IUPHAR DATABASE | Estrogen (G protein-coupled) receptor

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GPER

Family: Estrogen (G protein-coupled) receptor

Contents:

Gene and Protein Information

Previous and Unofficial Names

Database Links

Agonists

Antagonists

Transduction Mechanisms

Tissue Distribution

Expression Datasets

Functional Assays

Phenotypes, Alleles and Disease Models

References

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	GPER	G protein-coupled estrogen receptor 1	8-9
Mouse	7	375	5 G1	Gpr30	G protein-coupled receptor 30
Rat	7	375	12q11	Gper	G protein-coupled estrogen receptor 1	2

Previous and Unofficial Names
GPR30
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
IL8-related receptor DRY12
constitutively expressed peptide-like receptor
G-protein coupled estrogen receptor 1
heptahelix receptor
leucine rich protein
chemokine receptor-like 2
LYGPR
GPCR-BR
GPGR
flow-induced endothelial G-protein coupled receptor
GPE
G-protein coupled receptor 41
Ceprl
6330420K13Rik

Previous and Unofficial Names

GPR30

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

IL8-related receptor DRY12

constitutively expressed peptide-like receptor

G-protein coupled estrogen receptor 1

heptahelix receptor

leucine rich protein

chemokine receptor-like 2

LYGPR

GPCR-BR

GPGR

flow-induced endothelial G-protein coupled receptor

GPE

G-protein coupled receptor 41

Ceprl

6330420K13Rik

Database Links
ChEMBL Target	102690 (Hs)
Ensembl	ENSG00000164850 (Hs), ENSMUSG00000053647 (Mm), ENSRNOG00000001287 (Rn)
Entrez Gene	2852 (Hs), 76854 (Mm), 171104 (Rn)
GeneCards	GPER (Hs)
GenitoUrinary Development Molecular Anatomy Project	Gpr30 (Mm)
HomoloGene	15855 (Hs)
Human Protein Reference Database	03484 (Hs)
InterPro	Q99527 (Hs), Q8BMP4 (Mm), O08878 (Rn)
KEGG Gene	hsa:2852 (Hs), mmu:76854 (Mm), rno:171104 (Rn)
OMIM	601805 (Hs)
PharmGKB Gene	PA162390126 (Hs), PA28873 (Hs)
Protein Ontology (PRO)	PRO:000001111 (Hs)
RefSeq Nucleotide	NM_001505 (Hs), NM_029771 (Mm), NM_133573 (Rn)
RefSeq Protein	NP_001496 (Hs), NP_084047 (Mm), NP_598257 (Rn)
TreeFam	ENSG00000164850 (Hs), ENSMUSG00000053647 (Mm), ENSRNOG00000001287 (Rn)
UniGene Hs.	20961 (Hs)
UniProt	Q99527 (Hs), Q8BMP4 (Mm), O08878 (Rn)
Wikipedia	GPER
	Estrogen (G protein-coupled) receptor

Search for 3D structures on the PDB
Search by keyword: Estrogen (G protein-coupled) receptor GPER	Search by accession number: O08878, Q99527, Q8BMP4

Natural/Endogenous Ligand(s)
17β-estradiol

Agonists

Key to terms and symbols

View all chemical structures

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Ligand	Sp.	Action	Affinity	Units	Reference
[³H]17β-estradiol	Hs	Full agonist	8.5 – 8.6	pK_d	11
17β-estradiol	Hs	Full agonist	8.2 – 8.5	pK_i	10-11
G-1	Hs	Full agonist	8.0	pK_i	1
fulvestrant	Hs	Full agonist	7.0	pK_i	11
tamoxifen	Hs	Full agonist	6.0	pK_i	11

Antagonists

Key to terms and symbols

View all chemical structures

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Ligand					Sp.	Action	Affinity	Units	Reference
G15					Hs	Antagonist	6.7	pIC₅₀	4

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer	Effector/Response
G_i/G_o family	Phospholipase C stimulation
References: 5,7,10

Secondary Transduction Mechanisms
Transducer	Effector/Response
G_s family	Adenylate cyclase stimulation
References: 6,11

Tissue Distribution

Lung, liver (adult and fetal), prostate, colon.

Species:	Human
Technique:	Northern blotting.
References:	9

Placenta.

