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Protein

G-protein coupled estrogen receptor 1

Gene

GPER1

Organism
Homo sapiens (Human)
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.14 Publications

Kineticsi

Binds 17-beta-estradiol (E2) in plasma membranes with high affinity (Kd is 3.3 nM) and displays rapid kinetics of association and dissociation.3 Publications

Manual assertion based on experiment ini

      GO - Molecular functioni

      • chromatin binding Source: UniProtKB
      • estrogen receptor activity Source: UniProtKB
      • G-protein coupled receptor activity Source: ProtInc
      • mineralocorticoid receptor activity Source: UniProtKB
      • steroid binding Source: UniProtKB
      • steroid hormone binding Source: UniProtKB

      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

      Enzyme and pathway databases

      BioCyciZFISH:ENSG00000164850-MONOMER.
      ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
      R-HSA-418594. G alpha (i) signalling events.
      SIGNORiQ99527.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      G-protein coupled estrogen receptor 1
      Alternative name(s):
      Chemoattractant receptor-like 2
      Flow-induced endothelial G-protein coupled receptor 1
      Short name:
      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
      Short name:
      LYGPR
      Membrane estrogen receptor
      Short name:
      mER
      Gene namesi
      Name:GPER1
      Synonyms:CEPR, CMKRL2, DRY12, GPER, GPR30
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      Proteomesi
      • UP000005640 Componenti: Chromosome 7

      Organism-specific databases

      HGNCiHGNC:4485. GPER1.

      Subcellular locationi

      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

      GO - Cellular componenti

      • axon Source: UniProtKB
      • axon terminus Source: UniProtKB
      • 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 plasma membrane Source: ProtInc
      • intracellular Source: UniProtKB
      • keratin filament Source: UniProtKB
      • mitochondrial membrane Source: UniProtKB
      • nuclear envelope Source: UniProtKB
      • nucleus Source: UniProtKB
      • perinuclear region of cytoplasm Source: UniProtKB
      • plasma membrane Source: UniProtKB
      • postsynaptic density Source: UniProtKB
      • 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

      Organism-specific databases

      DisGeNETi2852.
      OpenTargetsiENSG00000164850.
      PharmGKBiPA28873.

      Chemistry databases

      ChEMBLiCHEMBL5872.
      GuidetoPHARMACOLOGYi221.

      Polymorphism and mutation databases

      BioMutaiGPER1.
      DMDMi3023539.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00000693101 – 375G-protein coupled estrogen receptor 1Add BLAST375

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Modified residuei1N-acetylmethionineCombined sources1
      Glycosylationi25N-linked (GlcNAc...)Sequence analysis1
      Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
      Glycosylationi44N-linked (GlcNAc...)Sequence analysis1
      Disulfide bondi130 ↔ 207PROSITE-ProRule annotation

      Post-translational modificationi

      Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation.1 Publication
      Glycosylated.1 Publication

      Keywords - PTMi

      Acetylation, Disulfide bond, Glycoprotein, Ubl conjugation

      Proteomic databases

      EPDiQ99527.
      PaxDbiQ99527.
      PeptideAtlasiQ99527.
      PRIDEiQ99527.

      Expressioni

      Tissue specificityi

      Expressed in placenta, endothelial and epithelial cells, non laboring and laboring term myometrium, fibroblasts and cancer-associated fibroblasts (CAF), prostate cancer cells and invasive adenocarcinoma (at protein level). Ubiquitously expressed, but is most abundant in placenta. In brain regions, expressed as a 2.8 kb transcript in basal forebrain, frontal cortex, thalamus, hippocampus, caudate and putamen.6 Publications

      Inductioni

      Up-regulated by EGF and TGF-alpha in endometrial, ovarian and breast tumor cells. Up-regulated by progestin and by phorbol 12-myristate 13-acetate (PMA) in breast cancer cell lines.2 Publications

      Gene expression databases

      BgeeiENSG00000164850.
      CleanExiHS_GPER.
      ExpressionAtlasiQ99527. baseline and differential.
      GenevisibleiQ99527. HS.

      Organism-specific databases

      HPAiHPA027052.

      Interactioni

      Subunit structurei

      Homodimer (Probable). Heterodimer; heterodimerizes with other G-protein-coupled receptor (GPCRs) like CRHR1, HTR1A and PAQR8. 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). 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 similarityCurated4 Publications

      Protein-protein interaction databases

      BioGridi109110. 2 interactors.
      IntActiQ99527. 1 interactor.
      STRINGi9606.ENSP00000297469.

      Chemistry databases

      BindingDBiQ99527.

