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{{Infobox_gene}}
The '''alpha-2B adrenergic receptor''' (α<sub>2B</sub> 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'''.<ref name="entrez" />
ADRA2B [[orthologs]]<ref name="OrthoMaM">{{cite web | title = OrthoMaM phylogenetic marker: ADRA2B coding sequence | url = http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000222040_ADRA2B.xml }}{{Dead link|date=October 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> have been identified in several [[mammals]].


== Receptor ==


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α<sub>2</sub>-adrenergic receptors include 3 highly homologous subtypes: α<sub>2A</sub>, α<sub>2B</sub>, and α<sub>2C</sub>. These receptors have a critical role in regulating [[neurotransmitter]] release from [[sympathetic nerves]] and from adrenergic neurons in the [[central nervous system]].
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== Clinical significance ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Adrenergic, alpha-2B-, receptor
| HGNCid = 282
| Symbol = ADRA2B
| AltSymbols =; ADRA2L1; ADRA2RL1; ADRARL1; ALPHA2BAR
| OMIM = 104260
| ECnumber = 
| Homologene = 553
| MGIid = 87935
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004935 |text = adrenoceptor activity}} {{GNF_GO|id=GO:0004938 |text = alpha2-adrenergic receptor activity}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 151
    | Hs_Ensembl = 
    | Hs_RefseqProtein = NP_000673
    | Hs_RefseqmRNA = NM_000682
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 11552
    | Mm_Ensembl = ENSMUSG00000058620
    | Mm_RefseqmRNA = NM_009633
    | Mm_RefseqProtein = NP_033763
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 127054727
    | Mm_GenLoc_end = 127058662
    | Mm_Uniprot = Q6NXV9
  }}
}}
The '''alpha-2B adrenergic receptor''' (α<sub>2B</sub> adrenoreceptor), also known as '''ADRA2B''', is an [[alpha-2 adrenergic receptor]], and also denotes the human [[gene]] encoding it.<ref name="entrez" />


<!-- The PBB_Summary template is not automatically maintained by Protein Box Bot. See Template:PBB_Controls to Continue updates. -->
This gene encodes the α<sub>2B</sub> subtype, which was observed to associate with [[eIF-2B]], a [[guanine nucleotide exchange protein]] that functions in regulation of [[mRNA translation|translation]]. A polymorphic variant of the α<sub>2B</sub> subtype, which lacks 3 [[glutamic acid]]s from a glutamic acid [[repeat element]], was identified to have decreased [[G protein-coupled receptor]] [[kinase]]-mediated phosphorylation and [[desensitization (medicine)|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 region|coding]] or [[untranslated sequence]]s.<ref name="entrez">{{cite web | title = Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=151| accessdate = }}</ref>
{{PBB_Summary
| section_title =  
| summary_text =  


==Receptor==
A deletion variant of the α<sub>2B</sub> adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.<ref name="pmid17660814">{{cite journal | vauthors = de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A | title = A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans | journal = Nature Neuroscience | volume = 10 | issue = 9 | pages = 1137–9 | date = Sep 2007 | pmid = 17660814 | doi = 10.1038/nn1945 }}</ref> This variant also predisposed people who had it to focus more on negative aspects of a situation.<ref name="pmid24058067">{{cite journal | vauthors = Todd RM, Müller DJ, Lee DH, Robertson A, Eaton T, Freeman N, Palombo DJ, Levine B, Anderson AK | title = Genes for emotion-enhanced remembering are linked to enhanced perceiving | journal = Psychol Sci | volume = 24 | issue = 11 | pages = 2244–53 | year = 2013 | pmid = 24058067 | doi = 10.1177/0956797613492423 | laysummary = http://news.ubc.ca/2013/10/10/genes-predispose-some-people-to-focus-on-the-negative/ | laysource = The University of British Columbia }}</ref> 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.<ref name="pmid24155306">{{cite journal | vauthors = Gibbs AA, Bautista CE, Mowlem FD, Naudts KH, Duka T | title = Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers | journal = J. Neurosci. | volume = 33 | issue = 43 | pages = 17023–8 | year = 2013 | pmid = 24155306 | doi = 10.1523/JNEUROSCI.2124-13.2013 | laysummary = http://www.sfn.org/Press-Room/News-Release-Archives/2013/Genetic-Variation-Alters-Efficacy-of-Antidepressant | laysource = Society for Neuroscience }}</ref>
Alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha<sub>2A</sub>, alpha<sub>2B</sub>, and alpha<sub>2C</sub>. These receptors have a critical role in regulating [[neurotransmitter]] release from [[sympathetic nerves]] and from adrenergic neurons in the [[central nervous system]].


