Alpha-2A adrenergic receptor

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Alpha-2A adrenergic receptor

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Adrenergic, alpha-2A-, receptor

PDB rendering based on 1hll.

Available structures
PDB	1HLL, 1HO9, 1HOD, 1HOF

Identifiers

Symbols

ADRA2A; ADRA2; ADRA2R; ADRAR; ALPHA2AAR; ZNF32

External IDs

OMIM: 104210 MGI: 87934 HomoloGene: 47944 IUPHAR: α_2A-adrenoceptor GeneCards: ADRA2A Gene

Gene Ontology
Molecular function	• receptor activity • G-protein coupled receptor activity • adrenergic receptor activity • alpha2-adrenergic receptor activity • alpha2-adrenergic receptor activity • protein binding • protein kinase binding • alpha-1B adrenergic receptor binding • alpha-2C adrenergic receptor binding • thioesterase binding • heterotrimeric G-protein binding • protein homodimerization activity • protein heterodimerization activity • protein heterodimerization activity • epinephrine binding • norepinephrine binding
Cellular component	• cytoplasm • plasma membrane • plasma membrane • integral to plasma membrane • basolateral plasma membrane • receptor complex
Biological process	• positive regulation of cytokine production • energy reserve metabolic process • cellular component movement • signal transduction • G-protein coupled receptor protein signaling pathway • negative regulation of adenylate cyclase activity • Ras protein signal transduction • Rho protein signal transduction • blood coagulation • positive regulation of cell proliferation • negative regulation of norepinephrine secretion • negative regulation of norepinephrine secretion • actin cytoskeleton organization • positive regulation of cell migration • negative regulation of cAMP biosynthetic process • negative regulation of cAMP biosynthetic process • activation of protein kinase activity • activation of protein kinase B activity • negative regulation of epinephrine secretion • cellular response to hormone stimulus • epidermal growth factor receptor transactivation by G-protein coupled receptor signaling pathway • glucose homeostasis • fear response • positive regulation of potassium ion transport • positive regulation of MAP kinase activity • positive regulation of epidermal growth factor receptor activity • negative regulation of calcium ion-dependent exocytosis • negative regulation of insulin secretion • regulation of insulin secretion • intestinal absorption • negative regulation of lipid catabolic process • positive regulation of membrane protein ectodomain proteolysis • negative regulation of calcium ion transport via voltage-gated calcium channel activity • negative regulation of insulin secretion involved in cellular response to glucose stimulus • inhibition of adenylate cyclase activity by adrenergic receptor signaling pathway • activation of phospholipase C activity by adrenergic receptor signaling pathway • activation of MAPK activity by adrenergic receptor signaling pathway • positive regulation of wound healing
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
112.84 – 112.84 Mb

Chr 19:
54.12 – 54.12 Mb

PubMed search

[1]

[2]

The alpha-2A adrenergic receptor (α_2A adrenoceptor), also known as ADRA2A, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.^[1]

Contents

1 Receptor
2 Gene
3 Role in Central Nervous System
4 Selective Ligands
- 4.1 Agonists
- 4.2 Antagonists
5 See also
6 References
7 External links
8 Further reading

Receptor

Alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha_2A, alpha_2B, and alpha_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 alpha_2A and alpha_2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha_2C subtype modulated neurotransmission at lower levels of nerve activity.

Gene

This gene encodes alpha_2A subtype and it contains no introns in either its coding or untranslated sequences.^[1]

Role in Central Nervous System

Although the pre-synaptic functions of alpha-2A receptors have been a major focus (see above), the majority of alpha-2 receptors in the brain are actually localized post-synaptic to noradrenergic terminals^{[citation needed]}. Many post-synaptic alpha-2A receptors have important effects on brain function; for example, alpha-2A receptors are localized on prefrontal cortical neurons where they regulate higher cognitive function.

Selective Ligands

Agonists

Guanfacine

Clonidine

Antagonists

References

^ ^a ^b "Entrez Gene: ADRA2A adrenergic, alpha-2A-, receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=150.

External links

"α_2A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2181.

Perälä M, Hirvonen H, Kalimo H et al. (1993). "Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues". Brain Res. Mol. Brain Res. 16 (1–2): 57–63. doi:10.1016/0169-328X(92)90193-F. PMID 1334200.
Surprenant A, Horstman DA, Akbarali H, Limbird LE (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 (1992). "Promoter region of the human alpha 2A adrenergic receptor gene". J. Biol. Chem. 267 (33): 24017–22. PMID 1385431.
Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK (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". J. Biol. Chem. 266 (23): 15488–92. PMID 1678390.
Wang CD, Buck MA, Fraser CM (1991). "Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists". Mol. Pharmacol. 40 (2): 168–79. PMID 1678850.
Chhajlani V, Rangel N, Uhlén S, Wikberg JE (1991). "Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR". FEBS Lett. 280 (2): 241–4. doi:10.1016/0014-5793(91)80301-I. PMID 1849485.
Guyer CA, Horstman DA, Wilson AL et al. (1990). "Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs". J. Biol. Chem. 265 (28): 17307–17. PMID 2170371.
Fraser CM, Arakawa S, McCombie WR, Venter JC (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". J. Biol. Chem. 264 (20): 11754–61. PMID 2568356.
Kobilka BK, Matsui H, Kobilka TS et al. (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 (1981). "Evidence for high and low affinity alpha 2-receptors. Comparison of [3H]norepinephrine and [3H]phentolamine binding to human platelet membranes". J. Biol. Chem. 256 (7): 3298–303. PMID 6259160.
Eason MG, Moreira SP, Liggett SB (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". J. Biol. Chem. 270 (9): 4681–8. doi:10.1074/jbc.270.9.4681. PMID 7876239.
Grassie MA, Milligan G (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". Biochem. J. 306 ( Pt 2) (Pt 2): 525–30. PMC 1136549. PMID 7887906. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1136549.
Shilo L, Sakaue M, Thomas JM et al. (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". Cell. Signal. 6 (1): 73–82. doi:10.1016/0898-6568(94)90062-0. PMID 8011430.
Valet P, Senard JM, Devedjian JC et al. (1993). "Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa". J. Clin. Invest. 91 (5): 2049–57. doi:10.1172/JCI116427. PMC 288203. PMID 8098045. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=288203.
Alblas J, van Corven EJ, Hordijk PL et al. (1993). "Gi-mediated activation of the p21ras-mitogen-activated protein kinase pathway by alpha 2-adrenergic receptors expressed in fibroblasts". J. Biol. Chem. 268 (30): 22235–8. PMID 8226727.
Klein U, Ramirez MT, Kobilka BK, von Zastrow M (1997). "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". J. Biol. Chem. 272 (31): 19099–102. doi:10.1074/jbc.272.31.19099. PMID 9235896.
Bétuing S, Daviaud D, Pagès C et al. (1998). "Gbeta gamma-independent coupling of alpha2-adrenergic receptor to p21(rhoA) in preadipocytes". J. Biol. Chem. 273 (25): 15804–10. doi:10.1074/jbc.273.25.15804. PMID 9624180.
Prezeau L, Richman JG, Edwards SW, Limbird LE (1999). "The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes". J. Biol. Chem. 274 (19): 13462–9. doi:10.1074/jbc.274.19.13462. PMID 10224112.
Hein L, Altman JD, Kobilka BK (2000). "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 et al. (2000). "Alpha2 adrenoceptors regulate proliferation of human intestinal epithelial cells". Gut 47 (2): 242–50. doi:10.1136/gut.47.2.242. PMC 1728001. PMID 10896916. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1728001.

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

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, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)

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

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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