      Structurei

      3D structure databases

      ProteinModelPortaliQ99527.
      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.
      HOVERGENiHBG005351.
      InParanoidiQ99527.
      KOiK04246.
      OMAiQHARLSC.
      PhylomeDBiQ99527.
      TreeFamiTF333506.

      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.

      Q99527-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MDVTSQARGV GLEMYPGTAQ PAAPNTTSPE LNLSHPLLGT ALANGTGELS
      60 70 80 90 100
      EHQQYVIGLF LSCLYTIFLF PIGFVGNILI LVVNISFREK MTIPDLYFIN
      110 120 130 140 150
      LAVADLILVA DSLIEVFNLH ERYYDIAVLC TFMSLFLQVN MYSSVFFLTW
      160 170 180 190 200
      MSFDRYIALA RAMRCSLFRT KHHARLSCGL IWMASVSATL VPFTAVHLQH
      210 220 230 240 250
      TDEACFCFAD VREVQWLEVT LGFIVPFAII GLCYSLIVRV LVRAHRHRGL
      260 270 280 290 300
      RPRRQKALRM ILAVVLVFFV CWLPENVFIS VHLLQRTQPG AAPCKQSFRH
      310 320 330 340 350
      AHPLTGHIVN LAAFSNSCLN PLIYSFLGET FRDKLRLYIE QKTNLPALNR
      360 370
      FCHAALKAVI PDSTEQSDVR FSSAV
      Length:375
      Mass (Da):42,248
      Last modified:May 1, 1997 - v1
      Checksum:i0A54EED8A698F075
      GO

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti20 – 21QP → HA in AAC52027 (PubMed:9479505).Curated2
      Sequence conflicti32 – 49Missing in AAB02736 (Ref. 7) CuratedAdd BLAST18
      Sequence conflicti104A → G in AAB02736 (Ref. 7) Curated1
      Sequence conflicti140 – 146NMYSSVF → QHVQAASS in AAB02736 (Ref. 7) Curated7
      Sequence conflicti179G → A in AAB02736 (Ref. 7) Curated1
      Sequence conflicti184A → S in AAB02736 (Ref. 7) Curated1
      Sequence conflicti312A → T in AAC51173 (PubMed:9070864).Curated1
      Sequence conflicti320N → T in AAB02736 (Ref. 7) Curated1
      Sequence conflicti355A → V in AAB02736 (Ref. 7) Curated1
      Sequence conflicti358A → V in AAB02736 (Ref. 7) Curated1

      Natural variant

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Natural variantiVAR_03331916P → L.2 PublicationsCorresponds to variant rs11544331dbSNPEnsembl.1

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      Y08162 mRNA. Translation: CAA69354.1.
      U77827 Genomic DNA. Translation: AAC51173.1.
      AF015257 mRNA. Translation: AAC51904.1.
      X98510 mRNA. Translation: CAA67133.1.
      U63917 mRNA. Translation: AAB88017.1.
      AF027956 Genomic DNA. Translation: AAC52027.1.
      U58828 mRNA. Translation: AAB02736.1.
      CR541741 mRNA. Translation: CAG46541.1.
      AK291590 mRNA. Translation: BAF84279.1.
      AB451427 mRNA. Translation: BAG70241.1.
      CH236953 Genomic DNA. Translation: EAL23938.1.
      CH471144 Genomic DNA. Translation: EAW87194.1.
      BC011634 mRNA. Translation: AAH11634.1.
      CCDSiCCDS5322.1.
      PIRiG02670.
      JC5069.
      RefSeqiNP_001035055.1. NM_001039966.1.
      NP_001091671.1. NM_001098201.1.
      NP_001496.1. NM_001505.2.
      UniGeneiHs.20961.

      Genome annotation databases

      EnsembliENST00000297469; ENSP00000297469; ENSG00000164850.
      ENST00000397088; ENSP00000380277; ENSG00000164850.
      ENST00000397092; ENSP00000380281; ENSG00000164850.
      ENST00000401670; ENSP00000385151; ENSG00000164850.
      GeneIDi2852.
      KEGGihsa:2852.
      UCSCiuc003sjz.1. human.