==Gene==
== Evolution ==
This gene encodes the alpha<sub>2B</sub> subtype, which was observed to associate with [[eIF-2B]], a [[guanine nucleotide exchange protein]] that functions in regulation of [[mRNA translation|translation]]. A polymorphic variant of the alpha<sub>2B</sub> subtype, which lacks 3 [[glutamic acid]]s 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 region|coding]] or [[untranslated sequence]]s.<ref name="entrez">{{cite web | title = Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=151| accessdate = }}</ref>
}}


==See also==
The ''ADRA2B'' gene (sometimes referenced as ''A2AB'') is used in animals as a [[nuclear DNA]] phylogenetic marker.<ref name="OrthoMaM"/> This intronless gene has first been used to explore the phylogeny of the major groups of [[mammals]],<ref name="pmid11214318">{{cite journal | vauthors = Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R, Amrine HM, Stanhope MJ, de Jong WW, Springer MS | title = Parallel adaptive radiations in two major clades of placental mammals | journal = Nature | volume = 409 | issue = 6820 | pages = 610–4 | date = Feb 2001 | pmid = 11214318 | doi = 10.1038/35054544 }}</ref> 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.<ref name="pmid12446807">{{cite journal | vauthors = Madsen O, Willemsen D, Ursing BM, Arnason U, de Jong WW | title = Molecular evolution of the mammalian alpha 2B adrenergic receptor | journal = Molecular Biology and Evolution | volume = 19 | issue = 12 | pages = 2150–60 | date = Dec 2002 | pmid = 12446807 | doi = 10.1093/oxfordjournals.molbev.a004040 }}</ref>
 
==Ligands==
; Agonists
* (−)-Dibromophakellin<ref name="pmid19243956">{{cite journal | vauthors = Davis RA, Fechner GA, Sykes M, Garavelas A, Pass DM, Carroll AR, Addepalli R, Avery VM, Hooper JN, Quinn RJ | title = (-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata | journal = Bioorganic & Medicinal Chemistry | volume = 17 | issue = 6 | pages = 2497–500 | date = Mar 2009 | pmid = 19243956 | doi = 10.1016/j.bmc.2009.01.065 }}</ref>
 
; Antagonists
* [[Imiloxan]]
* [[Yohimbine]]
 
== See also ==
*[[Adrenergic receptor]]
*[[Adrenergic receptor]]


==References==
== References ==
{{reflist|2}}
{{reflist|33em}}
==Further reading==
 
{{refbegin | 2}}
==External links==
{{PBB_Further_reading
* {{UCSC gene info|ADRA2B}}
| citations =
 
