Biomarker: GPR30

Histology type: endometrial carcinoma

Stage: high risk

Country: USA

Region: New Mexico

Followed up time :

Conclusion: GPR30 represents an alternative estrogen-responsive receptor that is overexpressed in tumors where estrogen and progesterone receptors are downregulated, and in high-risk endometrial cancer patients with lower survival rates.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression

Expression elevation: The intensity (0, 1, 2, 3) as ordinal and the percentage of epithelial cells stained as continuous data (0- 100%)

Statictics: Mean ;Range

Cohort age: 61.4;33 -84

Funtion Uniprot: 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.

UniProt ID: Q99527

UniProt Link: https://www.uniprot.org/uniprotkb/Q99527/entry

Biological function from UniProt: #Apoptosis #Cell cycle #Differentiation #Immunity #Inflammatory response

Molecular function from UniProt:

Tissue specificity from UniProt: 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

Subcellular UniProt: #Cell membrane #Cell projection #Cytoplasm #Cytoplasmic vesicle #Cytoskeleton

Alternative name from UniProt:

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). 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).

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

Recommended name: G-protein coupled estrogen receptor 1

Gene name from HGNC: GPER1 (CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, GPER, GPR30, LERGU, LERGU2, LyGPR)

HPA class: G-protein coupled receptors Transporters

AlphaFold DB: Q99527

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q99527

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.

HPA link: https://www.proteinatlas.org/ENSG00000164850-GPER1

Tissue specificity RNA from HPA: Tissue enhanced (stomach)

Tissue expression from HPA: Cytoplasmic and membranous expression in several tissues.

Single cell type specificity Cell type enhanced (Hepatocytes, Kupffer cells, Distal enterocytes, Endothelial cells, Adipocytes)

Immune cell specificity: Group enriched (myeloid DC, classical monocyte, intermediate monocyte)

Subcellular summary HPA Located in Nucleoplasm, Nucleoli, Vesicles, Cytosol

Cancer prognostic summary HPA Prognostic marker in endometrial cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000164850-GPER1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000164850-GPER1/pathology/endometrial+cancer

OMIM: 601805

OMIM link2: https://www.omim.org/entry/601805

HGNC ID: HGNC:4485

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4485