Alpha-2A adrenergic receptor

The alpha-2A adrenergic receptor (α_2A adrenoceptor), also known as ADRA2A, is an α₂ adrenergic receptor, and also denotes the human gene encoding it.[4]

ADRA2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1HLL, 1HO9, 1HOD, 1HOF
Identifiers
Aliases	ADRA2A, ADRA2, ADRA2R, ADRAR, ALPHA2AAR, ZNF32, adrenoceptor alpha 2A
External IDs	OMIM: 104210 MGI: 87934 HomoloGene: 47944 GeneCards: ADRA2A
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q25.2 Start 111,077,029 bp[1] End 111,080,907 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • alpha-2C adrenergic receptor binding • G-protein coupled receptor activity • protein homodimerization activity • epinephrine binding • norepinephrine binding • alpha-1B adrenergic receptor binding • signal transducer activity • adrenergic receptor activity • GO:0001948 protein binding • alpha2-adrenergic receptor activity • protein heterodimerization activity • thioesterase binding • heterotrimeric G-protein binding • protein kinase binding Cellular component • integral component of membrane • membrane • receptor complex • cell membrane • integral component of plasma membrane • basolateral plasma membrane • cytoplasm Biological process • G-protein coupled receptor signaling pathway • positive regulation of epidermal growth factor-activated receptor activity • activation of protein kinase B activity • negative regulation of insulin secretion • positive regulation of MAP kinase activity • negative regulation of epinephrine secretion • glucose homeostasis • regulation of smooth muscle contraction • positive regulation of cytokine production • regulation of insulin secretion • positive regulation of cell migration • positive regulation of potassium ion transport • phospholipase C-activating adrenergic receptor signaling pathway • positive regulation of wound healing • negative regulation of norepinephrine secretion • positive regulation of membrane protein ectodomain proteolysis • negative regulation of insulin secretion involved in cellular response to glucose stimulus • adenylate cyclase-inhibiting adrenergic receptor signaling pathway • negative regulation of calcium ion transmembrane transporter activity • cellular response to hormone stimulus • regulation of vasoconstriction • negative regulation of calcium ion-dependent exocytosis • Rho protein signal transduction • positive regulation of cell proliferation • negative regulation of calcium ion transport • intestinal absorption • Ras protein signal transduction • negative regulation of lipid catabolic process • activation of protein kinase activity • actin cytoskeleton organization • signal transduction • platelet activation • positive regulation of MAPK cascade • adrenergic receptor signaling pathway • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway • adenylate cyclase-activating G-protein coupled receptor signaling pathway • adenylate cyclase-activating adrenergic receptor signaling pathway • receptor transactivation • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	150	11551
Ensembl	ENSG00000150594	n/a
UniProt	P08913	Q01338
RefSeq (mRNA)	NM_000681	NM_007417
RefSeq (protein)	NP_000672	NP_031443
Location (UCSC)	Chr 10: 111.08 – 111.08 Mb	n/a
PubMed search	[2]	[3]
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. Studies in mice revealed that both the α_2A and α_2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the α_2A subtype inhibited transmitter release at high stimulation frequencies, whereas the α_2C subtype modulated neurotransmission at lower levels of nerve activity[5]

Gene

This gene encodes α_2A subtype and it contains no introns in either its coding or untranslated sequences.[4]

Role in central nervous system

Although the pre-synaptic functions of α_2A receptors have been a major focus (see above), the majority of α₂ receptors in the brain are actually localized post-synaptically to noradrenergic terminals, and therefore aid in the function of norepinephrine. Many post-synaptic α_2A receptors have important effects on brain function; for example, α_2A receptors are localized on prefrontal cortical neurons where they regulate higher cognitive function.

Ligands

Agonists

• Clonidine
• Lofexidine
• Dexmedetomidine
• Guanfacine
• Myrcene

Antagonists

• Idazoxan
• 1-PP (active metabolite of buspirone and gepirone)
• Asenapine
• BRL-44408
• Clozapine
• Lurasidone
• Mianserin
• Mirtazapine
• Paliperidone
• Risperidone
• Yohimbine

See also

• Adrenergic receptor

References

1. GRCh38: Ensembl release 89: ENSG00000150594 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: ADRA2A adrenergic, alpha-2A-, receptor".
5. Hein, Lutz; Altman, John D.; Kobilka, Brian K. (1999). "Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission". Nature. 402 (6758): 181–184. doi:10.1038/46040. PMID 10647009.

External links

• "α_2A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Human ADRA2A genome location and ADRA2A gene details page in the UCSC Genome Browser.
• Human ZNF32 genome location and ZNF32 gene details page in the UCSC Genome Browser.

