Browse ADORA2A

Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane; Multi-pass membrane protein.
Domain PF00001 7 transmembrane receptor (rhodopsin family)
Function

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

> Gene Ontology
 
Biological Process GO:0001973 adenosine receptor signaling pathway
GO:0003013 circulatory system process
GO:0006140 regulation of nucleotide metabolic process
GO:0006164 purine nucleotide biosynthetic process
GO:0006171 cAMP biosynthetic process
GO:0006909 phagocytosis
GO:0006968 cellular defense response
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway
GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008015 blood circulation
GO:0009150 purine ribonucleotide metabolic process
GO:0009152 purine ribonucleotide biosynthetic process
GO:0009165 nucleotide biosynthetic process
GO:0009187 cyclic nucleotide metabolic process
GO:0009190 cyclic nucleotide biosynthetic process
GO:0009260 ribonucleotide biosynthetic process
GO:0010578 regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway
GO:0010579 positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway
GO:0030799 regulation of cyclic nucleotide metabolic process
GO:0030801 positive regulation of cyclic nucleotide metabolic process
GO:0030802 regulation of cyclic nucleotide biosynthetic process
GO:0030804 positive regulation of cyclic nucleotide biosynthetic process
GO:0030808 regulation of nucleotide biosynthetic process
GO:0030810 positive regulation of nucleotide biosynthetic process
GO:0030814 regulation of cAMP metabolic process
GO:0030816 positive regulation of cAMP metabolic process
GO:0030817 regulation of cAMP biosynthetic process
GO:0030819 positive regulation of cAMP biosynthetic process
GO:0031279 regulation of cyclase activity
GO:0031281 positive regulation of cyclase activity
GO:0035587 purinergic receptor signaling pathway
GO:0035588 G-protein coupled purinergic receptor signaling pathway
GO:0045761 regulation of adenylate cyclase activity
GO:0045762 positive regulation of adenylate cyclase activity
GO:0045981 positive regulation of nucleotide metabolic process
GO:0046058 cAMP metabolic process
GO:0046390 ribose phosphate biosynthetic process
GO:0050817 coagulation
GO:0050878 regulation of body fluid levels
GO:0051339 regulation of lyase activity
GO:0051349 positive regulation of lyase activity
GO:0052652 cyclic purine nucleotide metabolic process
GO:0072522 purine-containing compound biosynthetic process
GO:1900371 regulation of purine nucleotide biosynthetic process
GO:1900373 positive regulation of purine nucleotide biosynthetic process
GO:1900542 regulation of purine nucleotide metabolic process
GO:1900544 positive regulation of purine nucleotide metabolic process
GO:1901293 nucleoside phosphate biosynthetic process
Molecular Function GO:0001609 G-protein coupled adenosine receptor activity
GO:0035586 purinergic receptor activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04015 Rap1 signaling pathway
hsa04020 Calcium signaling pathway
hsa04024 cAMP signaling pathway
hsa04080 Neuroactive ligand-receptor interaction
hsa04270 Vascular smooth muscle contraction
Reactome R-HSA-187015: Activation of TRKA receptors
R-HSA-417973: Adenosine P1 receptors
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-418555: G alpha (s) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-392499: Metabolism of proteins
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-187024: NGF-independant TRKA activation
R-HSA-418038: Nucleotide-like (purinergic) receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-166520: Signalling by NGF
R-HSA-5683826: Surfactant metabolism
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ADORA2A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between ADORA2A and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25377469MelanomaInhibit immunity (T and NK cell function)Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment.
28592285Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status.
23776241Triple-Negative Breast CarcinomaInhibit immunityUsing mouse models of breast cancer, we demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. Targeted blockade of CD73 enhanced doxorubicin-mediated antitumor immune responses and significantly prolonged the survival of mice with established metastatic breast cancer. Taken together, our data suggest that CD73 constitutes a therapeutic target in TNBC.
24986517melanoma & breast carcinomaInhibit immunity immunotherapy targetAdenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe clinical profile of adenosine A2A receptor inhibitors (A2ARi) in Parkinson disease.