*{{cite journal | author=Lomasney JW, Lorenz W, Allen LF, ''et al.'' |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 13 |pages= 5094-8 |year= 1990 |pmid= 2164221 |doi= }}
== Further reading ==
*{{cite journal | author=McClue SJ, Milligan G |title=The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108-15 cells, interacts directly with the guanine nucleotide binding protein, Gi2. |journal=FEBS Lett. |volume=269 |issue= 2 |pages= 430-4 |year= 1990 |pmid= 2169434 |doi= }}
{{refbegin|33em}}
*{{cite journal | author=Weinshank RL, Zgombick JM, Macchi M, ''et al.'' |title=Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor. |journal=Mol. Pharmacol. |volume=38 |issue= 5 |pages= 681-8 |year= 1990 |pmid= 2172775 |doi=  }}
* {{cite journal | vauthors = Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL, Caron MG, Lefkowitz RJ | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 13 | pages = 5094–8 | date = Jul 1990 | pmid = 2164221 | pmc = 54268 | doi = 10.1073/pnas.87.13.5094 }}
*{{cite journal | author=Chang AC, Ho TF, Chang NC |title=In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans. |journal=Biochem. Biophys. Res. Commun. |volume=172 |issue= 2 |pages= 817-23 |year= 1990 |pmid= 2173582 |doi= }}
* {{cite journal | vauthors = McClue SJ, Milligan G | title = The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108-15 cells, interacts directly with the guanine nucleotide binding protein, Gi2 | journal = FEBS Letters | volume = 269 | issue = 2 | pages = 430–4 | date = Sep 1990 | pmid = 2169434 | doi = 10.1016/0014-5793(90)81209-7 }}
*{{cite journal | author=Regan JW, Kobilka TS, Yang-Feng TL, ''et al.'' |title=Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 17 |pages= 6301-5 |year= 1988 |pmid= 2842764 |doi= }}
* {{cite journal | vauthors = Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR | title = Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor | journal = Molecular Pharmacology | volume = 38 | issue = 5 | pages = 681–8 | date = Nov 1990 | pmid = 2172775 | doi =  }}
*{{cite journal | author=Petrash AC, Bylund DB |title=Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain. |journal=Life Sci. |volume=38 |issue= 23 |pages= 2129-37 |year= 1986 |pmid= 3012234 |doi= }}
* {{cite journal | vauthors = Chang AC, Ho TF, Chang NC | title = In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans | journal = Biochemical and Biophysical Research Communications | volume = 172 | issue = 2 | pages = 817–23 | date = Oct 1990 | pmid = 2173582 | doi = 10.1016/0006-291X(90)90748-C }}
*{{cite journal | author=Klein U, Ramirez MT, Kobilka BK, von Zastrow M |title=A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B. |journal=J. Biol. Chem. |volume=272 |issue= 31 |pages= 19099-102 |year= 1997 |pmid= 9235896 |doi= }}
* {{cite journal | vauthors = Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK | title = Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 17 | pages = 6301–5 | date = Sep 1988 | pmid = 2842764 | pmc = 281957 | doi = 10.1073/pnas.85.17.6301 }}
*{{cite journal | author=Okusa MD, Huang L, Momose-Hotokezaka A, ''et al.'' |title=Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors. |journal=Am. J. Physiol. |volume=273 |issue= 6 Pt 2 |pages= F883-91 |year= 1998 |pmid= 9435676 |doi=  }}
* {{cite journal | vauthors = Petrash AC, Bylund DB | title = Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain | journal = Life Sciences | volume = 38 | issue = 23 | pages = 2129–37 | date = Jun 1986 | pmid = 3012234 | doi = 10.1016/0024-3205(86)90212-2 }}
*{{cite journal | author=Prezeau L, Richman JG, Edwards SW, Limbird LE |title=The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes. |journal=J. Biol. Chem. |volume=274 |issue= 19 |pages= 13462-9 |year= 1999 |pmid= 10224112 |doi= }}
* {{cite journal | vauthors = Klein U, Ramirez MT, Kobilka BK, von Zastrow M | title = A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B | journal = The Journal of Biological Chemistry | volume = 272 | issue = 31 | pages = 19099–102 | date = Aug 1997 | pmid = 9235896 | doi = 10.1074/jbc.272.31.19099 }}
*{{cite journal | author=Heinonen P, Koulu M, Pesonen U, ''et al.'' |title=Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects. |journal=J. Clin. Endocrinol. Metab. |volume=84 |issue= 7 |pages= 2429-33 |year= 1999 |pmid= 10404816 |doi= }}
