Molecule Information

General Information of the Molecule (ID: Mol04144)

• Name: Pyruvate kinase L/R (PKLR) ,Homo sapiens
• Synonyms: Pyruvate kinase 1; Pyruvate kinase isozymes L/R; R-type/L-type pyruvate kinase; Red cell/liver pyruvate kinase
• Molecule Type: Protein
• Gene Name: PKLR
• Gene ID: 5313
• Location: chr1:155289293-155301438[-]
• Sequence:
  MSIQENISSLQLRSWVSKSQRDLAKSILIGAPGGPAGYLRRASVAQLTQELGTAFFQQQQ
  LPAAMADTFLEHLCLLDIDSEPVAARSTSIIATIGPASRSVERLKEMIKAGMNIARLNFS
  HGSHEYHAESIANVREAVESFAGSPLSYRPVAIALDTKGPEIRTGILQGGPESEVELVKG
  SQVLVTVDPAFRTRGNANTVWVDYPNIVRVVPVGGRIYIDDGLISLVVQKIGPEGLVTQV
  ENGGVLGSRKGVNLPGAQVDLPGLSEQDVRDLRFGVEHGVDIVFASFVRKASDVAAVRAA
  LGPEGHGIKIISKIENHEGVKRFDEILEVSDGIMVARGDLGIEIPAEKVFLAQKMMIGRC
  NLAGKPVVCATQMLESMITKPRPTRAETSDVANAVLDGADCIMLSGETAKGNFPVEAVKM
  QHAIAREAEAAVYHRQLFEELRRAAPLSRDPTEVTAIGAVEAAFKCCAAAIIVLTTTGRS
  AQLLSRYRPRAAVIAVTRSAQAARQVHLCRGVFPLLYREPPEAIWADDVDRRVQFGIESG
  KLRGFLRVGDLVIVVTGWRPGSGYTNIMRVLSIS
• 3D-structure: PDB ID: 8TBT; Classification: Transferase/activator; Method: X-ray diffraction; Resolution: 2.34 Å
• Function: Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis. .
• Uniprot ID: KPYR_HUMAN
• Ensembl ID: ENSG00000143627
• HGNC ID: HGNC:9020

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

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.48E-20; Fold-change: 7.15E-01; Z-score: 1.03E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Metabolic pathways; Activation; hsa01100
• Cell Pathway Regulation: Transcriptional misregulation in cancer; Activation; hsa05202
• In Vivo Model: 6-week-old male nude mice, with LASCPC01 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Our study found significant correlations between ROMO1 and NE-related gene upregulation in PCa after ADT, which may have been caused by the nuclear translocation of PKLR and its interaction with the MYCN/MAX complex to promote ROMO1 and NE marker expression. Importantly, we found that this interaction decreased after treatment with a putative MYCN inhibitor. These data suggest that PKLR may also act as a transcription cofactor of MYCN, in addition to acting as a kinase, similar to PKM2, which acts as a transcription cofactor to activate hypoxia-inducible factor-1A (HIF1A) to promote castration resistance [22].

References

• Ref 1: Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer. Redox Biol. 2023 Jun;62:102686.