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Q99527 (GPER1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GPER1
Synonyms:CEPR, CMKRL2, DRY12, GPER, GPR30
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.14 Ref.16 Ref.17 Ref.21 Ref.22 Ref.24 Ref.25 Ref.27 Ref.28 Ref.30 Ref.32 Ref.33 Ref.35 Ref.36

Subunit structure

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. Ref.23 Ref.24 Ref.30 Ref.36

Subcellular location

Nucleus. Cytoplasm By similarity. Cytoplasmperinuclear region. Cytoplasmcytoskeleton. Cell membrane; Multi-pass membrane protein. Basolateral cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane protein. Early endosome. Recycling endosome. Golgi apparatus membrane; Multi-pass membrane protein By similarity. Golgi apparatustrans-Golgi network. Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell projectiondendrite By similarity. Cell projectiondendritic spine membrane; Multi-pass membrane protein By similarity. Cell projectionaxon By similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Mitochondrion membrane; Multi-pass membrane protein By similarity. Note: Colocalized with BSN to the active zone of presynaptic density. Colocalized with DLG4/PSD95 and neurabin-2 PPP1R9B in neuronal synaptosomes By similarity. Endocytosed in a agonist- and arrestin-independent manner. Colocalized with RAMP3 and clathrin-coated pits at the plasma membrane. Colocalized with transferrin receptor at the plasma membrane and perinuclear region. Accumulated and colocalized with RAB11 proteins in recycling endosomes and trans-Golgi network (TGN), but does neither recycle back to the cell surface nor traffics to late endosome or lysosome. Colocalized with calnexin in the endoplasmic reticulum. Traffics to intracellular sites via cytokeratin intermediate filaments like KRT7 and KRT8 after constitutive endocytosis in epithelial cells. Colocalized with EGFR in the nucleus of agonist-induced cancer-associated fibroblasts (CAF). Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.27 Ref.29 Ref.30 Ref.31 Ref.33 Ref.36

Tissue specificity

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. Ref.24 Ref.25 Ref.27 Ref.30 Ref.31 Ref.33

Induction

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. Ref.15 Ref.23

Post-translational modification

Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation. Ref.29

Glycosylated. Ref.27

Miscellaneous

Does not bind estradiol according to Ref.20 and Ref.18.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Caution

Data is conflicting regarding whether it fulfills the criteria of a membrane-bound estrogen receptor (Ref.17, Ref.19 and PubMed:16780796) or not (PubMed:12193550, Ref.18 and Ref.20).

Data is conflicting regarding whether it is localized either at the cell membrane (PM) (Ref.16, Ref.27, Ref.29, Ref.31, Ref.30 and Ref.36) or at the endoplasmic reticulum (ER) (Ref.17 and Ref.20).

Biophysicochemical properties

Kinetic parameters:

KM=3.3 mM for 17-beta-estradiol (Ref.26) Ref.16 Ref.17 Ref.26

KM=6.6 mM for 17-beta-estradiol (Ref.17)

KM=3.3 mM for 17-beta-estradiol (Ref.16)

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Differentiation
Immunity
Inflammatory response
Innate immunity
Neurogenesis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Endoplasmic reticulum
Endosome
Golgi apparatus
Membrane
Mitochondrion
Nucleus
Postsynaptic cell membrane
Synapse
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMAcetylation
Disulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

apoptotic chromosome condensation

Inferred from sequence or structural similarity. Source: UniProtKB

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to estradiol stimulus

Inferred from direct assay Ref.16Ref.17Ref.24Ref.30Ref.27Ref.29Ref.33. Source: UniProtKB

cellular response to glucose stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to mineralocorticoid stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to peptide hormone stimulus

Inferred from direct assay Ref.27. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from direct assay Ref.33. Source: UniProtKB

cytosolic calcium ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular steroid hormone receptor signaling pathway

Inferred from direct assay Ref.17. Source: UniProtKB

mineralocorticoid receptor signaling pathway

Inferred from sequence or structural similarity. Source: GOC

negative regulation of DNA metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of inflammatory response

Inferred from direct assay Ref.33. Source: UniProtKB

negative regulation of leukocyte activation

Inferred from direct assay Ref.33. Source: UniProtKB

negative regulation of lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal action potential

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear fragmentation involved in apoptotic nuclear change

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.24Ref.27. Source: UniProtKB

positive regulation of G-protein coupled receptor protein signaling pathway

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cAMP biosynthetic process

Inferred from direct assay Ref.16Ref.30. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epidermal growth factor receptor signaling pathway