      Keywords - Coding sequence diversityi

      Polymorphism

      Cross-referencesi

      Web resourcesi

      Atlas of Genetics and Cytogenetics in Oncology and Haematology

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      Y08162 mRNA. Translation: CAA69354.1.
      U77827 Genomic DNA. Translation: AAC51173.1.
      AF015257 mRNA. Translation: AAC51904.1.
      X98510 mRNA. Translation: CAA67133.1.
      U63917 mRNA. Translation: AAB88017.1.
      AF027956 Genomic DNA. Translation: AAC52027.1.
      U58828 mRNA. Translation: AAB02736.1.
      CR541741 mRNA. Translation: CAG46541.1.
      AK291590 mRNA. Translation: BAF84279.1.
      AB451427 mRNA. Translation: BAG70241.1.
      CH236953 Genomic DNA. Translation: EAL23938.1.
      CH471144 Genomic DNA. Translation: EAW87194.1.
      BC011634 mRNA. Translation: AAH11634.1.
      CCDSiCCDS5322.1.
      PIRiG02670.
      JC5069.
      RefSeqiNP_001035055.1. NM_001039966.1.
      NP_001091671.1. NM_001098201.1.
      NP_001496.1. NM_001505.2.
      UniGeneiHs.20961.

      3D structure databases

      ProteinModelPortaliQ99527.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi109110. 2 interactors.
      IntActiQ99527. 1 interactor.
      STRINGi9606.ENSP00000297469.

      Chemistry databases

      BindingDBiQ99527.
      ChEMBLiCHEMBL5872.
      GuidetoPHARMACOLOGYi221.

      Protein family/group databases

      GPCRDBiSearch...

      Polymorphism and mutation databases

      BioMutaiGPER1.
      DMDMi3023539.

      Proteomic databases

      EPDiQ99527.
      PaxDbiQ99527.
      PeptideAtlasiQ99527.
      PRIDEiQ99527.

      Protocols and materials databases

      DNASUi2852.
      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENST00000297469; ENSP00000297469; ENSG00000164850.
      ENST00000397088; ENSP00000380277; ENSG00000164850.
      ENST00000397092; ENSP00000380281; ENSG00000164850.
      ENST00000401670; ENSP00000385151; ENSG00000164850.
      GeneIDi2852.
      KEGGihsa:2852.
      UCSCiuc003sjz.1. human.

      Organism-specific databases

      CTDi2852.
      DisGeNETi2852.
      GeneCardsiGPER1.
      H-InvDBHIX0167652.
      HGNCiHGNC:4485. GPER1.
      HPAiHPA027052.
      MIMi601805. gene.
      neXtProtiNX_Q99527.
      OpenTargetsiENSG00000164850.
      PharmGKBiPA28873.
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiENOG410IEGB. Eukaryota.
      ENOG4111653. LUCA.
      GeneTreeiENSGT00530000063910.
      HOVERGENiHBG005351.
      InParanoidiQ99527.
      KOiK04246.
      OMAiQHARLSC.
      PhylomeDBiQ99527.
      TreeFamiTF333506.

      Enzyme and pathway databases

      BioCyciZFISH:ENSG00000164850-MONOMER.
      ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
      R-HSA-418594. G alpha (i) signalling events.
      SIGNORiQ99527.

      Miscellaneous databases

      GeneWikiiGPR30.
      GenomeRNAii2852.
      PROiQ99527.
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSG00000164850.
      CleanExiHS_GPER.
      ExpressionAtlasiQ99527. baseline and differential.
      GenevisibleiQ99527. HS.

      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...

      Entry informationi

      Entry nameiGPER1_HUMAN
      AccessioniPrimary (citable) accession number: Q99527
      Secondary accession number(s): A8K6C5
      , B5BUJ1, O00143, O43494, Q13631, Q6FHL1, Q96F42, Q99981
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: July 15, 1998
      Last sequence update: May 1, 1997
      Last modified: November 2, 2016
      This is version 156 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program
      DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

      Miscellaneousi

      Miscellaneous

      Does not bind estradiol according to PubMed:18566127 and PubMed:16645038.

      Caution

      Data is conflicting regarding whether it fulfills the criteria of a membrane-bound estrogen receptor (PubMed:15705806, PubMed:17379646) or not (PubMed:16645038, PubMed:18566127).4 Publications
      Data is conflicting regarding whether it is localized either at the cell membrane (PM) (PubMed:15539556, PubMed:21427217, PubMed:21540189, PubMed:21354433, PubMed:21149639 and PubMed:23674134) or at the endoplasmic reticulum (ER) (PubMed:15705806 and PubMed:18566127).Curated

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. 7-transmembrane G-linked receptors
        List of 7-transmembrane G-linked receptor entries
      2. Human chromosome 7
        Human chromosome 7: entries, gene names and cross-references to MIM
      3. Human entries with polymorphisms or disease mutations
        List of human entries with polymorphisms or disease mutations
      4. Human polymorphisms and disease mutations
        Index of human polymorphisms and disease mutations
      5. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      6. 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.