ADORA2B:Adenosine receptor A2b

Gene Name
Adenosine receptor A2b
Protein ID
Chromosome ID
HPP Status
Protein Name
Adenosine receptor A2b

adenosine receptor A2b

adenosine A2b receptor


[Reference: ]
Chromosomal Position
17p12 | Start:15944917 End:15944917

Entrez Gene Summary for ADORA2B
This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. (provided by RefSeq, Jul 2008)

UniProtKB Summary for ADORA2B
Function: Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Tocris Summary for ADORA2B
Adenosine A2B receptors are members of the adenosine receptor group of G-protein-coupled receptors that also includes A1, A2A and A3. A2B receptors display high expression levels in the cecum, colon and bladder, with lower levels found in the lung, blood vessels, eye, median eminence and mast cells. A2B receptors play a role in the relaxation of smooth muscle in the vasculature and intestines, inhibit monocyte and macrophage function and stimulate mast cell mediator release. The human A2B receptor gene is localized on chromosome 17 (17p12-p11.2).

[Reference: ]
External IDs
Hgnc ID: 264 EntrezGene ID: 136 Ensembl ID: ENSG00000170425
[Reference: ]
Reference Source

Gene Reference Into Function (GeneRIF)

PubMed IDGeneRIF TextLast Update
119062911,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists2010-01-21
12080047A2BR binds to E3KARP and Ezrin upon agonist stimulation.2010-01-21
12600879Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors.2010-01-21
12939345Selectively up-regulated by hypoxia (>5-fold increase in mRNA), and antagonists neutralize ATP-mediated endothelial permeability2010-01-21
15187156demonstrated induction of IgE synthesis by the interaction between adenosine-stimulated mast cells and B lymphocytes involves up-regulation of IL-4 and IL-13 mediated by A(2B) receptors2010-01-21
15550390Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and inhibits the expression of adenylate cyclase2010-01-21
15637124adenosine A2B receptors mediate the adenosine-induced contraction vasomotor effect in human chorionic vessels and that this involves synthesis of a thromboxane receptor activator or a related prostanoid.2010-01-21
15769552The PKC delta and epsilon isoforms are also involved in adenosine receptor A(2b) dependent upregulation of IL-6 expression.2010-01-21
16103269A(2B) receptors may play role in regulating glomerular remodeling associated with glomerular mesangial cell proliferation. Activation of A(2B) receptors may prevent glomerular remodeling associated with renal disease, hypertension, and diabetes.2010-01-21
16631311A2bR signals through adenylate cyclase (AC) 6 isoform in intestinal epithelial cells2010-01-21
16707627A(2B) receptors up-regulate IL-4 through G(q) signaling that is potentiated via cross-talk with G(s)-coupled pathways.2010-01-21
16778150Data indicate that adenosine increases the release of IL-19 from bronchial epithelial cells via activation of adenosine A(2B) receptors, and IL-19 in turn activates human monocytes to release TNF-alpha, which upregulates A(2B) receptor expression.2010-01-21
17077301Transcriptional coordination of adenosine a2B receptor by HIF-1alpha and amplified adenosine signaling during hypoxia.2010-01-21
17301835adenosine treatment of dermal papilla cells upregulates FGF-7 expression via the A2b adenosine receptor and that cAMP acts as one of the second messengers in this pathway2010-01-21
17428235Adenosine is not a direct GHSR agonist. In human embryonic kidney 293s (HEK) cells expressing GHSR, adenosine activates endogenously expressed A(2B)R resulting in calcium mobilization.2010-01-21
17565009Epac1 activation in HUVEC results in ERK1/2 activation, and this protein, at least in part, mediates response to the physiologically relevant event of A(2B)AR stimulation2010-01-21
18004767Short-term TNF-alpha cell treatment caused A(2B) AR phosphorylation inducing, in turn, impairment in A(2B) AR-G protein coupling and cAMP production2010-01-21
18056839Pharmacologic and genetic evidence for vascular A2BAR signaling as central control point of hypoxia-associated vascular leak.2010-01-21
18215420The results herein provide initial evidence that the inhibitory effect of hypoxia on MMP-9 by mature dendritic cells requires the activation of A(2b) in a cAMP/PKA-dependent pathway.2010-01-21
18351132our findings revealed the role of adenosine receptors in breast cancer cell lines on growth modulation role of A3 and functional form of A2B, although its involvement in cell growth modulation was not seen2010-01-21
18367727A(2B)-R are required for ASL volume homeostasis in human airways, and therapies directed at inhibiting A(2B)-R may lead to a cystic fibrosis-like phenotype with depleted ASL volume and mucus stasis.2010-01-21
18703227A2B adenosine receptors may differentially modulate hENTs in hPMEC, which could be a mechanism attempting to re-establish physiological extracellular adenosine levels in pre-eclampsia.2010-01-21
