Biology:Endothelin B receptor
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Endothelin receptor type B, also known as ETB is a protein that in humans is encoded by the EDNRB gene.[1]
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.[2]
Regulation
In melanocytic cells the EDNRB gene is regulated by the microphthalmia-associated transcription factor. Mutations in either gene are links to Waardenburg syndrome.[3][4]
Clinical significance
The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.[5]
Animals
In horses, a mutation in the middle of the EDNRB gene, Ile118Lys, when homozygous, causes Lethal White Syndrome.[6] In this mutation, a mismatch in the DNA replication causes lysine to be made instead of isoleucine.[6] 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.[7]
Interactions
Endothelin receptor type B has been shown to interact with Caveolin 1.[8]
Ligands
- Agonists
- IRL-1620[9]
- Antagonists
- A-192,621
- BQ-788
- Bosentan (unselective ETA / ETB antagonist)
See also
References
- ↑ "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochemical and Biophysical Research Communications 181 (1): 184–90. Nov 1991. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806.
- ↑ "Entrez Gene: EDNRB endothelin receptor type B". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1910.
- ↑ "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders". FASEB Journal 22 (4): 1155–68. Apr 2008. doi:10.1096/fj.07-9080com. PMID 18039926.
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. Dec 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ "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. May 1998. doi:10.1074/jbc.273.18.11378. PMID 9556633.
- ↑ 6.0 6.1 "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. Jun 1998. 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. -->".
- ↑ "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. 1998. doi:10.1007/s003359900790. PMID 9585428.
- ↑ "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry 270 (8): 1816–27. Apr 2003. doi:10.1046/j.1432-1033.2003.03544.x. PMID 12694195.
- ↑ "Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12". British Journal of Pharmacology 171 (24): 5555–72. Dec 2014. doi:10.1111/bph.12874. PMID 25131455.
Further reading
- "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype". European Journal of Human Genetics 5 (4): 180–5. 1998. doi:10.1159/000484760. PMID 9359036.
- "Molecular cloning of human endothelin (ET) receptors ETA and ETB". Journal of Cardiovascular Pharmacology 20 Suppl 12: S1–4. 1993. doi:10.1097/00005344-199204002-00002. PMID 1282938.
- "[Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells]". Japanese Circulation Journal 56 Suppl 5: 1303–7. 1993. doi:10.1253/jcj.56.supplementv_1303. PMID 1291713.
- "Molecular cloning of a non-isopeptide-selective human endothelin receptor". Biochemical and Biophysical Research Communications 178 (1): 248–55. Jul 1991. doi:10.1016/0006-291X(91)91806-N. PMID 1648908.
- "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochemical and Biophysical Research Communications 181 (1): 184–90. Nov 1991. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806.
- "Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor". Biochemical and Biophysical Research Communications 177 (1): 34–9. May 1991. doi:10.1016/0006-291X(91)91944-8. PMID 1710450.
- "Cloning and functional expression of human cDNA for the ETB endothelin receptor". Biochemical and Biophysical Research Communications 178 (2): 656–63. Jul 1991. doi:10.1016/0006-291X(91)90158-4. PMID 1713452.
- "Endothelins come home to roost". Nature 348 (6303): 673. 1991. doi:10.1038/348673a0. PMID 2175394.
- "Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22". Human Molecular Genetics 3 (8): 1217–25. Aug 1994. doi:10.1093/hmg/3.8.1217. PMID 7987295.
- "A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease". Cell 79 (7): 1257–66. Dec 1994. doi:10.1016/0092-8674(94)90016-7. PMID 8001158.
- "Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons". Cell 79 (7): 1277–85. Dec 1994. doi:10.1016/0092-8674(94)90018-3. PMID 8001160.
- "The human endothelin-B receptor gene. Structural organization and chromosomal assignment". The Journal of Biological Chemistry 268 (5): 3463–70. Feb 1993. doi:10.1016/S0021-9258(18)53717-0. PMID 8429023.
- "Molecular characterization and regulation of the human endothelin receptors". The Journal of Biological Chemistry 268 (6): 3873–9. Feb 1993. doi:10.1016/S0021-9258(18)53554-7. PMID 8440682.
- "A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome)". Nature Genetics 12 (4): 445–7. Apr 1996. doi:10.1038/ng0496-445. PMID 8630503. http://repub.eur.nl/pub/54507.
- "Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease". Human Molecular Genetics 4 (12): 2407–9. Dec 1995. doi:10.1093/hmg/4.12.2407. PMID 8634719.
- "Molecular characterization of a novel human endothelin receptor splice variant". The Journal of Biological Chemistry 271 (41): 25300–7. Oct 1996. doi:10.1074/jbc.271.41.25300. PMID 8810293.
- "Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease". Human Molecular Genetics 5 (3): 347–9. Mar 1996. doi:10.1093/hmg/5.3.347. PMID 8852658.
- "Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population". Human Molecular Genetics 5 (3): 351–4. Mar 1996. doi:10.1093/hmg/5.3.351. PMID 8852659.
- "Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease". Human Molecular Genetics 5 (3): 355–7. Mar 1996. doi:10.1093/hmg/5.3.355. PMID 8852660.
- "Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity". The Journal of Biological Chemistry 272 (28): 17734–43. Jul 1997. doi:10.1074/jbc.272.28.17734. PMID 9211925.
- "Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease". Biochemical Pharmacology 84 (2): 147–62. Jul 2012. doi:10.1016/j.bcp.2012.03.020. PMID 22484314.
- "Endothelin". Pharmacological Reviews 68 (2): 357–418. April 2016. doi:10.1124/pr.115.011833. PMID 26956245.
External links
- "Endothelin Receptors: ETB". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2265.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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