Nomenclature: GPER

Family: Estrogen (G protein-coupled) receptor

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

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 375 7p22.3 GPER1 G protein-coupled estrogen receptor 1 9-10
Mouse 7 375 5 G1 Gper1 G protein-coupled estrogen receptor 1
Rat 7 375 12q11 Gper G protein-coupled estrogen receptor 1 2
Previous and Unofficial Names
CMKRL2
DRY12
FEG-1
GPCR-Br
LERGU
LERGU2
LyGPR
CEPR
MGC99678
Gpr41
G protein-coupled estrogen receptor 1
G protein-coupled receptor 30
Membrane estrogen receptor
Flow-induced endothelial G-protein coupled receptor 1
Chemoattractant receptor-like 2
Lymphocyte-derived G-protein coupled receptor
mER
G-protein coupled receptor 30
constitutively expressed peptide-like receptor
G-protein coupled estrogen receptor 1
heptahelix receptor
leucine rich protein
chemokine receptor-like 2
LYGPR
GPGR
GPR30
IL8-related receptor DRY12
flow-induced endothelial G-protein coupled receptor
GPCR-BR
GPE
G-protein coupled receptor 41
Ceprl
6330420K13Rik
Gpr30
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
17β-estradiol
Comments: Proposed ligand in several publications but not replicated in a recent study based on β-arrestin recruitment [12].
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]17β-estradiol Hs Full agonist 8.5 – 8.6 pKd 13
pKd 8.5 – 8.6 (Kd 2.7x10-9 – 3.3x10-9 M) [13]
17β-estradiol Hs Full agonist 8.2 – 8.5 pKi 11,13
pKi 8.2 – 8.5 [11,13]
G-1 Hs Full agonist 8.0 pKi 1
pKi 8.0 [1]
fulvestrant Hs Full agonist 7.0 pKi 13
pKi 7.0 [13]
tamoxifen Hs Full agonist 6.0 pKi 13
pKi 6.0 [13]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
G36 Hs Antagonist 6.78 – 6.95 pIC50 5
pIC50 6.78 – 6.95 (IC50 1.12x10-7 – 1.65x10-7 M) [5]
G15 Hs Antagonist 6.7 pIC50 4
pIC50 6.7 [4]
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  6,8,11
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  7,13
Tissue Distribution
Lung, liver (adult and fetal), prostate, colon.
Species:  Human
Technique:  Northern blotting.
References:  10
Placenta.
Species:  Human
Technique:  Northern blotting.
References:  3
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
Measurement of EGFR activity in MB-MDA231 cells transfected with the human GPER receptor.
Species:  Human
Tissue:  MB-MDA231 cells.
Response measured:  Stimulation of EGFR phosphorylation.
References:  6
Measurement of MAP kinase activity in MB-MDA231 cells transfected with the human GPER receptor.
Species:  Human
Tissue:  MB-MDA231 cells.
Response measured:  Stimulation of ERK phosphorylation.
References:  6
Measurement of Ca2+ flux in COS-7 cells transfected with the human GPER receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in intracellular Ca2+ concentration.
References:  11
Measurement of PI3K activity in COS-7 cells transfected with the GPER receptor and SKBr3 cells endogenously expressing the GPER receptor.
Species:  Human
Tissue:  COS-7 and SKBr3 cells.
Response measured:  Translocation of fluorescent PH domain chimera.
References:  11
Measurement of cAMP levels in HEK 293 cells transfected with the GPER receptor and SKBr3 cells endogenously expressing the GPER receptor.
Species:  Human
Tissue:  HEK 293 and SKBr3 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  7
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr30tm1Cwan Gpr30tm1Cwan/Gpr30tm1Cwan
involves: 129S6/SvEvTac * C57BL/6J
MGI:1924104  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18063692 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0006135 artery stenosis PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0001258 decreased body length PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0001262 decreased body weight PMID: 18845638 
Gpr30tm1Dgen Gpr30tm1Dgen/Gpr30tm1Dgen
B6.129-Gpr30
MGI:1924104  MP:0008075 decreased CD4-positive T cell number PMID: 19095739 
Gpr30tm1Dgen Gpr30tm1Dgen/Gpr30tm1Dgen
B6.129-Gpr30
MGI:1924104  MP:0008079 decreased CD8-positive T cell number PMID: 19095739 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0002696 decreased circulating glucagon level PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0004701 decreased circulating insulin-like growth factor I level PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0002711 decreased glucagon secretion PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0003059 decreased insulin secretion PMID: 18845638 
Gpr30tm1135.2Arte Gpr30tm1135.2Arte/Gpr30tm1135.2Arte
involves: C57BL/6 * C57BL/6N
MGI:1924104  MP:0003402 decreased liver weight PMID: 18799753 
Gpr30tm1Dgen Gpr30tm1Dgen/Gpr30tm1Dgen
B6.129-Gpr30
MGI:1924104  MP:0005018 decreased T cell number PMID: 19095739 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0005293 impaired glucose tolerance PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0005559 increased circulating glucose level PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0004875 increased mean systemic arterial blood pressure PMID: 18845638 
Gpr30tm1.1Lmlf Gpr30tm1.1Lmlf/Gpr30tm1.1Lmlf
B6.129-Gpr30
MGI:1924104  MP:0003109 short femur PMID: 18845638 
Available Assays
DiscoveRx PathHunter® CHO-K1 GPR30 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0373C2A)
PathHunter® eXpress GPR30 CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0373E2ACP2M)
more info

