ID AA3R_HUMAN Reviewed; 318 AA.
AC P0DMS8; A2A3P4; P33765; Q6UWU0; Q9BYZ1;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 24-JAN-2024, entry version 60.
DE RecName: Full=Adenosine receptor A3;
GN Name=ADORA3 {ECO:0000312|HGNC:HGNC:268};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8399349; DOI=10.1016/0167-4889(93)90077-3;
RA Sajjadi F.G., Firestein G.S.;
RT "cDNA cloning and sequence analysis of the human A3 adenosine receptor.";
RL Biochim. Biophys. Acta 1179:105-107(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=8234299; DOI=10.1073/pnas.90.21.10365;
RA Salvatore C.A., Jacobson M.A., Taylor H.E., Linden J., Johnson R.G.;
RT "Molecular cloning and characterization of the human A3 adenosine
RT receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10365-10369(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-248.
RC TISSUE=Testis;
RA Meyerehof W., Hamm B., Schoenrock C., Fehr S., Wulfsen I., Richter D.;
RL Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Testis;
RA Atkinson M.R., Townsend-Nicholson A., Nicholl J.K., Sutherland G.R.,
RA Schofield P.R.;
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, and Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 166-272.
RX PubMed=11214319; DOI=10.1038/35054550;
RA Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A.,
RA O'Brien S.J.;
RT "Molecular phylogenetics and the origins of placental mammals.";
RL Nature 409:614-618(2001).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=27886186; DOI=10.1038/ncomms13561;
RA Iyer S.V., Ranjan A., Elias H.K., Parrales A., Sasaki H., Roy B.C.,
RA Umar S., Tawfik O.W., Iwakuma T.;
RT "Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of
RT NF-kappaB and osteosarcoma progression.";
RL Nat. Commun. 7:13561-13561(2016).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] THR-105.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: [Isoform 2]: Receptor for adenosine. The activity of this
CC receptor is mediated by G proteins which inhibits adenylyl cyclase
CC (PubMed:8234299). {ECO:0000269|PubMed:8234299}.
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=3;
CC Name=2; Synonyms=A3AR i2 {ECO:0000303|PubMed:27886186}, A3AR
CC {ECO:0000303|PubMed:27886186};
CC IsoId=P0DMS8-1; Sequence=Displayed;
CC Name=1; Synonyms=TMIGD3 i1 {ECO:0000303|PubMed:27886186}, A3AR i1
CC {ECO:0000303|PubMed:27886186};
CC IsoId=P0DMS9-2; Sequence=External;
CC Name=3; Synonyms=TMIGD3 i3, A3AR i3;
CC IsoId=P0DMS9-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed in the lung and bone. Expressed at lower
CC levels in osteosarcoma tissues (at protein level).
CC {ECO:0000269|PubMed:27886186}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; L20463; AAA16365.1; -; mRNA.
DR EMBL; L22607; AAA35949.1; -; mRNA.
DR EMBL; X76981; CAA54288.1; -; mRNA.
DR EMBL; L77730; AAB02790.1; -; Genomic_DNA.
DR EMBL; L77729; AAB02790.1; JOINED; Genomic_DNA.
DR EMBL; AY136749; AAN01275.1; -; mRNA.
DR EMBL; AL390195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029831; AAH29831.1; -; mRNA.
DR EMBL; AY011231; AAG35155.1; -; Genomic_DNA.
DR CCDS; CCDS839.1; -. [P0DMS8-1]
DR PIR; S38511; S38511.
DR RefSeq; NP_000668.1; NM_000677.3. [P0DMS8-1]
DR AlphaFoldDB; P0DMS8; -.
DR SMR; P0DMS8; -.
DR STRING; 9606.ENSP00000241356; -.
DR BindingDB; P0DMS8; -.
DR ChEMBL; CHEMBL256; -.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB01223; Aminophylline.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB00824; Enprofylline.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB05511; Piclidenoson.
DR DrugCentral; P0DMS8; -.
DR GuidetoPHARMACOLOGY; 21; -.
DR GlyCosmos; P0DMS8; 3 sites, No reported glycans.
DR GlyGen; P0DMS8; 3 sites.
