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GPER

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Target not currently curated in GtoImmuPdb

Target id: 221

Nomenclature: GPER

Family: G protein-coupled estrogen receptor

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 7 375 7p22.3 GPER1 G protein-coupled estrogen receptor 1 10-11
Mouse 7 375 5 G2 Gper1 G protein-coupled estrogen receptor 1
Rat 7 375 12q11 Gper1 G protein-coupled estrogen receptor 1 2
Previous and Unofficial Names Click here for help
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 Click here for help
Specialist databases
GPCRdb gper1_human (Hs), gper1_mouse (Mm), gper1_rat (Rn)
Other databases
Alphafold Q99527 (Hs), Q8BMP4 (Mm), O08878 (Rn)
ChEMBL Target CHEMBL5872 (Hs), CHEMBL3309103 (Rn)
Ensembl Gene ENSG00000164850 (Hs), ENSMUSG00000053647 (Mm), ENSRNOG00000001287 (Rn)
Entrez Gene 2852 (Hs), 76854 (Mm), 171104 (Rn)
Human Protein Atlas ENSG00000164850 (Hs)
KEGG Gene hsa:2852 (Hs), mmu:76854 (Mm), rno:171104 (Rn)
OMIM 601805 (Hs)
Pharos Q99527 (Hs)
RefSeq Nucleotide NM_001505 (Hs), NM_029771 (Mm), NM_133573 (Rn)
RefSeq Protein NP_001496 (Hs), NP_084047 (Mm), NP_598257 (Rn)
UniProtKB Q99527 (Hs), Q8BMP4 (Mm), O08878 (Rn)
Wikipedia GPER1 (Hs)
Natural/Endogenous Ligands Click here for help
17β-estradiol
Comments: Southern et al. (2013) were unable to detect 17β-estradiol-GPER engagement using the PathHunter™ β-Arrestin recruitment assay [14].

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]17β-estradiol Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 8.5 – 8.6 pKd 15
⤷ pKd 8.5 – 8.6 (Kd 3.3x10-9 – 2.7x10-9 M) [15]
2-Methoxyestradiol Small molecule or natural product Ligand has a PDB structure Hs Agonist 8.0 pKd 8
⤷ pKd 8.0 (Kd 1x10-8 M) [8]
Description: Specific binding affinity of [3H]2ME2 to GPER in vitro
17β-estradiol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 8.2 – 8.5 pKi 13,15
⤷ pKi 8.2 – 8.5 [13,15]
G-1 Small molecule or natural product Hs Full agonist 8.0 pKi 1
⤷ pKi 8.0 (Ki 1x10-8 M) [1]
fulvestrant Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.0 pKi 15
⤷ pKi 7.0 [15]
raloxifene Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.0 pKi 12
⤷ pKi 7.0 [12]
tamoxifen Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 pKi 15
⤷ pKi 6.0 [15]
4-hydroxytamoxifen Small molecule or natural product Click here for species-specific activity table Hs Agonist - - 13
⤷ [13]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
G36 Small molecule or natural product Hs Antagonist 6.8 – 6.9 pIC50 5
⤷ pIC50 6.8 – 6.9 (IC50 1.65x10-7 – 1.12x10-7 M) [5]
G15 Small molecule or natural product Hs Antagonist 6.7 pIC50 4
⤷ pIC50 6.7 (IC50 1.99x10-7 M) [4]
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0002695 negative regulation of leukocyte activation IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0071356 cellular response to tumor necrosis factor IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0002695 negative regulation of leukocyte activation IDA
GO:0050728 negative regulation of inflammatory response IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes, IEA only
GO:0050728 negative regulation of inflammatory response IDA
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
GO:0045087 innate immune response IEA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  6,9,13
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  7,15
Tissue Distribution Click here for help
Lung, liver (adult and fetal), prostate, colon.
Species:  Human
Technique:  Northern blotting.
References:  11
Placenta.
Species:  Human
Technique:  Northern blotting.
References:  3
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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Functional Assays Click here for help
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:  13
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:  13
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 Click here for help 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. Koganti S, Snyder R, Gumaste U, Karamyan VT, Thekkumkara T. (2014) 2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT(1) receptor. Eur J Pharmacol, 723: 131-40. [PMID:24262995]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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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