Further reading

• Perälä M, Hirvonen H, Kalimo H, Ala-Uotila S, Regan JW, Akerman KE, Scheinin M (Nov 1992). "Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues". Brain Research. Molecular Brain Research. 16 (1–2): 57–63. doi:10.1016/0169-328X(92)90193-F. PMID 1334200.
• Surprenant A, Horstman DA, Akbarali H, Limbird LE (Aug 1992). "A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents". Science. 257 (5072): 977–80. doi:10.1126/science.1354394. PMID 1354394.
• Handy DE, Gavras H (Nov 1992). "Promoter region of the human alpha 2A adrenergic receptor gene". The Journal of Biological Chemistry. 267 (33): 24017–22. PMID 1385431.
• Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK (Aug 1991). "A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists". The Journal of Biological Chemistry. 266 (23): 15488–92. PMID 1678390.
• Wang CD, Buck MA, Fraser CM (Aug 1991). "Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists". Molecular Pharmacology. 40 (2): 168–79. PMID 1678850.
• Chhajlani V, Rangel N, Uhlén S, Wikberg JE (Mar 1991). "Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR". FEBS Letters. 280 (2): 241–4. doi:10.1016/0014-5793(91)80301-I. PMID 1849485.
• Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ, Limbird LE (Oct 1990). "Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs". The Journal of Biological Chemistry. 265 (28): 17307–17. PMID 2170371.
• Fraser CM, Arakawa S, McCombie WR, Venter JC (Jul 1989). "Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation". The Journal of Biological Chemistry. 264 (20): 11754–61. PMID 2568356.
• Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW (Oct 1987). "Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor". Science. 238 (4827): 650–6. doi:10.1126/science.2823383. PMID 2823383.
• Lynch CJ, Steer ML (Apr 1981). "Evidence for high and low affinity alpha 2-receptors. Comparison of [3H]norepinephrine and [3H]phentolamine binding to human platelet membranes". The Journal of Biological Chemistry. 256 (7): 3298–303. PMID 6259160.
• Eason MG, Moreira SP, Liggett SB (Mar 1995). "Four consecutive serines in the third intracellular loop are the sites for beta-adrenergic receptor kinase-mediated phosphorylation and desensitization of the alpha 2A-adrenergic receptor". The Journal of Biological Chemistry. 270 (9): 4681–8. doi:10.1074/jbc.270.9.4681. PMID 7876239.
• Grassie MA, Milligan G (Mar 1995). "Analysis of the relative interactions between the alpha 2C10 adrenoceptor and the guanine-nucleotide-binding proteins G(o)1 alpha and Gi 2 alpha following co-expression of these polypeptides in rat 1 fibroblasts". The Biochemical Journal. 306 (Pt 2): 525–30. doi:10.1042/bj3060525. PMC 1136549. PMID 7887906.
• Shilo L, Sakaue M, Thomas JM, Philip M, Hoffman BB (Jan 1994). "Enhanced transcription of the human alpha 2A-adrenergic receptor gene by cAMP: evidence for multiple cAMP responsive sequences in the promoter region of this gene". Cellular Signalling. 6 (1): 73–82. doi:10.1016/0898-6568(94)90062-0. PMID 8011430.
• Valet P, Senard JM, Devedjian JC, Planat V, Salomon R, Voisin T, Drean G, Couvineau A, Daviaud D, Denis C (May 1993). "Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa". The Journal of Clinical Investigation. 91 (5): 2049–57. doi:10.1172/JCI116427. PMC 288203. PMID 8098045.
• Alblas J, van Corven EJ, Hordijk PL, Milligan G, Moolenaar WH (Oct 1993). "Gi-mediated activation of the p21ras-mitogen-activated protein kinase pathway by alpha 2-adrenergic receptors expressed in fibroblasts". The Journal of Biological Chemistry. 268 (30): 22235–8. PMID 8226727.
• 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.
• Bétuing S, Daviaud D, Pagès C, Bonnard E, Valet P, Lafontan M, Saulnier-Blache JS (Jun 1998). "Gbeta gamma-independent coupling of alpha2-adrenergic receptor to p21(rhoA) in preadipocytes". The Journal of Biological Chemistry. 273 (25): 15804–10. doi:10.1074/jbc.273.25.15804. PMID 9624180.
• 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.
• 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.
• Schaak S, Cussac D, Cayla C, Devedjian JC, Guyot R, Paris H, Denis C (Aug 2000). "Alpha(2) adrenoceptors regulate proliferation of human intestinal epithelial cells". Gut. 47 (2): 242–50. doi:10.1136/gut.47.2.242. PMC 1728001. PMID 10896916.