| Written | 2009-03 | Eric R Prossnitz |
| Cancer Research, Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA |
| Identity |
| Alias (NCBI) | GPER | GPR30 | CEPR | CMKRL2 | DRY12 | FEG-1 | GPCR-Br | LERGU | LERGU2 | LyGPR | mER |
| HGNC (Hugo) | GPER1 |
| HGNC Alias symb | FEG-1 | GPCR-Br | LERGU | LERGU2 | DRY12 | LyGPR | CEPR |
| HGNC Previous name | CMKRL2 | GPR30 | GPER |
| HGNC Previous name | G protein-coupled receptor 30 |
| LocusID (NCBI) | 2852 |
| Atlas_Id | 44344 |
| Location | 7p22.3 [Link to chromosome band 7p22] |
| Location_base_pair | Starts at 1087118 and ends at 1093810 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping GPER1.png] |
 | |
| Diagram from Entrez Gene. | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| DNA/RNA |
| Note | GPR30 is an estrogen-responsive GPCR (7-transmembrane G protein-coupled receptor). |
 | |
| Alternate transcriptional splice variants (involving the 5' UTR region of the gene) have been characterized. Diagram from Entrez Gene. | |
| Description | The open reading frame of GPR30 is encoded by a single exon (1125 bp) located at chromosome 7p22.3. |
| Transcription | GPR30 mRNA is about 3.0 kb in human with an 1125 bp open reading frame. |
| Protein |
| Description | The gene encodes a 7-transmembrane G protein-coupled receptor (GPCR) of 375 amino acids. |
| Expression | GPR30 is widely express throughout the body. |
| Localisation | Predominantly in the Endoplasmic Reticulum. |
| Function | Rapid and transcriptional responses to estrogen. GPR30 is a 7-transmembrane G protein-coupled receptor (GPCR) that has been shown to be an estrogen responsive receptor, expressed predominantly in the endoplasmic reticulum. Signaling occurs via heterotrimeric G protein activation resulting in matrix-metalloproteinase activation, release of heparin-binding EGF and transactivation of EGFR with subsequent MAPK and Akt activation. Calcium mobilization has also been reported in multiple cell types including neurons. This protein plays a role in the rapid non-genomic signaling events often seen following stimulation with estrogen. Transcriptional activation has also been reported secondary to kinase activation. Actions of GPR30 can occur in parallel to those mediated by ERalpha and ERbeta in cells where multiple receptor are expressed, or in the absence of ERalpha and ERbeta. Note that GPR30 does not appear to mediate transcription via classical estrogen-response elements. |
 | |
| Cellular activation by GPR30 and classical estrogen receptors (ERs). Receptor agonists and antagonists (indicated by upward and downward arrows, respectively) are shown for the indicated receptor (Tam, tamoxifen; G-1, GPR30-selective agonist; G15, GPR30-selective antagonist). Nuclear estrogen receptors classically mediate gene regulation although they can also mediate rapid signaling through kinases (not shown). GPR30 is found predominantly in the endoplasmic reticulum and mediates cell activation at least in part through the transactivation of EGFR leading to the stimulation of MAPK, PI3K and other rapid cellular processes, which can result in transcriptional activation. | |
| Homology | High homology between species. Low homology to other GPCRs. |
| Mutations |
| Note | None |
| Implicated in |
| Note | |
| Entity | Cancer |
| Prognosis | Expression levels correlated with HER-2/neu, tumor size and the presence of metastatic disease in breast cancer. Expression correlated with survival and high-risk disease in endometrial cancer. GPR30 mediates estrogen-dependent responses in breast, endometrial and ovarian cancer cell lines including proliferation and migration. |
| Entity | Other |
| Note | GPR30 has been implicated to play a role in estrogen-induced thymic atrophy, estrogen-mediated amelioration of autoimmune encephalomyelitis, depression, pain, vascular function and oocyte maturation. |
| Bibliography |
| Virtual and biomolecular screening converge on a selective agonist for GPR30. |
| Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, Parker MA, Tkachenko SE, Savchuck NP, Sklar LA, Oprea TI, Prossnitz ER. |
| Nat Chem Biol. 2006 Apr;2(4):207-12. Epub 2006 Mar 5. |
| PMID 16520733 |
| Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. |
| Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ. |
| Genomics. 1997 Nov 1;45(3):607-17. |
| PMID 9367686 |
| Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. |
| Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E. |
| Clin Cancer Res. 2006 Nov 1;12(21):6359-66. |
| PMID 17085646 |
| Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity. |
| Haas E, Bhattacharya I, Brailoiu E, Damjanovic M, Brailoiu GC, Gao X, Mueller-Guerre L, Marjon NA, Gut A, Minotti R, Meyer MR, Amann K, Ammann E, Perez-Dominguez A, Genoni M, Clegg DJ, Dun NJ, Resta TC, Prossnitz ER, Barton M. |
| Circ Res. 2009 Feb 13;104(3):288-91. Epub 2009 Jan 29. |
| PMID 19179659 |
| Discovery of three novel G-protein-coupled receptor genes. |
| O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, Kolakowski LF Jr, George SR. |
| Genomics. 1998 Jan 15;47(2):310-3. |
| PMID 9479505 |
| Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues. |
| Owman C, Blay P, Nilsson C, Lolait SJ. |
| Biochem Biophys Res Commun. 1996 Nov 12;228(2):285-92. |
| PMID 8920907 |
| Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. |
| Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ. |
| Annu Rev Physiol. 2008;70:165-90. |
| PMID 18271749 |
| A transmembrane intracellular estrogen receptor mediates rapid cell signaling. |
| Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. |
| Science. 2005 Mar 11;307(5715):1625-30. Epub 2005 Feb 10. |
| PMID 15705806 |
| GPR30: a novel indicator of poor survival for endometrial carcinoma. |
| Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE, Prossnitz ER. |
| Am J Obstet Gynecol. 2007 Apr;196(4):386.e1-9; discussion 386.e9-11. |
| PMID 17403429 |
| Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress. |
| Takada Y, Kato C, Kondo S, Korenaga R, Ando J. |
| Biochem Biophys Res Commun. 1997 Nov 26;240(3):737-41. |
| PMID 9398636 |
| Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. |
| Thomas P, Pang Y, Filardo EJ, Dong J. |
| Endocrinology. 2005 Feb;146(2):624-32. Epub 2004 Nov 11. |
| PMID 15539556 |
| GPR30 contributes to estrogen-induced thymic atrophy. |
| Wang C, Dehghani B, Magrisso IJ, Rick EA, Bonhomme E, Cody DB, Elenich LA, Subramanian S, Murphy SJ, Kelly MJ, Rosenbaum JS, Vandenbark AA, Offner H. |
| Mol Endocrinol. 2008 Mar;22(3):636-48. Epub 2007 Dec 6. |
| PMID 18063692 |
| Citation |
| This paper should be referenced as such : |
| Prossnitz, Eric R |
| GPER (G protein-coupled estrogen receptor 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):114-116. |
| Free journal version : [ pdf ] [ DOI ] |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Feb 19 17:51:44 CET 2021 |
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