Alpha-2B adrenergic receptor

ADRA2B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesADRA2B, ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, alpha-2BAR, FAME2, adrenoceptor alpha 2B
External IDsOMIM: 104260; MGI: 87935; HomoloGene: 553; GeneCards: ADRA2B; OMA:ADRA2B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000682

NM_009633

RefSeq (protein)

NP_000673

NP_033763

Location (UCSC)Chr 2: 96.11 – 96.12 MbChr 2: 127.21 – 127.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] ADRA2B orthologs[6] have been identified in several mammals.

Receptor

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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

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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.[5]

A deletion variant of the α2B 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

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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

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Agonists
  • (−)-Dibromophakellin[12]
Antagonists

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000274286Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000058620Ensembl, 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. ^ a b "Entrez Gene: ADRA2B adrenergic, alpha-2B-, receptor".
  6. ^ a b "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.
  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.
  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.
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Further reading

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