Biology:Endothelin B receptor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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
Antagonists
  • A-192,621
  • BQ-788
  • Bosentan (unselective ETA / ETB antagonist)

See also

References

  1. "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. 
  2. "Entrez Gene: EDNRB endothelin receptor type B". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1910. 
  3. "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. 
  4. "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. 
  5. "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. 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. -->". 
  7. "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. 
  8. "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. 
  9. "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

External links

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