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Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Also functions as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells"}],"commentType":"FUNCTION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15539556"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15705806"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19931550"}],"value":"Binds 17-beta-estradiol (E2) in plasma membranes with high affinity (Kd is 3.3 nM) and displays rapid kinetics of association and dissociation."}]}}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19749156"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20551055"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21149639"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23674134"},{"evidenceCode":"ECO:0000305"}],"value":"Homodimer (Probable). Heterodimer; heterodimerizes with other G protein-coupled receptor (GPCRs) like CRHR1, HTR1A and PAQR8. Interacts (via C-terminus tail motif) with DLG4 (via N-terminus tandem pair of PDZ domains); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner (By similarity). Interacts with RAMP3; the interaction confers proper subcellular localization and function in cardioprotection. Interacts with KRT7 and KRT8. Interacts with EGFR; the interaction increases after agonist-induced stimulation in cancer-associated fibroblasts (CAF). Interacts with EGFR and ESR1"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"P08588","geneName":"ADRB1","intActId":"EBI-991009"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"P24588","geneName":"AKAP5","intActId":"EBI-703640"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"O14745","geneName":"NHERF1","intActId":"EBI-349787"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"O60894","geneName":"RAMP1","intActId":"EBI-962893"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"O60895","geneName":"RAMP2","intActId":"EBI-9009040"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99527","intActId":"EBI-2833021"},"interactantTwo":{"uniProtKBAccession":"O60896","geneName":"RAMP3","intActId":"EBI-720447"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Colocalized with BSN to the active zone of presynaptic density. Colocalized with DLG4/PSD95 and neurabin-2 PPP1R9B in neuronal synaptosomes (By similarity). Endocytosed in a agonist- and arrestin-independent manner. Colocalized with RAMP3 and clathrin-coated pits at the plasma membrane. Colocalized with transferrin receptor at the plasma membrane and perinuclear region. Accumulated and colocalized with RAB11 proteins in recycling endosomes and trans-Golgi network (TGN), but does neither recycle back to the cell surface nor traffics to late endosome or lysosome. Colocalized with calnexin in the endoplasmic reticulum. Traffics to intracellular sites via cytokeratin intermediate filaments like KRT7 and KRT8 after constitutive endocytosis in epithelial cells. Colocalized with EGFR in the nucleus of agonist-induced cancer-associated fibroblasts (CAF)"}]},"subcellularLocations":[{"location":{"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"value":"Cytoplasm, perinuclear region","id":"SL-0198"}},{"location":{"value":"Cytoplasm, cytoskeleton","id":"SL-0090"}},{"location":{"value":"Cell membrane","id":"SL-0039"},"topology":{"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"value":"Basolateral cell membrane","id":"SL-0026"},"topology":{"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"value":"Cytoplasmic vesicle membrane","id":"SL-0089"},"topology":{"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"value":"Early endosome","id":"SL-0094"}},{"location":{"value":"Recycling endosome","id":"SL-0232"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Golgi apparatus membrane","id":"SL-0134"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"value":"Golgi apparatus, trans-Golgi network","id":"SL-0266"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18566127"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cell projection, dendrite","id":"SL-0283"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cell projection, dendritic spine membrane","id":"SL-0285"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cell projection, axon","id":"SL-0279"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Postsynaptic density","id":"SL-0297"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Mitochondrion membrane","id":"SL-0171"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20203690"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20551055"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21149639"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21354433"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21427217"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23285008"}],"value":"Expressed in placenta, endothelial and epithelial cells, non laboring and laboring term myometrium, fibroblasts and cancer-associated fibroblasts (CAF), prostate cancer cells and invasive adenocarcinoma (at protein level). Ubiquitously expressed, but is most abundant in placenta. In brain regions, expressed as a 2.8 kb transcript in basal forebrain, frontal cortex, thalamus, hippocampus, caudate and putamen"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12027886"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19749156"}],"value":"Up-regulated by EGF and TGF-alpha in endometrial, ovarian and breast tumor cells. Up-regulated by progestin and by phorbol 12-myristate 13-acetate (PMA) in breast cancer cell lines"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21540189"}],"value":"Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21427217"}],"value":"Glycosylated"}],"commentType":"PTM"},{"texts":[{"value":"Does not bind estradiol according to PubMed:18566127 and PubMed:16645038"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00521"}],"value":"Belongs to the G protein-coupled receptor 1 family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15705806"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"16645038"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17379646"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18566127"}],"value":"Data is conflicting regarding whether it fulfills the criteria of a membrane-bound estrogen receptor (PubMed:15705806, PubMed:17379646). Other reports suggest that it is not (PubMed:16645038, PubMed:18566127)"}],"commentType":"CAUTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15539556"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15705806"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18566127"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21149639"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21354433"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21427217"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21540189"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23674134"}],"value":"Data is conflicting regarding whether it is localized either at the cell membrane (PM) (PubMed:15539556, PubMed:21149639, PubMed:21354433, PubMed:21427217, PubMed:21540189, PubMed:23674134). Other reports suggest that it localizes at the endoplasmic reticulum (ER) (PubMed:15705806, PubMed:18566127)"}],"commentType":"CAUTION"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/44344/GPER","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":375,"modifier":"EXACT"}},"description":"G protein-coupled estrogen receptor 1","featureId":"PRO_0000069310"},{"type":"Topological domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":62,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":63,"modifier":"EXACT"},"end":{"value":84,"modifier":"EXACT"}},"description":"Helical; Name=1","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological 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