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ADORA3 adenosine A3 receptor [ Homo sapiens (human) ]

Gene ID: 140, updated on 28-Oct-2024

Summary

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Official Symbol
ADORA3provided by HGNC
Official Full Name
adenosine A3 receptorprovided by HGNC
Primary source
HGNC:HGNC:268
See related
Ensembl:ENSG00000282608 MIM:600445; AllianceGenome:HGNC:268
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A3AR
Summary
This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that are involved in a variety of intracellular signaling pathways and physiological functions. The receptor encoded by this gene mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Alternative splicing results in multiple transcript variants. This gene shares its 5' terminal exon with some transcripts from overlapping GeneID:57413, which encodes an immunoglobulin domain-containing protein. [provided by RefSeq, Nov 2014]
Expression
Broad expression in adrenal (RPKM 4.4), small intestine (RPKM 2.9) and 20 other tissues See more
Orthologs
all
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Genomic context

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See ADORA3 in Genome Data Viewer
Location:
1p13.2
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (111499429..111503633, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (111514110..111518318, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (112042051..112046255, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene chromosome 1 open reading frame 162 Neighboring gene RNA, U6 small nuclear 792, pseudogene Neighboring gene transmembrane and immunoglobulin domain containing 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1499 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1500 Neighboring gene RAP1A, member of RAS oncogene family Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1501 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1184 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1502 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1504 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1505 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1506 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:112150779-112151472 Neighboring gene long intergenic non-protein coding RNA 1160 Neighboring gene uncharacterized LOC107985184 Neighboring gene Sharpr-MPRA regulatory region 155 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1186

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Adenosine receptor expression in rheumatoid synovium: a basis for methotrexate action. Stamp LK, et al. Arthritis Res Ther, 2012 Jun 8. PMID 22682496, Free PMC Article
  2. Effect of a toggle switch mutation in TM6 of the human adenosine A₃ receptor on Gi protein-dependent signalling and Gi-independent receptor internalization. Stoddart LA, et al. Br J Pharmacol, 2014 Aug. PMID 24750014, Free PMC Article
  3. Different efficacy of adenosine and NECA derivatives at the human A3 adenosine receptor: insight into the receptor activation switch. Dal Ben D, et al. Biochem Pharmacol, 2014 Jan 15. PMID 24161786
  4. Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-kappaB in mediating receptor level. Madi L, et al. J Rheumatol, 2007 Jan. PMID 17216675
  5. Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome. Campbell NG, et al. Mol Autism, 2013 Aug 16. PMID 23953133, Free PMC Article

