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Protein

G-protein coupled estrogen receptor 1

Gene

GPER1

Organism
Homo sapiens (Human)
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.14 Publications

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). Other reports suggest that it is 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). Other reports suggest that it localizes at the endoplasmic reticulum (ER) (PubMed:15705806, PubMed:18566127).8 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

      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

      Keywordsi

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

      Enzyme and pathway databases

      ReactomeiR-HSA-375276 Peptide ligand-binding receptors
      R-HSA-418594 G alpha (i) signalling events
      SIGNORiQ99527

      Protein family/group databases

      TCDBi9.A.14.13.19 the g-protein-coupled receptor (gpcr) family

      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

      EuPathDBiHostDB:ENSG00000164850.14
      HGNCiHGNC:4485 GPER1
      MIMi601805 gene
      neXtProtiNX_Q99527

      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

      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...) asparagineSequence analysis1
      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.1 Publication
      Glycosylated.1 Publication

      Keywords - PTMi

      Acetylation, Disulfide bond, Glycoprotein, Ubl conjugation

      Proteomic databases

      PaxDbiQ99527
      PeptideAtlasiQ99527
      PRIDEiQ99527
      ProteomicsDBi78311

      PTM databases

      iPTMnetiQ99527
      PhosphoSitePlusiQ99527

      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 Expressed in 154 organ(s), highest expression level in fundus of stomach
      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

      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

      Sequence (1+)i

      Sequence statusi: Complete.

      This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

      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

      Computationally mapped potential isoform sequencesi

      There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
      EntryEntry nameProtein names
      Gene namesLengthAnnotation
      A0A087WVN0A0A087WVN0_HUMAN
      G-protein-coupled estrogen receptor...
      GPER1
      408Annotation score:
      C9J3W2C9J3W2_HUMAN
      G-protein-coupled estrogen receptor...
      GPER1
      73Annotation score:
      A0A087X0Z4A0A087X0Z4_HUMAN
      G-protein-coupled estrogen receptor...
      GPER1
      176Annotation score:

      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 → L2 PublicationsCorresponds to variant dbSNP:rs11544331Ensembl.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

      Similar proteinsi

      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

      TCDBi9.A.14.13.19 the g-protein-coupled receptor (gpcr) family
      GPCRDBiSearch...

      PTM databases

      iPTMnetiQ99527
      PhosphoSitePlusiQ99527

      Polymorphism and mutation databases

      BioMutaiGPER1
      DMDMi3023539

      Proteomic databases

      PaxDbiQ99527
      PeptideAtlasiQ99527
      PRIDEiQ99527
      ProteomicsDBi78311

      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
      EuPathDBiHostDB:ENSG00000164850.14
      GeneCardsiGPER1
      H-InvDBiHIX0167652
      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

      ReactomeiR-HSA-375276 Peptide ligand-binding receptors
      R-HSA-418594 G alpha (i) signalling events
      SIGNORiQ99527

      Miscellaneous databases

      GeneWikiiGPR30
      GenomeRNAii2852
      PROiPR:Q99527
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSG00000164850 Expressed in 154 organ(s), highest expression level in fundus of stomach
      CleanExiHS_GPER
      ExpressionAtlasiQ99527 baseline and differential
      GenevisibleiQ99527 HS

      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
      ProtoNetiSearch...

      Entry informationi

      Entry nameiGPER1_HUMAN
      AccessioniPrimary (citable) accession number: Q99527
      Secondary accession number(s): A8K6C5
      , B5BUJ1, O00143, O43494, Q13631, Q6FHL1, Q96F42, Q99981
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
      Last sequence update: May 1, 1997
      Last modified: November 7, 2018
      This is version 170 of the entry and version 1 of the sequence. See 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

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

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