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from direct assay Ref.36. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of inositol trisphosphate biosynthetic process

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of insulin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neurogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neurotransmitter secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from direct assay Ref.24Ref.27. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of release of sequestered calcium ion into cytosol

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.24. Source: UniProtKB

positive regulation of uterine smooth muscle contraction

Inferred from direct assay Ref.27. Source: UniProtKB

positive regulation of vasodilation

Inferred from sequence or structural similarity. Source: UniProtKB

steroid hormone mediated signaling pathway

Inferred from direct assay Ref.16Ref.17. Source: GOC

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.17. Source: UniProtKB

Golgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

axon

Inferred from sequence or structural similarity. Source: UniProtKB

axon terminus

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from direct assay Ref.29. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic shaft

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine head

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine membrane

Inferred from sequence or structural similarity. Source: UniProtKB

early endosome

Inferred from direct assay Ref.29. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.17Ref.29. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

intracellular

Inferred from sequence or structural similarity. Source: UniProtKB

keratin filament

Inferred from direct assay Ref.30. Source: UniProtKB

mitochondrial membrane

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear envelope

Inferred from direct assay Ref.17. Source: UniProtKB

nucleus

Inferred from direct assay Ref.24Ref.33. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.29. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.16Ref.30Ref.27Ref.29Ref.36. Source: UniProtKB

postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

presynaptic active zone

Inferred from sequence or structural similarity. Source: UniProtKB

presynaptic membrane

Inferred from sequence or structural similarity. Source: UniProtKB

recycling endosome

Inferred from direct assay Ref.29. Source: UniProtKB

trans-Golgi network

Inferred from direct assay Ref.29. Source: UniProtKB

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.1. Source: ProtInc

chromatin binding

Inferred from direct assay Ref.24. Source: UniProtKB

estrogen receptor activity

Inferred from direct assay Ref.16Ref.17. Source: UniProtKB

mineralocorticoid receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.24Ref.30Ref.36. Source: UniProtKB

steroid binding

Inferred from direct assay Ref.16Ref.17. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 375375G-protein coupled estrogen receptor 1
PRO_0000069310

Regions

Topological domain1 – 6262Extracellular Potential
Transmembrane63 – 8422Helical; Name=1; Potential
Topological domain85 – 9612Cytoplasmic Potential
Transmembrane97 – 12024Helical; Name=2; Potential
Topological domain121 – 13212Extracellular Potential
Transmembrane133 – 15321Helical; Name=3; Potential
Topological domain154 – 17522Cytoplasmic Potential
Transmembrane176 – 19419Helical; Name=4; Potential
Topological domain195 – 22026Extracellular Potential
Transmembrane221 – 23616Helical; Name=5; Potential
Topological domain237 – 25923Cytoplasmic Potential
Transmembrane260 – 28021Helical; Name=6; Potential
Topological domain281 – 30626Extracellular Potential
Transmembrane307 – 32721Helical; Name=7; Potential
Topological domain328 – 37548Cytoplasmic Potential

Amino acid modifications

Modified residue11N-acetylmethionine Ref.34
Glycosylation251N-linked (GlcNAc...) Potential
Glycosylation321N-linked (GlcNAc...) Potential
Glycosylation441N-linked (GlcNAc...) Potential
Disulfide bond130 ↔ 207 Potential

Natural variations

Natural variant161P → L. Ref.10 Ref.13
Corresponds to variant rs11544331 [ dbSNP | Ensembl ].
VAR_033319

Experimental info

Sequence conflict20 – 212QP → HA in AAC52027. Ref.6
Sequence conflict32 – 4918Missing in AAB02736. Ref.7
Sequence conflict1041A → G in AAB02736. Ref.7
Sequence conflict140 – 1467NMYSSVF → QHVQAASS in AAB02736. Ref.7
Sequence conflict1791G → A in AAB02736. Ref.7
Sequence conflict1841A → S in AAB02736. Ref.7
Sequence conflict3121A → T in AAC51173. Ref.2
Sequence conflict3201N → T in AAB02736. Ref.7
Sequence conflict3551A → V in AAB02736. Ref.7
Sequence conflict3581A → V in AAB02736. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q99527 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 0A54EED8A698F075

FASTA37542,248
        10         20         30         40         50         60 
MDVTSQARGV GLEMYPGTAQ PAAPNTTSPE LNLSHPLLGT ALANGTGELS EHQQYVIGLF 

