Protein / target
Adenosine receptor A3
Protein at a glance
Biological role
G protein-coupled adenosine receptor activity
Primary system
Nervous system
Strongest disease association
migraine disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
6 approved · 2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various physiological processes including immune regulation, cardioprotection and neuroprotection (PubMed:38627384, PubMed:40825947, PubMed:9837869). Also acts as a receptor for adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification, which are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs): activated by N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A) (PubMed:33472058, PubMed:39511145). Preferentially couples to the inhibitory G protein (Gi), leading to the suppression of adenylate cyclase activity and a reduction in intracellular cyclic AMP levels (PubMed:33472058, PubMed:38627384). Upon adenosine binding, mediates cardioprotection in cardiomyocytes through anti-apoptotic effects primarily via the ERK1/2 pathway as well as the PI3K pathway (PubMed:9837869). In the central nervous system, participates in the modulation of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus (By similarity). In lung mast cells, receptor activation contributes to the type I allergic response by facilitating mast cell degranulation and histamine release (By similarity). Highly expressed in inflammatory cells such as neutrophils and mast cells, inhibits neutrophil degranulation and reduces superoxide production, thereby modulating inflammatory responses (PubMed:9164961)
Subcellular location
Domains and Gene Ontology detail (18)Hide
Gene Ontology
- Cdendrite
- Cplasma membrane
- Cpresynaptic membrane
- CSchaffer collateral - CA1 synapse
- Csynapse
- FG protein-coupled adenosine receptor activity
- Pactivation of adenylate cyclase activity
- Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- PG protein-coupled adenosine receptor signaling pathway
- Pinflammatory response
- Pnegative regulation of cell migration
- Pnegative regulation of cell population proliferation
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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G protein-coupled signalling
- ·G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various…
- ·G protein-coupled adenosine receptor activity
- ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- ·G protein-coupled adenosine receptor signaling pathway
Immune signalling
- ·G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various…
- ·inflammatory response
- ·positive regulation of mast cell degranulation
Synaptic signalling
- ·presynaptic membrane
- ·Schaffer collateral - CA1 synapse
- ·synapse
- ·presynaptic modulation of chemical synaptic transmission
Transcriptional regulation
- ·G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various…
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Adenosine receptor agonist
Appears in clinical studies involving paroxysmal tachycardia, Wolff-Parkinson-White syndrome, cardiovascular disorder, Paroxysmal supraventricular tachycardia
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 718 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 8 total
asthma · chronic bronchitis · chronic obstructive pulmonary disease
Cough · Airway obstruction
hepatocellular carcinoma · Cirrhosis · metabolic dysfunction-associated steatohepatitis
migraine disorder · Apnea · Pain
paroxysmal tachycardia · Wolff-Parkinson-White syndrome · cardiovascular disorder
Apnea · Apnea · intracranial hemorrhage
Keratoconjunctivitis sicca · rheumatoid arthritis · psoriasis
asthma · Airway obstruction · Headache
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationAdenosine Receptors in Neuroinflammation and Neurodegeneration.
- New publicationREDIportal: toward an integrated view of the A-to-I editing.
- New publicationAdvances in A-to-I RNA editing in cancer.
- New publicationMicroglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling.
- New publicationAstrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice.
- New publicationWTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.
- New publicationAdenosine and adenosine receptors in metabolic imbalance-related neurological issues.
- New publicationAstrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.
- New publicationAdenosine and Cortical Plasticity.
- New publicationProgrammable RNA N<sup>6</sup>-methyladenosine editing with CRISPR/dCas13a in plants.
- New publicationm<sup>1</sup>A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration.
- New publicationUtilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.