GPR12

Target id: 86

Nomenclature: GPR12

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 GPR12 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 334 13q12 GPR12 G protein-coupled receptor 12 8
Mouse 7 334 5 G3 Gpr12 G-protein coupled receptor 12 7
Rat 7 334 12p11 Gpr12 G protein-coupled receptor 12
Previous and Unofficial Names
Gpcr01 | Gpcr20 | GPCR21 | GPCR12 | R334
Database Links
Specialist databases
GPCRDB gpr12_human (Hs), gpr12_mouse (Mm), gpr12_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
sphingosine 1-phosphate
Comments: Proposed ligand, single publication

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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
sphingosylphosphorylcholine Hs Full agonist 7.2 – 7.5 pEC50 4
pEC50 7.2 – 7.5 (EC50 6.6x10-8 – 3.2x10-8 M) [4]
sphingosine 1-phosphate Hs Full agonist 5.5 – 7.0 pEC50 11
pEC50 5.5 – 7.0 (EC50 3.1x10-6 – 1.2x10-6 M) [11]
Agonist Comments
Reports that sphingosine 1-phosphate was a ligand of GPR12 [4,11] were not reproduced in later studies using the β-arrestin PathHunter assay [9,12]. Tyrosol has been proposed to be a possible ligand for GPR12 [5].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Adenylate cyclase stimulation
Adenylate cyclase inhibition
References:  4,6,10-11
Tissue Distribution
Primary endothelial cells of pulmonary artery, coronary artery, iliac artery, aortic artery, lung microvasculature, umbilical vein, umbilical artery and dermal microvasculature. Primary vascular smooth muscle cells of aorta, bronchi, coronary artery, pulmonary artery, umbilical artery, uterus and skeletal muscle.
Species:  Human
Technique:  Western Blot
References:  11
Ovary. GPR3 RNA was not detected in human oocyte.
Species:  Human
Technique:  RT-PCR
References:  2
Vascular smooth muscle cells of aorta, coronary artery and pulmonary artery, microvascular endothelial cells of the lung, pulmonary artery, coronary artery and umbilical vein
Species:  Human
Technique:  RT-PCR
References:  11
Medial habenular nucleus, cerebral cortex, hippocampus, olfactory bulb, striatum
Species:  Mouse
Technique:  in situ hybridisation
References:  7
Limbic system: dentate gyrus, indusium griseum, fasciola cinereum, posteromedial cortical amygdala nucleus, anterior cingulate cortex, retrosplenial granular cortex, prelimbic cortex
Species:  Mouse
Technique:  Lac Z staining of Gpr12 KO mouse brain
References:  1
Highest expression in brain. A significant amount of GPR12 transcript was detected in liver.
Species:  Mouse
Technique:  RT-PCR
References:  10
Embyronic brain: Cortical plate, piriform cortex, hippocampus, dorsomedial and arcuate nuclei, motor and sensory nuclei of the hindbrain in the medullary reticular formation, caudate putamen, mammillary body
Species:  Mouse
Technique:  in situ hybridisation
References:  4
Forebrain, hindbrain, testis
Species:  Mouse
Technique:  Northern blot
References:  7
Oocytes
Species:  Mouse
Technique:  RT-PCR
References:  3
Mature brain: somatosensory and retrosplenial complex, hippocampus with the highest expression in the pyramidal cells of CA2 region, nucleus accumbens, piriform cortex, septum, the mitral and glomerular cell layers of the olfactory bulb, amygdala, geniculate nucleus. No gpr12 expression was detected in fiber tracts in the corpus callosum.
Species:  Mouse
Technique:  in situ hybridisation
References:  4
Oocytes
Species:  Rat
Technique:  RT-PCR and in situ hybridisation.
References:  3
Tissue Distribution Comments
Higher expresssion of GPR12 was detected in areas of neuronal differentiation, whereas GPR12 transcritpts were not detected in the regions of neuroblast proliferation [4]. GPR12 protein expression was upregulated in human vascular endothelial cells exposed to fluid shear stress, despite that there was no increase of GPR12 expression in the mRNA level [11]. GPR12 RNA was not detected in human oocytes examined by RT-PCR [2].
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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Functional Assays
Inhibition of RhoA activation through PKA activation
Species:  Rat
Tissue:  Cerebellar granule neuron
Response measured: 
References:  10
Physiological Functions
Involved in sphingosylphosphorycholine-induced cell proliferation.
Species:  Mouse
Tissue:  Hippocampus
References:  4
Stimulate synaptophysin production
Species:  Rat
Tissue:  Neuron
References:  10
Involved in meiotic arrest in rat oocytes.
Species:  Rat
Tissue:  Oocytes
References:  3,6,13
Physiological Consequences of Altering Gene Expression
Oocyte maturation. Rat oocytes with Gpr12 knockdown undergo meiotic resumption.
Species:  Rat
Tissue:  Oocytes
Technique:  RNA interference
References:  3-4
Mice with Gpr12 knockout have higher body weight and body fat mass, lower respiratory exchange ratio, lower energy expenditure, hepatic steatosis and are dyslipidermic.
Species:  Mouse
Tissue:  Limbic and sensory systems
Technique:  Gene Knockout
References:  1
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0005278 abnormal cholesterol homeostasis PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0005450 abnormal energy expenditure PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0010379 decreased respiratory quotient PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0001260 increased body weight PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0005178 increased circulating cholesterol level PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0005559 increased circulating glucose level PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0001556 increased circulating HDL cholesterol level PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0000182 increased circulating LDL cholesterol level PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0009285 increased gonadal fat pad weight PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0009355 increased liver triglyceride level PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0002981 increased liver weight PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0005458 increased percent body fat PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0009304 increased retroperitoneal fat pad weight PMID: 16887097 
Gpr12tm1Dgen Gpr12tm1Dgen/Gpr12tm1Dgen
B6.129P2-Gpr12
MGI:101909  MP:0001261 obese PMID: 16887097 