* {{cite journal | vauthors = Okusa MD, Huang L, Momose-Hotokezaka A, Huynh LP, Mangrum AJ | title = Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors | journal = The American Journal of Physiology | volume = 273 | issue = 6 Pt 2 | pages = F883–91 | date = Dec 1997 | pmid = 9435676 | doi =  }}
*{{cite journal | author=Hein L, Altman JD, Kobilka BK |title=Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. |journal=Nature |volume=402 |issue= 6758 |pages= 181-4 |year= 2000 |pmid= 10647009 |doi= 10.1038/46040 }}
* {{cite journal | vauthors = Prezeau L, Richman JG, Edwards SW, Limbird LE | title = The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes | journal = The Journal of Biological Chemistry | volume = 274 | issue = 19 | pages = 13462–9 | date = May 1999 | pmid = 10224112 | doi = 10.1074/jbc.274.19.13462 }}
*{{cite journal | author=Small KM, Brown KM, Forbes SL, Liggett SB |title=Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization. |journal=J. Biol. Chem. |volume=276 |issue= 7 |pages= 4917-22 |year= 2001 |pmid= 11056163 |doi= 10.1074/jbc.M008118200 }}
* {{cite journal | vauthors = Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M, Valve R, Uusitupa M, Scheinin M | title = Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 84 | issue = 7 | pages = 2429–33 | date = Jul 1999 | pmid = 10404816 | doi = 10.1210/jc.84.7.2429 }}
*{{cite journal | author=Snapir A, Mikkelsson J, Perola M, ''et al.'' |title=Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death. |journal=J. Am. Coll. Cardiol. |volume=41 |issue= 2 |pages= 190-4 |year= 2003 |pmid= 12535806 |doi= }}
* {{cite journal | vauthors = Hein L, Altman JD, Kobilka BK | title = Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission | journal = Nature | volume = 402 | issue = 6758 | pages = 181–4 | date = Nov 1999 | pmid = 10647009 | doi = 10.1038/46040 }}
*{{cite journal | author=Sykiotis GP, Polyzogopoulou E, Georgopoulos NA, ''et al.'' |title=The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity. |journal=Clin. Auton. Res. |volume=13 |issue= 3 |pages= 203-7 |year= 2004 |pmid= 12822042 |doi= 10.1007/s10286-003-0087-5 }}
* {{cite journal | vauthors = Small KM, Brown KM, Forbes SL, Liggett SB | title = Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization | journal = The Journal of Biological Chemistry | volume = 276 | issue = 7 | pages = 4917–22 | date = Feb 2001 | pmid = 11056163 | doi = 10.1074/jbc.M008118200 }}
*{{cite journal | author=Chotani MA, Mitra S, Su BY, ''et al.'' |title=Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells. |journal=Am. J. Physiol. Heart Circ. Physiol. |volume=286 |issue= 1 |pages= H59-67 |year= 2004 |pmid= 12946937 |doi= 10.1152/ajpheart.00268.2003 }}
* {{cite journal | vauthors = Snapir A, Mikkelsson J, Perola M, Penttilä A, Scheinin M, Karhunen PJ | title = Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death | journal = Journal of the American College of Cardiology | volume = 41 | issue = 2 | pages = 190–4 | date = Jan 2003 | pmid = 12535806 | doi = 10.1016/S0735-1097(02)02702-X }}
*{{cite journal | author=Von Wowern F, Bengtsson K, Lindblad U, ''et al.'' |title=Functional variant in the (alpha)2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension. |journal=Hypertension |volume=43 |issue= 3 |pages= 592-7 |year= 2004 |pmid= 14744925 |doi= 10.1161/01.HYP.0000116224.51189.80 }}
* {{cite journal | vauthors = Sykiotis GP, Polyzogopoulou E, Georgopoulos NA, Trakada G, Spyropoulos K, Kalfarentzos F, Papavassiliou AG, Vagenakis AG, Flordellis CS | title = The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity | journal = Clinical Autonomic Research | volume = 13 | issue = 3 | pages = 203–7 | date = Jun 2003 | pmid = 12822042 | doi = 10.1007/s10286-003-0087-5 }}
*{{cite journal | author=Cayla C, Heinonen P, Viikari L, ''et al.'' |title=Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene. |journal=Biochem. Pharmacol. |volume=67 |issue= 3 |pages= 469-78 |year= 2004 |pmid= 15037199 |doi= 10.1016/j.bcp.2003.09.029 }}
* {{cite journal | vauthors = Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR, Montague CR, Paris H, Handy DE, Flavahan NA | title = Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 286 | issue = 1 | pages = H59–67 | date = Jan 2004 | pmid = 12946937 | doi = 10.1152/ajpheart.00268.2003 }}
*{{cite journal | author=Phares DA, Halverstadt AA, Shuldiner AR, ''et al.'' |title=Association between body fat response to exercise training and multilocus ADR genotypes. |journal=Obes. Res. |volume=12 |issue= 5 |pages= 807-15 |year= 2004 |pmid= 15166301 |doi= }}