18996102Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)2009-03-25
19019667Observational study of gene-disease association. (HuGE Navigator)2008-12-03
19086053Observational study of gene-disease association. (HuGE Navigator)2009-01-11
19794965Data suggest that adenosine receptor modulation may be useful for refining the use of chemotherapeutic drugs to treat human cancer more effectively.2010-01-21
19841638Hypoxic mature dendritic cells predominantly express adenosine receptor A2b.2010-05-31
19883624Studies indicate that adenosine mediates its actions by means of activation of specifiic G protein-coupled receptors, for which 4 subbtypes: A1R, A2AR, A2BR and A3R have2010-04-12
19913121Observational study of gene-disease association. (HuGE Navigator)2010-09-15
19948975Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator)2010-04-07
20008542Oxidative/nitrosative stress selectively altered A(2B) adenosine receptors in chronic obstructive pulmonary disease.2010-05-03
20011598Development of Chlamydia trachomatis is reversibly retarded by prolonged exposure of infected cells to extracellular adenosine mediated by the A2b adenosine receptor.2010-03-22
20029460demonstrated that hypoxia-induced apoptosis of T cells was mediated by A(2a )and A(2b) receptors.2010-03-15
20237496Observational study of gene-disease association. (HuGE Navigator)2010-04-07
20388705TNF-alpha-induced A(2B)AR expression in colonic epithelial cells is post-transcriptionally regulated by miR27b and miR128a2010-07-05
20619442ADORA2B was overexpressed in colorectal carcinomas grown under a hypoxic state, presumably promoting cancer cell growth.2010-11-13
20628086Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)2010-09-15
20926384Adenosine A2A receptor is involved in cell surface expression of A2B receptor2011-01-15
21030693The results of this study suggest that deterioration of structure in the extracellular domains of GPCRs compromises overall receptor structure with profound consequences for receptor activation and constitutive activity.2011-04-09
21109603Adenosine A(B) receptors mediate an early induction of NR4A1 and a decrease in cell proliferation via the cAMP/Epac pathway in coronary artery smooth muscle cells.2011-07-16
21242513The ability of transgenic A2BR blockade to reduce circulating interleukin (IL)-6 levels by 24 hr may be explained by the reduction of bacterial load, and reflects that transgenic mice are going to live.2011-04-30
21335481[review] There is evidence that the ADORA2B receptor has cardioprotective effects upon its activation. However, controversy remains regarding the precise timing of activation required to induce cardioprotection.2012-10-13
21480628The main differences between the general dynamic behaviors of the A(2A)AR receptors and A(2B)AR receptors explored can be explained in terms of their particular sequences, loops lengths, and disulfide bridges.2011-08-06
21506953Inhibition of human mast cell activation would be a mechanism for A AR antagonists, but not A(2B) AR antagonists.2012-03-24
21590734Adenosine receptor expression and activation during the differentiation of mesenchymal stem cell to osteoblasts and adipocytes, was investigated.2011-12-17
21620804Only the disulfide bond of the adenosine A2B receptor is essential for ligand binding and receptor activation.2011-09-17
216228272',3'-cAMP inhibits proliferation of vascular smooth muscle cells from the aorta and coronary arteries. This effect is due in part to metabolism of 2',3'-cAMP to adenosine, with engagement of the A2B receptor.2011-10-01
21730968data show that expression of A1Rs induced adipocyte differentiation, whereas A2bR expression inhibited adipogenesis and stimulated an osteoblastic phenotype2012-06-23
21966389IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by increasing expression levels of adenosine receptors A2B and decreasing A2A2012-06-09
22119961A2B receptors are expressed in neuroendocrine tumors during cellular stress, damage and hypoxia.2013-07-13
22217884adenosine stimulates human endothelial progenitor cells migration by activating A2A and A, but not A2B, receptors and provides evidence to support a role of adenosine in modulating angiogenic capacity of hEPC2012-09-22
22504483studies identify adenosine-elicited stabilization of Per2 in the control of HIF-dependent cardiac metabolism and ischemia tolerance and implicate Per2 stabilization2012-07-28
22679008ADORA2B is a candidate gene known to modify the severity of sickle cell disease.2012-12-08
22767505Binding of A(2B)AR to specific sites on p105 prevents polyubiquitylation and degradation of p105 protein.2013-04-27
22848385study identified the A2bAR as a significant regulator of HFD-induced hallmarks of T2D, thereby pointing to its therapeutic potential.2013-04-06
22867902A(1) and A(2B)adenosine receptors could be potential biomarkers to provide an early indication of SA risk and their stimulation may turn out to improve fetoplacental perfusion by increasing vascular endothelial growth factor (VEGF) and nitric oxide (NO).2012-11-17