        70         80         90        100        110        120 
LSCLYTIFLF PIGFVGNILI LVVNISFREK MTIPDLYFIN LAVADLILVA DSLIEVFNLH 

       130        140        150        160        170        180 
ERYYDIAVLC TFMSLFLQVN MYSSVFFLTW MSFDRYIALA RAMRCSLFRT KHHARLSCGL 

       190        200        210        220        230        240 
IWMASVSATL VPFTAVHLQH TDEACFCFAD VREVQWLEVT LGFIVPFAII GLCYSLIVRV 

       250        260        270        280        290        300 
LVRAHRHRGL RPRRQKALRM ILAVVLVFFV CWLPENVFIS VHLLQRTQPG AAPCKQSFRH 

       310        320        330        340        350        360 
AHPLTGHIVN LAAFSNSCLN PLIYSFLGET FRDKLRLYIE QKTNLPALNR FCHAALKAVI 

       370 
PDSTEQSDVR FSSAV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues."
Owman C.S.O., Blay P., Nilsson C., Lolait S.J.
Biochem. Biophys. Res. Commun. 228:285-292(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning of a novel member of the G protein-coupled receptor family related to peptide receptors."
Feng Y., Gregor P.
Biochem. Biophys. Res. Commun. 231:651-654(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress."
Takada Y., Kato C., Kondo S., Korenaga R., Ando J.
Biochem. Biophys. Res. Commun. 240:737-741(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue."
Kvingedal A.M., Smeland E.B.
FEBS Lett. 407:59-62(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer."
Carmeci C., Thompson D.A., Ring H.Z., Francke U., Weigel R.J.
Genomics 45:607-617(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Discovery of three novel G-protein-coupled receptor genes."
O'Dowd B.F., Nguyen T., Marchese A., Cheng R., Lynch K.R., Heng H.H.Q., Kolakowski L.F. Jr., George S.R.
Genomics 47:310-313(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Cloning of novel IL8-related receptors from human hepatic tissue."
McCoy R.L., Perlmutter D.H.
Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[10]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-16.
[11]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-16.
Tissue: Uterus.
[14]"Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF."
Filardo E.J., Quinn J.A., Bland K.I., Frackelton A.R. Jr.
Mol. Endocrinol. 14:1649-1660(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells."
Ahola T.M., Purmonen S., Pennanen P., Zhuang Y.H., Tuohimaa P., Ylikomi T.
Eur. J. Biochem. 269:2485-2490(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[16]"Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells."
Thomas P., Pang Y., Filardo E.J., Dong J.
Endocrinology 146:624-632(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ESTROGEN-BINDING, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[17]"A transmembrane intracellular estrogen receptor mediates rapid cell signaling."
Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R.
Science 307:1625-1630(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ESTROGEN-BINDING, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[18]"Nature of functional estrogen receptors at the plasma membrane."
Pedram A., Razandi M., Levin E.R.
Mol. Endocrinol. 20:1996-2009(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ABSENCE OF ESTROGEN-BINDING, SUBCELLULAR LOCATION.
[19]"Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane."
Filardo E., Quinn J., Pang Y., Graeber C., Shaw S., Dong J., Thomas P.
Endocrinology 148:3236-3245(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[20]"G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol."
Otto C., Rohde-Schulz B., Schwarz G., Fuchs I., Klewer M., Brittain D., Langer G., Bader B., Prelle K., Nubbemeyer R., Fritzemeier K.H.
Endocrinology 149:4846-4856(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ABSENCE OF ESTROGEN-BINDING, SUBCELLULAR LOCATION.
[21]"Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity."
Haas E., Bhattacharya I., Brailoiu E., Damjanovic M., Brailoiu G.C., Gao X., Mueller-Guerre L., Marjon N.A., Gut A., Minotti R., Meyer M.R., Amann K., Ammann E., Perez-Dominguez A., Genoni M., Clegg D.J., Dun N.J., Resta T.C., Prossnitz E.R., Barton M.
Circ. Res. 104:288-291(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30."
Quinn J.A., Graeber C.T., Frackelton A.R. Jr., Kim M., Schwarzbauer J.E., Filardo E.J.
Mol. Endocrinol. 23:1052-1064(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells."
Vivacqua A., Lappano R., De Marco P., Sisci D., Aquila S., De Amicis F., Fuqua S.A., Ando S., Maggiolini M.
Mol. Endocrinol. 23:1815-1826(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EGFR AND ESR1, INDUCTION.
[24]"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EGFR, ASSOCIATION WITH CHROMATIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[25]"Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G(2) cell-cycle arrest."
Chan Q.K., Lam H.M., Ng C.F., Lee A.Y., Chan E.S., Ng H.K., Ho S.M., Lau K.M.
Cell Death Differ. 17:1511-1523(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[26]"Conserved estrogen binding and signaling functions of the G protein-coupled estrogen receptor 1 (GPER) in mammals and fish."
Thomas P., Alyea R., Pang Y., Peyton C., Dong J., Berg A.H.
Steroids 75:595-602(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ESTROGEN-BINDING, BIOPHYSICOCHEMICAL PROPERTIES.
[27]"G-1-activated membrane estrogen receptors mediate increased contractility of the human myometrium."
Maiti K., Paul J.W., Read M., Chan E.C., Riley S.C., Nahar P., Smith R.
Endocrinology 152:2448-2455(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY.
[28]"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: ALDOSTERONE-BINDING, FUNCTION.
[29]"Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway."
Cheng S.B., Quinn J.A., Graeber C.T., Filardo E.J.
J. Biol. Chem. 286:22441-22455(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, UBIQUITINATION.
[30]"G protein-coupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments."
Sanden C., Broselid S., Cornmark L., Andersson K., Daszkiewicz-Nilsson J., Martensson U.E., Olde B., Leeb-Lundberg L.M.
Mol. Pharmacol. 79:400-410(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KRT7 AND KRT8, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[31]"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.
[32]"G protein-coupled estrogen receptor mediates the up-regulation of fatty acid synthase induced by 17beta-estradiol in cancer cells and cancer-associated fibroblasts."
Santolla M.F., Lappano R., De Marco P., Pupo M., Vivacqua A., Sisci D., Abonante S., Iacopetta D., Cappello A.R., Dolce V., Maggiolini M.
J. Biol. Chem. 287:43234-43245(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[33]"G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation."
Chakrabarti S., Davidge S.T.
PLoS ONE 7:E52357-E52357(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[34]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"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: ALDOSTERONE-BINDING, FUNCTION.
[36]"G-protein-coupled receptor 30 interacts with receptor activity-modifying protein 3 and confers sex-dependent cardioprotection."
Lenhart P.M., Broselid S., Barrick C.J., Leeb-Lundberg L.M., Caron K.M.
J. Mol. Endocrinol. 51:191-202(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAMP3, SUBCELLULAR LOCATION.
[37]"Position paper: The membrane estrogen receptor GPER--Clues and questions."
Barton M.
Steroids 77:935-942(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[38]"Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology."
Filardo E.J., Thomas P.
Endocrinology 153:2953-2962(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5322.1.
PIRG02670.
JC5069.
RefSeqNP_001035055.1. NM_001039966.1.
NP_001091671.1. NM_001098201.1.
NP_001496.1. NM_001505.2.
UniGeneHs.20961.

