AA2AR_RAT
ID AA2AR_RAT Reviewed; 410 AA.
AC P30543;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Adenosine receptor A2a;
GN Name=Adora2a;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=1599465; DOI=10.1016/s0006-291x(05)90000-4;
RA Chern Y., King K., Lai H.-L., Lai H.-T.;
RT "Molecular cloning of a novel adenosine receptor gene from rat brain.";
RL Biochem. Biophys. Res. Commun. 185:304-309(1992).
RN [2]
RP SEQUENCE REVISION TO 183.
RC TISSUE=Brain;
RA Chern Y.;
RL Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Corpus striatum;
RX PubMed=1279342; DOI=10.1016/0169-328x(92)90173-9;
RA Fink J.S., Weaver D.R., Rivkees S.A., Peterfreund R.A., Pollack A.E.,
RA Adler E.M., Reppert S.M.;
RT "Molecular cloning of the rat A2 adenosine receptor: selective co-
RT expression with D2 dopamine receptors in rat striatum.";
RL Brain Res. Mol. Brain Res. 14:186-195(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yip L., Hewitt J., Kwok Y.;
RT "Rattus norvegicus mucosa A2A adenosine receptor mRNA.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=16339847; DOI=10.1124/mol.105.015818;
RA Milojevic T., Reiterer V., Stefan E., Korkhov V.M., Dorostkar M.M.,
RA Ducza E., Ogris E., Boehm S., Freissmuth M., Nanoff C.;
RT "The ubiquitin-specific protease Usp4 regulates the cell surface level of
RT the A2A receptor.";
RL Mol. Pharmacol. 69:1083-1094(2006).
RN [7]
RP FUNCTION, INTERACTION WITH GAS2L2, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=23994616; DOI=10.1016/j.bbamcr.2013.08.009;
RA Wu Y.C., Lai H.L., Chang W.C., Lin J.T., Liu Y.J., Chern Y.;
RT "A novel Galphas-binding protein, Gas-2 like 2, facilitates the signaling
RT of the A2A adenosine receptor.";
RL Biochim. Biophys. Acta 1833:3145-3154(2013).
CC -!- FUNCTION: Receptor for adenosine (By similarity). The activity of this
CC receptor is mediated by G proteins which activate adenylyl cyclase
CC (PubMed:23994616). {ECO:0000250|UniProtKB:P11617,
CC ECO:0000269|PubMed:23994616}.
CC -!- SUBUNIT: Interacts (via cytoplasmic C-terminal domain) with USP4; the
CC interaction is direct (By similarity). May interact with DRD4 (By
CC similarity). Interacts with NECAB2 (By similarity). Interacts (via
CC cytoplasmic C-terminal domain) with GAS2L2; interaction enhances
CC receptor-mediated adenylyl cyclase activity (PubMed:23994616).
CC {ECO:0000250|UniProtKB:P29274, ECO:0000269|PubMed:23994616}.
CC -!- INTERACTION:
CC P30543; P20272: Cnr1; NbExp=3; IntAct=EBI-2902822, EBI-2909800;
CC P30543; Q9QZE7: Tsnax; Xeno; NbExp=6; IntAct=EBI-2902822, EBI-2910751;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16339847,
CC ECO:0000269|PubMed:23994616}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16339847}. Note=Colocalizes with GAS2L2 at neuronal
CC processes. {ECO:0000269|PubMed:23994616}.
CC -!- TISSUE SPECIFICITY: Expressed in striatal neurons (at protein level).
CC {ECO:0000269|PubMed:23994616}.
CC -!- DOMAIN: The cytoplasmic C-terminal domain is necessary for targeting
CC the non-ubiquitinated form of this protein to the cell surface.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by USP4; leading to stabilization
CC and expression at the cell surface (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M91214; AAA70305.2; -; mRNA.
DR EMBL; L08102; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S47609; AAA11888.1; -; mRNA.
DR EMBL; AF228684; AAF61924.1; -; mRNA.
DR EMBL; BC081727; AAH81727.1; -; mRNA.
DR PIR; A48974; A48974.
DR RefSeq; NP_445746.3; NM_053294.4.
DR RefSeq; XP_017457041.1; XM_017601552.1.
DR RefSeq; XP_017457042.1; XM_017601553.1.
DR RefSeq; XP_017457043.1; XM_017601554.1.
DR RefSeq; XP_017457044.1; XM_017601555.1.
DR AlphaFoldDB; P30543; -.
DR SMR; P30543; -.
DR BioGRID; 247408; 6.
DR IntAct; P30543; 7.
DR STRING; 10116.ENSRNOP00000001759; -.
DR BindingDB; P30543; -.
DR ChEMBL; CHEMBL302; -.
DR DrugCentral; P30543; -.
DR GuidetoPHARMACOLOGY; 19; -.
DR GlyGen; P30543; 2 sites.
DR PhosphoSitePlus; P30543; -.
DR PaxDb; P30543; -.
