GPR19

Target id: 90

Nomenclature: GPR19

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

This receptor has a proposed ligand; see the Latest Pairings page for more information.

   GtoImmuPdb view: OFF :     Currently no data for GPR19 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 415 12p12.3 GPR19 G protein-coupled receptor 19
Mouse 7 415 6 G1 Gpr19 G protein-coupled receptor 19
Rat 7 415 4q43 Gpr19 G protein-coupled receptor 19 4
Previous and Unofficial Names
GPR-NGA
Database Links
Specialist databases
GPCRDB gpr19_human (Hs), gpr19_mouse (Mm), gpr19_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
adropin {Sp: Human} Hs Agonist 8.1 pEC50 5
pEC50 8.1 (EC50 7.7x10-9 M) [5]
Description: In a TGFα-shedding assay using synthetic adropin.
Tissue Distribution
Caudate nucleus, putamen, thalamus
Species:  Human
Technique:  Northern blot
References: 
Embryonic stem cells
Species:  Human
Technique:  Microarray analysis
References:  1
Brain, testis, E11
Expression level:  High
Species:  Mouse
Technique:  Northern blot
References:  2
Olfactory bulb, cerebral cortex, hippocampal formation, dentate gyrus, cerebellum, hypothalamic nuclei
Species:  Mouse
Technique:  In situ hybridization.
References:  2
Liver, heart, kidney
Expression level:  Low
Species:  Mouse
Technique:  Northern blot
References:  2
Pachytene spermatocytes
Species:  Mouse
Technique:  Microarray analysis
References:  7
Brain (pituitary, cerebellum, olfactory tubercle, thalamus, striatum, hippocampus, frontal cortex, hypothalamus, medulla pons), kidney, heart, spleen, liver, kidney
Species:  Rat
Technique:  Northern blot
References: 
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 Comments
Embryonic GPR19 expression in mice implies a role for the receptor in nervous system development. Additional functions are suspected in the adult, which may differ between species [2]. Expression of GPR19 in hESCs may offer a possibility for in vitro intervention on proliferation or pluripotency [1].
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr19tm1Dgen Gpr19tm1Dgen/Gpr19tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:892973  MP:0001363 increased anxiety-related response
Clinically-Relevant Mutations and Pathophysiology Comments
GPR19 is mapped at approximately 40kb from CDKN1B and although excluded from the region commonly deleted in acute lymphoblastic leukemia (ALL) it may be the target of genetic alterations in other cancers. Increased expression of GPR19, determined by microarray analysis, is seen in primary human metastatic melanoma samples [3,6].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  V189I
Global MAF (%):  10
Subpopulation MAF (%):  ARF|AMR|EUR: 29|9|6
Minor allele count:  C=0.103/225
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Isoleucine289 -> Val polymorphism in TM4 has significant incidence and may facilitate linkage analysis of neuropsychiatric disease
Amino acid change:  I289V
References:  4
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  G82C
Comment on frequency:  Low frequency (<10% of all tested populations)
SNP accession: 
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  P36Q
Comment on frequency:  Low frequency (<10% of all tested populations)
SNP accession: 
General Comments
Rao et al. (2017) [5] report in vitro signalling studies with the lysates of cells overexpressing the Energy Homeostasis Associated gene (ENHO) that encodes the peptide hormone adropin. Adropin was found to inhibit forskolin-induced increases in cAMP and this effect was replicated by using synthetic adropin (EC50 = 8 nM). GPR19 signals via MAPK/ERK1/2 and the authors suggest that it may play a role in metastasis by promoting the mesenchymal-epithelial transition (MET) through the ERK/MAPK pathway, thus facilitating colonization of metastatic breast tumor cells. This study supports the observation of Stein et al. (2016) [9] in which the authors showed that reduction in GPR19 mRNA levels in medial basal hypothalamus of male rats resulted in the loss of the inhibitory effect of adropin on water deprivation-induced thirst. Interestingly, adropin-(34-76) was screened in a β-arrestin assay as part of a library of 10, 000 compounds against ~80 orphan receptors which included GPR19 but no activity was detected, suggesting the possibility that adropin is more effective in signalling via G-proteins [8]. Further characterization in pharmacological assays is required to establish adropin as the cognate ligand for GPR19.

References

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1. Assou S, Le Carrour T, Tondeur S, Ström S, Gabelle A, Marty S, Nadal L, Pantesco V, Réme T, Hugnot JP, Gasca S, Hovatta O, Hamamah S, Klein B, De Vos J. (2007) A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas. Stem Cells25 (4): 961-73. [PMID:17204602]

2. Hoffmeister-Ullerich SA, Süsens U, Schaller HC. (2004) The orphan G-protein-coupled receptor GPR19 is expressed predominantly in neuronal cells during mouse embryogenesis. Cell Tissue Res.318 (2): 459-63. [PMID:15452705]

3. Montpetit A, Sinnett D. (1999) Physical mapping of the G-protein coupled receptor 19 (GPR19) in the chromosome 12p12.3 region frequently rearranged in cancer cells. Hum. Genet.105 (1-2): 162-4. [PMID:10480372]

4. O'Dowd BF, Nguyen T, Lynch KR, Kolakowski LF, Thompson M, Cheng R, Marchese A, Ng G, Heng HH, George SR. (1996) A novel gene codes for a putative G protein-coupled receptor with an abundant expression in brain. FEBS Lett.394 (3): 325-9. [PMID:8830667]

5. Rao A, Herr DR. (2017) G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells. Biochim. Biophys. Acta1864 (7): 1318-1327 [Epub ahead of print]. [PMID:28476646]

6. Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B, Samant RS, Shevde LA, Li W, Eschrich S, Daud A, Ju J, Matta J. (2008) The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics1: 13. [PMID:18442402]

7. Rossi P, Dolci S, Sette C, Capolunghi F, Pellegrini M, Loiarro M, Di Agostino S, Paronetto MP, Grimaldi P, Merico D, Martegani E, Geremia R. (2004) Analysis of the gene expression profile of mouse male meiotic germ cells. Gene Expr. Patterns4 (3): 267-81. [PMID:15053975]

8. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen18 (5): 599-609. [PMID:23396314]

9. Stein LM, Yosten GL, Samson WK. (2016) Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19. Am. J. Physiol. Regul. Integr. Comp. Physiol.310 (6): R476-80. [PMID:26739651]

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: GPR19. Last modified on 18/05/2017. Accessed on 22/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=90.