ID ADA2A_RAT Reviewed; 465 AA. AC P22909; M0R9R3; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 11-DEC-2019, sequence version 3. DT 02-SEP-2026, entry version 173. DE RecName: Full=Alpha-2A adrenergic receptor {ECO:0000305}; DE AltName: Full=Alpha-2A adrenoreceptor; DE Short=Alpha-2A adrenoceptor; DE Short=Alpha-2AAR; DE AltName: Full=Alpha-2D adrenergic receptor; DE AltName: Full=CA2-47 {ECO:0000303|PubMed:7623790}; GN Name=Adra2a {ECO:0000312|RGD:2056}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-465. RX PubMed=2177834; DOI=10.1007/bf00221058; RA Chalberg S.C., Duda T., Rhine J.A., Sharma R.K.; RT "Molecular cloning, sequencing and expression of an alpha 2-adrenergic RT receptor complementary DNA from rat brain."; RL Mol. Cell. Biochem. 97:161-172(1990). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-465. RX PubMed=1645350; DOI=10.1016/s0021-9258(18)99248-3; RA Lanier S.M., Downing S., Duzic E., Homcy C.J.; RT "Isolation of rat genomic clones encoding subtypes of the alpha 2- RT adrenergic receptor. Identification of a unique receptor subtype."; RL J. Biol. Chem. 266:10470-10478(1991). RN [5] RP TISSUE SPECIFICITY. RX PubMed=7623790; DOI=10.1007/bf00944398; RA Wypijewski K., Duda T., Sharma R.K.; RT "Structural, genetic and pharmacological identity of the rat alpha 2- RT adrenergic receptor subtype cA2-47 and its molecular characterization in RT rat adrenal, adrenocortical carcinoma and bovine retina."; RL Mol. Cell. Biochem. 144:181-190(1995). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-346, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [7] RP FUNCTION. RX PubMed=15213003; DOI=10.1016/j.brainres.2004.04.025; RA Timmons S.D., Geisert E., Stewart A.E., Lorenzon N.M., Foehring R.C.; RT "alpha2-Adrenergic receptor-mediated modulation of calcium current in RT neocortical pyramidal neurons."; RL Brain Res. 1014:184-196(2004). CC -!- FUNCTION: Alpha-2 adrenergic receptors are G protein-coupled receptors CC for catecholamines that activate the G(i/o) protein pathway, thereby CC promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage- CC gated calcium channels suppression (PubMed:15213003). ADRA2A and ADRA2C CC mediates the presynaptic feedback inhibition of neurotransmitter CC release from noradrenergic nerve terminals in sympathetic and central CC nervous systems. ADRA2A inhibits transmitter release at high CC stimulation frequencies, whereas ADRA2C modulates neurotransmission at CC lower levels of nerve activity (By similarity). CC {ECO:0000250|UniProtKB:Q01338, ECO:0000269|PubMed:15213003}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08913}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P08913}. CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:7623790}. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRA2A sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-16 is the initiator. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AABR07006974; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH473986; EDL94449.1; -; Genomic_DNA. DR EMBL; U79031; AAC24959.1; -; mRNA. DR EMBL; M62372; AAA42034.1; -; Genomic_DNA. DR PIR; B40392; B40392. DR PIR; JH0190; JH0190. DR RefSeq; NP_036871.3; NM_012739.3. DR AlphaFoldDB; P22909; -. DR BMRB; P22909; -. DR SMR; P22909; -. DR CORUM; P22909; -. DR FunCoup; P22909; 449. DR STRING; 10116.ENSRNOP00000066242; -. DR BindingDB; P22909; -. DR ChEMBL; CHEMBL327; -. DR DrugCentral; P22909; -. DR GuidetoPHARMACOLOGY; 25; -. DR GlyCosmos; P22909; 2 sites, No reported glycans. DR GlyGen; P22909; 2 sites. DR iPTMnet; P22909; -. DR PhosphoSitePlus; P22909; -. DR PaxDb; 10116-ENSRNOP00000066242; -. DR Ensembl; ENSRNOT00000071541.3; ENSRNOP00000066242.1; ENSRNOG00000047545.3. DR Ensembl; ENSRNOT00055049903; ENSRNOP00055041101; ENSRNOG00055028819. DR Ensembl; ENSRNOT00060028861; ENSRNOP00060023231; ENSRNOG00060016882. DR Ensembl; ENSRNOT00065017573; ENSRNOP00065013499; ENSRNOG00065010837. DR GeneID; 25083; -. DR KEGG; rno:25083; -. DR AGR; RGD:2056; -. DR CTD; 150; -. DR RGD; 2056; Adra2a. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000161451; -. DR HOGENOM; CLU_009579_11_1_1; -. DR InParanoid; P22909; -. DR OMA; FFTYMLM; -. DR OrthoDB; 5975661at2759; -. DR PhylomeDB; P22909; -. DR Reactome; R-RNO-390696; Adrenoceptors. DR Reactome; R-RNO-392023; Adrenaline signalling through Alpha-2 adrenergic receptor. DR Reactome; R-RNO-400042; Adrenaline,noradrenaline inhibits insulin secretion. DR Reactome; R-RNO-418594; G alpha (i) signalling events. DR Reactome; R-RNO-418597; G alpha (z) signalling events. DR Reactome; R-RNO-5683826; Surfactant metabolism. DR PRO; PR:P22909; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000047545; Expressed in brain and 18 other cell types or tissues. DR GO; GO:0043679; C:axon terminus; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0098691; C:dopaminergic synapse; ISO:RGD. DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO. DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO. DR GO; GO:0048787; C:presynaptic active zone membrane; IDA:SynGO. DR GO; GO:0043235; C:signaling receptor complex; ISO:RGD. DR GO; GO:0004935; F:adrenergic receptor activity; ISO:RGD. DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; ISO:RGD. DR GO; GO:0031696; F:alpha-2C adrenergic receptor binding; ISO:RGD. DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; IDA:RGD. DR GO; GO:0051379; F:epinephrine binding; ISO:RGD. DR GO; GO:0032795; F:heterotrimeric G-protein binding; ISO:RGD. DR GO; GO:0051380; F:norepinephrine binding; ISO:RGD. