Molecule Information

General Information of the Molecule (ID: Mol04106)

• Name: Estrogen-related receptor alpha (ERRalpha) ,Homo sapiens
• Synonyms: Estrogen receptor-like 1; Estrogen-related receptor alpha; Nuclear receptor subfamily 3 group B member 1
• Molecule Type: Protein
• Gene Name: ESRRA
• Gene ID: 2101
• Location: chr11:64305497-64316743[+]
• Sequence:
  MSSQVVGIEPLYIKAEPASPDSPKGSSETETEPPVALAPGPAPTRCLPGHKEEEDGEGAG
  PGEQGGGKLVLSSLPKRLCLVCGDVASGYHYGVASCEACKAFFKRTIQGSIEYSCPASNE
  CEITKRRRKACQACRFTKCLRVGMLKEGVRLDRVRGGRQKYKRRPEVDPLPFPGPFPAGP
  LAVAGGPRKTAAPVNALVSHLLVVEPEKLYAMPDPAGPDGHLPAVATLCDLFDREIVVTI
  SWAKSIPGFSSLSLSDQMSVLQSVWMEVLVLGVAQRSLPLQDELAFAEDLVLDEEGARAA
  GLGELGAALLQLVRRLQALRLEREEYVLLKALALANSDSVHIEDAEAVEQLREALHEALL
  EYEAGRAGPGGGAERRRAGRLLLTLPLLRQTAGKVLAHFYGVKLEGKVPMHKLFLEMLEA
  MMD
• 3D-structure: PDB ID: 3D24; Classification: Transcription; Method: X-ray diffraction; Resolution: 2.11 Å
• Function: Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium- chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle. .
• Uniprot ID: ERR1_HUMAN
• Ensembl ID: ENSG00000173153
• HGNC ID: HGNC:3471

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NOD-like receptor signaling pathway; Activation; hsa04621
• Cell Pathway Regulation: Neutrophil extracellular trap formation; Activation; hsa04613
• In Vitro Model: HEC-1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: KLE cells; Ovary; Homo sapiens (Human); CVCL_1329
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: High expression of ERRalpha, triggered by the hypoxic microenvironment, enhances cell resistance to pyroptosis by direct target binding to the promoter of NLRP3 with the sequence 3'-ACAACTTGAACACGGAAACG-5', inhibiting the downstream pyroptosis signaling pathway. Moreover, overexpression of ERRalpha participates in the malignant progression of EC through the reprogramming of glycolysis, accompanied by increased extracellular acidification rate, which leads to the resistance of EC cells to pyroptosis and cisplatin chemotherapy (Fig. 7).

Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NOD-like receptor signaling pathway; Activation; hsa04621
• Cell Pathway Regulation: Neutrophil extracellular trap formation; Activation; hsa04613
• In Vivo Model: Female BALB/c nude mice, with KLE cell lines; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: High expression of ERRalpha, triggered by the hypoxic microenvironment, enhances cell resistance to pyroptosis by direct target binding to the promoter of NLRP3 with the sequence 3'-ACAACTTGAACACGGAAACG-5', inhibiting the downstream pyroptosis signaling pathway. Moreover, overexpression of ERRalpha participates in the malignant progression of EC through the reprogramming of glycolysis, accompanied by increased extracellular acidification rate, which leads to the resistance of EC cells to pyroptosis and cisplatin chemotherapy (Fig. 7).

References

• Ref 1: ERRalpha promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer. J Exp Clin Cancer Res. 2023 Oct 20;42(1):274.