ADA2A_MOUSE
ID ADA2A_MOUSE Reviewed; 465 AA.
AC Q01338; Q3URE6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Alpha-2A adrenergic receptor {ECO:0000305};
DE AltName: Full=Alpha-2A adrenoreceptor;
DE Short=Alpha-2A adrenoceptor;
DE Short=Alpha-2AAR;
GN Name=Adra2a {ECO:0000312|MGI:MGI:87934};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1353249;
RA Link R.E., Daunt D.A., Barsh G., Chruscinski A.J., Kobilka B.K.;
RT "Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes
RT and identification of a single amino acid in the mouse alpha 2-C10 homolog
RT responsible for an interspecies variation in antagonist binding.";
RL Mol. Pharmacol. 42:16-27(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-368, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Alpha-2 adrenergic receptors mediate the catecholamine-
CC induced inhibition of adenylate cyclase through the action of G
CC proteins.
CC -!- INTERACTION:
CC Q01338; Q14232: EIF2B1; Xeno; NbExp=2; IntAct=EBI-491073, EBI-491065;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAA37213.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA37213.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M99377; AAA37213.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK141573; BAE24742.1; -; mRNA.
DR EMBL; AC113491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC138531; AAI38532.1; -; mRNA.
DR CCDS; CCDS29905.1; -.
DR PIR; I49481; I49481.
DR RefSeq; NP_031443.4; NM_007417.4.
DR AlphaFoldDB; Q01338; -.
DR BMRB; Q01338; -.
DR SMR; Q01338; -.
DR IntAct; Q01338; 1.
DR STRING; 10090.ENSMUSP00000036203; -.
DR ChEMBL; CHEMBL4075; -.
DR DrugCentral; Q01338; -.
DR GlyGen; Q01338; 2 sites.
DR iPTMnet; Q01338; -.
DR PhosphoSitePlus; Q01338; -.
DR MaxQB; Q01338; -.
DR PaxDb; Q01338; -.
DR PeptideAtlas; Q01338; -.
DR PRIDE; Q01338; -.
DR ProteomicsDB; 285608; -.
DR ProteomicsDB; 344753; -.
DR Antibodypedia; 31769; 349 antibodies from 37 providers.
DR DNASU; 11551; -.
DR Ensembl; ENSMUST00000036700; ENSMUSP00000036203; ENSMUSG00000033717.
DR Ensembl; ENSMUST00000237285; ENSMUSP00000157421; ENSMUSG00000033717.
DR GeneID; 11551; -.
DR KEGG; mmu:11551; -.
DR UCSC; uc008hxi.1; mouse.
DR CTD; 150; -.
DR MGI; MGI:87934; Adra2a.
DR VEuPathDB; HostDB:ENSMUSG00000033717; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161451; -.
DR HOGENOM; CLU_009579_11_1_1; -.
DR InParanoid; Q01338; -.
DR OMA; KILCRVD; -.
DR OrthoDB; 737211at2759; -.
DR PhylomeDB; Q01338; -.
DR TreeFam; TF316350; -.
DR Reactome; R-MMU-390696; Adrenoceptors.
DR Reactome; R-MMU-392023; Adrenaline signalling through Alpha-2 adrenergic receptor.
DR Reactome; R-MMU-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR Reactome; R-MMU-418597; G alpha (z) signalling events.
DR Reactome; R-MMU-5683826; Surfactant metabolism.
DR BioGRID-ORCS; 11551; 4 hits in 74 CRISPR screens.
DR PRO; PR:Q01338; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q01338; protein.
DR Bgee; ENSMUSG00000033717; Expressed in pontine nuclear group and 169 other tissues.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0098691; C:dopaminergic synapse; IMP:SynGO.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0004935; F:adrenergic receptor activity; IMP:MGI.
DR GO; GO:0031696; F:alpha-2C adrenergic receptor binding; ISO:MGI.
DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; ISO:MGI.
DR GO; GO:0051379; F:epinephrine binding; ISO:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0032795; F:heterotrimeric G-protein binding; ISO:MGI.
DR GO; GO:0051380; F:norepinephrine binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0031996; F:thioesterase binding; ISO:MGI.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:MGI.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:MGI.
DR GO; GO:0002526; P:acute inflammatory response; ISO:MGI.
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:MGI.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; ISO:MGI.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:MGI.
DR GO; GO:0006260; P:DNA replication; ISO:MGI.
DR GO; GO:0042596; P:fear response; IMP:MGI.
DR GO; GO:0007565; P:female pregnancy; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0042593; P:glucose homeostasis; ISO:MGI.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; ISO:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:MGI.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:MGI.
DR GO; GO:0070473; P:negative regulation of uterine smooth muscle contraction; ISO:MGI.
DR GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; ISO:MGI.
DR GO; GO:0030168; P:platelet activation; IEA:InterPro.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR GO; GO:0035624; P:receptor transactivation; ISO:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IMP:SynGO.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0050955; P:thermoception; ISO:MGI.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
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_0000069081"
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..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..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:0000250|UniProtKB:P22909"
FT MOD_RES 368
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
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"
SQ SEQUENCE 465 AA; 50555 MW; 0F23BA14F516F701 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 ERGAGPTGAE AEPLPTQLNG APGEPAPAGP
RDGDALDLEE SSSSEHAERP PGPRRPDRGP RAKGKTRASQ VKPGDSLPRR GPGAAGPGAS
GSGHGEERGG GAKASRWRGR QNREKRFTFV LAVVIGVFVV CWFPFFFTYT LIAVGCPVPS
QLFNFFFWFG YCNSSLNPVI YTIFNHDFRR AFKKILCRGD RKRIV
