Alpha-2A adrenergic receptor

Details

Name
Alpha-2A adrenergic receptor
Synonyms
  • ADRA2R
  • ADRAR
  • Alpha-2 adrenergic receptor subtype C10
  • Alpha-2A adrenoceptor
  • Alpha-2A adrenoreceptor
  • Alpha-2AAR
Gene Name
ADRA2A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021255|Alpha-2A adrenergic receptor
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Number of residues
450
Molecular Weight
48956.275
Theoretical pI
10.2
GO Classification
Functions
alpha-1B adrenergic receptor binding / alpha-2C adrenergic receptor binding / alpha2-adrenergic receptor activity / epinephrine binding / heterotrimeric G-protein binding / norepinephrine binding / protein heterodimerization activity / protein homodimerization activity / protein kinase binding / thioesterase binding
Processes
actin cytoskeleton organization / activation of MAPK activity by adrenergic receptor signaling pathway / activation of protein kinase activity / activation of protein kinase B activity / acute inflammatory response / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / blood coagulation / cell-cell signaling / cellular response to hormone stimulus / DNA replication / energy reserve metabolic process / epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway / fear response / female pregnancy / G-protein coupled receptor signaling pathway / glucose homeostasis / intestinal absorption / movement of cell or subcellular component / negative regulation of adenylate cyclase activity / negative regulation of adrenergic receptor signaling pathway / negative regulation of calcium ion transmembrane transporter activity / negative regulation of calcium ion transport / negative regulation of calcium ion-dependent exocytosis / negative regulation of cAMP biosynthetic process / negative regulation of epinephrine secretion / negative regulation of insulin secretion / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of lipid catabolic process / negative regulation of norepinephrine secretion / negative regulation of uterine smooth muscle contraction / phospholipase C-activating adrenergic receptor signaling pathway / platelet activation / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cytokine production / positive regulation of epidermal growth factor-activated receptor activity / positive regulation of MAP kinase activity / positive regulation of membrane protein ectodomain proteolysis / positive regulation of potassium ion transport / positive regulation of vasodilation / positive regulation of wound healing / Ras protein signal transduction / regulation of insulin secretion / regulation of vasoconstriction / Rho protein signal transduction / signal transduction / small molecule metabolic process / thermoception
Components
basolateral plasma membrane / cytoplasm / integral component of plasma membrane / plasma membrane / receptor complex / synapse
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Pfam Domain Function
Transmembrane Regions
34-59 71-96 107-129 152-172 195-217 375-395 410-429
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021256|Alpha-2A adrenergic receptor (ADRA2A)
ATGTTCCGCCAGGAGCAGCCGTTGGCCGAGGGCAGCTTTGCGCCCATGGGCTCCCTGCAG
CCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGGGGCGGCGCCCGGGCC
ACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCCGGCCTGCTCATGCTG
CTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACGAGCCGCGCGCTCAAG
GCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATCCTGGTGGCCACGCTC
GTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTACTTCGGCAAGGCTTGG
TGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCCATCGTGCACCTGTGC
GCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAGTACAACCTGAAGCGC
ACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATCTCGGCCGTCATCTCC
TTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGCCCGCAGCCGGCCGAG
CCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCGTGCATCGGCTCCTTC
TTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTACCAGATCGCCAAGCGT
CGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCCGCGCCGCCGGGGGGC
ACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGCCCGGGGGGCGCAGAG
GCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCCGCGCCGGCCGGGCCG
CGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGACCACGCCGAGCGGCCT
CCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAGGCCCGAGCGAGCCAG
GTGAAGCCGGGCGACAGCCTGCCGCGGCGCGGGCCGGGGGCGACGGGGATCGGGACGCCG
GCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCGCGCTGGCGCGGGCGG
CAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATCGGAGTGTTCGTGGTG
TGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGGTGCTCCGTGCCACGC
ACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCGTTGAACCCGGTCATC
TACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATCCTCTGTCGGGGGGAC
AGGAAGCGGATCGTGTGA
Chromosome Location
10
Locus
10q24-q26
External Identifiers
ResourceLink
UniProtKB IDP08913
UniProtKB Entry NameADA2A_HUMAN
GenBank Protein ID178196
GenBank Gene IDM23533
GenAtlas IDADRA2A
HGNC IDHGNC:281
General References
  1. Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW: Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650-6. [PubMed:2823383]
  2. Fraser CM, Arakawa S, McCombie WR, Venter JC: 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. 1989 Jul 15;264(20):11754-61. [PubMed:2568356]
  3. Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE: 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. 1990 Oct 5;265(28):17307-17. [PubMed:2170371]
  4. Small KM, Forbes SL, Brown KM, Liggett SB: An asn to lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling. J Biol Chem. 2000 Dec 8;275(49):38518-23. [PubMed:10948191]
  5. Small KM, Brown KM, Seman CA, Theiss CT, Liggett SB: Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5472-7. Epub 2006 Mar 27. [PubMed:16567612]
  6. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  8. Chhajlani V, Rangel N, Uhlen S, Wikberg JE: Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. 1991 Mar 25;280(2):241-4. [PubMed:1849485]
  9. Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK: 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. 1991 Aug 15;266(23):15488-92. [PubMed:1678390]
  10. Wang CD, Buck MA, Fraser CM: Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol. 1991 Aug;40(2):168-79. [PubMed:1678850]
  11. Li C, Fan Y, Lan TH, Lambert NA, Wu G: Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi. J Biol Chem. 2012 Dec 14;287(51):42784-94. doi: 10.1074/jbc.M112.410936. Epub 2012 Oct 26. [PubMed:23105096]
  12. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR: NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry. 2002 Mar 19;41(11):3596-604. [PubMed:11888275]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00449DipivefrinapprovedyesagonistDetails
DB00484BrimonidineapprovedyesagonistDetails
DB00575ClonidineapprovedyesagonistDetails
DB00629Guanabenzapproved, investigationalyesagonistDetails
DB00633Dexmedetomidineapproved, vet_approvedyesagonistDetails
DB00692PhentolamineapprovedyesantagonistDetails
DB00865Benzphetamineapproved, illicityesagonistDetails
DB00964ApraclonidineapprovedyesagonistDetails
DB00968MethyldopaapprovedyesDetails
DB01018Guanfacineapproved, investigationalyesagonistDetails
DB00370MirtazapineapprovedyesantagonistDetails
DB00656Trazodoneapproved, investigationalnoantagonistDetails
DB00800FenoldopamapprovedunknownantagonistDetails
DB00852PseudoephedrineapprovedyesagonistDetails
DB00935Oxymetazolineapproved, investigationalyesagonistpartial agonistDetails
DB01392Yohimbineapproved, investigational, vet_approvedyesantagonistDetails
DB00321AmitriptylineapprovednoantagonistagonistDetails
DB014724-Methoxyamphetamineexperimental, illicityesagonistDetails
DB00368NorepinephrineapprovedyesagonistDetails
DB00696Ergotamineapprovedunknownpartial agonistDetails
DB04855DronedaroneapprovedyesantagonistDetails
DB00751Epinastineapproved, investigationalunknownunknownDetails
DB06148Mianserinapproved, investigationalunknownantagonistDetails
DB04948Lofexidineapproved, investigationalyesagonistDetails
DB05492Epicept NP-1investigationalunknownDetails
DB06262Droxidopaapproved, investigationalyesagonistDetails
DB06216AsenapineapprovedunknownantagonistDetails
DB06229OcaperidoneinvestigationalunknownDetails
DB06623FlupirtineinvestigationalunknownDetails
