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G-protein coupled estrogen receptor 1; chemoattractant receptor-like 2; Flow-induced endothelial G-protein coupled receptor 1; FEG-1; G protein-coupled estrogen receptor 1; G-protein coupled receptor 30; GPCR-Br; IL8-related receptor DRY12; lymphocyte-derived G-protein coupled receptor; LYGPR; membrane estrogen receptor; mER (GPER1, CEPR, CMKRL2, DRY12, GPER, GPR30)
Function:
- G-protein coupled estrogen receptor
- binds to 17- beta-estradiol (E2) with high affinity, leading to rapid & transient activation of numerous intracellular signaling pathways
- stimulates cAMP production, Ca+2 mobilization & c-Src inducing release of heparin-bound EGF & subsequent transactivation of EGFR, activating downstream signaling pathways such as PI3K/Akt & ERK/MAPK
- mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune & central nervous systems
- role in cardioprotection by reducing cardiac hypertrophy & perivascular fibrosis in a RAMP3-dependent manner
- regulates arterial blood pressure by stimulating vasodilation & reducing vascular smooth muscle & microvascular endothelial cell proliferation
- 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.
- role in acute neuroprotection against NMDA-induced excitotoxic neuronal death
- increases firing activity & intracellular Ca+2 oscillations in LHRH neurons
- inhibits early osteoblast proliferation at growth plate during skeletal development
- inhibits mature adipocyte differentiation & lipid accumulation
- involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells
- functions s 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 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 & fibronectin matrix assembly in breast cancer cells
- ubiquitinated
- ubiquitination occurs at the plasma membrane & leads to proteasome-mediated degradation
- glycosylated
- homodimer (probable)
- heterodimerizes with other G-protein-coupled receptor like CRHR1, HTR1A & PAQR8
- interacts (via C-terminus tail motif) with DLG4 (via N-terminus tandem pair of PDZ domains)
- interaction induces the increase of GPER1 protein levels residing at the plasma membrane surface in an estradiol- independent manner
- interacts with RAMP3
- interacts with KRT7 & KRT8
- interacts with EGFR
- interaction increases after agonist-induced stimulation in cancer-associated fibroblasts
- interacts with ESR1
Kinetic parameters:
- KM=3.3-6.6 mM for 17-beta-estradiol
Structure: belongs to the G-protein coupled receptor 1 family
Compartment:
- plasma membrane, endoplasmic reticulum membrane, Golgi
- mitochondria, lysosome, cytoplasm
- currently unclear whether this is a cell surface receptor or intracellular receptor
Expression:
- ubiquitously expressed
- most abundant in placenta
- in brain regions, expressed as a 2.8 kb transcript in basal forebrain, frontal cortex, thalamus, hippocampus, caudate & putamen
- up-regulated by EGF & TGF-alpha in endometrial, ovarian & breast tumor cells
- up-regulated by progestin & by phorbol 12-myristate 13-acetate (PMA) in breast cancer cell lines
General
estrogen receptor
glycoprotein
G-protein coupled receptor; serpentine receptor
Properties
SIZE: entity length = 375 aa
MW = 42 kD
COMPARTMENT: mitochondria
lysosome
cytoplasm
cell nucleus
golgi
endoplasmic reticulum
MOTIF: exoplasmic domain {1-62}
acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
N-glycosylation site {N25}
N-glycosylation site {N32}
N-glycosylation site {N44}
transmembrane domain {63-84}
cytoplasmic loop {85-96}
transmembrane domain {97-120}
exoplasmic loop {121-132}
MOTIF: cysteine residue {C130}
MODIFICATION: cysteine residue {C207}
transmembrane domain {133-153}
cytoplasmic loop {154-175}
transmembrane domain {176-194}
exoplasmic loop {195-220}
MOTIF: cysteine residue {C207}
MODIFICATION: cysteine residue {C130}
transmembrane domain {221-236}
cytoplasmic loop {237-259}
transmembrane domain {260-280}
exoplasmic loop {281-306}
transmembrane domain {307-327}
cytoplasmic domain {328-375}
Database Correlations
OMIM 601805
UniProt Q99527
Pfam PF00001
Entrez Gene 2852
Kegg hsa:2852
References
- UniProt :accession Q99527
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/GPERID44344ch7p22.html