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Protein

Adenosine receptor A2a

Gene

ADORA2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • G-protein coupled adenosine receptor activity Source: UniProtKB
  • identical protein binding Source: IntAct

GO - Biological processi

  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: ProtInc
  • apoptotic process Source: ProtInc
  • blood circulation Source: ProtInc
  • blood coagulation Source: ProtInc
  • cAMP biosynthetic process Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • cellular defense response Source: ProtInc
  • cellular protein metabolic process Source: Reactome
  • central nervous system development Source: ProtInc
  • inflammatory response Source: ProtInc
  • phagocytosis Source: ProtInc
  • positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: UniProtKB
  • sensory perception Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128271-MONOMER.
ReactomeiR-HSA-187024. NGF-independant TRKA activation.
R-HSA-417973. Adenosine P1 receptors.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-5683826. Surfactant metabolism.

Protein family/group databases

TCDBi9.A.14.3.8. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosine receptor A2a
Gene namesi
Name:ADORA2A
Synonyms:ADORA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:263. ADORA2A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7Extracellular1 Publication7
Transmembranei8 – 32Helical; Name=1Add BLAST25
Topological domaini33 – 42Cytoplasmic1 Publication10
Transmembranei43 – 66Helical; Name=2Add BLAST24
Topological domaini67 – 77Extracellular1 PublicationAdd BLAST11
Transmembranei78 – 100Helical; Name=3Add BLAST23
Topological domaini101 – 120Cytoplasmic1 PublicationAdd BLAST20
Transmembranei121 – 143Helical; Name=4Add BLAST23
Topological domaini144 – 173Extracellular1 PublicationAdd BLAST30
Transmembranei174 – 198Helical; Name=5Add BLAST25
Topological domaini199 – 234Cytoplasmic1 PublicationAdd BLAST36
Transmembranei235 – 258Helical; Name=6Add BLAST24
Topological domaini259 – 266Extracellular1 Publication8
Transmembranei267 – 290Helical; Name=7Add BLAST24
Topological domaini291 – 412Cytoplasmic1 PublicationAdd BLAST122

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi135.
MalaCardsiADORA2A.
OpenTargetsiENSG00000128271.
Orphaneti363549. Acute encephalopathy with biphasic seizures and late reduced diffusion.
PharmGKBiPA24584.

Chemistry databases

ChEMBLiCHEMBL251.
DrugBankiDB00640. Adenosine.
DB00201. Caffeine.
DB04932. Defibrotide.
DB00651. Dyphylline.
DB00824. Enprofylline.
DB00358. Mefloquine.
DB01303. Oxtriphylline.
DB00806. Pentoxifylline.
DB06213. Regadenoson.
DB01412. Theobromine.
DB00277. Theophylline.
GuidetoPHARMACOLOGYi19.

Polymorphism and mutation databases

DMDMi543740.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689991 – 412Adenosine receptor A2aAdd BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi71 ↔ 159PROSITE-ProRule annotation1 Publication
Disulfide bondi74 ↔ 146PROSITE-ProRule annotation1 Publication
Disulfide bondi77 ↔ 166PROSITE-ProRule annotation1 Publication
Glycosylationi154N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi259 ↔ 262PROSITE-ProRule annotation1 Publication

Post-translational modificationi

Ubiquitinated. Deubiquitinated by USP4; leading to stabilization and expression at the cell surface.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP29274.
PeptideAtlasiP29274.
PRIDEiP29274.

PTM databases

iPTMnetiP29274.
PhosphoSitePlusiP29274.

Expressioni

Gene expression databases

BgeeiENSG00000128271.
CleanExiHS_ADORA2A.
ExpressionAtlasiP29274. baseline and differential.
GenevisibleiP29274. HS.

Interactioni

Subunit structurei

Interacts (via cytoplasmic C-terminal domain) with USP4; the interaction is direct. May interact with DRD4.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself6EBI-2902702,EBI-2902702
ADORA1P305424EBI-2902702,EBI-2903663
CALM3P621583EBI-2902702,EBI-397435
CYTH2Q994186EBI-2902702,EBI-448974
DRD2P144162EBI-2902702,EBI-2928178
Grm5P31424-13EBI-2902702,EBI-2902778From a different organism.
NECAB2Q7Z6G35EBI-2902702,EBI-950070
USP4Q131074EBI-2902702,EBI-723290

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi106647. 8 interactors.
IntActiP29274. 9 interactors.
MINTiMINT-4823612.
STRINGi9606.ENSP00000336630.

Chemistry databases

BindingDBiP29274.

