ADA2A_RAT
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 03-AUG-2022, entry version 154.
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;
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).
CC -!- FUNCTION: Alpha-2 adrenergic receptors mediate the catecholamine-
CC induced inhibition of adenylate cyclase through the action of G
CC proteins.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
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}.
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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 STRING; 10116.ENSRNOP00000066242; -.
DR BindingDB; P22909; -.
DR ChEMBL; CHEMBL327; -.
DR DrugCentral; P22909; -.
DR GlyGen; P22909; 2 sites.
DR iPTMnet; P22909; -.
DR PhosphoSitePlus; P22909; -.
DR PaxDb; P22909; -.
DR PRIDE; P22909; -.
DR Ensembl; ENSRNOT00000071541; ENSRNOP00000066242; ENSRNOG00000047545.
DR GeneID; 25083; -.
DR KEGG; rno:25083; -.
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; KILCRVD; -.
DR OrthoDB; 737211at2759; -.
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 Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000047545; Expressed in brain and 18 other tissues.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA: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:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0004935; F:adrenergic receptor activity; 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:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
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:0032147; P:activation of protein kinase activity; ISO:RGD.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:RGD.
DR GO; GO:0002526; P:acute inflammatory response; IMP:RGD.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic 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: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: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: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:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; 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:0090303; P:positive regulation of wound healing; ISO:RGD.
DR GO; GO:0035624; P:receptor transactivation; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEP:RGD.
DR GO; GO:0050955; P:thermoception; IDA:RGD.
DR GO; GO:0042311; P:vasodilation; IDA:RGD.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR001946; ADRA2A_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
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 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..48
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 49..74
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 75..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 86..111
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 112..121
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 122..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 145..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 165..188
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 189..207
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 208..232
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 233..389
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 390..414
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 415..424
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 425..445
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 446..465
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 242..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..334
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 128
FT /note="Implicated in ligand binding"
FT /evidence="ECO:0000250"
FT SITE 215
FT /note="Implicated in catechol agonist binding"
FT /evidence="ECO:0000250"
FT SITE 219
FT /note="Implicated in catechol agonist binding"
FT /evidence="ECO:0000250"
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
