<i>GPR21</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

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GPR21

Target id: 92

Nomenclature: GPR21

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for GPR21 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 349 9q33 GPR21 G protein-coupled receptor 21 1
Mouse 7 349 2 B Gpr21 G protein-coupled receptor 21
Rat 7 349 3q11 Gpr21 G protein-coupled receptor 21
Database Links
Specialist databases
GPCRDB gpr21_human (Hs), gpr21_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Primary Transduction Mechanisms
Comments:  GPR21 was reported to activate the Gq pathway based on its effect on calcium-sensitive CHO cells using a transcription-based reporter assay.
References:  1
Tissue Distribution
Brain (especially pre-optic area of the hypothalamus), adipose tissue, liver, bone marrow, spleen, macrophages
Species:  Mouse
Technique:  Quantitative real time PCR
References:  2-3
Tissue Distribution Comments
GPR21 was isolated originally from the brain, but the transcripts of GPR21 gene were not detected in the human brain regions (thalamus, putamen, caudate, frontal cortex, pons, hypothalamus, hippocampus) examined by Northern blot analysis [1].
Expression Datasets

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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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Physiological Functions
Migration of macrophages into inflammatory tissue in obesity
Species:  Mouse
Tissue:  Adipose tissue and liver
References:  3
Regulation of body weight and glucose metabolism
Species:  Mouse
Tissue: 
References:  2
Physiological Consequences of Altering Gene Expression
Resistant to diet-induced obesity. Mice deficient for the GPR21 gene exhibit an increase in glucose tolerance and insulin sensitivity and a modest lean phenotype.
Species:  Mouse
Tissue:  Embryonic stem cells
Technique:  Knockout (deletion of exon)
References:  2-3
Mice with deletion of GPR21 are protected from obesity-induced inflammation and insulin resistance, with reduced macrophage infiltration into adipose tissue and liver. GPR21 KO macrophages do not undergo cytoskeletal reorganisation and display defective chemotactic activity in response to adipocyte conditioned medium.
Species:  Mouse
Tissue:  Macrophage
Technique:  Knockout
References:  3
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  F212V
Global MAF (%):  2
Subpopulation MAF (%):  AFR|AMR: 6|1
Minor allele count:  G=0.017/38
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
General Comments
GPR21 contains a lysine residue in an analogous position to that of the endothelin receptor which is important for its binding to a peptide agonist [2].

References

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1. Bresnick JN, Skynner HA, Chapman KL, Jack AD, Zamiara E, Negulescu P, Beaumont K, Patel S, McAllister G. (2003) Identification of signal transduction pathways used by orphan g protein-coupled receptors. Assay Drug Dev Technol, 1 (2): 239-49. [PMID:15090189]

2. Gardner J, Wu S, Ling L, Danao J, Li Y, Yeh WC, Tian H, Baribault H. (2012) G-protein-coupled receptor GPR21 knockout mice display improved glucose tolerance and increased insulin response. Biochem. Biophys. Res. Commun., 418 (1): 1-5. [PMID:22155242]

3. Osborn O, Oh da Y, McNelis J, Sanchez-Alavez M, Talukdar S, Lu M, Li P, Thiede L, Morinaga H, Kim JJ et al.. (2012) G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. J. Clin. Invest., 122 (7): 2444-53. [PMID:22653059]

Contributors

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How to cite this page

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR21. Last modified on 31/07/2015. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=92.