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 33Combined sources32
Helixi35 – 37Combined sources3
Helixi40 – 57Combined sources18
Helixi59 – 67Combined sources9
Beta strandi71 – 73Combined sources3
Helixi74 – 107Combined sources34
Helixi109 – 115Combined sources7
Helixi118 – 136Combined sources19
Helixi138 – 141Combined sources4
Helixi145 – 147Combined sources3
Helixi151 – 156Combined sources6
Beta strandi163 – 165Combined sources3
Helixi168 – 171Combined sources4
Helixi174 – 179Combined sources6
Helixi180 – 186Combined sources7
Helixi187 – 208Combined sources22
Beta strandi213 – 216Combined sources4
Helixi219 – 258Combined sources40
Beta strandi260 – 262Combined sources3
Helixi267 – 291Combined sources25
Helixi293 – 304Combined sources12
Turni308 – 310Combined sources3
Helixi312 – 317Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MMHmodel-16-36[»]
242-69[»]
378-102[»]
4117-143[»]
5175-203[»]
6233-260[»]
7264-296[»]
1UPEmodel-A1-304[»]
2YDOX-ray3.00A1-317[»]
2YDVX-ray2.60A1-317[»]
3EMLX-ray2.60A2-208[»]
A222-316[»]
3PWHX-ray3.30A1-317[»]
3QAKX-ray2.71A2-208[»]
A222-316[»]
3REYX-ray3.31A1-317[»]
3RFMX-ray3.60A1-317[»]
3UZAX-ray3.27A1-317[»]
3UZCX-ray3.34A1-317[»]
3VG9X-ray2.70A1-316[»]
3VGAX-ray3.10A1-316[»]
4EIYX-ray1.80A2-208[»]
A219-316[»]
4UG2X-ray2.60A/B1-317[»]
4UHRX-ray2.60A1-317[»]
5G53X-ray3.40A/B1-308[»]
5IU4X-ray1.72A2-208[»]
A219-318[»]
5IU7X-ray1.90A2-208[»]
A219-315[»]
5IU8X-ray2.00A2-208[»]
A219-315[»]
5IUAX-ray2.20A2-208[»]
A219-315[»]
5IUBX-ray2.10A2-208[»]
A219-315[»]
5K2AX-ray2.50A2-208[»]
A219-316[»]
5K2BX-ray2.50A2-208[»]
A219-316[»]
5K2CX-ray1.90A2-208[»]
A219-316[»]
5K2DX-ray1.90A2-208[»]
A219-316[»]
ProteinModelPortaliP29274.
SMRiP29274.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29274.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni168 – 177Agonist binding10
Regioni246 – 253Agonist binding8
Regioni264 – 274Agonist bindingAdd BLAST11

Domaini

The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface.

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00550000074524.
HOGENOMiHOG000015770.
HOVERGENiHBG106962.
InParanoidiP29274.
KOiK04266.
OMAiPGVWANG.
OrthoDBiEOG091G0I3U.
TreeFamiTF325296.

Family and domain databases

InterProiIPR001513. Adeno_A2A_rcpt.
IPR001634. Adenosn_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24246:SF28. PTHR24246:SF28. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00553. ADENOSINA2AR.
PR00424. ADENOSINER.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P29274-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPIMGSSVYI TVELAIAVLA ILGNVLVCWA VWLNSNLQNV TNYFVVSLAA
60 70 80 90 100
ADIAVGVLAI PFAITISTGF CAACHGCLFI ACFVLVLTQS SIFSLLAIAI
110 120 130 140 150
DRYIAIRIPL RYNGLVTGTR AKGIIAICWV LSFAIGLTPM LGWNNCGQPK
160 170 180 190 200
EGKNHSQGCG EGQVACLFED VVPMNYMVYF NFFACVLVPL LLMLGVYLRI
210 220 230 240 250
FLAARRQLKQ MESQPLPGER ARSTLQKEVH AAKSLAIIVG LFALCWLPLH
260 270 280 290 300
IINCFTFFCP DCSHAPLWLM YLAIVLSHTN SVVNPFIYAY RIREFRQTFR
310 320 330 340 350
KIIRSHVLRQ QEPFKAAGTS ARVLAAHGSD GEQVSLRLNG HPPGVWANGS
360 370 380 390 400
APHPERRPNG YALGLVSGGS AQESQGNTGL PDVELLSHEL KGVCPEPPGL
410
DDPLAQDGAG VS
Length:412
Mass (Da):44,707
Last modified:June 1, 1994 - v2
Checksum:i9438E9D64A6BE61B
GO

Sequence cautioni

The sequence AAA58356 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01183550A → V.1 PublicationCorresponds to variant rs4530dbSNPEnsembl.1
Natural variantiVAR_011836300R → H.Corresponds to variant rs4990dbSNPEnsembl.1
Natural variantiVAR_003451392G → R.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13826.1.
PIRiA48978.
RefSeqiNP_000666.2. NM_000675.5.
NP_001265426.1. NM_001278497.1.
NP_001265427.1. NM_001278498.1.
NP_001265428.1. NM_001278499.1.
NP_001265429.1. NM_001278500.1.
UniGeneiHs.197029.

