| EDNRB | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Endothelin receptor type B, (ET-B) is a protein that in humans is encoded by the EDNRB gene.[5]
Function[edit]
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[edit]
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[edit]
The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.[9]
Animals[edit]
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[edit]
Endothelin receptor type B has been shown to interact with Caveolin 1.[12]
Ligands[edit]
- Agonists
- Antagonists
- A-192,621
- BQ-788
- Bosentan (unselective ETA / ETB antagonist)
See also[edit]
References[edit]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000136160 - Ensembl, May 2017
- ^ a b c 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. S2CID 14304386.
- ^ 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.
- ^ a b 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. S2CID 19536624.
- ^ Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (Apr 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry. 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.
Further reading[edit]
- Hofstra RM, Osinga J, Buys CH (1998). "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype". European Journal of Human Genetics. 5 (4): 180–5. doi:10.1159/000484760. PMID 9359036.
- Haendler B, Hechler U, Schleuning WD (1993). "Molecular cloning of human endothelin (ET) receptors ETA and ETB". Journal of Cardiovascular Pharmacology. 20 (Suppl 12): S1–4. doi:10.1097/00005344-199204002-00002. PMID 1282938. S2CID 37973815.
- Arai H, Nakao K, Hosoda K, Ogawa Y, Nakagawa O, Komatsu Y, Imura H (1993). "[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. doi:10.1253/jcj.56.supplementv_1303. PMID 1291713.
- Ogawa Y, Nakao K, Arai H, Nakagawa O, Hosoda K, Suga S, Nakanishi S, Imura H (Jul 1991). "Molecular cloning of a non-isopeptide-selective human endothelin receptor". Biochemical and Biophysical Research Communications. 178 (1): 248–55. doi:10.1016/0006-291X(91)91806-N. PMID 1648908.
- 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.
- Nakamuta M, Takayanagi R, Sakai Y, Sakamoto S, Hagiwara H, Mizuno T, Saito Y, Hirose S, Yamamoto M, Nawata H (May 1991). "Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor". Biochemical and Biophysical Research Communications. 177 (1): 34–9. doi:10.1016/0006-291X(91)91944-8. PMID 1710450.
- Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T (Jul 1991). "Cloning and functional expression of human cDNA for the ETB endothelin receptor". Biochemical and Biophysical Research Communications. 178 (2): 656–63. doi:10.1016/0006-291X(91)90158-4. PMID 1713452.
- Vane J (1991). "Endothelins come home to roost". Nature. 348 (6303): 673. doi:10.1038/348673a0. PMID 2175394. S2CID 4351182.
- Puffenberger EG, Kauffman ER, Bolk S, Matise TC, Washington SS, Angrist M, Weissenbach J, Garver KL, Mascari M, Ladda R (Aug 1994). "Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22". Human Molecular Genetics. 3 (8): 1217–25. doi:10.1093/hmg/3.8.1217. PMID 7987295.
- Puffenberger EG, Hosoda K, Washington SS, Nakao K, deWit D, Yanagisawa M, Chakravart A (Dec 1994). "A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease". Cell. 79 (7): 1257–66. doi:10.1016/0092-8674(94)90016-7. PMID 8001158. S2CID 24894649.
- Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M (Dec 1994). "Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons". Cell. 79 (7): 1277–85. doi:10.1016/0092-8674(94)90018-3. PMID 8001160. S2CID 32577813.
- Arai H, Nakao K, Takaya K, Hosoda K, Ogawa Y, Nakanishi S, Imura H (Feb 1993). "The human endothelin-B receptor gene. Structural organization and chromosomal assignment". The Journal of Biological Chemistry. 268 (5): 3463–70. doi:10.1016/S0021-9258(18)53717-0. PMID 8429023.
- Elshourbagy NA, Korman DR, Wu HL, Sylvester DR, Lee JA, Nuthalaganti P, Bergsma DJ, Kumar CS, Nambi P (Feb 1993). "Molecular characterization and regulation of the human endothelin receptors". The Journal of Biological Chemistry. 268 (6): 3873–9. doi:10.1016/S0021-9258(18)53554-7. PMID 8440682.
- Hofstra RM, Osinga J, Tan-Sindhunata G, Wu Y, Kamsteeg EJ, Stulp RP, van Ravenswaaij-Arts C, Majoor-Krakauer D, Angrist M, Chakravarti A, Meijers C, Buys CH (Apr 1996). "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. doi:10.1038/ng0496-445. hdl:1765/54507. PMID 8630503. S2CID 935271.
- Attié T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S (Dec 1995). "Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease". Human Molecular Genetics. 4 (12): 2407–9. doi:10.1093/hmg/4.12.2407. PMID 8634719.
- Elshourbagy NA, Adamou JE, Gagnon AW, Wu HL, Pullen M, Nambi P (Oct 1996). "Molecular characterization of a novel human endothelin receptor splice variant". The Journal of Biological Chemistry. 271 (41): 25300–7. doi:10.1074/jbc.271.41.25300. PMID 8810293.
- Kusafuka T, Wang Y, Puri P (Mar 1996). "Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease". Human Molecular Genetics. 5 (3): 347–9. doi:10.1093/hmg/5.3.347. PMID 8852658.
- Auricchio A, Casari G, Staiano A, Ballabio A (Mar 1996). "Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population". Human Molecular Genetics. 5 (3): 351–4. doi:10.1093/hmg/5.3.351. PMID 8852659.
- Amiel J, Attié T, Jan D, Pelet A, Edery P, Bidaud C, Lacombe D, Tam P, Simeoni J, Flori E, Nihoul-Fékété C, Munnich A, Lyonnet S (Mar 1996). "Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease". Human Molecular Genetics. 5 (3): 355–7. doi:10.1093/hmg/5.3.355. PMID 8852660.
- Freedman NJ, Ament AS, Oppermann M, Stoffel RH, Exum ST, Lefkowitz RJ (Jul 1997). "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. doi:10.1074/jbc.272.28.17734. PMID 9211925.
- Mazzuca MQ, Khalil RA (Jul 2012). "Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease". Biochemical Pharmacology. 84 (2): 147–62. doi:10.1016/j.bcp.2012.03.020. PMC 3358417. PMID 22484314.
- Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ (April 2016). "Endothelin". Pharmacological Reviews. 68 (2): 357–418. doi:10.1124/pr.115.011833. PMC 4815360. PMID 26956245.
External links[edit]
- "Endothelin Receptors: ETB". 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.