P33765 (AA3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenosine receptor A3

Gene names

Name:	ADORA3
ORF Names:	UNQ1931/PRO4406

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	318 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Post-translational modification	Phosphorylation on Ser-317 may be crucial for rapid desensitization By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Traceable author statement PubMed 9380026. Source: ProtInc histamine secretion by mast cell Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement PubMed 9164961. Source: ProtInc positive regulation of calcium-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of leukocyte migration Inferred from electronic annotation. Source: Compara positive regulation of mast cell degranulation Inferred from electronic annotation. Source: Compara positive regulation of mucus secretion Inferred from electronic annotation. Source: Compara positive regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara regulation of heart contraction Traceable author statement PubMed 9837869. Source: ProtInc signal transduction Traceable author statement Ref.1PubMed 9380026. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled adenosine receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P33765-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P33765-2)

The sequence of this isoform differs from the canonical sequence as follows:
     118-318: YKRVTTHRRI...LDTSIEKNSE → FRIPGLPGCI...PKEMAPTEQM

Isoform 3 (identifier: Q6P2N6-1)

The sequence of this isoform can be found in the external entry Q6P2N6.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 318

318

Adenosine receptor A3

PRO_0000069010

Regions

Topological domain

1 – 14

14

Extracellular By similarity

Transmembrane

15 – 37

23

Helical; Name=1; By similarity

Topological domain

38 – 48

11

Cytoplasmic By similarity

Transmembrane

49 – 72

24

Helical; Name=2; By similarity

Topological domain

73 – 84

12

Extracellular By similarity

Transmembrane

85 – 106

22

Helical; Name=3; By similarity

Topological domain

107 – 126

20

Cytoplasmic By similarity

Transmembrane

127 – 148

22

Helical; Name=4; By similarity

Topological domain

149 – 177

29

Extracellular By similarity

Transmembrane

178 – 198

21

Helical; Name=5; By similarity

Topological domain

199 – 231

33

Cytoplasmic By similarity

Transmembrane

232 – 255

24

Helical; Name=6; By similarity

Topological domain

256 – 261

6

Extracellular By similarity

Transmembrane

262 – 284

23

Helical; Name=7; By similarity

Topological domain

285 – 318

34

Cytoplasmic By similarity

Amino acid modifications

Lipidation

303

1

S-palmitoyl cysteine Potential

Glycosylation

3

1

N-linked (GlcNAc...) Potential

Glycosylation

4

1

N-linked (GlcNAc...) Potential

Glycosylation

12

1

N-linked (GlcNAc...) Potential

Disulfide bond

83 ↔ 166

By similarity

Natural variations

Alternative sequence

118 – 318

201

YKRVT…EKNSE → FRIPGLPGCILSFQLKVCFL PVMWLFILLSLALISDAMVM DEKVKRSFVLDTASAICNYN AHYKNHPKYWCRGYFRDYCN IIAFSPNSTNHVALRDTGNQ LIVTMSCLTKEDTGWYWCGI QRDFARDDMDFTELIVTDDK GTLANDFWSGKDLSGNKTRS CKAPKVVRKADRSRTSILII CILITGLGIISVISHLTKRR RSQRNRRVGNTLKPFSRVLT PKEMAPTEQM in isoform 2.

VSP_013320

Natural variant

105

1

A → T in a colorectal cancer sample; somatic mutation. Ref.10

VAR_035755

Natural variant

248

1

I → L. Ref.3
Corresponds to variant rs35511654 [ dbSNP | Ensembl ].

VAR_049366

Natural variant

266

1

M → K.
Corresponds to variant rs2800889 [ dbSNP | Ensembl ].

VAR_049367

Experimental info

Sequence conflict

7

1

A → T in AAA16365. Ref.1

Sequence conflict

175

1

D → V Ref.9

Secondary structure

1

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318

Helix Strand Turn

Details...

