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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
 
 
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