GPER | G protein-coupled estrogen receptor | IUPHAR/BPS Guide to PHARMACOLOGY

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GPER

Target not currently curated in GtoImmuPdb

Target id: 221

Nomenclature: GPER

Family: G protein-coupled estrogen receptor

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

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 Gper1 G protein-coupled estrogen receptor 1 2
Previous and Unofficial Names
CEPR | CMKRL2 | DRY12 | FEG-1 | Gpr41 | LERGU | LERGU2 | chemokine receptor-like 2 | Flow-induced endothelial G-protein coupled receptor 1 | GPGR | LYGPR | Lymphocyte-derived G-protein coupled receptor | Membrane estrogen receptor | mER | GPCR-BR | GPR30 | IL8-related receptor DRY12
Database Links
Specialist databases
GPCRDB gper1_human (Hs), gper1_mouse (Mm), gper1_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
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 [13].

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 Value Parameter Reference
[3H]17β-estradiol Hs Full agonist 8.5 – 8.6 pKd 14
pKd 8.5 – 8.6 (Kd 3.3x10-9 – 2.7x10-9 M) [14]
17β-estradiol Hs Full agonist 8.2 – 8.5 pKi 12,14
pKi 8.2 – 8.5 [12,14]
G-1 Hs Full agonist 8.0 pKi 1
pKi 8.0 (Ki 1x10-8 M) [1]
fulvestrant Hs Full agonist 7.0 pKi 14
pKi 7.0 [14]
raloxifene Hs Full agonist 7.0 pKi 11
pKi 7.0 [11]
tamoxifen Hs Full agonist 6.0 pKi 14
pKi 6.0 [14]
4-hydroxytamoxifen Hs Agonist - - 12
[12]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
G36 Hs Antagonist 6.8 – 6.9 pIC50 5
pIC50 6.8 – 6.9 (IC50 1.65x10-7 – 1.12x10-7 M) [5]
G15 Hs Antagonist 6.7 pIC50 4
pIC50 6.7 (IC50 1.99x10-7 M) [4]
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  6,8,12
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  7,14
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:  12
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:  12
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 

References

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1. Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, Parker MA, Tkachenko SE, Savchuck NP, Sklar LA et al.. (2006) Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat. Chem. Biol., 2 (4): 207-12. [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. Commun., 234 (1): 190-3. [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. Genomics, 45 (3): 607-17. [PMID:9367686]

4. Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, Bologa CG, Leitao A, Brailoiu E, Deliu E et al.. (2009) In vivo effects of a GPR30 antagonist. Nat. Chem. Biol., 5 (6): 421-7. [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 Jr 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. Endocrinol., 14 (10): 1649-60. [PMID:11043579]

7. Filardo EJ, Quinn JA, Frackelton Jr 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. Endocrinol., 16 (1): 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. Chem., 279 (26): 27008-16. [PMID:15090535]

9. O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, Kolakowski Jr LF, George SR. (1998) Discovery of three novel G-protein-coupled receptor genes. Genomics, 47 (2): 310-3. [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. Commun., 228 (2): 285-92. [PMID:8920907]

11. Petrie WK, Dennis MK, Hu C, Dai D, Arterburn JB, Smith HO, Hathaway HJ, Prossnitz ER. (2013) G protein-coupled estrogen receptor-selective ligands modulate endometrial tumor growth. Obstet Gynecol Int, 2013: 472720. [PMID:24379833]

12. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science, 307 (5715): 1625-30. [PMID:15705806]

13. 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 Screen, 18 (5): 599-609. [PMID:23396314]

14. 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. Endocrinology, 146 (2): 624-32. [PMID:15539556]

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