DR Ensembl; ENSRNOT00000001759; ENSRNOP00000001759; ENSRNOG00000001302.
DR GeneID; 25369; -.
DR KEGG; rno:25369; -.
DR UCSC; RGD:2049; rat.
DR CTD; 135; -.
DR RGD; 2049; Adora2a.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234555; -.
DR HOGENOM; CLU_009579_11_5_1; -.
DR InParanoid; P30543; -.
DR OMA; YTNGEIH; -.
DR OrthoDB; 550297at2759; -.
DR PhylomeDB; P30543; -.
DR TreeFam; TF325296; -.
DR Reactome; R-RNO-417973; Adenosine P1 receptors.
DR Reactome; R-RNO-5683826; Surfactant metabolism.
DR PRO; PR:P30543; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000001302; Expressed in heart and 18 other tissues.
DR Genevisible; P30543; RN.
DR GO; GO:0032279; C:asymmetric synapse; IDA:RGD.
DR GO; GO:0030673; C:axolemma; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0012505; C:endomembrane system; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO-UCL.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO-UCL.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
DR GO; GO:0048786; C:presynaptic active zone; IDA:RGD.
DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD.
DR GO; GO:0051393; F:alpha-actinin binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0001609; F:G protein-coupled adenosine receptor activity; IDA:RGD.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IPI:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0048143; P:astrocyte activation; IMP:RGD.
DR GO; GO:0110148; P:biomineralization; ISO:RGD.
DR GO; GO:0042755; P:eating behavior; IMP:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IDA:RGD.
DR GO; GO:0001973; P:G protein-coupled adenosine receptor signaling pathway; IDA:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; IMP:RGD.
DR GO; GO:0051899; P:membrane depolarization; IMP:RGD.
DR GO; GO:0046636; P:negative regulation of alpha-beta T cell activation; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0040013; P:negative regulation of locomotion; IDA:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:RGD.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:RGD.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; IMP:RGD.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0045938; P:positive regulation of circadian sleep/wake cycle, sleep; IDA:RGD.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; IDA:RGD.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IMP:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:RGD.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IDA:RGD.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISO:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IDA:RGD.
DR GO; GO:0035810; P:positive regulation of urine volume; IMP:RGD.
DR GO; GO:0060134; P:prepulse inhibition; IMP:RGD.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0051924; P:regulation of calcium ion transport; IMP:RGD.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:RGD.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IMP:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0043279; P:response to alkaloid; IMP:RGD.
DR GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR GO; GO:0031000; P:response to caffeine; IDA:RGD.
DR GO; GO:0010035; P:response to inorganic substance; ISO:RGD.
DR GO; GO:0014074; P:response to purine-containing compound; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; IMP:RGD.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; ISO:RGD.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IDA:RGD.
DR GO; GO:0042311; P:vasodilation; IMP:RGD.
DR InterPro; IPR001513; Adeno_A2A_rcpt.
DR InterPro; IPR001634; Adenosn_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00553; ADENOSINA2AR.
DR PRINTS; PR00424; ADENOSINER.
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 Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..410
FT /note="Adenosine receptor A2a"
FT /id="PRO_0000069001"
FT TOPO_DOM 1..4
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 5..29
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 30..39
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 40..63
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 64..74
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 75..97
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 98..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 118..140
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 141..168
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 169..193
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 194..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 230..253
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 254..261
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 262..285
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 286..410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 322..410
FT /note="Interaction with GAS2L2"
FT /evidence="ECO:0000269|PubMed:23994616"
FT REGION 344..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 164
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P29274"
FT BINDING 248
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P29274"
FT BINDING 272
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P29274"
FT BINDING 273
FT /ligand="adenosine"
FT /ligand_id="ChEBI:CHEBI:16335"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P29274"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 71..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 74..161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 254..257
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 268
FT /note="A -> T (in Ref. 1; AAA70305)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 44999 MW; D87B256CD2336BAC CRC64;
MGSSVYITVE LAIAVLAILG NVLVCWAVWI NSNLQNVTNF FVVSLAAADI AVGVLAIPFA
ITISTGFCAA CHGCLFFACF VLVLTQSSIF SLLAIAIDRY IAIRIPLRYN GLVTGVRAKG
IIAICWVLSF AIGLTPMLGW NNCSQKDGNS TKTCGEGRVT CLFEDVVPMN YMVYYNFFAF
VLLPLLLMLA IYLRIFLAAR RQLKQMESQP LPGERTRSTL QKEVHAAKSL AIIVGLFALC
WLPLHIINCF TFFCSTCRHA PPWLMYLAII LSHSNSVVNP FIYAYRIREF RQTFRKIIRT
HVLRRQEPFQ AGGSSAWALA AHSTEGEQVS LRLNGHPLGV WANGSATHSG RRPNGYTLGL
GGGGSAQGSP RDVELPTQER QEGQEHPGLR GHLVQARVGA SSWSSEFAPS