22963436The most recent evidence concerning the role of ADORA2B and its potential therapeutic relevance is discussed. [Review Article]2013-06-08
23045479A(2B)ARs mediate C. difficile toxin-induced enteritis and disease.2013-02-09
23286920Distinct interactions of structurally diverse ligands with the human A(2B) receptor and differences between closely related receptor subtypes.2013-03-30
23483055Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis.2013-05-25
23584256CD73 promotes the production of renal adenosine that is a prominent driver of renal hypertension by enhanced ADORA2B signaling-mediated endothelin-1 induction in a hypoxia-inducible factor-alpha-dependent manner.2013-07-27
23638125Hypoxia induced serotonin synthesis and secretion is amplified by ADORA2B signaling via MAPK/CREB and TPH-1 activation.2013-11-16
23682121Adenosine regulates bone metabolism via A1, A2A, and A2B receptors.2013-11-16
23716716High concentrations of extracellular adenosine in the tumor microenvironment can chronically activate A2B receptors to suppress Rap1B prenylation and signaling at the cell membrane, resulting in reduced cell-cell contact and promoting cell scattering.2014-11-08
23855769increased expression levels of the adenosine A2B receptor and a heightened deposition of hyaluronan (a component of the extracellular matrix) in remodeled vessels of patients with pulmonary hypertension associated with COPD2014-02-01
24136993an important role of the A2B receptor-dependent upregulation of JunB in VEGF production and possibly other AP-1-regulated events.2014-03-08
24391213ADORA2B was induced in lung cells after cyclic mechanical stress. A prominent region within the ADORA2B promoter conveys stretch responsiveness and has a binding site for HIF-1.2014-03-29
24434023Data indicate that hypoxia regulates prostatic acid phosphatase (PAP) through hypoxia-inducible factor 2 alpha (HIF2alpha) and from stimulated A2B adenosine receptors.2014-11-22
24464644Activation of the adenosine A2B receptor is regulated by the C-terminus of G protein alpha-subunits.2015-06-20
24502579the adenosine A2b receptor was shown to be the only one of the adenosine receptors whose cardiac expression is induced by ischemia in both mice and humans and whose function is implicated in ischemic pre- or post-conditioning2015-05-23
24584483After myocardial infarction, A2B receptor signaling regulates myocardial repair and remodeling.2015-06-20
24589267Studies indicate that adenosine signaling through the adenosine A2A receptor (A2AR) and A2B receptor (A2BR) were involved in sickle cell disease (SCD).2014-11-22
24652540The effects of extracellular cAMP on monocytes are mediated by CD73 ecto-5'-nucleotidase and A2A and A2B adenosine receptors, as selective antagonists could reverse its effects.2014-09-13
24877077HUVECs from preeclampsia exhibit elevated protein level of A2BAR and impairment of A2BAR-mediated NO/VEGF signaling pathway.2015-02-14
24928509study implicates the A2bAR as a regulator of adipocyte differentiation and the A2bAR-KLF4 axis as a potentially significant modulator of adipose biology.2015-02-14
24966910Findings support a potentially destructive role for A2BAR under intestinal ischemia/reperfusion and acute hypoxic conditions.2015-02-28
25002363A2B receptor activation blunts trophoblast migration possibly as a result of reduced activation of the MAPK signaling pathway and lower proMMP-2 levels.2015-05-16
25087184Data indicate adenosine receptor ADORA2B as the specific receptor and signalling pathway for the metabolite 5'-methylthioadenosine (MTA).2014-12-20
25429616Stimulation of A1AR and A2BAR had a prominent anti-proliferative/pro-apoptotic effect on the glioblastoma stem cells.2015-06-20
25587035the A2B adenosine receptor (ADORA2B) is essential for adenosine-induced SphK1 activity in human and mouse normal and sickle erythrocytes in vitro2015-05-02
25629231The rs7208480 of ADORA2B as well as the haplotypes were not found to be associated with chronic heart failure susceptibility.2015-09-26
25765819our data suggest that adenosine A2b signaling represses CIITA transcription in VSMCs by manipulating the interaction between STAT1 and the epigenetic machinery.2015-08-29
25966978the A2B AR activation-driven angiogenesis via cAMP-PKA-CREB mediates VEGF production and PI3K/AKT-dependent upregulation of eNOS in HMEC-12016-02-27
26228921Data show that ADORA2B mRNA and protein were significantly up-regulated in oral squamous cell carcinoma (OSCC) and that ADORA2B controls cellular proliferation via HIF-1alpha activation, suggesting it may be a key regulator of tumoral progression in OSCCs.2016-05-14
26478435ADORA2B is a target gene of miR-128b.MiR-128b represses cell proliferation, migration and invasion and promotes apoptosis by targeting ADORA2B in gastric cancer.2016-05-07