Genome annotation databases

EnsembliENST00000337539; ENSP00000336630; ENSG00000128271.
ENST00000610595; ENSP00000480012; ENSG00000128271.
ENST00000611543; ENSP00000483102; ENSG00000128271.
ENST00000618076; ENSP00000481552; ENSG00000128271.
GeneIDi135.
KEGGihsa:135.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13826.1.
PIRiA48978.
RefSeqiNP_000666.2. NM_000675.5.
NP_001265426.1. NM_001278497.1.
NP_001265427.1. NM_001278498.1.
NP_001265428.1. NM_001278499.1.
NP_001265429.1. NM_001278500.1.
UniGeneiHs.197029.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MMHmodel-16-36[»]
242-69[»]
378-102[»]
4117-143[»]
5175-203[»]
6233-260[»]
7264-296[»]
1UPEmodel-A1-304[»]
2YDOX-ray3.00A1-317[»]
2YDVX-ray2.60A1-317[»]
3EMLX-ray2.60A2-208[»]
A222-316[»]
3PWHX-ray3.30A1-317[»]
3QAKX-ray2.71A2-208[»]
A222-316[»]
3REYX-ray3.31A1-317[»]
3RFMX-ray3.60A1-317[»]
3UZAX-ray3.27A1-317[»]
3UZCX-ray3.34A1-317[»]
3VG9X-ray2.70A1-316[»]
3VGAX-ray3.10A1-316[»]
4EIYX-ray1.80A2-208[»]
A219-316[»]
4UG2X-ray2.60A/B1-317[»]
4UHRX-ray2.60A1-317[»]
5G53X-ray3.40A/B1-308[»]
5IU4X-ray1.72A2-208[»]
A219-318[»]
5IU7X-ray1.90A2-208[»]
A219-315[»]
5IU8X-ray2.00A2-208[»]
A219-315[»]
5IUAX-ray2.20A2-208[»]
A219-315[»]
5IUBX-ray2.10A2-208[»]
A219-315[»]
5K2AX-ray2.50A2-208[»]
A219-316[»]
5K2BX-ray2.50A2-208[»]
A219-316[»]
5K2CX-ray1.90A2-208[»]
A219-316[»]
5K2DX-ray1.90A2-208[»]
A219-316[»]
ProteinModelPortaliP29274.
SMRiP29274.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106647. 8 interactors.
IntActiP29274. 9 interactors.
MINTiMINT-4823612.
STRINGi9606.ENSP00000336630.

Chemistry databases

BindingDBiP29274.
ChEMBLiCHEMBL251.
DrugBankiDB00640. Adenosine.
DB00201. Caffeine.
DB04932. Defibrotide.
DB00651. Dyphylline.
DB00824. Enprofylline.
DB00358. Mefloquine.
DB01303. Oxtriphylline.
DB00806. Pentoxifylline.
DB06213. Regadenoson.
DB01412. Theobromine.
DB00277. Theophylline.
GuidetoPHARMACOLOGYi19.

Protein family/group databases

TCDBi9.A.14.3.8. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiP29274.
PhosphoSitePlusiP29274.

Polymorphism and mutation databases

DMDMi543740.

Proteomic databases

PaxDbiP29274.
PeptideAtlasiP29274.
PRIDEiP29274.

Protocols and materials databases

DNASUi135.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000337539; ENSP00000336630; ENSG00000128271.
ENST00000610595; ENSP00000480012; ENSG00000128271.
ENST00000611543; ENSP00000483102; ENSG00000128271.
ENST00000618076; ENSP00000481552; ENSG00000128271.
GeneIDi135.
KEGGihsa:135.

Organism-specific databases

CTDi135.
DisGeNETi135.
GeneCardsiADORA2A.
SPECC1L-ADORA2A.
HGNCiHGNC:263. ADORA2A.
MalaCardsiADORA2A.
MIMi102776. gene.
neXtProtiNX_P29274.
OpenTargetsiENSG00000128271.
Orphaneti363549. Acute encephalopathy with biphasic seizures and late reduced diffusion.
PharmGKBiPA24584.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00550000074524.
HOGENOMiHOG000015770.
HOVERGENiHBG106962.
InParanoidiP29274.
KOiK04266.
OMAiPGVWANG.
OrthoDBiEOG091G0I3U.
TreeFamiTF325296.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128271-MONOMER.
ReactomeiR-HSA-187024. NGF-independant TRKA activation.
R-HSA-417973. Adenosine P1 receptors.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-5683826. Surfactant metabolism.

Miscellaneous databases

EvolutionaryTraceiP29274.
GeneWikiiAdenosine_A2A_receptor.
GenomeRNAii135.
PROiP29274.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128271.
CleanExiHS_ADORA2A.
ExpressionAtlasiP29274. baseline and differential.
GenevisibleiP29274. HS.

Family and domain databases

InterProiIPR001513. Adeno_A2A_rcpt.
IPR001634. Adenosn_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24246:SF28. PTHR24246:SF28. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00553. ADENOSINA2AR.
PR00424. ADENOSINER.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAA2AR_HUMAN
AccessioniPrimary (citable) accession number: P29274
Secondary accession number(s): B2R7E0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 177 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.