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 et al. (Sep 2007). "A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans". Nature Neuroscience 10 (9): 1137–9. doi:10.1038/nn1945. PMID 17660814. 
  4. ^ Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R et al. (Feb 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 (Dec 2002). "Molecular evolution of the mammalian alpha 2B adrenergic receptor". Molecular Biology and Evolution 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 et al. (Mar 2009). "(-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata". Bioorganic & Medicinal Chemistry 17 (6): 2497–500. doi:10.1016/j.bmc.2009.01.065. PMID 19243956. 

Further reading[edit]

  • Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL et al. (Jul 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". Proceedings of the National Academy of Sciences of the United States of America 87 (13): 5094–8. doi:10.1073/pnas.87.13.5094. PMC 54268. PMID 2164221. 
  • McClue SJ, Milligan G (Sep 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 Letters 269 (2): 430–4. doi:10.1016/0014-5793(90)81209-7. PMID 2169434. 
  • Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA et al. (Nov 1990). "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor". Molecular Pharmacology 38 (5): 681–8. PMID 2172775. 
  • Chang AC, Ho TF, Chang NC (Oct 1990). "In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans". Biochemical and Biophysical Research Communications 172 (2): 817–23. doi:10.1016/0006-291X(90)90748-C. PMID 2173582. 
  • Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK (Sep 1988). "Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype". Proceedings of the National Academy of Sciences of the United States of America 85 (17): 6301–5. doi:10.1073/pnas.85.17.6301. PMC 281957. PMID 2842764. 
  • Petrash AC, Bylund DB (Jun 1986). "Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain". Life Sciences 38 (23): 2129–37. doi:10.1016/0024-3205(86)90212-2. PMID 3012234. 
  • Klein U, Ramirez MT, Kobilka BK, von Zastrow M (Aug 1997). "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". The Journal of Biological Chemistry 272 (31): 19099–102. doi:10.1074/jbc.272.31.19099. PMID 9235896. 
  • Okusa MD, Huang L, Momose-Hotokezaka A, Huynh LP, Mangrum AJ (Dec 1997). "Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors". The American Journal of Physiology 273 (6 Pt 2): F883–91. PMID 9435676. 
  • Prezeau L, Richman JG, Edwards SW, Limbird LE (May 1999). "The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes". The Journal of Biological Chemistry 274 (19): 13462–9. doi:10.1074/jbc.274.19.13462. PMID 10224112. 
  • Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M et al. (Jul 1999). "Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects". The Journal of Clinical Endocrinology and Metabolism 84 (7): 2429–33. doi:10.1210/jc.84.7.2429. PMID 10404816. 
  • Hein L, Altman JD, Kobilka BK (Nov 1999). "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 (Feb 2001). "Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization". The Journal of Biological Chemistry 276 (7): 4917–22. doi:10.1074/jbc.M008118200. PMID 11056163. 
  • Snapir A, Mikkelsson J, Perola M, Penttilä A, Scheinin M, Karhunen PJ (Jan 2003). "Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death". Journal of the American College of Cardiology 41 (2): 190–4. doi:10.1016/S0735-1097(02)02702-X. PMID 12535806.  Vancouver style error (help)
  • Sykiotis GP, Polyzogopoulou E, Georgopoulos NA, Trakada G, Spyropoulos K, Kalfarentzos F et al. (Jun 2003). "The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity". Clinical Autonomic Research 13 (3): 203–7. doi:10.1007/s10286-003-0087-5. PMID 12822042. 
  • Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR et al. (Jan 2004). "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". American Journal of Physiology. Heart and Circulatory Physiology 286 (1): H59–67. doi:10.1152/ajpheart.00268.2003. PMID 12946937. 
  • Von Wowern F, Bengtsson K, Lindblad U, Råstam L, Melander O (Mar 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.  Vancouver style error (help)
  • Cayla C, Heinonen P, Viikari L, Schaak S, Snapir A, Bouloumié A et al. (Feb 2004). "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene". Biochemical Pharmacology 67 (3): 469–78. doi:10.1016/j.bcp.2003.09.029. PMID 15037199.  Vancouver style error (help)
  • Phares DA, Halverstadt AA, Shuldiner AR, Ferrell RE, Douglass LW, Ryan AS et al. (May 2004). "Association between body fat response to exercise training and multilocus ADR genotypes". Obesity Research 12 (5): 807–15. doi:10.1038/oby.2004.97. PMID 15166301. 
  • Siitonen N, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P et al. (Aug 2004). "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.  Vancouver style error (help)
  • Belfer I, Buzas B, Hipp H, Phillips G, Taubman J, Lorincz I et al. (2005). "Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene". Journal of Human Genetics 50 (1): 12–20. doi:10.1007/s10038-004-0211-y. PMID 15592690.