* {{cite journal | vauthors = Von Wowern F, Bengtsson K, Lindblad U, Råstam L, Melander O | title = Functional variant in the (alpha)2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension | journal = Hypertension | volume = 43 | issue = 3 | pages = 592–7 | date = Mar 2004 | pmid = 14744925 | doi = 10.1161/01.HYP.0000116224.51189.80 }}
*{{cite journal | author=Siitonen N, Lindström J, Eriksson J, ''et al.'' |title=Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study. |journal=Diabetologia |volume=47 |issue= 8 |pages= 1416-24 |year= 2005 |pmid= 15309292 |doi= 10.1007/s00125-004-1462-z }}
* {{cite journal | vauthors = Cayla C, Heinonen P, Viikari L, Schaak S, Snapir A, Bouloumié A, Karvonen MK, Pesonen U, Scheinin M, Paris H | title = Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene | journal = Biochemical Pharmacology | volume = 67 | issue = 3 | pages = 469–78 | date = Feb 2004 | pmid = 15037199 | doi = 10.1016/j.bcp.2003.09.029 }}
*{{cite journal | author=Belfer I, Buzas B, Hipp H, ''et al.'' |title=Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene. |journal=J. Hum. Genet. |volume=50 |issue= 1 |pages= 12-20 |year= 2005 |pmid= 15592690 |doi= 10.1007/s10038-004-0211-y }}
* {{cite journal | vauthors = Phares DA, Halverstadt AA, Shuldiner AR, Ferrell RE, Douglass LW, Ryan AS, Goldberg AP, Hagberg JM | title = Association between body fat response to exercise training and multilocus ADR genotypes | journal = Obesity Research | volume = 12 | issue = 5 | pages = 807–15 | date = May 2004 | pmid = 15166301 | doi = 10.1038/oby.2004.97 }}
}}
* {{cite journal | vauthors = Siitonen N, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Laakso M, Uusitupa M | title = Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study | journal = Diabetologia | volume = 47 | issue = 8 | pages = 1416–24 | date = Aug 2004 | pmid = 15309292 | doi = 10.1007/s00125-004-1462-z }}
* {{cite journal | vauthors = Belfer I, Buzas B, Hipp H, Phillips G, Taubman J, Lorincz I, Evans C, Lipsky RH, Enoch MA, Max MB, Goldman D | title = Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene | journal = Journal of Human Genetics | volume = 50 | issue = 1 | pages = 12–20 | year = 2005 | pmid = 15592690 | doi = 10.1007/s10038-004-0211-y }}
{{refend}}
{{refend}}


{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
[[Category:Adrenergic receptors‎]]
[[Category:G protein coupled receptors]]
[[es:Receptor alfa 2B adrenérgico]]


{{WH}}
[[Category:Adrenergic receptors]]
{{WS}}

Latest revision as of 14:31, 13 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

The alpha-2B adrenergic receptor (α2B 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

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.

Clinical significance

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] This variant also predisposed people who had it to focus more on negative aspects of a situation.[4] 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.[5]

Evolution

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,[6] 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.[7]

Ligands

Agonists
  • (−)-Dibromophakellin[8]
Antagonists

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor".
  2. ↑ 2.0 2.1 "OrthoMaM phylogenetic marker: ADRA2B coding sequence".[permanent dead link]
  3. ↑ 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.
  4. ↑ 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. Lay summary – The University of British Columbia.
  5. ↑ 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. PMID 24155306. Lay summary – Society for Neuroscience.
  6. ↑ 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. doi:10.1038/35054544. PMID 11214318.
  7. ↑ 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.
  8. ↑ 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. PMID 19243956.

External links

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. 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, 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. 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, 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/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.
  • 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.
  • 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.
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