Alpha-2B adrenergic receptor

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Adrenoceptor alpha 2B
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ADRA2B ; ADRA2L1; ADRA2RL1; ADRARL1; ALPHA2BAR; alpha-2BAR
External IDs OMIM104260 MGI87935 HomoloGene553 IUPHAR: α2B-adrenoceptor ChEMBL: 1942 GeneCards: ADRA2B Gene
Orthologs
Species Human Mouse
Entrez 151 11552
Ensembl ENSG00000222040 ENSMUSG00000058620
UniProt P18089 P30545
RefSeq (mRNA) NM_000682 NM_009633
RefSeq (protein) NP_000673 NP_033763
Location (UCSC) Chr 2:
96.78 – 96.78 Mb
Chr 2:
127.36 – 127.37 Mb
PubMed search [1] [2]

The alpha-2B adrenergic receptor2B adrenoceptor), is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B.[1] ADRA2B orthologs[2] have been identified in several mammals.

Receptor[edit]

α2-adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system.

Gene[edit]

This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no introns in either its coding or untranslated sequences.[1]

A deletion variant of the α2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.[3]

In October 2013 researchers from the University of British Columbia confirmed this and further reported that the variant predisposed those people who had it to focus more on negative aspects of a situation. Prof. Rebecca Todd claimed "This is the first study to find that this genetic variation can significantly affect how people see and experience the world.” http://news.ubc.ca/2013/10/10/genes-predispose-some-people-to-focus-on-the-negative/

Evolution[edit]

The ADRA2B gene (sometimes referenced as A2AB) is used in animals as a nuclear DNA phylogenetic marker.[2] This intronless gene has first been used to explore the phylogeny of the major groups of mammals,[4] and contributed to reveal that placental orders are distributed into four major clades: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein–coupling. However, great variations are observed in the very long, third intracellular loop, with a polyglutamyl domain displaying pervasive length differences.[5]

Ligands[edit]

Agonists
  • (-)-Dibromophakellin[6]
Antagonists

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor". 
  2. ^ a b "OrthoMaM phylogenetic marker: ADRA2B coding sequence". 
  3. ^ de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A (2007). "A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans". Nat. Neurosci. 10 (9): 1137–9. doi:10.1038/nn1945. PMID 17660814. 
  4. ^ Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R, Amrine HM, Stanhope MJ, de Jong WW, Springer MS (February 2001). "Parallel adaptive radiations in two major clades of placental mammals". Nature 409 (6820): 610–4. doi:10.1038/35054544. PMID 11214318. 
  5. ^ Madsen O, Willemsen D, Ursing BM, Arnason U, de Jong WW (December 2002). "Molecular evolution of the mammalian alpha 2B adrenergic receptor". Mol. Biol. Evol. 19 (12): 2150–60. doi:10.1093/oxfordjournals.molbev.a004040. PMID 12446807. 
  6. ^ Davis RA, Fechner GA, Sykes M, Garavelas A, Pass DM, Carroll AR, Addepalli R, Avery VM, Hooper JN, Quinn RJ (2009). "(-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata". Bioorg. Med. Chem. 17 (6): 2497–500. doi:10.1016/j.bmc.2009.01.065. PMID 19243956. 

Further reading[edit]

  • Lomasney JW, Lorenz W, Allen LF et al. (1990). "Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2". Proc. Natl. Acad. Sci. U.S.A. 87 (13): 5094–8. doi:10.1073/pnas.87.13.5094. PMC 54268. PMID 2164221. 
  • McClue SJ, Milligan G (1990). "The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108-15 cells, interacts directly with the guanine nucleotide binding protein, Gi2". FEBS Lett. 269 (2): 430–4. doi:10.1016/0014-5793(90)81209-7. PMID 2169434. 
  • Weinshank RL, Zgombick JM, Macchi M et al. (1990). "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor". Mol. Pharmacol. 38 (5): 681–8. PMID 2172775. 
  • Chang AC, Ho TF, Chang NC (1990). "In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans". Biochem. Biophys. Res. Commun. 172 (2): 817–23. doi:10.1016/0006-291X(90)90748-C. PMID 2173582. 
  • Regan JW, Kobilka TS, Yang-Feng TL et al. (1988). "Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype". Proc. Natl. Acad. Sci. U.S.A. 85 (17): 6301–5. doi:10.1073/pnas.85.17.6301. PMC 281957. PMID 2842764. 
  • Petrash AC, Bylund DB (1986). "Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain". Life Sci. 38 (23): 2129–37. doi:10.1016/0024-3205(86)90212-2. PMID 3012234. 
  • Klein U, Ramirez MT, Kobilka BK, von Zastrow M (1997). "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". J. Biol. Chem. 272 (31): 19099–102. doi:10.1074/jbc.272.31.19099. PMID 9235896. 
  • Okusa MD, Huang L, Momose-Hotokezaka A et al. (1998). "Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors". Am. J. Physiol. 273 (6 Pt 2): F883–91. PMID 9435676. 
  • Prezeau L, Richman JG, Edwards SW, Limbird LE (1999). "The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes". J. Biol. Chem. 274 (19): 13462–9. doi:10.1074/jbc.274.19.13462. PMID 10224112. 
  • Heinonen P, Koulu M, Pesonen U et al. (1999). "Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects". J. Clin. Endocrinol. Metab. 84 (7): 2429–33. doi:10.1210/jc.84.7.2429. PMID 10404816. 
  • Hein L, Altman JD, Kobilka BK (2000). "Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission". Nature 402 (6758): 181–4. doi:10.1038/46040. PMID 10647009. 
  • Small KM, Brown KM, Forbes SL, Liggett SB (2001). "Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization". J. Biol. Chem. 276 (7): 4917–22. doi:10.1074/jbc.M008118200. PMID 11056163. 
  • Snapir A, Mikkelsson J, Perola M et al. (2003). "Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death". J. Am. Coll. Cardiol. 41 (2): 190–4. doi:10.1016/S0735-1097(02)02702-X. PMID 12535806. 
  • Sykiotis GP, Polyzogopoulou E, Georgopoulos NA et al. (2004). "The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity". Clin. Auton. Res. 13 (3): 203–7. doi:10.1007/s10286-003-0087-5. PMID 12822042. 
  • Chotani MA, Mitra S, Su BY et al. (2004). "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". Am. J. Physiol. Heart Circ. Physiol. 286 (1): H59–67. doi:10.1152/ajpheart.00268.2003. PMID 12946937. 
  • Von Wowern F, Bengtsson K, Lindblad U et al. (2004). "Functional variant in the (alpha)2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension". Hypertension 43 (3): 592–7. doi:10.1161/01.HYP.0000116224.51189.80. PMID 14744925. 
  • Cayla C, Heinonen P, Viikari L et al. (2004). "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene". Biochem. Pharmacol. 67 (3): 469–78. doi:10.1016/j.bcp.2003.09.029. PMID 15037199. 
  • Phares DA, Halverstadt AA, Shuldiner AR et al. (2004). "Association between body fat response to exercise training and multilocus ADR genotypes". Obes. Res. 12 (5): 807–15. doi:10.1038/oby.2004.97. PMID 15166301. 
  • Siitonen N, Lindström J, Eriksson J et al. (2005). "Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study". Diabetologia 47 (8): 1416–24. doi:10.1007/s00125-004-1462-z. PMID 15309292. 
  • Belfer I, Buzas B, Hipp H et al. (2005). "Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene". J. Hum. Genet. 50 (1): 12–20. doi:10.1007/s10038-004-0211-y. PMID 15592690.