GPER1

This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function.

G Protein-Coupled Estrogen Receptor 1

G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. 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. Functions also 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.

Adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: UniProtKB
Apoptotic chromosome condensation Source: UniProtKB
Cell cycle Source: UniProtKB-KW
Cellular response to estradiol stimulus Source: UniProtKB
Cellular response to glucose stimulus Source: UniProtKB
Cellular response to mineralocorticoid stimulus Source: UniProtKB
Cellular response to peptide hormone stimulus Source: UniProtKB
Cellular response to tumor necrosis factor Source: UniProtKB
G protein-coupled receptor signaling pathway Source: AgBase
Inflammatory response Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Intracellular steroid hormone receptor signaling pathway Source: UniProtKB
Negative regulation of cell cycle process Source: AgBase
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of ERK1 and ERK2 cascade Source: AgBase
Negative regulation of fat cell differentiation Source: UniProtKB
Negative regulation of gene expression Source: AgBase
Negative regulation of inflammatory response Source: UniProtKB
Negative regulation of leukocyte activation Source: UniProtKB
Negative regulation of lipid biosynthetic process Source: UniProtKB
Negative regulation of protein kinase B signaling Source: AgBase
Negative regulation of vascular associated smooth muscle cell proliferation Source: AgBase
Neuronal action potential Source: UniProtKB
Nuclear fragmentation involved in apoptotic nuclear change Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of cardiac vascular smooth muscle cell differentiation Source: AgBase
Positive regulation of cell migration Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Positive regulation of cytosolic calcium ion concentration Source: UniProtKB
Positive regulation of endothelial cell apoptotic process Source: UniProtKB
Positive regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of gene expression Source: AgBase
Positive regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
Positive regulation of inositol trisphosphate biosynthetic process Source: UniProtKB
Positive regulation of insulin secretion Source: UniProtKB
Positive regulation of MAPK cascade Source: UniProtKB
Positive regulation of neurogenesis Source: UniProtKB
Positive regulation of neurotransmitter secretion Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
Positive regulation of protein localization to plasma membrane Source: UniProtKB
Positive regulation of protein phosphorylation Source: UniProtKB
Positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
Positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of uterine smooth muscle contraction Source: UniProtKB
Regulation of cell cycle Source: UniProtKB
Regulation of cytosolic calcium ion concentration Source: UniProtKB
Steroid hormone mediated signaling pathway Source: UniProtKB
Vasodilation Source: UniProtKB

Extracellular: 1-62
Helical: 63-84
Cytoplasmic: 85-96
Helical: 97-120
Extracellular: 121-132
Helical: 133-153
Cytoplasmic: 154-175
Helical: 176-194
Extracellular: 195-220
Helical: 221-236
Cytoplasmic: 237-259
Helical: 260-280
Extracellular: 281-306
Helical: 307-327
Cytoplasmic: 328-375

Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation.
Glycosylated.