References

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1. Bjursell M, Gerdin AK, Jönsson M, Surve VV, Svensson L, Huang XF, Törnell J, Bohlooly-Y M. (2006) G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice. Biochem. Biophys. Res. Commun.348 (2): 359-66. [PMID:16887097]

2. DiLuigi A, Weitzman VN, Pace MC, Siano LJ, Maier D, Mehlmann LM. (2008) Meiotic arrest in human oocytes is maintained by a Gs signaling pathway. Biol. Reprod.78 (4): 667-72. [PMID:18184921]

3. Hinckley M, Vaccari S, Horner K, Chen R, Conti M. (2005) The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes. Dev. Biol.287 (2): 249-61. [PMID:16229830]

4. Ignatov A, Lintzel J, Hermans-Borgmeyer I, Kreienkamp HJ, Joost P, Thomsen S, Methner A, Schaller HC. (2003) Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development. J. Neurosci.23 (3): 907-14. [PMID:12574419]

5. Lin ZJ, Lu XM, Zhu TJ, Fang YC, Gu QQ, Zhu W. (2008) GPR12 selections of the metabolites from an endophytic Streptomyces sp. associated with Cistanches deserticola. Arch. Pharm. Res.31 (9): 1108-14. [PMID:18806952]

6. Meyer zu Heringdorf D, Jakobs KH. (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim. Biophys. Acta1768 (4): 923-40. [PMID:17078925]

7. Saeki Y, Ueno S, Mizuno R, Nishimura T, Fujimura H, Nagai Y, Yanagihara T. (1993) Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) which is expressed predominantly in mouse central nervous system. FEBS Lett.336 (2): 317-22. [PMID:8262253]

8. Song ZH, Modi W, Bonner TI. (1995) Molecular cloning and chromosomal localization of human genes encoding three closely related G protein-coupled receptors. Genomics28 (2): 347-9. [PMID:8530049]

9. 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]

10. Tanaka S, Ishii K, Kasai K, Yoon SO, Saeki Y. (2007) Neural expression of G protein-coupled receptors GPR3, GPR6, and GPR12 up-regulates cyclic AMP levels and promotes neurite outgrowth. J. Biol. Chem.282 (14): 10506-15. [PMID:17284443]

11. Uhlenbrock K, Gassenhuber H, Kostenis E. (2002) Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors. Cell Signal14: 941-953. [PMID:12220620]

12. Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA. (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J Biol Chem284: 12328-12338. [PMID:19286662]

13. Zhang M, Xia G. (2012) Hormonal control of mammalian oocyte meiosis at diplotene stage. Cell. Mol. Life Sci.69 (8): 1279-88. [PMID:22045555]

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: GPR12. Last modified on 30/07/2015. Accessed on 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=86.