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

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]
Band	10q25.2	End	111,080,907 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 19 (mouse)^[2]

Band	19 D2\|19 49.04 cM	Start	54,032,582 bp^[2]
Band	19 D2\|19 49.04 cM	End	54,037,413 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

subcutaneous adipose tissue

canal of the cervix

pericardium

gallbladder

ganglionic eminence

body of pancreas

abdominal fat

germinal epithelium

pancreatic ductal cell

lymph node

Top expressed in

pontine nuclei

islet of Langerhans

dorsomedial hypothalamic nucleus

subiculum

mammillary body

medullary collecting duct

conjunctival fornix

lateral hypothalamus

anterior horn of spinal cord

inferior colliculus

More reference expression data

BioGPS


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 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 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 population 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


ENSMUSG00000033717

UniProt


P08913


Q01338

RefSeq (mRNA)


NM_000681


NM_007417

RefSeq (protein)


NP_000672


NP_031443

Location (UCSC)

Chr 10: 111.08 – 111.08 Mb

Chr 19: 54.03 – 54.04 Mb

PubMed search

^[3]

^[4]

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 gene encoding it.^[5]

YouTube Encyclopedic

1/5
Views:
1 233 965
2 611
71 818
117 076
665

Transcription

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^[6]

Gene

This gene encodes α_2A subtype and it contains no introns in either its coding or untranslated sequences.^[5]

Ligands

Agonists

Antagonists

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

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000150594 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033717 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ADRA2A adrenergic, alpha-2A-, receptor".
^ Hein, Lutz; Altman, John D.; Kobilka, Brian K. (1999). "Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission". Nature. 402 (6758): 181–184. Bibcode:1999Natur.402..181H. doi:10.1038/46040. PMID 10647009. S2CID 205047992.
^ Fink EA, Xu J, Hübner H, Braz JM, Seemann P, Avet C, et al. (September 2022). "Structure-based discovery of nonopioid analgesics acting through the α_2A-adrenergic receptor". Science. 377 (6614): eabn7065. doi:10.1126/science.abn7065. PMC 10360211. PMID 36173843.

External links

"α_2A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2015-04-02. Retrieved 2008-11-25.
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.

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. Bibcode:1992Sci...257..977S. 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. doi:10.1016/S0021-9258(18)35938-6. 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. doi:10.1016/S0021-9258(18)98642-4. 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. S2CID 26642747.
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. doi:10.1016/S0021-9258(17)44904-0. 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. doi:10.1016/S0021-9258(18)80130-2. 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. Bibcode:1987Sci...238..650K. 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. doi:10.1016/S0021-9258(19)69606-7. 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. doi:10.1016/S0021-9258(18)41514-1. 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. Bibcode:1999Natur.402..181H. doi:10.1038/46040. PMID 10647009. S2CID 205047992.
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 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 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) Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) 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 (1
2))
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)
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

Taste, bitter	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 type 1
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 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, sweet	TAS1R 1 2 3 Vomeronasal receptor, type 2
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)