Biology:Alpha-2B adrenergic receptor

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

Generic protein structure example

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. ADRA2B orthologs have been identified in several mammals.

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.

A deletion variant of the α_2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans. This variant also predisposed people who had it to focus more on negative aspects of a situation. 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.

Evolution

The ADRA2B gene (sometimes referenced as A2AB) is used in animals as a nuclear DNA phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of mammals, 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.

Ligands

Agonists

• (−)-Dibromophakellin

Antagonists

• Imiloxan
• Yohimbine

See also

• Adrenergic receptor

External links

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

Further reading

• "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. Jul 1990. doi:10.1073/pnas.87.13.5094. PMID 2164221. Bibcode: 1990PNAS...87.5094L. 
• "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. Sep 1990. doi:10.1016/0014-5793(90)81209-7. PMID 2169434. 
• "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor". Molecular Pharmacology 38 (5): 681–8. Nov 1990. PMID 2172775. 
• "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. Oct 1990. doi:10.1016/0006-291X(90)90748-C. PMID 2173582. 
• "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. Sep 1988. doi:10.1073/pnas.85.17.6301. PMID 2842764. Bibcode: 1988PNAS...85.6301R. 
• "Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain". Life Sciences 38 (23): 2129–37. Jun 1986. doi:10.1016/0024-3205(86)90212-2. PMID 3012234. 
• "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". The Journal of Biological Chemistry 272 (31): 19099–102. Aug 1997. doi:10.1074/jbc.272.31.19099. PMID 9235896. 
• "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. Dec 1997. doi:10.1152/ajprenal.1997.273.6.F883. PMID 9435676. 
• "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. May 1999. doi:10.1074/jbc.274.19.13462. PMID 10224112. 
• "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. Jul 1999. doi:10.1210/jcem.84.7.5818. PMID 10404816. 
• "Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission". Nature 402 (6758): 181–4. Nov 1999. doi:10.1038/46040. PMID 10647009. Bibcode: 1999Natur.402..181H. 
• "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. Feb 2001. doi:10.1074/jbc.M008118200. PMID 11056163. 
• "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. Jan 2003. doi:10.1016/S0735-1097(02)02702-X. PMID 12535806. 
• "The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity". Clinical Autonomic Research 13 (3): 203–7. Jun 2003. doi:10.1007/s10286-003-0087-5. PMID 12822042. 
• "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". American Journal of Physiology. Heart and Circulatory Physiology 286 (1): H59–67. Jan 2004. doi:10.1152/ajpheart.00268.2003. PMID 12946937. 
• "Functional variant in the (alpha)2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension". Hypertension 43 (3): 592–7. Mar 2004. doi:10.1161/01.HYP.0000116224.51189.80. PMID 14744925. 
• "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene". Biochemical Pharmacology 67 (3): 469–78. Feb 2004. doi:10.1016/j.bcp.2003.09.029. PMID 15037199. 
• "Association between body fat response to exercise training and multilocus ADR genotypes". Obesity Research 12 (5): 807–15. May 2004. doi:10.1038/oby.2004.97. PMID 15166301. 
• "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. Aug 2004. doi:10.1007/s00125-004-1462-z. PMID 15309292. 
• "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. 2005. doi:10.1007/s10038-004-0211-y. PMID 15592690.