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Protein

G-protein coupled estrogen receptor 1

Gene

Gper1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.2 Publications

GO - Molecular functioni

  • drug binding Source: RGD
  • estrogen receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • hormone binding Source: RGD
  • mineralocorticoid receptor activity Source: UniProtKB
  • steroid binding Source: RGD
  • steroid hormone binding Source: UniProtKB
  • steroid hormone receptor activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Apoptosis, Cell cycle, Differentiation, Immunity, Inflammatory response, Innate immunity, Neurogenesis

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
G-protein coupled receptor 41
Membrane estrogen receptor
Short name:
mER
Gene namesi
Name:Gper1
Synonyms:Cmkrl2, Gper, Gpr30, Gpr41
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619845. Gper1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6262ExtracellularSequence analysisAdd
BLAST
Transmembranei63 – 8422Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini85 – 9612CytoplasmicSequence analysisAdd
BLAST
Transmembranei97 – 12024Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini121 – 13212ExtracellularSequence analysisAdd
BLAST
Transmembranei133 – 15321Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini154 – 17522CytoplasmicSequence analysisAdd
BLAST
Transmembranei176 – 19419Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini195 – 22026ExtracellularSequence analysisAdd
BLAST
Transmembranei221 – 23616Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini237 – 25923CytoplasmicSequence analysisAdd
BLAST
Transmembranei260 – 28021Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini281 – 30626ExtracellularSequence analysisAdd
BLAST
Transmembranei307 – 32721Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini328 – 37548CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • axon Source: UniProtKB
  • axon terminus Source: UniProtKB
  • basolateral plasma membrane Source: UniProtKB-SubCell
  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle membrane Source: UniProtKB
  • dendrite Source: UniProtKB
  • dendritic shaft Source: UniProtKB
  • dendritic spine head Source: UniProtKB
  • dendritic spine membrane Source: UniProtKB
  • early endosome Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: GO_Central
  • intracellular Source: UniProtKB
  • keratin filament Source: UniProtKB
  • mitochondrial membrane Source: UniProtKB
  • neuronal postsynaptic density Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-KW
  • presynaptic active zone Source: UniProtKB
  • presynaptic membrane Source: UniProtKB
  • recycling endosome Source: UniProtKB
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

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

Chemistry

ChEMBLiCHEMBL3309103.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 375375G-protein coupled estrogen receptor 1PRO_0000069312Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Glycosylationi32 – 321N-linked (GlcNAc...)Sequence analysis
Glycosylationi44 – 441N-linked (GlcNAc...)Sequence analysis
Disulfide bondi130 ↔ 207PROSITE-ProRule annotation

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiO08878.
PRIDEiO08878.

Expressioni

Tissue specificityi

Expressed in the brain. Expressed in neurons of the hippocampus, hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON) and the median eminence. Expressed in magnocellular neurosecretory cells (MNCs) which secrete oxytocin but not in MNCs which secrete vasopressin. Expressed in glial cells. Expressed in the nucleus ambiguous. Expressed in epithelial cells, in pachytene spermatocytes (PS) (at protein level). Expressed strongly in vascular endothelial cells and poorly in vascular smooth muscle cells (VSMC). Expressed in the brain, lung, pituitary gland, adrenal medulla, renal pelvis and ovary. Expressed in CA1 hippocampus. Expressed weakly in heart, skeletal muscle and kidney.9 Publications

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001732.

Structurei

3D structure databases

ProteinModelPortaliO08878.
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.
HOGENOMiHOG000013114.
HOVERGENiHBG005351.
InParanoidiO08878.
KOiK04246.
PhylomeDBiO08878.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08878-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAATTPAQDV 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 LGFIVPFAII GLCYSLIVRA LIRAHRHRGL
260 270 280 290 300
RPRRQKALRM IFAVVLVFFI CWLPENVFIS VHLLQWAQPG DTPCKQSFRH
310 320 330 340 350
AYPLTGHIVN LAAFSNSCLS PLIYSFLGET FRDKLRLYVA QKTSLPALNR
360 370
FCHATLKAVI PDSTEQSDVK FSSAV
Length:375
Mass (Da):42,260
Last modified:July 1, 1997 - v1
Checksum:i08B60576B0DBE314
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92802 mRNA. Translation: AAC53208.1.
PIRiJC5509.
RefSeqiNP_598257.1. NM_133573.1.
UniGeneiRn.9806.

