Molecule Information

General Information of the Molecule (ID: Mol04004)

• Name: Phosphoglycerate kinase 1 (PGK1) ,Rattus norvegicus
• Molecule Type: Protein
• Gene Name: Pgk1
• Gene ID: 24644
• Sequence:
  MSLSNKLTLDKLDVKGKRVVMRVDFNVPMKNNQITNNQRIKAAVPSIKFCLDNGAKSVVL
  MSHLGRPDGVPMPDKYSLEPVAAELKSLLGKDVLFLKDCVGSEVENACANPAAGTVILLE
  NLRFHVEEEGKGKDASGNKVKAEPAKIDAFRASLSKLGDVYVNDAFGTAHRAHSSMVGVN
  LPQKAGGFLMKKELNYFAKALESPERPFLAILGGAKVADKIQLINNMLDKVNEMIIGGGM
  AFTFLKVLNNMEIGTSLYDEEGAKIVKDLMAKAEKNGVKITLPVDFVTADKFDENAKTGQ
  ATVASGIPAGWMGLDCGTESSKKYAEAVARAKQIVWNGPVGVFEWEAFARGTKSLMDEVV
  KATSRGCITIIGGGDTATCCAKWNTEDKVSHVSTGGGASLELLEGKVLPGVDALSNV
• Function: Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3- diphosphoglycerate to 3-phosphoglycerate. Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines. In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis. May play a role in sperm motility. .
• Uniprot ID: PGK1_RAT

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Rattus
Species: Rattus norvegicus

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

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.42E-42; Fold-change: 8.52E-01; Z-score: 2.05E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Human immunodeficiency virus 1 infection; Activation; hsa05170
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• In Vitro Model: OS-RC-2 cells; Kidney; Homo sapiens (Human); CVCL_E313
• Experiment for Molecule Alteration: LC-MS/MS
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: In the KIRC tissues, a high expression of PGK1 is often accompanied with an increase of glycolysis-related enzymes and CXCR4. PGK1 exhibits pro-tumorigenic properties in vitro and in a xenograft tumor model by accelerating glycolysis and inducing CXCR4-mediated phosphorylation of AKT and ERK. Moreover, PGK1 promotes sorafenib resistance via increasing CXCR4-mediated ERK phosphorylation.

References

• Ref 1: PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis. Cell Death Dis. 2022 Feb 4;13(2):118.