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Protein

G-protein coupled estrogen receptor 1

Gene

Gper1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.11 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processApoptosis, Cell cycle, Differentiation, Immunity, Inflammatory response, Innate immunity, Neurogenesis

Enzyme and pathway databases

ReactomeiR-MMU-375276 Peptide ligand-binding receptors
R-MMU-418594 G alpha (i) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein coupled estrogen receptor 1
Alternative name(s):
Chemoattractant receptor-like 2
G protein-coupled estrogen receptor 1
G-protein coupled receptor 30
Membrane estrogen receptor
Short name:
mER
Gene namesi
Name:Gper1
Synonyms:Cmkrl2, Gper, Gpr30
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1924104 Gper1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 62ExtracellularSequence analysisAdd BLAST62
Transmembranei63 – 84Helical; Name=1Sequence analysisAdd BLAST22
Topological domaini85 – 96CytoplasmicSequence analysisAdd BLAST12
Transmembranei97 – 120Helical; Name=2Sequence analysisAdd BLAST24
Topological domaini121 – 132ExtracellularSequence analysisAdd BLAST12
Transmembranei133 – 153Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini154 – 175CytoplasmicSequence analysisAdd BLAST22
Transmembranei176 – 194Helical; Name=4Sequence analysisAdd BLAST19
Topological domaini195 – 220ExtracellularSequence analysisAdd BLAST26
Transmembranei221 – 236Helical; Name=5Sequence analysisAdd BLAST16
Topological domaini237 – 259CytoplasmicSequence analysisAdd BLAST23
Transmembranei260 – 280Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini281 – 306ExtracellularSequence analysisAdd BLAST26
Transmembranei307 – 327Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini328 – 375CytoplasmicSequence analysisAdd BLAST48

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Mitochondrion, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Strong variations in phenotypes, probably depending on the distinct targeting strategies, genetic background and experimental conditions used in the different experiments. According to PubMed:18063692, mice are viable and fertile and do not display any gross physical, immunological, reproductive and neurological abnormalities, but show 17-beta-estradiol (E2)-induced alleviated thymic atrophy. According to PubMed:20734455, male mice display increased body size, femur length, bone mass and cell proliferative activity within the growth plate. According to PubMed:18845638, female mice, but not male, show reduced body weight and skeletal growth, hyperglycemia, impaired glucose tolerance with reduced glucose-stimulated insulin release and increased blood pressure. According to PubMed:19179659 mice show increased body weight, visceral adiposity, vascular tone and blood pressure. No visible phenotype according to PubMed:18799753.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi375V → A: Loss of interaction with DLG4. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693111 – 375G-protein coupled estrogen receptor 1Add BLAST375

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Glycosylationi32N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi44N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi130 ↔ 207PROSITE-ProRule annotation

Post-translational modificationi

Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation.By similarity
N-glycosylated.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8BMP4
PRIDEiQ8BMP4

PTM databases

PhosphoSitePlusiQ8BMP4

Expressioni

Tissue specificityi

Expressed in brain, heart, spleen, preadipocytes, mature adipocytes and primary hippocampal neurons. Expressed in neurons of the hippocampus, hypothalamic paraventricular nucleus (PVH), supraoptic nucleus (SON) and the median eminence. Expressed in the nucleus ambiguous (at protein level). Expressed in brain, pituitary gland, adrenal medulla, renal pelvis, ovary, endothelial cells, visceral fat tissues and islets of Langerhans.6 Publications

Inductioni

Up-regulated during adipogenesis.1 Publication

Gene expression databases

BgeeiENSMUSG00000053647
CleanExiMM_GPER
GenevisibleiQ8BMP4 MM

Interactioni

Subunit structurei

Interacts with RAMP3. 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. 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). Homodimer (Probable). Heterodimer; heterodimerizes with other G-protein-coupled receptor (GPCRs) like CRHR1, HTR1A and PAQR8.By similarityCurated1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080370

Structurei

3D structure databases

ProteinModelPortaliQ8BMP4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEGB Eukaryota
ENOG4111653 LUCA
GeneTreeiENSGT00530000063910
HOGENOMiHOG000013114
HOVERGENiHBG005351
InParanoidiQ8BMP4
KOiK04246
OMAiQHARLSC
OrthoDBiEOG091G09A2
TreeFamiTF333506

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q8BMP4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDATTPAQTV GVEIYLGPVW PAPSNSTPLA LNLSLALRED APGNLTGDLS
60 70 80 90 100
EHQQYVIALF LSCLYTIFLF PIGFVGNILI LVVNISFREK MTIPDLYFIN
110 120 130 140 150
LAAADLILVA DSLIEVFNLD EQYYDIAVLC TFMSLFLQIN MYSSVFFLTW
160 170 180 190 200
MSFDRYLALA KAMRCGLFRT KHHARLSCGL IWMASVSATL VPFTAVHLRH
210 220 230 240 250
TEEACFCFAD VREVQWLEVT LGFIMPFAII GLCYSLIVRA LIRAHRHRGL
260 270 280 290 300
RPRRQKALRM IFAVVLVFFI CWLPENVFIS VHLLQWTQPG DTPCKQSFRH
310 320 330 340 350
AYPLTGHIVN LAAFSNSCLN PLIYSFLGET FRDKLRLYVE QKTSLPALNR
360 370
FCHATLKAVI PDSTEQSEVR FSSAV
Length:375
Mass (Da):42,479
Last modified:July 27, 2011 - v2
Checksum:iAF7E4795C3A9A405
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti314F → I in BAC26930 (PubMed:16141072).Curated1
Sequence conflicti369V → I in BAB31118 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK018203 mRNA Translation: BAB31118.1
AK030375 mRNA Translation: BAC26930.1
CH466529 Genomic DNA Translation: EDL19153.1
BC138598 mRNA Translation: AAI38599.1
BC138616 mRNA Translation: AAI38617.1
CCDSiCCDS19811.1
RefSeqiNP_084047.2, NM_029771.3
XP_006504820.1, XM_006504757.3
UniGeneiMm.389706

Genome annotation databases

EnsembliENSMUST00000066211; ENSMUSP00000080370; ENSMUSG00000053647
GeneIDi76854
KEGGimmu:76854
UCSCiuc009agr.2 mouse

Similar proteinsi

Entry informationi

Entry nameiGPER1_MOUSE
AccessioniPrimary (citable) accession number: Q8BMP4
Secondary accession number(s): B2RRW0, Q9D392
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 120 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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