Relevant citations within the PubMed literature


Putative/known Functions


Homologues, Orthologues, Paralogues and Family

Sequence Similarity and Functional Annotation

Sequence Similarity

Db NameQuery UniSubject UniSequence LengthAlignment LengthIdentityCoverageMismatchesGap OpeningsQuery StartQuery EndSubject StartSubject EndEvalueBit Score
Reviewed non-human mammalian with experimental evidenceAA2BR_HUMANAA2BR_RAT33231688.2995.18370131613162.00E-166581
Islam MT, Garg G, Hancock WS, Risk BA, Baker MS, Ranganathan S (2014) Protannotator: A Semiautomated Pipeline for Chromosome-Wise Functional Annotation of the "Missing" Human Proteome. J Proteome Res. 13, 76-83.

InterProScan Annotation

Uniprot IDInterpro IDGo IDTypeNameCategoryDescription
AA2BR_HUMANIPR000276GO:0004930FamilyG protein-coupled receptor, rhodopsin-likeMolecular FunctionG-protein coupled receptor activity
AA2BR_HUMANIPR000276GO:0007186FamilyG protein-coupled receptor, rhodopsin-likeBiological ProcessG-protein coupled receptor signaling pathway
AA2BR_HUMANIPR000276GO:0016021FamilyG protein-coupled receptor, rhodopsin-likeCellular Componentintegral to membrane
AA2BR_HUMANIPR001435GO:0007186FamilyAdenosine A2B receptorBiological ProcessG-protein coupled receptor signaling pathway
AA2BR_HUMANIPR001435GO:0016021FamilyAdenosine A2B receptorCellular Componentintegral to membrane
AA2BR_HUMANIPR001634GO:0001609FamilyAdenosine receptorMolecular FunctionG-protein coupled adenosine receptor activity
AA2BR_HUMANIPR001634GO:0001973FamilyAdenosine receptorBiological Processadenosine receptor signaling pathway
AA2BR_HUMANIPR001634GO:0016021FamilyAdenosine receptorCellular Componentintegral to membrane
Islam MT, Garg G, Hancock WS, Risk BA, Baker MS, Ranganathan S (2014) Protannotator: A Semiautomated Pipeline for Chromosome-Wise Functional Annotation of the "Missing" Human Proteome. J Proteome Res. 13, 76-83.

KEGG Pathways

Pathway IDDatabase NamePathway Name
hsa04020KEGG PATHWAYCalcium signaling pathway
hsa04080KEGG PATHWAYNeuroactive ligand-receptor interaction
hsa04270KEGG PATHWAYVascular smooth muscle contraction
Islam MT, Garg G, Hancock WS, Risk BA, Baker MS, Ranganathan S (2014) Protannotator: A Semiautomated Pipeline for Chromosome-Wise Functional Annotation of the "Missing" Human Proteome. J Proteome Res. 13, 76-83.

Post Translational Modifications

Protein Protein Interactions

Best Available Mass Spectra without FDR


Evidence File
Fenyö, David; Beavis, Ronald C. (2015). "The GPMDB REST interface". Bioinformatics 31 (12): 2056–2058. doi:10.1093/bioinformatics/btv107. ISSN 1367-4803. ">Global Proteome Machine Database - THE GPM

Showing 1-1 of 1 item.


Peptide SequenceScoresPride IDSpectrum IDAnnotation
Evidence File
Vizcaino JA, et al. 2016 update of the PRIDE database and related tools. Nucleic Acids Res. 2016 Jan 1;44(D1):D447-D456. ">PRIDE Archive

Proteomics DB

Evidence File
Wilhelm, M et al. (2014) Mass-spectrometry-based draft of the human proteome. Nature. 509:582-7. ">Proteomics DB