Endothelin B receptor

EDNRB
Identifiers
Aliases	EDNRB, ABCDS, ET-B, ET-BR, ETB, ETBR, ETRB, HSCR, HSCR2, WS4A, ETB1, endothelin receptor type B
External IDs	OMIM: 131244 MGI: 102720 HomoloGene: 89 GeneCards: EDNRB
Gene location (Human)
Chr.	Chromosome 13 (human)[1]
End	77,975,529 bp[1]
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)[2]
End	103,844,402 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• endothelin receptor activity; • G-protein coupled receptor activity; • signal transducer activity; • peptide hormone binding; • GO:0001948 protein binding; • type 1 angiotensin receptor binding;
Cellular component	• integral component of membrane; • not the membrane; • membrane; • integral component of plasma membrane; • membrane raft; • cell membrane;
Biological process	• enteric smooth muscle cell differentiation; • negative regulation of adenylate cyclase activity; • positive regulation of protein phosphorylation; • peripheral nervous system development; • negative regulation of cellular protein metabolic process; • positive regulation of renal sodium excretion; • response to organic cyclic compound; • regulation of sensory perception of pain; • positive regulation of urine volume; • vasoconstriction; • positive regulation of cytosolic calcium ion concentration; • epithelial fluid transport; • aging; • vasodilation; • negative regulation of apoptotic process; • negative regulation of transcription from RNA polymerase II promoter; • cGMP-mediated signaling; • regulation of fever generation; • nervous system development; • regulation of blood pressure; • phospholipase C-activating G-protein coupled receptor signaling pathway; • cell surface receptor signaling pathway; • enteric nervous system development; • vein smooth muscle contraction; • response to lipopolysaccharide; • macrophage chemotaxis; • response to pain; • neural crest cell migration; • positive regulation of cell proliferation; • posterior midgut development; • developmental pigmentation; • pigmentation; • nociception; • negative regulation of neuron maturation; • positive regulation of penile erection; • regulation of epithelial cell proliferation; • melanocyte differentiation; • cellular response to lipopolysaccharide; • regulation of pH; • signal transduction; • endothelin receptor signaling pathway; • calcium-mediated signaling; • G-protein coupled receptor signaling pathway; • response to endothelin;
	Sources:Amigo / QuickGO
Orthologs
	1910
	13618
	ENSG00000136160
	ENSMUSG00000022122
	P24530
	P48302
	NM_000115; NM_001122659; NM_001201397; NM_003991
	NM_001136061; NM_001276296; NM_007904
	NP_000106; NP_001116131; NP_001188326; NP_003982
	NP_001129533; NP_001263225; NP_031930
	Wikidata
View/Edit Human	View/Edit Mouse

Endothelin receptor type B, also known as ET_B is a protein that in humans is encoded by the EDNRB gene.[5]

Function

Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET₁, ET₂, and ET₃. A splice variant, named SVR, has been described; the sequence of the ETB-SVR receptor is identical to ETRB except for the intracellular C-terminal domain. While both splice variants bind ET₁, they exhibit different responses upon binding which suggests that they may be functionally distinct.[6]

Regulation

In melanocytic cells the EDNRB gene is regulated by the microphthalmia-associated transcription factor. Mutations in either gene are links to Waardenburg syndrome.[7][8]

Clinical significance

The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.[9]

Animals

In horses, a mutation in the middle of the EDNRB gene, Ile118Lys, when homozygous, causes Lethal White Syndrome.[10] In this mutation, a mismatch in the DNA replication causes lysine to be made instead of isoleucine.[10] The resulting EDNRB protein is unable to fulfill its role in the development of the embryo, limiting the migration of the melanocyte and enteric neuron precursors. A single copy of the EDNRB mutation, the heterozygous state, produces an identifiable and completely benign spotted coat color called frame overo.[11]

Interactions

Endothelin receptor type B has been shown to interact with Caveolin 1.[12]

Ligands

Agonists

IRL-1620[13]

Antagonists

A-192,621
BQ-788
Bosentan (unselective ET_A / ET_B antagonist)

References

GRCh38: Ensembl release 89: ENSG00000136160 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000022122 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Cyr C, Huebner K, Druck T, Kris R (Nov 1991). "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochemical and Biophysical Research Communications. 181 (1): 184–90. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806.
"Entrez Gene: EDNRB endothelin receptor type B".
Sato-Jin K, Nishimura EK, Akasaka E, Huber W, Nakano H, Miller A, Du J, Wu M, Hanada K, Sawamura D, Fisher DE, Imokawa G (Apr 2008). "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders". FASEB Journal. 22 (4): 1155–68. doi:10.1096/fj.07-9080com. PMID 18039926.
Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
Tanaka H, Moroi K, Iwai J, Takahashi H, Ohnuma N, Hori S, Takimoto M, Nishiyama M, Masaki T, Yanagisawa M, Sekiya S, Kimura S (May 1998). "Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization". The Journal of Biological Chemistry. 273 (18): 11378–83. doi:10.1074/jbc.273.18.11378. PMID 9556633.
Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D (Jun 1998). "A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease". Human Molecular Genetics. 7 (6): 1047–52. doi:10.1093/hmg/7.6.1047. PMID 9580670. AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous. -->
Metallinos DL, Bowling AT, Rine J (1998). "A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease". Mamm. Genome. 9 (6): 426–31. doi:10.1007/s003359900790. PMID 9585428.
Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (Apr 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry / FEBS. 270 (8): 1816–27. doi:10.1046/j.1432-1033.2003.03544.x. PMID 12694195.
Maguire JJ, Davenport AP (Dec 2014). "Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12". British Journal of Pharmacology. 171 (24): 5555–72. doi:10.1111/bph.12874. PMC 4290702. PMID 25131455.

External links

"Endothelin Receptors: ET_B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136160 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022122 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1659806-5] Cyr C, Huebner K, Druck T, Kris R (Nov 1991). "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochemical and Biophysical Research Communications. 181 (1): 184–90. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806.

[6] "Entrez Gene: EDNRB endothelin receptor type B".

[pmid18039926-7] Sato-Jin K, Nishimura EK, Akasaka E, Huber W, Nakano H, Miller A, Du J, Wu M, Hanada K, Sawamura D, Fisher DE, Imokawa G (Apr 2008). "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders". FASEB Journal. 22 (4): 1155–68. doi:10.1096/fj.07-9080com. PMID 18039926.

[pmid19067971-8] Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid9556633-9] Tanaka H, Moroi K, Iwai J, Takahashi H, Ohnuma N, Hori S, Takimoto M, Nishiyama M, Masaki T, Yanagisawa M, Sekiya S, Kimura S (May 1998). "Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization". The Journal of Biological Chemistry. 273 (18): 11378–83. doi:10.1074/jbc.273.18.11378. PMID 9556633.

[19a-10] Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D (Jun 1998). "A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease". Human Molecular Genetics. 7 (6): 1047–52. doi:10.1093/hmg/7.6.1047. PMID 9580670. AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous. -->

[pmid9585428-11] Metallinos DL, Bowling AT, Rine J (1998). "A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease". Mamm. Genome. 9 (6): 426–31. doi:10.1007/s003359900790. PMID 9585428.

[pmid12694195-12] Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (Apr 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry / FEBS. 270 (8): 1816–27. doi:10.1046/j.1432-1033.2003.03544.x. PMID 12694195.

[13] Maguire JJ, Davenport AP (Dec 2014). "Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12". British Journal of Pharmacology. 171 (24): 5555–72. doi:10.1111/bph.12874. PMC 4290702. PMID 25131455.