Reviewed, UniProtKB/Swiss-Prot P29274 (AA2AR_HUMAN)

Names and origin

Protein names

Recommended name:
    Adenosine receptor A2a

Gene names

Name:	ADORA2A
Synonyms:	ADORA2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Traceable author statement. Source: ProtInc activation of adenylate cyclase activity Inferred from Experiment. Source: Reactome apoptosis Traceable author statement. Source: ProtInc blood circulation Traceable author statement. Source: ProtInc blood coagulation Traceable author statement. Source: ProtInc cAMP biosynthetic process Traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc central nervous system development Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc phagocytosis Traceable author statement. Source: ProtInc sensory perception Traceable author statement. Source: ProtInc transmembrane receptor protein tyrosine kinase signaling pathway Inferred from Experiment. Source: Reactome
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	adenosine receptor activity, G-protein coupled Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 412	412	Adenosine receptor A2a		PRO_0000068999
Regions
	Topological domain	1 – 7	7	Extracellular
	Transmembrane	8 – 32	25	1
	Topological domain	33 – 42	10	Cytoplasmic
	Transmembrane	43 – 66	24	2
	Topological domain	67 – 77	11	Extracellular
	Transmembrane	78 – 100	23	3
	Topological domain	101 – 120	20	Cytoplasmic
	Transmembrane	121 – 143	23	4
	Topological domain	144 – 173	30	Extracellular
	Transmembrane	174 – 198	25	5
	Topological domain	199 – 234	36	Cytoplasmic
	Transmembrane	235 – 258	24	6
	Topological domain	259 – 266	8	Extracellular
	Transmembrane	267 – 290	24	7
	Topological domain	291 – 412	122	Cytoplasmic
	Region	168 – 177	10	Agonist binding
	Region	246 – 253	8	Agonist binding
	Region	264 – 274	11	Agonist binding
Amino acid modifications
	Glycosylation	154	1	N-linked (GlcNAc...) Potential
	Disulfide bond	71 ↔ 159		Ref.10
	Disulfide bond	74 ↔ 146		Ref.10
	Disulfide bond	77 ↔ 166		Ref.10
	Disulfide bond	259 ↔ 262		Ref.10
Natural variations
	Natural variant	50	1	A → V: dbSNP rs4530. Ref.11		VAR_011835
	Natural variant	300	1	R → H: dbSNP rs4990.		VAR_011836
	Natural variant	392	1	G → R		VAR_003451

Sequences

	Sequence		Length	Mass (Da)
	P29274-1 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 9438E9D64A6BE61B	FASTA	412	44,707
	10 20 30 40 50 60 MPIMGSSVYI TVELAIAVLA ILGNVLVCWA VWLNSNLQNV TNYFVVSLAA ADIAVGVLAI 70 80 90 100 110 120 PFAITISTGF CAACHGCLFI ACFVLVLTQS SIFSLLAIAI DRYIAIRIPL RYNGLVTGTR 130 140 150 160 170 180 AKGIIAICWV LSFAIGLTPM LGWNNCGQPK EGKNHSQGCG EGQVACLFED VVPMNYMVYF 190 200 210 220 230 240 NFFACVLVPL LLMLGVYLRI FLAARRQLKQ MESQPLPGER ARSTLQKEVH AAKSLAIIVG 250 260 270 280 290 300 LFALCWLPLH IINCFTFFCP DCSHAPLWLM YLAIVLSHTN SVVNPFIYAY RIREFRQTFR 310 320 330 340 350 360 KIIRSHVLRQ QEPFKAAGTS ARVLAAHGSD GEQVSLRLNG HPPGVWANGS APHPERRPNG 370 380 390 400 410 YALGLVSGGS AQESQGNTGL PDVELLSHEL KGVCPEPPGL DDPLAQDGAG VS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Tiffany H.L., Murphy P.M. Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Salvatore C.A., Luneau C.J., Johnson R.G., Jacobson M. Submitted (SEP-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Molecular characterization of a human brain adenosine A2 receptor." Furlong T.J., Pierce K.D., Selbie L.A., Shine J. Brain Res. Mol. Brain Res. 15:62-66(1992) [PubMed: 1331670] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[4]	"Characterization and chromosomal localization of the human A2a adenosine receptor gene: ADORA2A." Le F., Townsend-Nicholson A., Baker E., Sutherland G.R., Schofield P.R. Biochem. Biophys. Res. Commun. 223:461-467(1996) [PubMed: 8670304] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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].
[6]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[9]	"Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2a adenosine receptor." Kim J., Wess J., van Rhee A.M., Schoneberg T., Jacobson K.A. J. Biol. Chem. 270:13987-13997(1995) [PubMed: 7775460] [Abstract] Cited for: 3D-STRUCTURE MODELING OF TRANSMEMBRANE DOMAINS.
[10]	"The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist." Jaakola V.-P., Griffith M.T., Hanson M.A., Cherezov V., Chien E.Y.T., Lane J.R., Ijzerman A.P., Stevens R.C. Science 322:1211-1217(2008) [PubMed: 18832607] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2-316 IN COMPLEX WITH ANTAGONIST, TOPOLOGY, DISULFIDE BONDS.
[11]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANT VAL-50.
[12]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M97370 mRNA. Translation: AAA58356.1. Different initiation.
X68486 mRNA. Translation: CAA48504.1.
S46950 mRNA. Translation: AAB23956.1.
U40771, U40770 Genomic DNA. Translation: AAA83270.1.
AY136747 mRNA. Translation: AAN01273.1.
CR456367 mRNA. Translation: CAG30253.1.
BT006999 mRNA. Translation: AAP35645.1.
BC013780 mRNA. Translation: AAH13780.1.

IPI

IPI00020974.

PIR

A48978.

RefSeq

NP_000666.2.

UniGene

Hs.197029
Hs.712771

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MMH	model	-	1	6-36	[»]
			2	42-69	[»]
			3	78-102	[»]
			4	117-143	[»]
			5	175-203	[»]
			6	233-260	[»]
			7	264-296	[»]
1UPE	model	-	A	1-304	[»]
3EML	X-ray	2.60	A	2-316	[»]

ModBase

Search...

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P29274.

Proteomic databases

PRIDE

P29274.

Genome annotation databases

Ensembl

ENSG00000128271. Homo sapiens. [Contig view]

GeneID

135.

KEGG

hsa:135.

Organism-specific databases

GeneCards

GC22P022997.

HGNC

HGNC:263. ADORA2A.

MIM

102776. gene.

PharmGKB

PA24584.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P29274.

HOVERGEN

P29274.

OMA

P29274. CSHAPLW.

Enzyme and pathway databases

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

P29274.

Bgee

P29274.

CleanEx

HS_ADORA2A.

GermOnline

ENSG00000128271. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR001513. Adeno_A2A_rcpt.
IPR001634. Adenosn_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]

Pfam

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

PRINTS

PR00553. ADENOSINA2AR.
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 Resources

DrugBank

DB00201. Caffeine.
DB04932. Defibrotide.
DB00061. Pegademase bovine.
DB00277. Theophylline.

NextBio

543.

SOURCE

Search...

Entry information

Entry name

AA2AR_HUMAN

Accession

Primary (citable) accession number: P29274

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	June 1, 1994
Last modified:	June 16, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)