DR iPTMnet; P0DMS8; -.
DR PhosphoSitePlus; P0DMS8; -.
DR BioMuta; ADORA3; -.
DR MassIVE; P0DMS8; -.
DR Antibodypedia; 77173; 190 antibodies from 18 providers.
DR DNASU; 140; -.
DR Ensembl; ENST00000241356.5; ENSP00000241356.4; ENSG00000282608.2. [P0DMS8-1]
DR GeneID; 140; -.
DR KEGG; hsa:140; -.
DR MANE-Select; ENST00000241356.5; ENSP00000241356.4; NM_000677.4; NP_000668.1.
DR AGR; HGNC:268; -.
DR CTD; 140; -.
DR DisGeNET; 140; -.
DR GeneCards; ADORA3; -.
DR HGNC; HGNC:268; ADORA3.
DR HPA; ENSG00000282608; Tissue enhanced (brain).
DR MIM; 600445; gene.
DR neXtProt; NX_P0DMS8; -.
DR OpenTargets; ENSG00000282608; -.
DR VEuPathDB; HostDB:ENSG00000282608; -.
DR GeneTree; ENSGT01030000234555; -.
DR HOGENOM; CLU_009579_11_5_1; -.
DR InParanoid; P0DMS8; -.
DR OMA; FYIIRTK; -.
DR OrthoDB; 2909020at2759; -.
DR PhylomeDB; P0DMS8; -.
DR PathwayCommons; P0DMS8; -.
DR Reactome; R-HSA-417973; Adenosine P1 receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P0DMS8; -.
DR SIGNOR; P0DMS8; -.
DR BioGRID-ORCS; 140; 5 hits in 1136 CRISPR screens.
DR GenomeRNAi; 140; -.
DR Pharos; P0DMS8; Tchem.
DR PRO; PR:P0DMS8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P0DMS8; Protein.
DR Bgee; ENSG00000282608; Expressed in C1 segment of cervical spinal cord and 132 other cell types or tissues.
DR ExpressionAtlas; P0DMS8; baseline and differential.
DR Genevisible; P0DMS8; HS.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0001609; F:G protein-coupled adenosine receptor activity; IBA:GO_Central.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0001973; P:G protein-coupled adenosine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000466; Adeno_A3_rcpt.
DR InterPro; IPR001634; Adenosn_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24246:SF2; ADENOSINE RECEPTOR A3; 1.
DR PANTHER; PTHR24246; OLFACTORY RECEPTOR AND ADENOSINE RECEPTOR; 1.
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 SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 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 Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..318
FT /note="Adenosine receptor A3"
FT /id="PRO_0000069010"
FT TOPO_DOM 1..14
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 15..37
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 38..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 49..72
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 73..84
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 85..106
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 107..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 127..148
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 149..177
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 178..198
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 199..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 232..255
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 256..261
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 262..284
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 285..318
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT LIPID 303
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 12
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 105
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs746154553)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035755"
FT VARIANT 248
FT /note="I -> L (in dbSNP:rs35511654)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_049366"
FT VARIANT 266
FT /note="M -> K (in dbSNP:rs2800889)"
FT /id="VAR_049367"
FT CONFLICT 7
FT /note="A -> T (in Ref. 1; AAA16365)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="D -> V (in Ref. 8; AAG35155)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 318 AA; 36185 MW; 690E67986130FC28 CRC64;
MPNNSTALSL ANVTYITMEI FIGLCAIVGN VLVICVVKLN PSLQTTTFYF IVSLALADIA
VGVLVMPLAI VVSLGITIHF YSCLFMTCLL LIFTHASIMS LLAIAVDRYL RVKLTVRYKR
VTTHRRIWLA LGLCWLVSFL VGLTPMFGWN MKLTSEYHRN VTFLSCQFVS VMRMDYMVYF
SFLTWIFIPL VVMCAIYLDI FYIIRNKLSL NLSNSKETGA FYGREFKTAK SLFLVLFLFA
LSWLPLSIIN CIIYFNGEVP QLVLYMGILL SHANSMMNPI VYAYKIKKFK ETYLLILKAC
VVCHPSDSLD TSIEKNSE
//
