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Showing Protein G-protein coupled estrogen receptor 1 (HMDBP12793)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 2 metabolites
Identification
HMDB Protein ID HMDBP12793
Secondary Accession Numbers None
Name G-protein coupled estrogen receptor 1
Synonyms
  1. Chemoattractant receptor-like 2
  2. Flow-induced endothelial G-protein coupled receptor 1
  3. G protein-coupled estrogen receptor 1
  4. G-protein coupled receptor 30
  5. GPCR-Br
  6. IL8-related receptor DRY12
  7. Lymphocyte-derived G-protein coupled receptor
  8. Membrane estrogen receptor
  9. FEG-1
  10. LYGPR
  11. mER
Gene Name GPER1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. 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.
Pathways
  • Endocrine resistance
  • Estrogen signaling pathway
  • GnRH secretion
Reactions Not Available
GO Classification
Biological Process
cell cycle
negative regulation of lipid biosynthetic process
elevation of cytosolic calcium ion concentration
positive regulation of apoptotic process
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of neurogenesis
cellular response to peptide hormone stimulus
negative regulation of inflammatory response
negative regulation of fat cell differentiation
negative regulation of protein kinase B signaling cascade
positive regulation of release of cytochrome c from mitochondria
apoptotic chromosome condensation
cellular response to mineralocorticoid stimulus
negative regulation of cell cycle process
negative regulation of leukocyte activation
neuronal action potential
G-protein coupled receptor signaling pathway
nuclear fragmentation involved in apoptotic nuclear change
positive regulation of cardiac vascular smooth muscle cell differentiation
positive regulation of extrinsic apoptotic signaling pathway
positive regulation of inositol trisphosphate biosynthetic process
positive regulation of neurotransmitter secretion
positive regulation of uterine smooth muscle contraction
inflammatory response
vasodilation
cellular response to tumor necrosis factor
cellular response to glucose stimulus
positive regulation of insulin secretion
cellular response to estradiol stimulus
positive regulation of protein phosphorylation
negative regulation of vascular associated smooth muscle cell proliferation
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of protein localization to plasma membrane
positive regulation of ERK1 and ERK2 cascade
positive regulation of release of sequestered calcium ion into cytosol
innate immune response
steroid hormone mediated signaling pathway
cytosolic calcium ion homeostasis
positive regulation of transcription from RNA polymerase II promoter
positive regulation of endothelial cell apoptotic process
positive regulation of MAPK cascade
intracellular steroid hormone receptor signaling pathway
negative regulation of cell proliferation
negative regulation of ERK1 and ERK2 cascade
positive regulation of gene expression
positive regulation of phosphatidylinositol 3-kinase cascade
negative regulation of cell cycle arrest
negative regulation of gene expression
adenylate cyclase-activating G-protein coupled receptor signaling pathway
positive regulation of epidermal growth factor receptor signaling pathway
positive regulation of G-protein coupled receptor protein signaling pathway
Cellular Component
endoplasmic reticulum membrane
cytosol
mitochondrial membrane
cytoplasm
endoplasmic reticulum
nucleolus
plasma membrane
dendrite
Golgi apparatus
perinuclear region of cytoplasm
dendritic spine head
presynaptic membrane
keratin filament
nucleus
cytoplasmic vesicle membrane
early endosome
dendritic spine membrane
nucleoplasm
axon terminus
recycling endosome
nuclear envelope
trans-Golgi network
presynaptic active zone
axon
postsynaptic density
intracellular membrane-bounded organelle
dendritic shaft
Golgi membrane
integral to plasma membrane
Molecular Function
estrogen receptor activity
steroid hormone binding
chromatin binding
steroid hormone receptor activity
steroid binding
G protein-coupled receptor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 375
Molecular Weight 42247.12
Theoretical pI 8.293
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 63-84;97-120;133-153;176-194;221-236;260-280;307-327;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q99527
UniProtKB/Swiss-Prot Entry Name GPER1_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  8. Kvingedal AM, Smeland EB: A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue. FEBS Lett. 1997 Apr 21;407(1):59-62. [PubMed:9141481 ]
  9. Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ: Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics. 1997 Nov 1;45(3):607-17. [PubMed:9367686 ]
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  11. Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr: 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. 2000 Oct;14(10):1649-60. [PubMed:11043579 ]
  12. Thomas P, Pang Y, Filardo EJ, Dong J: Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology. 2005 Feb;146(2):624-32. Epub 2004 Nov 11. [PubMed:15539556 ]
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  27. Cheng SB, Quinn JA, Graeber CT, Filardo EJ: Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway. J Biol Chem. 2011 Jun 24;286(25):22441-55. doi: 10.1074/jbc.M111.224071. Epub 2011 May 2. [PubMed:21540189 ]
  28. Sanden C, Broselid S, Cornmark L, Andersson K, Daszkiewicz-Nilsson J, Martensson UE, Olde B, Leeb-Lundberg LM: G protein-coupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments. Mol Pharmacol. 2011 Mar;79(3):400-10. doi: 10.1124/mol.110.069500. Epub 2010 Dec 13. [PubMed:21149639 ]
  29. Cheng SB, Graeber CT, Quinn JA, Filardo EJ: Retrograde transport of the transmembrane estrogen receptor, G-protein-coupled-receptor-30 (GPR30/GPER) from the plasma membrane towards the nucleus. Steroids. 2011 Aug;76(9):892-6. doi: 10.1016/j.steroids.2011.02.018. Epub 2011 Feb 25. [PubMed:21354433 ]
  30. Chakrabarti S, Davidge ST: G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation. PLoS One. 2012;7(12):e52357. doi: 10.1371/journal.pone.0052357. Epub 2012 Dec 20. [PubMed:23285008 ]
  31. Gros R, Ding Q, Liu B, Chorazyczewski J, Feldman RD: Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation. Am J Physiol Cell Physiol. 2013 Mar;304(6):C532-40. doi: 10.1152/ajpcell.00203.2012. Epub 2013 Jan 2. [PubMed:23283935 ]
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