Adenosine receptor A3

UniProt P0DMS8 Organism Homo sapiens Gene ADORA3

Also known as: ADORA3

Function

G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various physiological processes including immune regulation, cardioprotection and neuroprotection. 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). Preferentially couples to the inhibitory G protein (Gi), leading to the suppression of adenylate cyclase activity and a reduction in intracellular cyclic AMP levels. Upon adenosine binding, mediates cardioprotection in cardiomyocytes through anti-apoptotic effects primarily via the ERK1/2 pathway as well as the PI3K pathway. 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.

Classification

Family (Pfam): PF00001 7tm_1
InterPro: Adeno_A3_rcpt, Adenosn_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 5

8X16 EM 3.29A
8X17 EM 3.19A
9EBH EM 3.60A
9EBI EM 3.60A
9EHS EM 3.20A

A predicted model is available from AlphaFold.

Gene Ontology · 18

Drugs targeting this protein · 9

CAFFEINE antagonist
OXTRIPHYLLINE antagonist
CAFFEINE CITRATE antagonist
THEOPHYLLINE SODIUM GLYCINATE antagonist
THEOPHYLLINE antagonist
AMINOPHYLLINE antagonist
PICLIDENOSON agonist
NAMODENOSON agonist
ADENOSINE agonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Transmembrane domain-containing protein TMIGD3 1 shared papers
Adenosine receptor A3 1 shared papers
Adenosine receptor A3 1 shared papers
Neurotrophic factor BDNF precursor form 1 shared papers
5'-3' exoribonuclease 1 1 shared papers
Copper-transporting ATPase 1 1 shared papers
Neurotrophic factor BDNF precursor form 1 shared papers
Tyrosinase 1 shared papers

Literature · 13 cited papers

Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor. Nat. Commun. · 2025
Structural insights into the agonist selectivity of the adenosine A3 receptor. Nat. Commun. · 2024
Cryo-EM structures of adenosine receptor A3AR bound to selective agonists. Nat. Commun. · 2024
N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand. Mol. Cell · 2021
Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-kappaB and osteosarcoma progression. Nat. Commun. · 2016
The consensus coding sequences of human breast and colorectal cancers. Science · 2006
The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Molecular phylogenetics and the origins of placental mammals. Nature · 2001
Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor. FASEB J. · 1998
Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 receptors. J. Immunol. · 1997
cDNA cloning and sequence analysis of the human A3 adenosine receptor. Biochim. Biophys. Acta · 1993
… and 1 more in the literature graph

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.