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD. DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0031996; F:thioesterase binding; ISO:RGD. DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; ISO:RGD. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; ISO:RGD. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0071875; P:adrenergic receptor signaling pathway; ISO:RGD. DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:RGD. DR GO; GO:0006260; P:DNA replication; IMP:RGD. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0042596; P:fear response; ISO:RGD. DR GO; GO:0007565; P:female pregnancy; IMP:RGD. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0042593; P:glucose homeostasis; IMP:BHF-UCL. DR GO; GO:0051926; P:negative regulation of calcium ion transport; ISO:RGD. DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IMP:BHF-UCL. DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:RGD. DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:BHF-UCL. DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:RGD. DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; ISS:UniProtKB. DR GO; GO:0070473; P:negative regulation of uterine smooth muscle contraction; IMP:RGD. DR GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; ISO:RGD. DR GO; GO:0030168; P:platelet activation; IEA:InterPro. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:RGD. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0043268; P:positive regulation of potassium ion transport; ISO:RGD. DR GO; GO:0090303; P:positive regulation of wound healing; ISO:RGD. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD. DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro. DR GO; GO:0097305; P:response to alcohol; IEP:RGD. DR GO; GO:0043278; P:response to morphine; IEP:RGD. DR GO; GO:0050955; P:thermoception; IDA:RGD. DR GO; GO:0042311; P:vasodilation; IDA:RGD. DR CDD; cd15322; 7tmA_alpha2A_AR; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR001946; ADRA2A_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24248:SF24; ALPHA-2A ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00558; ADRENRGCA2AR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 1: Evidence at protein level; KW Cell membrane; Disulfide bond; G protein-coupled receptor; Glycoprotein; KW Lipoprotein; Membrane; Methylation; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..465 FT /note="Alpha-2A adrenergic receptor" FT /id="PRO_0000069083" FT TOPO_DOM 1..47 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 48..71 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 72..85 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 86..107 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 108..120 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 121..144 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 145..167 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 168..181 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 182..208 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 209..232 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 233..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 389..413 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 414..421 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 422..443 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P08913" FT TOPO_DOM 444..465 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 242..377 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 313..330 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 353..364 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 128 FT /note="Implicated in norepinephrine binding" FT /evidence="ECO:0000250|UniProtKB:P08913" FT SITE 215 FT /note="Implicated in catechol and norepinephrine agonist FT binding and receptor activation" FT /evidence="ECO:0000250|UniProtKB:P08913" FT SITE 219 FT /note="Implicated in catechol agonist binding and receptor FT activation" FT /evidence="ECO:0000250|UniProtKB:P08913" FT SITE 409 FT /note="Implicated in norepinephrine binding and receptor FT activation" FT /evidence="ECO:0000250|UniProtKB:P08913" FT SITE 427 FT /note="Implicated in norepinephrine binding and receptor FT activation" FT /evidence="ECO:0000250|UniProtKB:P08913" FT SITE 431 FT /note="Implicated in norepinephrine binding and receptor FT activation" FT /evidence="ECO:0000250|UniProtKB:P08913" FT MOD_RES 346 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 368 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q01338" FT LIPID 457 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CARBOHYD 25 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 29 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 121..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT CONFLICT 267..268 FT /note="GL -> AV (in Ref. 4; AAA42034)" FT /evidence="ECO:0000305" FT CONFLICT 319..320 FT /note="RP -> PR (in Ref. 4; AAA42034)" FT /evidence="ECO:0000305" FT CONFLICT 348 FT /note="P -> R (in Ref. 4; AAA42034)" FT /evidence="ECO:0000305" SQ SEQUENCE 465 AA; 50630 MW; 50FDE09BC56F4C96 CRC64; MFRQEQPLAE GSFAPMGSLQ PDAGNSSWNG TEAPGGGTRA TPYSLQVTLT LVCLAGLLML FTVFGNVLVI IAVFTSRALK APQNLFLVSL ASADILVATL VIPFSLANEV MGYWYFGKVW CEIYLALDVL FCTSSIVHLC AISLDRYWSI TQAIEYNLKR TPRRIKAIIV TVWVISAVIS FPPLISIEKK GAGGGQQPAE PSCKINDQKW YVISSSIGSF FAPCLIMILV YVRIYQIAKR RTRVPPSRRG PDACSAPPGG ADRRPNGLGP ERGAGTAGAE AEPLPTQLNG APGEPAPTRP RDGDALDLEE SSSSEHAERP QGPGKPERGP RAKGKTKASQ VKPGDSLPRR GPGAAGPGAS GSGQGEERAG GAKASRWRGR QNREKRFTFV LAVVIGVFVV CWFPFFFTYT LIAVGCPVPY QLFNFFFWFG YCNSSLNPVI YTIFNHDFRR AFKKILCRGD RKRIV //