Alpha-2A adrenergic receptor

ADRA2A

Available structures

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

MGI: 87934 HomoloGene: 47944 GeneCards: ADRA2A

Targeted by Drug

apraclonidine, guanabenz, epinephrine, brimonidine, norepinephrine, apomorphine, clonidine, dexmedetomidine, guanfacine, oxymetazoline, pergolide, xylazine, brl-44408, bromocriptine, cabergoline, chlorpromazine, lisuride, lurasidone, mirtazapine, phentolamine, piribedil, prazosin, α-yohimbine, spiroxatrine, terguride, tolazoline, wb-4101, yohimbine^[1]

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 • 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 • plasma 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 • negative regulation of adenylate cyclase activity • movement of cell or subcellular component • 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 • epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway • 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 • activation of MAPK activity by adrenergic receptor signaling pathway • adenylate cyclase-activating adrenergic receptor signaling pathway • 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 cAMP biosynthetic process • negative regulation of calcium ion transport • intestinal absorption • negative regulation of adrenergic receptor signaling pathway • Ras protein signal transduction • negative regulation of lipid catabolic process • activation of protein kinase activity • actin cytoskeleton organization • signal transduction • platelet activation
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


150


11551

Ensembl


ENSG00000150594


ENSMUSG00000033717

UniProt


P08913


Q01338

RefSeq (mRNA)


NM_000681


NM_007417

RefSeq (protein)


NP_000672.3


n/a

Location (UCSC)

Chr 10: 111.08 – 111.08 Mb

Chr 19: 54.05 – 54.05 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

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

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.

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

Antagonists

References

External links

"α_2A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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.

PDB gallery

1hll: NMR STRUCTURE OF T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA-2A ADRENERGIC RECEPTOR

1ho9: BEST 20 NMR CONFORMERS OF D130I MUTANT T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA 2A ADRENERGIC RECEPTOR

1hod: NMR STRUCTURE OF D130I MUTANT T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA 2A ADRENERGIC RECEPTOR

1hof: NMR STRUCTURE OF T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA-2A ADRENERGIC RECEPTOR

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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