Endothelin receptor type B

Endothelin receptor type B
Identifiers
Symbols EDNRB; ABCDS; ET-B; ET-BR; ETB; ETBR; ETRB; HSCR; HSCR2; WS4A
External IDs OMIM: 131244 MGI: 102720 HomoloGene: 89 IUPHAR: ETB GeneCards: EDNRB Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1910 13618
Ensembl ENSG00000136160 ENSMUSG00000022122
UniProt P24530 Q8K1V9
RefSeq (mRNA) NM_000115.3 NM_007904
RefSeq (protein) NP_000106.1 NP_031930
Location (UCSC) Chr 13:
78.47 – 78.49 Mb		 Chr 14:
104.21 – 104.24 Mb
PubMed search [1] [2]

Endothelin receptor type B, also known as ETB is a protein that in humans is encoded by the EDNRB gene.[1]

Contents

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 signficance

The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.[5]

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 isoleucine to be made instead of lysine.[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]

See also

References

  1. ^ Cyr C, Huebner K, Druck T, Kris R (November 1991). "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochem. Biophys. Res. Commun. 181 (1): 184–90. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806. 
  2. ^ "Entrez Gene: EDNRB endothelin receptor type B". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1910. 
  3. ^ Sato-Jin K, Nishimura EK, Akasaka E, et al. (2008). "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders". FASEB J. 22 (4): 1155–68. doi:10.1096/fj.07-9080com. PMID 18039926. 
  4. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  5. ^ 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". J. Biol. Chem. 273 (18): 11378–83. doi:10.1074/jbc.273.18.11378. PMID 9556633. 
  6. ^ a b Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D (June 1998). "A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease". Hum. Mol. Genet. 7 (6): 1047–52. doi:10.1093/hmg/7.6.1047. PMID 9580670. http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9580670. "sequence analysis, together with allele-specific PCR and the amplification-created restriction site (ACRS) technique, revealed a dinucleotide TC-->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." 
  7. ^ Metallinos DL, Bowling AT, Rine J (1998). "In three unrelated lethal white foals, the EDNRB gene contained a 2-bp nucleotide change leading to a missense mutation (I118K) in the first transmembrane domain of the receptor, a highly conserved region of this protein among different species. Seven additional unrelated lethal white foal samples were found to be homozygous for this mutation. No other homozygotes were identified in 138 samples analyzed, suggesting that homozygosity was restricted to lethal white foals. All (40/40) horses with the frame overo pattern (a distinct coat color pattern that is a subset of overo horses) that were tested were heterozygous for this allele, defining a heterozygous coat color phenotype for this mutation."
  8. ^ Yamaguchi, Tomohiro; Murata Yasunobu, Fujiyoshi Yoshinori, Doi Tomoko (April 2003). "Regulated interaction of endothelin B receptor with caveolin-1". Eur. J. Biochem. (Germany) 270 (8): 1816–27. doi:10.1046/j.1432-1033.2003.03544.x. ISSN 0014-2956. PMID 12694195. 

External links

Further reading

  • Hofstra RM, Osinga J, Buys CH (1998). "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype.". Eur. J. Hum. Genet. 5 (4): 180–5. PMID 9359036. 
  • Haendler B, Hechler U, Schleuning WD (1993). "Molecular cloning of human endothelin (ET) receptors ETA and ETB.". J. Cardiovasc. Pharmacol. 20 Suppl 12: S1–4. PMID 1282938. 
  • Arai H, Nakao K, Hosoda K, et al. (1993). "[Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells]". Jpn. Circ. J. 56 Suppl 5: 1303–7. PMID 1291713. 
  • Ogawa Y, Nakao K, Arai H, et al. (1991). "Molecular cloning of a non-isopeptide-selective human endothelin receptor.". Biochem. Biophys. Res. Commun. 178 (1): 248–55. doi:10.1016/0006-291X(91)91806-N. PMID 1648908. 
  • Cyr C, Huebner K, Druck T, Kris R (1992). "Cloning and chromosomal localization of a human endothelin ETA receptor.". Biochem. Biophys. Res. Commun. 181 (1): 184–90. doi:10.1016/S0006-291X(05)81399-3. PMID 1659806. 
  • Nakamuta M, Takayanagi R, Sakai Y, et al. (1991). "Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor.". Biochem. Biophys. Res. Commun. 177 (1): 34–9. doi:10.1016/0006-291X(91)91944-8. PMID 1710450. 
  • Sakamoto A, Yanagisawa M, Sakurai T, et al. (1991). "Cloning and functional expression of human cDNA for the ETB endothelin receptor.". Biochem. Biophys. Res. Commun. 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. 
  • Puffenberger EG, Kauffman ER, Bolk S, et al. (1995). "Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22.". Hum. Mol. Genet. 3 (8): 1217–25. doi:10.1093/hmg/3.8.1217. PMID 7987295. 
  • Puffenberger EG, Hosoda K, Washington SS, et al. (1995). "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. 
  • Baynash AG, Hosoda K, Giaid A, et al. (1995). "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. 
  • Arai H, Nakao K, Takaya K, et al. (1993). "The human endothelin-B receptor gene. Structural organization and chromosomal assignment.". J. Biol. Chem. 268 (5): 3463–70. PMID 8429023. 
  • Elshourbagy NA, Korman DR, Wu HL, et al. (1993). "Molecular characterization and regulation of the human endothelin receptors.". J. Biol. Chem. 268 (6): 3873–9. PMID 8440682. 
  • Hofstra RM, Osinga J, Tan-Sindhunata G, et al. (1996). "A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome).". Nat. Genet. 12 (4): 445–7. doi:10.1038/ng0496-445. PMID 8630503. 
  • Attié T, Till M, Pelet A, et al. (1996). "Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease.". Hum. Mol. Genet. 4 (12): 2407–9. doi:10.1093/hmg/4.12.2407. PMID 8634719. 
  • Elshourbagy NA, Adamou JE, Gagnon AW, et al. (1996). "Molecular characterization of a novel human endothelin receptor splice variant.". J. Biol. Chem. 271 (41): 25300–7. doi:10.1074/jbc.271.41.25300. PMID 8810293. 
  • Kusafuka T, Wang Y, Puri P (1997). "Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.". Hum. Mol. Genet. 5 (3): 347–9. doi:10.1093/hmg/5.3.347. PMID 8852658. 
  • Auricchio A, Casari G, Staiano A, Ballabio A (1997). "Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population.". Hum. Mol. Genet. 5 (3): 351–4. doi:10.1093/hmg/5.3.351. PMID 8852659. 
  • Amiel J, Attié T, Jan D, et al. (1997). "Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.". Hum. Mol. Genet. 5 (3): 355–7. doi:10.1093/hmg/5.3.355. PMID 8852660. 
  • Freedman NJ, Ament AS, Oppermann M, et al. (1997). "Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity.". J. Biol. Chem. 272 (28): 17734–43. doi:10.1074/jbc.272.28.17734. PMID 9211925. 

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