23964122B16 Malignant MelanomaInhibit immunity (NK cell function)In this study, we revealed that A2A/A2B receptor antagonists were effective in reducing the metastasis of tumors expressing CD73 endogenously (4T1.2 breast tumors) and when CD73 was ectopically expressed (B16F10 melanoma). A2A(-/-) mice were strongly protected against tumor metastasis, indicating that host A2A receptors enhanced tumor metastasis. A2A blockade enhanced natural killer (NK) cell maturation and cytotoxic function in vitro, reduced metastasis in a perforin-dependent manner, and enhanced NK cell expression of granzyme B in vivo, strongly suggesting that the antimetastatic effect of A2A blockade was due to enhanced NK cell function.
29802128SarcomaInhibit immunity (T cell function); Resistant to immunotherapyIn studies of A2AR and/or A2BR gene-deficient mice, we found that A2AR deletion-but not A2BR deletion-liberates endogenous CD8+ T cell antitumor immunity against weakly immunogenic MCA205 sarcomas. Studies of adoptively transferred A2AR-/-, A2BR-/-, or A2AR-/-/A2BR-/- tumor-reactive T cells confirmed that immunosuppression in the tumor microenvironment was mediated by A2AR on CD8+ T cells. The blockade of the A2AR on adoptively transferred T cells by synthetic A2AR antagonist led to higher levels of IFN-γ secretion by tumor-infiltrating CD8+ T cells.
16916931MelanomaInhibit immunityWe hypothesized that A2AR also protects cancerous tissues by inhibiting incoming antitumor T lymphocytes. Here we confirm this hypothesis by showing that genetic deletion of A2AR in the host resulted in rejection of established immunogenic tumors in approximately 60% of A2AR-deficient mice with no rejection observed in control WT mice.
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ADORA2A in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ADORA2A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3210.412
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2950.737
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3430.639
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-1.0610.19
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.5090.207
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.4920.723
729033130MelanomaallAnti-PD-1 (nivolumab) 262301
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 151101
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 111201
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.080.946
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.0930.956
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0540.507
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ADORA2A in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ADORA2A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ADORA2A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ADORA2A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ADORA2A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ADORA2A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ADORA2A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolADORA2A
Nameadenosine A2a receptor
Aliases RDC8; A2aR; adenosine receptor subtype A2a; Adenosine receptor A2a
Chromosomal Location22q11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ADORA2A collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ADORA2A.
ID Name Drug Type Targets #Targets
DB00201CaffeineSmall MoleculeADORA1, ADORA2A, ATM, ITPR1, ITPR2, ITPR3, PDE10A, PDE11A, PDE1A, ......33
DB00277TheophyllineSmall MoleculeADORA1, ADORA2A, ADORA2B, CPNE1, HDAC2, HM13, NOMO1, PARP1, PDE3A, ......14
DB00358MefloquineSmall MoleculeADORA2A, HBA12
DB00555LamotrigineSmall MoleculeADORA1, ADORA2A, ADRA1A, ADRA2A, ADRB1, CACNA1E, CHRM1, CHRM2, CHR ......44
DB00640AdenosineSmall MoleculeADORA1, ADORA2A, ADORA2B, ADORA34
DB00651DyphyllineSmall MoleculeADORA1, ADORA2A, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B8
DB00806PentoxifyllineSmall MoleculeADORA1, ADORA2A, NT5E, PDE4A, PDE4B, PDE5A6
DB00824EnprofyllineSmall MoleculeADORA1, ADORA2A, ADORA2B, ADORA3, PDE4A, PDE4B6
DB01303OxtriphyllineSmall MoleculeADORA1, ADORA2A, HDAC2, PDE3A, PDE4A5
DB01412TheobromineSmall MoleculeADORA1, ADORA2A, PDE4B3
DB04853BinodenosonSmall MoleculeADORA2A1
DB04932DefibrotideBiotechADORA1, ADORA2A, ADORA2B3
DB05009ApadenosonSmall MoleculeADORA2A1
DB05191Atl146eSmall MoleculeADORA2A1
DB06213RegadenosonSmall MoleculeADORA2A1
DB087704-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenolSmall MoleculeADORA2A1
DB09273DoxofyllineSmall MoleculeADORA2A, ADRB22