Helix

11 – 39

29

Helix

48 – 51

4

Helix

55 – 63

9

Helix

66 – 72

7

Turn

79 – 81

3

Helix

84 – 96

13

Helix

102 – 111

10

Turn

112 – 114

3

Beta strand

116 – 119

4

Helix

125 – 137

13

Turn

140 – 143

4

Helix

144 – 147

4

Beta strand

152 – 154

3

Beta strand

159 – 161

3

Beta strand

166 – 168

3

Helix

176 – 180

5

Turn

183 – 186

4

Helix

187 – 198

12

Beta strand

219 – 223

5

Helix

226 – 230

5

Helix

233 – 241

9

Turn

244 – 246

3

Helix

249 – 255

7

Helix

262 – 270

9

Helix

277 – 285

9

Helix

287 – 296

10

Helix

308 – 312

5

Helix

315 – 317

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 690E67986130FC28	FASTA	318	36,185
	10 20 30 40 50 60 MPNNSTALSL ANVTYITMEI FIGLCAIVGN VLVICVVKLN PSLQTTTFYF IVSLALADIA 70 80 90 100 110 120 VGVLVMPLAI VVSLGITIHF YSCLFMTCLL LIFTHASIMS LLAIAVDRYL RVKLTVRYKR 130 140 150 160 170 180 VTTHRRIWLA LGLCWLVSFL VGLTPMFGWN MKLTSEYHRN VTFLSCQFVS VMRMDYMVYF 190 200 210 220 230 240 SFLTWIFIPL VVMCAIYLDI FYIIRNKLSL NLSNSKETGA FYGREFKTAK SLFLVLFLFA 250 260 270 280 290 300 LSWLPLSIIN CIIYFNGEVP QLVLYMGILL SHANSMMNPI VYAYKIKKFK ETYLLILKAC 310 VVCHPSDSLD TSIEKNSE
	Isoform 2 [UniParc]. Checksum: 7F4974135F4F04A6	FASTA	347	38,976
	10 20 30 40 50 60 MPNNSTALSL ANVTYITMEI FIGLCAIVGN VLVICVVKLN PSLQTTTFYF IVSLALADIA 70 80 90 100 110 120 VGVLVMPLAI VVSLGITIHF YSCLFMTCLL LIFTHASIMS LLAIAVDRYL RVKLTVRFRI 130 140 150 160 170 180 PGLPGCILSF QLKVCFLPVM WLFILLSLAL ISDAMVMDEK VKRSFVLDTA SAICNYNAHY 190 200 210 220 230 240 KNHPKYWCRG YFRDYCNIIA FSPNSTNHVA LRDTGNQLIV TMSCLTKEDT GWYWCGIQRD 250 260 270 280 290 300 FARDDMDFTE LIVTDDKGTL ANDFWSGKDL SGNKTRSCKA PKVVRKADRS RTSILIICIL 310 320 330 340 ITGLGIISVI SHLTKRRRSQ RNRRVGNTLK PFSRVLTPKE MAPTEQM
	Isoform 3 [UniParc]. See Q6P2N6.		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and sequence analysis of the human A3 adenosine receptor." Sajjadi F.G., Firestein G.S. Biochim. Biophys. Acta 1179:105-107(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[2]	"Molecular cloning and characterization of the human A3 adenosine receptor." Salvatore C.A., Jacobson M.A., Taylor H.E., Linden J., Johnson R.G. Proc. Natl. Acad. Sci. U.S.A. 90:10365-10369(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	Meyerehof W., Hamm B., Schoenrock C., Fehr S., Wulfsen I., Richter D. Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-248. Tissue: Testis.
[4]	Atkinson M.R., Townsend-Nicholson A., Nicholl J.K., Sutherland G.R., Schofield P.R. Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Testis.
[5]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain, Lung and Testis.
[9]	"Molecular phylogenetics and the origins of placental mammals." Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., O'Brien S.J. Nature 409:614-618(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 166-272 (ISOFORM 1).
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-105.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L20463 mRNA. Translation: AAA16365.1.
L22607 mRNA. Translation: AAA35949.1.
X76981 mRNA. Translation: CAA54288.1.
L77730, L77729 Genomic DNA. Translation: AAB02790.1.
AY136749 mRNA. Translation: AAN01275.1.
AY358644 mRNA. Translation: AAQ89007.1.
AL390195 Genomic DNA. Translation: CAC36045.1.
AL390195 Genomic DNA. Translation: CAM21993.1.
BC029831 mRNA. Translation: AAH29831.1.
AY011231 Genomic DNA. Translation: AAG35155.1.

IPI

IPI00016753.
IPI00419658.

PIR

S38511.

RefSeq

NP_000668.1. NM_000677.3.
NP_065734.5. NM_020683.6.

UniGene

Hs.281342.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OEA	model	-	A	1-298	[»]
1R7N	model	-	A	1-318	[»]

ProteinModelPortal

P33765.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000358730.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P33765.

Polymorphism databases

DMDM

1351831.

Proteomic databases

PaxDb

P33765.

PRIDE

P33765.

Protocols and materials databases

DNASU

140.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000241356; ENSP00000241356; ENSG00000121933.
ENST00000369716; ENSP00000358730; ENSG00000121933.

GeneID

140.

KEGG

hsa:140.

UCSC

uc001ebf.3. human.
uc001ebh.4. human.

Organism-specific databases

CTD

140.

GeneCards

GC01M112025.

HGNC

HGNC:268. ADORA3.

HPA

HPA028509.
HPA028566.
HPA028568.

MIM

600445. gene.

neXtProt

NX_P33765.

PharmGKB

PA24589.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG133889.

HOGENOM

HOG000015770.

HOVERGEN

HBG106962.

KO

K04268.

OMA

SHANSMM.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P33765.

Bgee

P33765.

CleanEx

HS_ADORA3.

Genevestigator

P33765.

GermOnline

ENSG00000121933. Homo sapiens.

Family and domain databases

InterPro

IPR000466. Adeno_A3_rcpt.
IPR001634. Adenosn_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00555. ADENOSINEA3R.
PR00424. ADENOSINER.
PR00237. GPCRRHODOPSN.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P33765.

ChEMBL

CHEMBL256.

DrugBank

DB00640. Adenosine.
DB01223. Aminophylline.

GenomeRNAi

140.

NextBio

553.

SOURCE

Search...

Entry information

Entry name

AA3R_HUMAN

Accession

Primary (citable) accession number: P33765
Secondary accession number(s): A2A3P4, Q6UWU0, Q9BYZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.