AA3R_RAT
ID AA3R_RAT Reviewed; 320 AA.
AC P28647; Q63792;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Adenosine receptor A3;
DE AltName: Full=TGPCR1;
GN Name=Adora3;
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] (ISOFORM A), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=1323836; DOI=10.1073/pnas.89.16.7432;
RA Zhou Q.Y., Li C.Y., Olah M.E., Johnson R.A., Stiles G.L., Civelli O.;
RT "Molecular cloning and characterization of an adenosine receptor: the A3
RT adenosine receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7432-7436(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Wistar; TISSUE=Testis;
RX PubMed=1647979; DOI=10.1016/0014-5793(91)80674-r;
RA Meyerhof W., Mueller-Brechlin R., Richter D.;
RT "Molecular cloning of a novel putative G-protein coupled receptor expressed
RT during rat spermiogenesis.";
RL FEBS Lett. 284:155-160(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Brain;
RX PubMed=8612733; DOI=10.1016/0014-5793(96)00150-0;
RA Sajjadi F.G., Boyle D.L., Domingo R.C., Firestein G.S.;
RT "cDNA cloning and characterization of A3i, an alternatively spliced rat A3
RT adenosine receptor variant.";
RL FEBS Lett. 382:125-129(1996).
RN [4]
RP PHOSPHORYLATION AT THR-307; THR-318 AND THR-319, AND MUTAGENESIS OF
RP 302-CYS--CYS-305; THR-307; THR-318 AND THR-319.
RX PubMed=10692494; DOI=10.1124/mol.57.3.539;
RA Palmer T.M., Stiles G.L.;
RT "Identification of threonine residues controlling the agonist-dependent
RT phosphorylation and desensitization of the rat A(3) adenosine receptor.";
RL Mol. Pharmacol. 57:539-545(2000).
CC -!- FUNCTION: Receptor for adenosine. The activity of this receptor is
CC mediated by G proteins which inhibits adenylyl cyclase
CC (PubMed:1323836). May play a role during reproduction (PubMed:1647979).
CC {ECO:0000269|PubMed:1323836, ECO:0000303|PubMed:1647979}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q28309};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P28647-1; Sequence=Displayed;
CC Name=B; Synonyms=A3i;
CC IsoId=P28647-2; Sequence=VSP_001859;
CC -!- TISSUE SPECIFICITY: Testis, particularly in spermatocytes and
CC spermatids but not in spermatogonia. Low levels in the brain.
CC {ECO:0000269|PubMed:1647979}.
CC -!- DEVELOPMENTAL STAGE: Expressed during spermiogenesis.
CC {ECO:0000269|PubMed:1647979}.
CC -!- PTM: Phosphorylation on Thr-318 and Thr-319 may be crucial for rapid
CC desensitization. Phosphorylation on Thr-318 may be necessary for
CC phosphorylation on Thr-319 to occur. {ECO:0000269|PubMed:10692494}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; X59249; CAA41937.1; -; mRNA.
DR EMBL; M94152; AAA40680.1; -; mRNA.
DR EMBL; X93219; CAA63702.1; -; mRNA.
DR PIR; A46152; A46152.
DR PIR; S17177; S17177.
DR PIR; S68678; S68678.
DR RefSeq; NP_001289679.1; NM_001302750.1. [P28647-2]
DR RefSeq; NP_001289680.1; NM_001302751.1. [P28647-1]
DR RefSeq; NP_001289684.1; NM_001302755.1. [P28647-2]
DR RefSeq; NP_037028.2; NM_012896.3. [P28647-1]
DR AlphaFoldDB; P28647; -.
DR SMR; P28647; -.
DR DIP; DIP-217N; -.
DR STRING; 10116.ENSRNOP00000021236; -.
DR BindingDB; P28647; -.
DR ChEMBL; CHEMBL3360; -.
DR DrugCentral; P28647; -.
DR GuidetoPHARMACOLOGY; 21; -.
DR GlyGen; P28647; 2 sites.