REFERENCES

1. Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, Parker MA, Tkachenko SE, Savchuck NP, Sklar LA, Oprea TI, Prossnitz ER. (2006) Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat Chem Biol2: 207-212. [PMID:16520733]

2. Bonini JA, Anderson SM, Steiner DF. (1997) Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem Biophys Res Commun234: 190-193. [PMID:9168987]

3. Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ. (1997) Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics45: 607-617. [PMID:9367686]

4. Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, Bologa CG, Leitao A, Brailoiu E, Deliu E, Dun NJ, Sklar LA, Hathaway HJ, Arterburn JB, Oprea TI, Prossnitz ER. (2009) In vivo effects of a GPR30 antagonist. Nat Chem Biol5: 421-427. [PMID:19430488]

5. Dennis MK, Field AS, Burai R, Ramesh C, Petrie WK, Bologa CG, Oprea TI, Yamaguchi Y, Hayashi S, Sklar LA et al.. (2011) Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity. J. Steroid Biochem. Mol. Biol.127 (3-5): 358-66. [PMID:21782022]

6. Filardo EJ, Quinn JA, Bland KI, Frackelton AR. (2000) Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol14: 1649-1660. [PMID:11043579]

7. Filardo EJ, Quinn JA, Frackelton AR, Bland KI. (2002) Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol16: 70-84. [PMID:11773440]

8. Maggiolini M, Vivacqua A, Fasanella G, Recchia AG, Sisci D, Pezzi V, Montanaro D, Musti AM, Picard D, Andò S. (2004) The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem279: 27008-27016. [PMID:15090535]

9. O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, Kolakowski LF, George SR. (1998) Discovery of three novel G-protein-coupled receptor genes. Genomics47: 310-313. [PMID:9479505]

10. Owman C, Blay P, Nilsson C, Lolait SJ. (1996) Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues. Biochem Biophys Res Commun228: 285-292. [PMID:8920907]

11. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science307: 1625-1630. [PMID:15705806]

12. 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]

13. Thomas P, Pang Y, Filardo EJ, Dong J. (2005) Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology146: 624-632. [PMID:15539556]

To cite this database page, please use the following:

Edward Filardo, Eric Prossnitz.
Estrogen (G protein-coupled) receptor: GPER. Last modified on 16/08/2013. Accessed on 29/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=221.

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