P29274 (AA2AR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
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.
Subunit structure	Interacts (via cytoplasmic C-terminal domain) with USP4; the interaction is direct. May interact with DRD4. Ref.11 Ref.13
Subcellular location	Cell membrane; Multi-pass membrane protein.
Domain	The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface. Ref.12
Post-translational modification	Ubiquitinated. Deubiquitinated by USP4; leading to stabilization and expression at the cell surface. Ref.13
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence AAA58356.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Traceable author statement. Source: ProtInc activation of adenylate cyclase activity Traceable author statement. Source: Reactome apoptotic process 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 nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phagocytosis Traceable author statement. Source: ProtInc sensory perception Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc intracellular organelle part Inferred from direct assay Ref.13. Source: UniProtKB membrane fraction Traceable author statement. Source: ProtInc
Molecular function	G-protein coupled adenosine receptor activity Inferred from electronic annotation. Source: InterPro enzyme binding Inferred from physical interaction Ref.13. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADORA1	P30542	4	EBI-2902702,EBI-2903663
CALM1	P62158	3	EBI-2902702,EBI-397435
CYTH2	Q99418	6	EBI-2902702,EBI-448974
DRD2	P14416	2	EBI-2902702,EBI-2928178
Grm5	P31424-1	3	EBI-2902702,EBI-2902778	From a different organism.
NECAB2	Q7Z6G3	5	EBI-2902702,EBI-950070
USP4	Q13107	4	EBI-2902702,EBI-723290

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 Ref.14

Transmembrane

8 – 32

25

Helical; Name=1

Topological domain

33 – 42

10

Cytoplasmic Ref.14

Transmembrane

43 – 66

24

Helical; Name=2

Topological domain

67 – 77

11

Extracellular Ref.14

Transmembrane

78 – 100

23

Helical; Name=3

Topological domain

101 – 120

20

Cytoplasmic Ref.14

Transmembrane

121 – 143

23

Helical; Name=4

Topological domain

144 – 173

30

Extracellular Ref.14

Transmembrane

174 – 198

25

Helical; Name=5

Topological domain

199 – 234

36

Cytoplasmic Ref.14

Transmembrane

235 – 258

24

Helical; Name=6

Topological domain

259 – 266

8

Extracellular Ref.14

Transmembrane

267 – 290

24

Helical; Name=7

Topological domain

291 – 412

122

Cytoplasmic Ref.14

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.14

Disulfide bond

74 ↔ 146

Ref.14

Disulfide bond

77 ↔ 166

Ref.14

Disulfide bond

259 ↔ 262

Ref.14

Natural variations

Natural variant

50

1

A → V. Ref.15
Corresponds to variant rs4530 [ dbSNP | Ensembl ].

VAR_011835

Natural variant

300

1

R → H.
Corresponds to variant rs4990 [ dbSNP | Ensembl ].

VAR_011836

Natural variant

392

1

G → R.

VAR_003451

Secondary structure

1

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412

Helix Strand Turn

Details...

Helix

7 – 21

15

Helix

25 – 33

9

Helix

35 – 37

3

Helix

41 – 54

14

Helix

59 – 66

8

Helix

78 – 106

29

Helix

109 – 111

3

Helix

125 – 134

10

Turn

138 – 140

3

Helix

168 – 171

4

Helix

174 – 178

5

Turn

179 – 181

3

Helix

182 – 185

4

Helix

187 – 193

7

Helix

197 – 204

8

Helix

210 – 214

5

Helix

219 – 238

20

Helix

242 – 258

17

Helix

267 – 291

25

Helix

293 – 305

13

Sequences

	Sequence		Length	Mass (Da)
	P29274 [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:R84.1-R84.11(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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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.
[11]	"The dopamine D(4) receptor, the ultimate disordered protein." Woods A.S. J. Recept. Signal Transduct. 30:331-336(2010) [PubMed: 20836733] [Abstract] Cited for: POSSIBLE INTERACTION WITH DRD4.
[12]	"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.
[13]	"The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor." Milojevic T., Reiterer V., Stefan E., Korkhov V.M., Dorostkar M.M., Ducza E., Ogris E., Boehm S., Freissmuth M., Nanoff C. Mol. Pharmacol. 69:1083-1094(2006) [PubMed: 16339847] [Abstract] Cited for: INTERACTION WITH USP4, UBIQUITINATION, DEUBIQUITINATION BY USP4.
[14]	"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.
[15]	"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.
[16]	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

EMBL
GenBank
DDBJ

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.
AK312946 mRNA. Translation: BAG35787.1.
CH471095 Genomic DNA. Translation: EAW59658.1.
BC013780 mRNA. Translation: AAH13780.1.

IPI

IPI00020974.

PIR

A48978.

RefSeq

NP_000666.2. NM_000675.4.

UniGene

Hs.197029.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2YDO	X-ray	3.00	A	1-317	[»]
2YDV	X-ray	2.60	A	1-317	[»]
3EML	X-ray	2.60	A	2-316	[»]
3PWH	X-ray	3.30	A	1-317	[»]
3QAK	X-ray	2.71	A	2-316	[»]
3REY	X-ray	3.31	A	1-317	[»]
3RFM	X-ray	3.60	A	1-317	[»]

ProteinModelPortal

P29274.

SMR

P29274. Positions 3-318.

ModBase

Search...

Protein-protein interaction databases

IntAct

P29274. 8 interactions.

MINT

MINT-4823612.

STRING

P29274.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P29274.

Polymorphism databases

DMDM

543740.

Proteomic databases

PRIDE

P29274.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000337539; ENSP00000336630; ENSG00000128271.

GeneID

135.

KEGG

hsa:135.

UCSC

uc002zzx.1. human.

Organism-specific databases

CTD

135.

GeneCards

GC22P024813.

HGNC

HGNC:263. ADORA2A.

MIM

102776. gene.

neXtProt

NX_P29274.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10218.

GeneTree

ENSGT00530000062761.
ENSGT00550000074524.

HOGENOM

HBG445348.

HOVERGEN

HBG106962.

InParanoid

P29274.

OMA

PGVWANG.

PhylomeDB

P29274.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

CleanEx

HS_ADORA2A.

Genevestigator

P29274.

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]

KO

K04266.

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

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
Secondary accession number(s): B2R7E0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 128 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.