DB06694Xylometazolineapproved, investigationalyesagonistDetails
DB01186Pergolideapproved, investigational, vet_approved, withdrawnunknownagonistDetails
DB01200Bromocriptineapproved, investigationalunknownagonistDetails
DB00589Lisurideapproved, investigationalunknownother/unknownDetails
DB00248CabergolineapprovedunknownantagonistDetails
DB00413Pramipexoleapproved, investigationalunknownagonistDetails
DB00714Apomorphineapproved, investigationalunknownagonistDetails
DB00734Risperidoneapproved, investigationalunknownantagonistDetails
DB01267PaliperidoneapprovedunknownantagonistDetails
DB01224QuetiapineapprovedunknownantagonistDetails
DB00246ZiprasidoneapprovednoantagonistDetails
DB00363ClozapineapprovednoantagonistDetails
DB01238Aripiprazoleapproved, investigationalnoantagonistDetails
DB01403Methotrimeprazineapproved, investigationalunknownantagonistDetails
DB01608Periciazineapproved, investigationalyesantagonistDetails
DB01624Zuclopenthixolapproved, investigationalunknownantagonistDetails
DB01149Nefazodoneapproved, withdrawnunknownantagonistDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB00797Tolazolineapproved, vet_approvedunknownantagonistDetails
DB00320Dihydroergotamineapproved, investigationalunknownagonistDetails
DB06711Naphazolineapproved, investigationalyesagonistDetails
DB00925PhenoxybenzamineapprovedyesantagonistDetails
DB01363Ephedra sinica rootnutraceuticalyesagonistDetails
DB01577Metamfetamineapproved, illicityesagonistDetails
DB00668Epinephrineapproved, vet_approvedyesagonistDetails
DB08815Lurasidoneapproved, investigationalunknownDetails
DB00408LoxapineapprovedunknownbinderDetails
DB01136Carvedilolapproved, investigationalunknownantagonistDetails
DB00726Trimipramineapprovedunknowndesensitize the targetDetails
DB00457PrazosinapprovedunknownbinderDetails
DB09242Moxonidineapproved, investigationalyesagonistDetails
DB11738Rilmenidineapproved, investigationalunknownDetails
DB00555Lamotrigineapproved, investigationalunknowninhibitorDetails
DB09244PirlindoleexperimentalunknownantagonistDetails
DB09286PipamperoneinvestigationalunknownantagonistDetails
DB11124RacepinephrineapprovedyesagonistDetails
DB06153PizotifenapprovedunknownantagonistDetails
DB11278DL-MethylephedrineapprovedyesagonistDetails
DB04846Celiprololapproved, investigationalunknownantagonistDetails
DB14185Aripiprazole lauroxilapproved, investigationalnoDetails
DB00502HaloperidolapprovedunknownDetails
DB00697Tizanidineapproved, investigationalunknownagonistDetails
DB00217BethanidineapprovedyesagonistDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedunknowninhibitorDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB00540NortriptylineapprovedunknownantagonistDetails
DB00934Maprotilineapproved, investigationalunknownantagonistDetails
DB01151Desipramineapproved, investigationalunknownbinderDetails
DB09202CirazolineexperimentalyesantagonistDetails
DB06678EsmirtazapineinvestigationalunknownantagonistDetails
DB06707LevonordefrinapprovedyesagonistDetails
DB13025TiaprideinvestigationalyesantagonistDetails
DB09167DosulepinapprovedyesantagonistDetails
DB09304SetiptilineexperimentalunknownantagonistDetails
DB00397Phenylpropanolamineapproved, vet_approved, withdrawnunknownDetails
DB09194EtoperidonewithdrawnunknownantagonistDetails
DB09195LorpiprazoleapprovedyesantagonistDetails
DB11477Xylazinevet_approvedyesagonistDetails
DB00433Prochlorperazineapproved, vet_approvednoantagonistDetails
DB00715Paroxetineapproved, investigationalunknownbinderDetails
DB00193Tramadolapproved, investigationalyesstimulatorDetails
DB01175EscitalopramapprovedunknowninhibitorDetails
DB01365MephentermineapprovedyesagonistDetails
DB00182Amphetamineapproved, illicit, investigationalunknownagonistDetails
DB09205Moxisylyteapproved, investigationalyesantagonistDetails
DB09229AranidipineexperimentalunknownagonistDetails
DB11577Indigotindisulfonic acidapprovednoagonistDetails
DB13345Dihydroergocristineapproved, experimentalyesantagonistagonistDetails
DB01049Ergoloid mesylateapprovedyesantagonistagonistDetails
DB11273DihydroergocornineapprovedyesantagonistagonistDetails
DB11278DL-MethylephedrineapprovedyesagonistDetails
DB00268Ropiniroleapproved, investigationalunknownantagonistDetails