ABCDS, ETB, HSCR

DNA

TYPE	functioning gene
STRUCTURE	80.05 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	cytosine-phosphate-guanine/HTF
text structure	promoter with site specific methylation pattern

MAPPING

cloned

Y

linked

status

confirmed

Map	cen - D13S782 - D13S1306 - EDNRB - D13S1281 - D13S160 - qter

RNA

TRANSCRIPTS	type	messenger

text	a binding sites for SOX10 and a SRY-related transcription factor associated with HSCR in the EDNRB ENS enhancer (PMID: 15170213)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001122659 (transcript variant 3) 7 splicing 4320 NP_001116131 - 442 retinal arterioles, neural retinal tissue 2009 19151386 NM_003991 (transcript variant 2) 7 splicing 2544 NP_003982 - 436 retinal arterioles, neural retinal tissue 2009 19151386 NM_000115 (transcript variant 1) 7 splicing 4296 NP_000106 - 442 retinal arterioles, neural retinal tissue 2009 19151386

EXPRESSION

Type

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       lowly Endocrine adrenal gland       lowly   thyroid       lowly Nervous brain         Homo sapiens Reproductive female system uterus     highly   female system placenta     highly Urinary kidney renal medulla     moderately Visual eye retina     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane domains

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to Ednrb, Mus musculus
	ortholog to EDNRB, Pan troglodytes
	ortholog to Ednrb, Rattus norvegicus

Homologene

FAMILY

G protein coupled receptor superfamily

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	interaction of EDN3 with the endothelin-B receptor is essential in the development of neural crest-derived cell lineages
	plays an essential role in the normal development of two neural crest-derived cell lineages, epidermal melanocytes and enteric neurons in humans, mice and rats
	required for the development and migration of melanocytes and enteric neuroblasts
	required during a restricted period of neural crest development between embryonic days 10 and 12.5
	mediates autoinduction of endothelin-1 (ET-1)
	in human GnRH-secreting cells ETB induces DNA synthesis and mitogen-activated protein kinase p44ERK1 expression
	ET(B) receptor activation after skin injury induces the release of beta-endorphin from keratinocytes and the activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs) linked to opioid receptors on nociceptors
	may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions
	endothelins, acting through EDNRA and/or EDNRB receptors, may play an important role in mediating pain resulting from activation of most trigeminal nerve branches (

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

EDN2/EDNRB are a regenerative pathway, suggesting that EDNRB agonists represent a promising therapeutic approach to promote myelin regeneration

a component

components of the endothelin system, are EDN1, EDNRB and ECE1

INTERACTION

DNA

RNA

small molecule

protein	endothelin-3, EDN3
	nitric oxide synthase 3, NOS3
	guanine nucleotide binding protein (G protein) alpha 13, GNA13
	caveolin-1, CAV1
	SRY (sex determining region Y)-box 10, SOX10
	interacting with COPS5 (regulates degradation rate of EDNRA and EDNRB by modulating ubiquitination of these receptors, leading to changes in EDNRA and EDNRB levels)
	EDNRB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by EDN1

cell & other

REGULATION

Other	cell surface expression of the receptor is regulated by N-terminal proteolysis
	Spatio-temporally by SOX10 in enteric nervous system

ASSOCIATED DISORDERS

corresponding disease(s)

HSCR2 , WS4A , ABCD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       loss of function hypermethylated in cancer prostate, bladder, nasopharyngeal carcinoma(loss of function) tumoral       gain of function in clear cell renal carcinomas with good outcome constitutional       gain of function of EDNRB and AGTR1 in vascular smooth muscle cells in ischemic heart disease

Susceptibility

could be associated with glaucomatous pathologic abnormalities associated with Lethal white foal syndrome (LWFS)

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	spotting lethal (sl) rats with a natural null mutation of the EDNRB gene exhibit aganglionic megacolon associated with white coat color
	null allele of Ednrb results in homozygous mice that are predominantly white and die as juveniles from megacolon
	endothelin-B receptor-deficient rats die shortly after birth due to congenital distal intestinal aganglionosis
	dopamine--hydroxylase (DBH)-ET(B) transgene/ET(B)(sl/sl) rats are hypertensive because they lack the normal tonic inhibition of the renal epithelial sodium channel
	mouse with spontaneous mutation of the endothelin-B receptor gene display Waardenburg syndrome type 4
	ET-B receptor-deficient rats display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an ET-mediated increase in lung VEGF content
	EdnrB/Sox10 double mutants display more severe aganglionosis
	Sox10-EdnrB interactions can influence development of the enteric nervous system in mouse models and could contribute to the epistatic network producing variation between patients with aganglionosis