Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NameAlpha-2A adrenergic receptor
Synonyms
  • ADRA2R
  • ADRAR
  • Alpha-2 adrenergic receptor subtype C10
  • Alpha-2A adrenoceptor
  • Alpha-2A adrenoreceptor
  • Alpha-2AAR
Gene NameADRA2A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0021255|Alpha-2A adrenergic receptor
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Number of residues450
Molecular Weight48956.275
Theoretical pI10.2
GO Classification
Functions
  • heterotrimeric G-protein binding
  • alpha2-adrenergic receptor activity
  • epinephrine binding
  • norepinephrine binding
  • protein kinase binding
  • thioesterase binding
  • protein homodimerization activity
  • alpha-1B adrenergic receptor binding
  • protein heterodimerization activity
  • alpha-2C adrenergic receptor binding
Processes
  • Rho protein signal transduction
  • DNA replication
  • positive regulation of epidermal growth factor-activated receptor activity
  • negative regulation of epinephrine secretion
  • negative regulation of adrenergic receptor signaling pathway
  • cellular response to hormone stimulus
  • positive regulation of potassium ion transport
  • positive regulation of cell migration
  • negative regulation of insulin secretion involved in cellular response to glucose stimulus
  • negative regulation of calcium ion transmembrane transporter activity
  • negative regulation of norepinephrine secretion
  • Ras protein signal transduction
  • negative regulation of uterine smooth muscle contraction
  • negative regulation of calcium ion-dependent exocytosis
  • female pregnancy
  • negative regulation of cAMP biosynthetic process
  • phospholipase C-activating adrenergic receptor signaling pathway
  • fear response
  • cell-cell signaling
  • positive regulation of wound healing
  • movement of cell or subcellular component
  • negative regulation of calcium ion transport
  • platelet activation
  • energy reserve metabolic process
  • intestinal absorption
  • negative regulation of adenylate cyclase activity
  • regulation of vasoconstriction
  • positive regulation of vasodilation
  • G-protein coupled receptor signaling pathway
  • positive regulation of membrane protein ectodomain proteolysis
  • thermoception
  • positive regulation of MAP kinase activity
  • small molecule metabolic process
  • activation of MAPK activity by adrenergic receptor signaling pathway
  • regulation of insulin secretion
  • positive regulation of cytokine production
  • acute inflammatory response
  • activation of protein kinase B activity
  • positive regulation of cell proliferation
  • activation of protein kinase activity
  • signal transduction
  • negative regulation of insulin secretion
  • glucose homeostasis
  • adenylate cyclase-inhibiting adrenergic receptor signaling pathway
  • blood coagulation
  • negative regulation of lipid catabolic process
  • actin cytoskeleton organization
  • epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway
Components
  • integral component of plasma membrane
  • plasma membrane
  • receptor complex
  • basolateral plasma membrane
  • synapse
  • cytoplasm
General FunctionThioesterase binding
Specific FunctionAlpha-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 Regions34-59 71-96 107-129 152-172 195-217 375-395 410-429
GenBank Protein ID178196
UniProtKB IDP08913
UniProtKB Entry NameADA2A_HUMAN
Cellular LocationCell 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
GenBank Gene IDM23533
GeneCard IDNot Available
GenAtlas IDADRA2A
HGNC IDHGNC:281
Chromosome Location10
Locus10q24-q26
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 11888275