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GPR21

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Target not currently curated in GtoImmuPdb

Target id: 92

Nomenclature: GPR21

Family: Class A Orphans

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 349 9q33.2 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 Click here for help
Specialist databases
GPCRdb gpr21_human (Hs), gpr21_mouse (Mm)
Other databases
Alphafold Q99679 (Hs), Q8BX79 (Mm)
ChEMBL Target CHEMBL4523913 (Hs)
Ensembl Gene ENSG00000188394 (Hs), ENSMUSG00000053164 (Mm), ENSRNOG00000042269 (Rn)
Entrez Gene 2844 (Hs), 338346 (Mm), 311911 (Rn)
Human Protein Atlas ENSG00000188394 (Hs)
KEGG Gene hsa:2844 (Hs), mmu:338346 (Mm), rno:311911 (Rn)
OMIM 601909 (Hs)
Pharos Q99679 (Hs)
RefSeq Nucleotide NM_005294 (Hs), NM_177383 (Mm), NM_001109554 (Rn)
RefSeq Protein NP_005285 (Hs), NP_796357 (Mm), NP_001103024 (Rn)
UniProtKB Q99679 (Hs), Q8BX79 (Mm)
Wikipedia GPR21 (Hs)
Primary Transduction Mechanisms Click here for help
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 Click here for help
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 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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Physiological Functions Click here for help
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 Click here for help
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 Click here for help
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:  rs61736065
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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