DR iPTMnet; P28647; -.
DR PhosphoSitePlus; P28647; -.
DR PaxDb; P28647; -.
DR Ensembl; ENSRNOT00000021236; ENSRNOP00000021236; ENSRNOG00000015788. [P28647-2]
DR GeneID; 100911796; -.
DR GeneID; 25370; -.
DR KEGG; rno:100911796; -.
DR UCSC; RGD:2051; rat. [P28647-1]
DR CTD; 140; -.
DR RGD; 2051; Adora3.
DR VEuPathDB; HostDB:ENSRNOG00000015788; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234555; -.
DR HOGENOM; CLU_009579_11_5_1; -.
DR InParanoid; P28647; -.
DR OMA; INCITYF; -.
DR OrthoDB; 550297at2759; -.
DR PhylomeDB; P28647; -.
DR TreeFam; TF325296; -.
DR Reactome; R-RNO-417973; Adenosine P1 receptors.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:P28647; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000015788; Expressed in testis and 10 other tissues.
DR Genevisible; P28647; RN.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; EXP:SynGO.
DR GO; GO:0045202; C:synapse; 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:0001973; P:G protein-coupled adenosine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0002553; P:histamine secretion by mast cell; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:RGD.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISO:RGD.
DR GO; GO:0070257; P:positive regulation of mucus secretion; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IMP:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; EXP:SynGO.
DR InterPro; IPR000466; Adeno_A3_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; PR00555; ADENOSINEA3R.
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 Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..320
FT /note="Adenosine receptor A3"
FT /id="PRO_0000069013"
FT TOPO_DOM 1..16
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 17..39
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 40..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 51..74
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 75..86
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 87..108
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 109..128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 129..150
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 151..179
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 180..200
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 201..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 234..257
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 258..263
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 264..286
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 287..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT MOD_RES 307
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:10692494"
FT MOD_RES 318
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:10692494"
FT MOD_RES 319
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:10692494"
FT LIPID 305
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 85..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 119
FT /note="R -> RLSFLVVNLPFSSPHSNR (in isoform B)"
FT /evidence="ECO:0000303|PubMed:8612733"
FT /id="VSP_001859"
FT MUTAGEN 302..305
FT /note="CRLC->ARLA: Promotes agonist-independent
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10692494"
FT MUTAGEN 307
FT /note="T->A: Small decrease in agonist-stimulated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10692494"
FT MUTAGEN 318
FT /note="T->A,E: Strong decrease in agonist-stimulated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10692494"
FT MUTAGEN 319
FT /note="T->A: 50% decrease in agonist-stimulated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10692494"
FT CONFLICT 18
FT /note="I -> V (in Ref. 1; AAA40680)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="I -> V (in Ref. 3; CAA63702)"
FT /evidence="ECO:0000305"
FT CONFLICT 74..83
FT /note="VSLEVQMHFY -> SAWRSRCTSM (in Ref. 2; CAA41937)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="F -> L (in Ref. 3; CAA63702)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="S -> F (in Ref. 1; AAA40680)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="I -> N (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 291..295
FT /note="FKETY -> VQRNH (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 320 AA; 36629 MW; 59DBA40C594ACDAB CRC64;
MKANNTTTSA LWLQITYITM EAAIGLCAVV GNMLVIWVVK LNRTLRTTTF YFIVSLALAD
IAVGVLVIPL AIAVSLEVQM HFYACLFMSC VLLVFTHASI MSLLAIAVDR YLRVKLTVRY
RTVTTQRRIW LFLGLCWLVS FLVGLTPMFG WNRKVTLELS QNSSTLSCHF RSVVGLDYMV
FFSFITWILI PLVVMCIIYL DIFYIIRNKL SQNLTGFRET RAFYGREFKT AKSLFLVLFL
FALCWLPLSI INFVSYFNVK IPEIAMCLGI LLSHANSMMN PIVYACKIKK FKETYFVILR
ACRLCQTSDS LDSNLEQTTE