Alpha-2B adrenergic receptor

The alpha-2B adrenergic receptor (α_2B 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.^[5] ADRA2B orthologs^[6] have been identified in several mammals.

ADRA2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CVA
Identifiers
Aliases	ADRA2B, ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, alpha-2BAR, FAME2, adrenoceptor alpha 2B
External IDs	OMIM: 104260; MGI: 87935; HomoloGene: 553; GeneCards: ADRA2B; OMA:ADRA2B - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q11.2 Start 96,112,876 bp[1] End 96,116,571 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 F1|2 61.95 cM Start 127,205,128 bp[2] End 127,209,141 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart gastrocnemius muscle left ventricle right lobe of liver spleen subcutaneous adipose tissue muscle of thigh tibial nerve ascending aorta gastric mucosa Top expressed in right kidney proximal tubule human kidney yolk sac decidua embryo embryo hepatobiliary system liver secondary oocyte More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity alpha2-adrenergic receptor activity adrenergic receptor activity epinephrine binding protein binding Cellular component integral component of membrane plasma membrane membrane integral component of plasma membrane intracellular anatomical structure cell surface Biological process platelet activation female pregnancy G protein-coupled receptor signaling pathway positive regulation of blood pressure adrenergic receptor signaling pathway regulation of vasoconstriction regulation of vascular associated smooth muscle contraction positive regulation of uterine smooth muscle contraction regulation of smooth muscle contraction signal transduction activation of protein kinase B activity negative regulation of epinephrine secretion cell-cell signaling adenylate cyclase-activating adrenergic receptor signaling pathway positive regulation of neuron differentiation negative regulation of norepinephrine secretion positive regulation of MAPK cascade receptor transactivation adenylate cyclase-modulating G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 151 11552 Ensembl ENSG00000274286 ENSMUSG00000058620 UniProt P18089 P30545 RefSeq (mRNA) NM_000682 NM_009633 RefSeq (protein) NP_000673 NP_033763 Location (UCSC) Chr 2: 96.11 – 96.12 Mb Chr 2: 127.21 – 127.21 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Receptor

α₂-adrenergic receptors include 3 highly homologous subtypes: α_2A, α_2B, and α_2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system.

Clinical significance

This gene encodes the α_2B 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 α_2B 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.^[5]

A deletion variant of the α_2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.^[7] This variant also predisposed people who had it to focus more on negative aspects of a situation.^[8] This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant reboxetine, but was weakened in people without the variant.^[9]

Evolution

The ADRA2B gene (sometimes referenced as A2AB) is used in animals as a nuclear DNA phylogenetic marker.^[6] This intronless gene has first been used to explore the phylogeny of the major groups of mammals,^[10] and contributed to reveal that placental orders are distributed into four major clades: Xenarthra, Afrotheria, Laurasiatheria, and Euarchontoglires. 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.^[11]

Ligands

Agonists

• (−)-Dibromophakellin^[12]

Antagonists

• Imiloxan
• Yohimbine

See also

• Adrenergic receptor

References

1. GRCh38: Ensembl release 89: ENSG00000274286 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000058620 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor".
6. "OrthoMaM phylogenetic marker: ADRA2B coding sequence".^{[permanent dead link]}
7. de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A (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. S2CID 899166.
8. Todd RM, Müller DJ, Lee DH, Robertson A, Eaton T, Freeman N, Palombo DJ, Levine B, Anderson AK (2013). "Genes for emotion-enhanced remembering are linked to enhanced perceiving". Psychol Sci. 24 (11): 2244–53. doi:10.1177/0956797613492423. PMID 24058067. S2CID 9603198.

   • Lay summary in: "Genes predispose some people to focus on the negative". The University of British Columbia. October 10, 2013.
9. Gibbs AA, Bautista CE, Mowlem FD, Naudts KH, Duka T (2013). "Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers". J. Neurosci. 33 (43): 17023–8. doi:10.1523/JNEUROSCI.2124-13.2013. PMC 6618435. PMID 24155306.

   • Lay summary in: "Genetic variation alters efficacy of antidepressant". Society for Neuroscience (Press release). 2013-10-22. Archived from the original on 2013-10-24.
10. Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R, Amrine HM, Stanhope MJ, de Jong WW, Springer MS (Feb 2001). "Parallel adaptive radiations in two major clades of placental mammals". Nature. 409 (6820): 610–4. Bibcode:2001Natur.409..610M. doi:10.1038/35054544. PMID 11214318. S2CID 4398233.
11. 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.
12. Davis RA, Fechner GA, Sykes M, Garavelas A, Pass DM, Carroll AR, Addepalli R, Avery VM, Hooper JN, Quinn RJ (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. hdl:10072/28568. PMID 19243956.

External links

• Human ADRA2B genome location and ADRA2B gene details page in the UCSC Genome Browser.

Further reading

• Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL, Caron MG, Lefkowitz RJ (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. Bibcode:1990PNAS...87.5094L. 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. S2CID 24246875.
• Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR (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. Bibcode:1988PNAS...85.6301R. 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. doi:10.1152/ajprenal.1997.273.6.F883. 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, Valve R, Uusitupa M, Scheinin M (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/jcem.84.7.5818. PMID 10404816.
• Hein L, Altman JD, Kobilka BK (Nov 1999). "Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission". Nature. 402 (6758): 181–4. Bibcode:1999Natur.402..181H. doi:10.1038/46040. PMID 10647009. S2CID 205047992.
• 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.
• Sykiotis GP, Polyzogopoulou E, Georgopoulos NA, Trakada G, Spyropoulos K, Kalfarentzos F, Papavassiliou AG, Vagenakis AG, Flordellis CS (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. S2CID 10913264.
• Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR, Montague CR, Paris H, Handy DE, Flavahan NA (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.
• Cayla C, Heinonen P, Viikari L, Schaak S, Snapir A, Bouloumié A, Karvonen MK, Pesonen U, Scheinin M, Paris H (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.
• Phares DA, Halverstadt AA, Shuldiner AR, Ferrell RE, Douglass LW, Ryan AS, Goldberg AP, Hagberg JM (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, Keinänen-Kiukaanniemi S, Tuomilehto J, Laakso M, Uusitupa M (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.
• Belfer I, Buzas B, Hipp H, Phillips G, Taubman J, Lorincz I, Evans C, Lipsky RH, Enoch MA, Max MB, Goldman D (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.