Genome annotation databases

GeneIDi171104.
KEGGirno:171104.
UCSCiRGD:619845. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92802 mRNA. Translation: AAC53208.1.
PIRiJC5509.
RefSeqiNP_598257.1. NM_133573.1.
UniGeneiRn.9806.

3D structure databases

ProteinModelPortaliO08878.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001732.

Chemistry

ChEMBLiCHEMBL3309103.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiO08878.
PRIDEiO08878.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi171104.
KEGGirno:171104.
UCSCiRGD:619845. rat.

Organism-specific databases

CTDi2852.
RGDi619845. Gper1.

Phylogenomic databases

eggNOGiENOG410IEGB. Eukaryota.
ENOG4111653. LUCA.
HOGENOMiHOG000013114.
HOVERGENiHBG005351.
InParanoidiO08878.
KOiK04246.
PhylomeDBiO08878.

Miscellaneous databases

PROiO08878.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung."
    Bonini J.A., Anderson S.M., Steiner D.F.
    Biochem. Biophys. Res. Commun. 234:190-193(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Lung.
  2. "G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane."
    Funakoshi T., Yanai A., Shinoda K., Kawano M.M., Mizukami Y.
    Biochem. Biophys. Res. Commun. 346:904-910(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  3. "Expression of G protein-coupled receptor-30, a G protein-coupled membrane estrogen receptor, in oxytocin neurons of the rat paraventricular and supraoptic nuclei."
    Sakamoto H., Matsuda K., Hosokawa K., Nishi M., Morris J.F., Prossnitz E.R., Kawata M.
    Endocrinology 148:5842-5850(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  4. Cited for: FUNCTION.
  5. "Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues."
    Hazell G.G., Yao S.T., Roper J.A., Prossnitz E.R., O'Carroll A.M., Lolait S.J.
    J. Endocrinol. 202:223-236(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha."
    Chimento A., Sirianni R., Delalande C., Silandre D., Bois C., Ando S., Maggiolini M., Carreau S., Pezzi V.
    Mol. Cell. Endocrinol. 320:136-144(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone."
    Gros R., Ding Q., Sklar L.A., Prossnitz E.E., Arterburn J.B., Chorazyczewski J., Feldman R.D.
    Hypertension 57:442-451(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "Retrograde transport of the transmembrane estrogen receptor, G-protein-coupled-receptor-30 (GPR30/GPER) from the plasma membrane towards the nucleus."
    Cheng S.B., Graeber C.T., Quinn J.A., Filardo E.J.
    Steroids 76:892-896(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. "Estrogen receptors are found in glia and at extranuclear neuronal sites in the dorsal striatum of female rats: evidence for cholinergic but not dopaminergic colocalization."
    Almey A., Filardo E.J., Milner T.A., Brake W.G.
    Endocrinology 153:5373-5383(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  10. "Role of ERbeta and GPR30 in the endocrine pancreas: A matter of estrogen dose."
    Ropero A.B., Pang Y., Alonso-Magdalena P., Thomas P., Nadal A.
    Steroids 77:951-958(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ESTROGEN-BINDING, SUBCELLULAR LOCATION.
  11. "Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation."
    Gros R., Ding Q., Liu B., Chorazyczewski J., Feldman R.D.
    Am. J. Physiol. 304:C532-C540(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  12. "Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines."
    Akama K.T., Thompson L.I., Milner T.A., McEwen B.S.
    J. Biol. Chem. 288:6438-6450(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DLG4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  13. "GPER 1: trials and tribulations of a membrane oestrogen receptor."
    Srivastava D.P., Evans P.D.
    J. Neuroendocrinol. 25:1219-1230(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiGPER1_RAT
AccessioniPrimary (citable) accession number: O08878
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: July 6, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.