See all (114) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ADORA3 activation promotes goblet cell differentiation via enhancing HMGCS2-mediated ketogenesis in ulcerative colitis.
    Title: ADORA3 activation promotes goblet cell differentiation via enhancing HMGCS2-mediated ketogenesis in ulcerative colitis.
  2. Inhibition of ADORA3 promotes microglial phagocytosis and alleviates chronic ischemic white matter injury.
    Title: Inhibition of ADORA3 promotes microglial phagocytosis and alleviates chronic ischemic white matter injury.
  3. Increased expression of adenosine A3 receptor in tumor-infiltrating natural killer cells.
    Title: Increased expression of adenosine A3 receptor in tumor-infiltrating natural killer cells.
  4. Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the A3 Receptor Subtype.
    Title: Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the A(3) Receptor Subtype.
  5. Analysis of association of ADORA2A and ADORA3 polymorphisms genotypes/haplotypes with efficacy and toxicity of methotrexate in patients with Rheumatoid arthritis.
    Title: Analysis of association of ADORA(2)A and ADORA(3) polymorphisms genotypes/haplotypes with efficacy and toxicity of methotrexate in patients with Rheumatoid arthritis.
  6. Systematic deletion of adenosine receptors reveals novel roles in inflammation and pyroptosis in THP-1 macrophages.
    Title: Systematic deletion of adenosine receptors reveals novel roles in inflammation and pyroptosis in THP-1 macrophages.
  7. N(6)-methyladenosine (m(6)A) is an endogenous A3 adenosine receptor ligand.
    Title: N(6)-methyladenosine (m(6)A) is an endogenous A3 adenosine receptor ligand.
  8. Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.
    Title: Activation of Adenosine A(3) Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.
  9. Adenosine A2A and A3 Receptors Are Able to Interact with Each Other. A Further Piece in the Puzzle of Adenosine Receptor-Mediated Signaling.
    Title: Adenosine A(2A) and A(3) Receptors Are Able to Interact with Each Other. A Further Piece in the Puzzle of Adenosine Receptor-Mediated Signaling.
  10. A3 adenosine receptor activation mechanisms: molecular dynamics analysis of inactive, active, and fully active states.
    Title: A(3) adenosine receptor activation mechanisms: molecular dynamics analysis of inactive, active, and fully active states.
Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of adenosine A3 receptor (ADORA3) in peptide-treated PBMCs PubMed
Tat tat HIV-1 Tat upregulates adenosine A3 receptor in HEK 293T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled adenosine receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in G protein-coupled adenosine receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in activation of adenylate cyclase activity TAS
Traceable Author Statement
more info
 PubMed 
involved_in inflammatory response TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in presynaptic modulation of chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of heart contraction TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of norepinephrine secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to wounding TAS
Traceable Author Statement
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in Schaffer collateral - CA1 synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in dendrite IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in presynaptic membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in synapse IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
adenosine receptor A3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032119.1 RefSeqGene

    Range
    5001..85628
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_424

mRNA and Protein(s)

  1. NM_000677.4 → NP_000668.1  adenosine receptor A3 isoform A

    See identical proteins and their annotated locations for NP_000668.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (A) encodes the longest isoform (A).
    Source sequence(s)
    AL390195
    Consensus CDS
    CCDS839.1
    UniProtKB/Swiss-Prot
    A2A3P4, P0DMS8, P33765, Q6UWU0, Q9BYZ1
    UniProtKB/TrEMBL
    B2R7S2, H6VQ59
    Related
    ENSP00000241356.4, ENST00000241356.5
    Conserved Domains (2) summary
    cd14964
    Location:15 → 39
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:13 → 293
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

  2. NM_001302678.2 → NP_001289607.1  adenosine receptor A3 isoform B

    Status: REVIEWED

    Description
    Transcript Variant: This variant (B) uses an alternate splice site in the 3' terminal exon, resulting in an alternate 3' coding region and 3' UTR, compared to variant A. The encoded isoform (B) has a distinct C-terminus and is shorter than isoform A.
    Source sequence(s)
    AL390195, BF432324, BM675096, CD013875, JN855714
    Consensus CDS
    CCDS81358.1
    UniProtKB/TrEMBL
    A0A0J9YWR0
    Related
    ENSP00000488073.1, ENST00000632535.1
    Conserved Domains (2) summary
    cd14964
    Location:14 → 40
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:13 → 116
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

  3. NM_001302679.2 → NP_001289608.1  adenosine receptor A3 isoform C

    Status: REVIEWED

    Description
    Transcript Variant: This variant (C) uses an alternate splice site in the 5' terminal exon, and it thus differs in its 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant A. The encoded isoform (C) is shorter at the N-terminus, compared to isoform A.
    Source sequence(s)
    AL390195, BF432324, BM675096, BX283401, JN855714
    UniProtKB/TrEMBL
    H6VQ59
    Conserved Domains (2) summary
    cd14964
    Location:29 → 59
    7tm_GPCRs; TM helix 5 [structural motif]
    cl28897
    Location:1 → 148
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    111499429..111503633 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    111514110..111518318 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P0DMS8.1 GenPept UniProtKB/Swiss-Prot:P0DMS8

Gene LinkOut

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