Alternative titles; symbols
HGNC Approved Gene Symbol: GPER1
Cytogenetic location: 7p22.3 Genomic coordinates (GRCh38): 7:1,087,118-1,093,810 (from NCBI)
Owman et al. (1996) performed PCR of template DNA from human B-cell lymphoblasts using degenerate primers to G protein-coupled receptors. They identified a full-length cDNA encoding a 375-amino acid protein, which they termed CMKRL2. CMKRL2 is expressed in the Burkitt lymphoma cell lines Raji and Daudi but not in T-cell lymphoma Jurkat cells, T- or B-cell leukemias, chronic myelogenous leukemia, or other cancer cell lines (Owman et al., 1996). Northern blot analysis of normal tissue showed expression of a 2.4-kb transcript in many tissues including the brain; there was no detectable mRNA in placenta, bone marrow, or peripheral blood leukocytes (Owman et al., 1996).
Using the technique of differential cDNA library screening to identify genes overexpressed in estrogen receptor (ESR)-positive breast carcinoma cell lines compared to ESR-negative cell lines, Carmeci et al. (1997) isolated a CMKRL2 cDNA and designated it GPR30. Sequence analysis determined that the clone shares significant homology to G protein-coupled receptors. This receptor was abundantly expressed in 3 ESR-positive breast carcinoma cell lines. Expression was absent or minimal in 3 ESR-negative breast carcinoma cell lines. It was ubiquitously expressed in all human tissues examined, but was most abundant in placenta. In 11 primary breast carcinomas, it was detected in all 4 ESR-positive tumors and in only 1 of 7 ESR-negative tumors. The pattern of expression of the gene indicated that the receptor may be involved in physiologic responses specific to hormonally responsive tissues.
Using PCR with degenerate primers to identify novel members of the G protein-coupled receptor family, Feng and Gregor (1997) also cloned GPR30. They designated the gene CEPR for 'constitutively/commonly expressed peptide-like receptor' because the 3.3-kb mRNA was detected in most human tissues on Northern blots. They found that CEPR is encoded by an intronless gene. Similarly, Kvingedal and Smeland (1997) cloned GPR30 using RT-PCR of B-cell mRNA to identify G protein-coupled receptors expressed in lymphocytes. They designated the gene LyGPR for 'lymphocyte-derived G protein-coupled receptor.' Takada et al. (1997) cloned GPR30 from endothelial cells exposed to fluid shear stress. They designated the gene FEG1 for 'flow-induced endothelial G protein-coupled receptor gene-1.'
Revankar et al. (2005) found that unlike other known G protein-coupled receptors, GPR30 localizes to the endoplasmic reticulum, where it specifically binds estrogen and estrogen derivatives. Activating GPR30 by estrogen resulted in intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. Revankar et al. (2005) concluded that GPR30 represents an intracellular transmembrane estrogen receptor that may contribute to normal estrogen physiology as well as pathophysiology. Pietras et al. (2005) questioned the conclusions raised by Revankar et al. (2005); Prossnitz et al. (2005) provided a response.
Owman et al. (1996) mapped the CMKRL2 gene to 7p22 by fluorescence in situ hybridization. Based upon PCR analysis in somatic hybrid cell lines, Carmeci et al. (1997) mapped the GPR30 gene to 7p22.
Carmeci, C., Thompson, D. A., Ring, H. Z., Francke, U., Weigel, R. J. 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, 1997. [PubMed: 9367686] [Full Text: https://doi.org/10.1006/geno.1997.4972]
Feng, Y., Gregor, P. Cloning of a novel member of the G protein-coupled receptor family related to peptide receptors. Biochem. Biophys. Res. Commun. 231: 651-654, 1997. [PubMed: 9070864] [Full Text: https://doi.org/10.1006/bbrc.1997.6161]
Kvingedal, A. M., Smeland, E. B. A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue. FEBS Lett. 407: 59-62, 1997. [PubMed: 9141481] [Full Text: https://doi.org/10.1016/s0014-5793(97)00278-0]
Owman, C., Blay, P., Nilsson, C., Lolait, S. J. 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, 1996. [PubMed: 8920907] [Full Text: https://doi.org/10.1006/bbrc.1996.1654]
Pietras, R. J., Levin, E. R., Szego, C. M. Estrogen receptors and cell signaling. (Letter) Science 310: 51-52, 2005. [PubMed: 16210518] [Full Text: https://doi.org/10.1126/science.310.5745.51]
Prossnitz, E. R., Revankar, C. M., Arterburn, J. B., Sklar, L. A. Response to Pietras et al. Science 310: 52-53, 2005.
Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., Prossnitz, E. R. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307: 1625-1630, 2005. [PubMed: 15705806] [Full Text: https://doi.org/10.1126/science.1106943]
Takada, Y., Kato, C., Kondo, S., Korenaga, R., Ando, J. Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress. Biochem. Biophys. Res. Commun. 240: 737-741, 1997. [PubMed: 9398636] [Full Text: https://doi.org/10.1006/bbrc.1997.7734]