Species:	Human
Technique:	Northern blotting.
References:	3

Expression Datasets

Click here to show/hide data

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:	5

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:	5

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:	10

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:	10

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:	6

Phenotypes, Alleles and Disease Models

Mouse data from MGI

Click here to show/hide data

Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Gpr30^tm1Cwan	Gpr30^tm1Cwan/Gpr30^tm1Cwan involves: 129S6/SvEvTac * C57BL/6J	MGI:1924104	MP:0003638	abnormal response/metabolism to endogenous compounds	PMID: 18063692
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0003638	abnormal response/metabolism to endogenous compounds	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0006135	artery stenosis	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0001258	decreased body length	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0001262	decreased body weight	PMID: 18845638
Gpr30^tm1Dgen	Gpr30^tm1Dgen/Gpr30^tm1Dgen B6.129-Gpr30	MGI:1924104	MP:0008075	decreased CD4-positive T cell number	PMID: 19095739
Gpr30^tm1Dgen	Gpr30^tm1Dgen/Gpr30^tm1Dgen B6.129-Gpr30	MGI:1924104	MP:0008079	decreased CD8-positive T cell number	PMID: 19095739
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0002696	decreased circulating glucagon level	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0004701	decreased circulating insulin-like growth factor I level	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0002711	decreased glucagon secretion	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0003059	decreased insulin secretion	PMID: 18845638
Gpr30^tm1135.2Arte	Gpr30^tm1135.2Arte/Gpr30^tm1135.2Arte involves: C57BL/6 * C57BL/6N	MGI:1924104	MP:0003402	decreased liver weight	PMID: 18799753
Gpr30^tm1Dgen	Gpr30^tm1Dgen/Gpr30^tm1Dgen B6.129-Gpr30	MGI:1924104	MP:0005018	decreased T cell number	PMID: 19095739
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0005293	impaired glucose tolerance	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0005559	increased circulating glucose level	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0004875	increased mean systemic arterial blood pressure	PMID: 18845638
Gpr30^tm1.1Lmlf	Gpr30^tm1.1Lmlf/Gpr30^tm1.1Lmlf B6.129-Gpr30	MGI:1924104	MP:0003109	short femur	PMID: 18845638

REFERENCES

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1. Bologa, C. G., Revankar, C. M., Young, S. M., Edwards, B. S., Arterburn, J. B., Kiselyov, A. S., Parker, M. A., Tkachenko, S. E., Savchuck, N. P., Sklar, L. A., Oprea, T. I. and Prossnitz, E. R. (2006) Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat Chem Biol, 2: 207-212. [PMID:16520733]

2. Bonini, J. A., Anderson, S. M. and Steiner, D. F. (1997) Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem Biophys Res Commun, 234: 190-193. [PMID:9168987]

3. Carmeci, C., Thompson, D. A., Ring, H. Z., Francke, U. and Weigel, R. J. (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: 607-617. [PMID:9367686]

4. Dennis, M.K., Burai, R., Ramesh, C., Petrie, W.K., Alcon, S.N., Nayak, T.K., Bologa, C.G., Leitao, A., Brailoiu, E., Deliu, E., Dun, N.J., Sklar, L.A., Hathaway, H.J., Arterburn, J.B., Oprea, T.I. and Prossnitz, E.R. (2009) In vivo effects of a GPR30 antagonist. Nat Chem Biol, 5: 421-427. [PMID:19430488]

5. Filardo, E. J., Quinn, J. A., Bland, K. I. and Frackelton, A. R. (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: 1649-1660. [PMID:11043579]

6. Filardo, E. J., Quinn, J. A., Frackelton, A. R. and Bland, K. I. (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: 70-84. [PMID:11773440]

7. Maggiolini, M., Vivacqua, A., Fasanella, G., Recchia, A. G., Sisci, D., Pezzi, V., Montanaro, D., Musti, A. M., Picard, D. and 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: 27008-27016. [PMID:15090535]

8. O'Dowd, B. F., Nguyen, T., Marchese, A., Cheng, R., Lynch, K. R., Heng, H. H., Kolakowski, L. F. and George, S. R. (1998) Discovery of three novel G-protein-coupled receptor genes. Genomics, 47: 310-313. [PMID:9479505]

9. Owman, C., Blay, P., Nilsson, C. and Lolait, S. J. (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: 285-292. [PMID:8920907]

10. Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B. and Prossnitz, E. R. (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science, 307: 1625-1630. [PMID:15705806]

11. Thomas, P., Pang, Y., Filardo, E. J. and Dong, J. (2005) Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology, 146: 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 28/01/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=221.