ADA2A_PIG
ID ADA2A_PIG Reviewed; 465 AA.
AC P18871;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Alpha-2A adrenergic receptor {ECO:0000250|UniProtKB:P08913};
DE AltName: Full=Alpha-2A adrenoreceptor;
DE Short=Alpha-2A adrenoceptor;
DE Short=Alpha-2AAR;
GN Name=ADRA2A {ECO:0000250|UniProtKB:P08913}; Synonyms=A2AR;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 227-247.
RC TISSUE=Liver;
RX PubMed=2170371; DOI=10.1016/s0021-9258(17)44904-0;
RA Guyer C.A., Horstman D.A., Wilson A.L., Clark J.D., Kragoe E.J. Jr.,
RA Limbird L.E.;
RT "Cloning, sequencing, and expression of the gene encoding the porcine alpha
RT 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride
RT analogs.";
RL J. Biol. Chem. 265:17307-17317(1990).
RN [2]
RP PALMITOYLATION AT CYS-457, AND MUTAGENESIS OF CYS-457.
RX PubMed=8385131; DOI=10.1016/s0021-9258(18)53056-8;
RA Kennedy M.E., Limbird L.E.;
RT "Mutations of the alpha 2A-adrenergic receptor that eliminate detectable
RT palmitoylation do not perturb receptor-G-protein coupling.";
RL J. Biol. Chem. 268:8003-8011(1993).
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 -!- MISCELLANEOUS: Alpha2-adrenergic receptor shows an allosteric
CC modulation by Na(+), H(+) and amiloride analogs.
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=AAA30984.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; J05652; AAA30984.1; ALT_INIT; Genomic_DNA.
DR PIR; A38316; A38316.
DR RefSeq; NP_999565.1; NM_214400.1.
DR AlphaFoldDB; P18871; -.
DR BMRB; P18871; -.
DR SMR; P18871; -.
DR STRING; 9823.ENSSSCP00000011323; -.
DR ChEMBL; CHEMBL2350; -.
DR DrugCentral; P18871; -.
DR SwissPalm; P18871; -.
DR PaxDb; P18871; -.
DR PRIDE; P18871; -.
DR Ensembl; ENSSSCT00000011625; ENSSSCP00000011323; ENSSSCG00000010629.
DR Ensembl; ENSSSCT00015028889; ENSSSCP00015011354; ENSSSCG00015021867.
DR Ensembl; ENSSSCT00025092632; ENSSSCP00025040649; ENSSSCG00025067450.
DR Ensembl; ENSSSCT00030075296; ENSSSCP00030034415; ENSSSCG00030054037.
DR Ensembl; ENSSSCT00035084472; ENSSSCP00035035142; ENSSSCG00035062837.
DR Ensembl; ENSSSCT00040016783; ENSSSCP00040006763; ENSSSCG00040012693.
DR Ensembl; ENSSSCT00045040543; ENSSSCP00045028217; ENSSSCG00045023737.
DR Ensembl; ENSSSCT00050057601; ENSSSCP00050024621; ENSSSCG00050042390.
DR Ensembl; ENSSSCT00055021131; ENSSSCP00055016718; ENSSSCG00055010776.
DR Ensembl; ENSSSCT00060016376; ENSSSCP00060006468; ENSSSCG00060012491.
DR Ensembl; ENSSSCT00065018548; ENSSSCP00065007578; ENSSSCG00065013945.
DR Ensembl; ENSSSCT00070016176; ENSSSCP00070013391; ENSSSCG00070008384.
DR GeneID; 399501; -.
DR KEGG; ssc:399501; -.
DR CTD; 150; -.
DR VGNC; VGNC:85156; ADRA2A.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161451; -.
DR HOGENOM; CLU_009579_11_1_1; -.
DR InParanoid; P18871; -.
DR OMA; KILCRVD; -.
DR OrthoDB; 737211at2759; -.
DR TreeFam; TF316350; -.
DR SABIO-RK; P18871; -.
DR Proteomes; UP000008227; Chromosome 14.
DR Proteomes; UP000314985; Chromosome 14.
DR Bgee; ENSSSCG00000010629; Expressed in uterus and 30 other tissues.
DR ExpressionAtlas; P18871; baseline and differential.
DR Genevisible; P18871; SS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043235; C:receptor complex; IEA:Ensembl.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; IPI:BHF-UCL.
DR GO; GO:0031696; F:alpha-2C adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; IDA:BHF-UCL.
DR GO; GO:0051379; F:epinephrine binding; IDA:BHF-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0032795; F:heterotrimeric G-protein binding; IEA:Ensembl.
DR GO; GO:0051380; F:norepinephrine binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0031996; F:thioesterase binding; IEA:Ensembl.
DR GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
DR GO; GO:0042596; P:fear response; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:1901020; P:negative regulation of calcium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
DR GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; IEA:InterPro.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0090303; P:positive regulation of wound healing; IEA:Ensembl.
DR GO; GO:0035624; P:receptor transactivation; IEA:Ensembl.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; IEA:InterPro.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
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; Direct protein sequencing; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW Methylation; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..465
FT /note="Alpha-2A adrenergic receptor"
FT /id="PRO_0000069082"
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 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:0000250|UniProtKB:Q01338"
FT LIPID 457
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8385131"
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 MUTAGEN 457
FT /note="C->A,S: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:8385131"
SQ SEQUENCE 465 AA; 50666 MW; 868A4DF315CB5974 CRC64;
MFRQEQPLAE GSFAPMGSLQ PEAGNASWNG TEAPGGGARA TPYSLQVTLT LVCLAGLLML
FTVFGNVLVI IAVFTSRALK APQNLFLVSL ASADILVATL VIPFSLANEV MGYWYFGKAW
CEIYLALDVL FCTSSIVHLC AISLDRYWSI TQAIEYNLKR TPRRIKAIIV TVWVISAVIS
FPPLISIEKK AGGGGQQPAE PRCEINDQKW YVISSCIGSF FAPCLIMILV YVRIYQIAKR
RTRVPPSRRG PDAAAALPGG AERRPNGLGP ERGVGRVGAE AEPLPVQLNG APGEPAPAGP
RDADGLDLEE SSSSEHAERP PGPRRSERGP RAKSKARASQ VKPGDSLPRR GPGAPGPGAP
ATGAGEERGG VAKASRWRGR QNREKRFTFV LAVVIGVFVV CWFPFFFTYT LTAVGCSVPP
TLFKFFFWFG YCNSSLNPVI YTIFNHDFRR AFKKILCRGD RKRIV
