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ADGRG3

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Target id: 188

Nomenclature: ADGRG3

Family: Adhesion Class GPCRs

Gene and Protein Information Click here for help
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 549 16q21 ADGRG3 adhesion G protein-coupled receptor G3 4
Mouse 7 542 8 C5 Adgrg3 adhesion G protein-coupled receptor G3
Rat 7 547 19q13 Adgrg3 adhesion G protein-coupled receptor G3
Previous and Unofficial Names Click here for help
GPR97 (G protein-coupled receptor 97) | Pb99 | PGR26
Database Links Click here for help
Specialist databases
GPCRdb agrg3_human (Hs), agrg3_mouse (Mm)
Other databases
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
beclometasone dipropionate Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Full agonist 8.5 pEC50 5
pEC50 8.5 (EC50 3.1x10-9 M) [5]
Antagonist Comments
Treatment with pertussis toxin abolished the agonist-like effect of treatment with beclomethasone dipropionate [5].
Immunopharmacology Comments
ADGRG3 is expressed by immune cells. It is required for proper B cell development in the spleen [10], and has been shown to regulate macrophage-mediated local inflammation in obesity-relevant tissues in rodent models [8].
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  ADGRG3 is involved in regulating B cell development.
References:  10
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gi/Go family
Comments:  ADGRG3 (GPR97) requires chimeric protein Gqo3 to induce inositol phosphate accumulation, indicating it primarily couples to Gαo-protein [5]. A recent study showed that GPR97 conducts Gαs/cAMP signaling, while a CTF-only mutant or crosslinking of the receptor triggered Gαo/i/ERK/NF-κB signaling [6].
References:  5-6
Tissue Distribution Click here for help
Unigene expression profile: high frequency in bone marrow, blood, lung.
Species:  Human
Technique: 
References: 
Lung, liver, bone marrow, leukemia cells
Species:  Human
Technique:  EST
References:  1-2,4
Granulocytes
Species:  Human
Technique:  Microarray analysis, RNA sequencing and mass-spectrometry.
References:  6-7
Unigene expression profile: high frequency in blood, bone marrow, inner ear, thymus, liver, lung, mammary gland.
Species:  Mouse
Technique: 
References: 
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Beclomethasone dipropionate mediated G protein signaling
Species:  Human
Tissue:  Transfected CHO cell line
Response measured:  Elevated aequorin luminescence signal, [35S]GTPγS binding assay
References:  5
Physiological Consequences of Altering Gene Expression Click here for help
Adgrg3 is involved in regulating B-cell development.
Species:  Mouse
Tissue: 
Technique: 
References:  10
Physiological Consequences of Altering Gene Expression Comments
Adgrg3 knockout mice do not show defects in lymphocyte development [9].
General Comments
ADGRG3 (formerly GPR97) is an orphan receptor belonging to Family VIII Adhesion-GPCRs together with ADGRG1, 2, and 4-7 [3]. The genes of ADGRG1, ADGRG3 and ADGRG5 are syntenically clustered on human chromosome 16 and mouse chromosome 8 suggesting the evolution from an ancestral gene through gene duplication and exon shuffling [7]. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation [6].

References

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1. Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB. (2004) The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics, 84 (1): 23-33. [PMID:15203201]

2. Bjarnadóttir TK, Geirardsdóttir K, Ingemansson M, Mirza MA, Fredriksson R, Schiöth HB. (2007) Identification of novel splice variants of Adhesion G protein-coupled receptors. Gene, 387 (1-2): 38-48. [PMID:17056209]

3. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun, 301 (3): 725-34. [PMID:12565841]

4. Fredriksson R, Lagerström MC, Höglund PJ, Schiöth HB. (2002) Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions. FEBS Lett, 531 (3): 407-14. [PMID:12435584]

5. Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X. (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett, 586 (8): 1214-9. [PMID:22575658]

6. Hsiao CC, Chu TY, Wu CJ, van den Biggelaar M, Pabst C, Hébert J, Kuijpers TW, Scicluna BP, I KY, Chen TC et al.. (2018) The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions. Front Immunol, 9: 2830. [PMID:30559745]

7. Peng YM, van de Garde MD, Cheng KF, Baars PA, Remmerswaal EB, van Lier RA, Mackay CR, Lin HH, Hamann J. (2011) Specific expression of GPR56 by human cytotoxic lymphocytes. J Leukoc Biol, 90 (4): 735-40. [PMID:21724806]

8. Shi J, Zhang X, Wang S, Wang J, Du B, Wang Z, Liu M, Jiang W, Qian M, Ren H. (2016) Gpr97 is dispensable for metabolic syndrome but is involved in macrophage inflammation in high-fat diet-induced obesity in mice. Sci Rep, 6: 24649. [PMID:27089991]

9. Sleckman BP, Khan WN, Xu W, Bassing CH, Malynn BA, Copeland NG, Bardon CG, Breit TM, Davidson L, Oltz EM et al.. (2000) Cloning and functional characterization of the early-lymphocyte-specific Pb99 gene. Mol Cell Biol, 20 (12): 4405-10. [PMID:10825203]

10. Wang JJ, Zhang LL, Zhang HX, Shen CL, Lu SY, Kuang Y, Wan YH, Wang WG, Yan HM, Dang SY et al.. (2013) Gpr97 is essential for the follicular versus marginal zone B-lymphocyte fate decision. Cell Death Dis, 4: e853. [PMID:24113187]

Contributors

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