3D structure databases

ProteinModelPortalQ99527.
SMRQ99527. Positions 19-338.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ99527. 1 interaction.

Chemistry

BindingDBQ99527.
ChEMBLCHEMBL5872.
GuidetoPHARMACOLOGY221.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM3023539.

Proteomic databases

MaxQBQ99527.
PaxDbQ99527.
PRIDEQ99527.

Protocols and materials databases

DNASU2852.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297469; ENSP00000297469; ENSG00000164850.
ENST00000397088; ENSP00000380277; ENSG00000164850.
ENST00000397092; ENSP00000380281; ENSG00000164850.
ENST00000401670; ENSP00000385151; ENSG00000164850.
GeneID2852.
KEGGhsa:2852.
UCSCuc003sjz.1. human.

Organism-specific databases

CTD2852.
GeneCardsGC07P001122.
H-InvDBHIX0167652.
HGNCHGNC:4485. GPER1.
HPAHPA027052.
MIM601805. gene.
neXtProtNX_Q99527.
PharmGKBPA28873.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG151076.
HOVERGENHBG005351.
KOK04246.
OMAQHARLSC.
OrthoDBEOG7WX08J.
PhylomeDBQ99527.
TreeFamTF333506.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ99527.
BgeeQ99527.
CleanExHS_GPER.
GenevestigatorQ99527.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGPR30.
GenomeRNAi2852.
NextBio11247.
PROQ99527.
SOURCESearch...

Entry information

Entry nameGPER1_HUMAN
AccessionPrimary (citable) accession number: Q99527
Secondary accession number(s): A8K6C5 expand/collapse secondary AC list , B5BUJ1, O00143, O43494, Q13631, Q6FHL1, Q96F42, Q99981
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries