Molecule Information

General Information of the Molecule (ID: Mol04133)

• Name: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: MTHFD2
• Gene ID: 10797
• Location: chr2:74186172-74217565[+]
• Sequence:
  MAATSLMSALAARLLQPAHSCSLRLRPFHLAAVRNEAVVISGRKLAQQIKQEVRQEVEEW
  VASGNKRPHLSVILVGENPASHSYVLNKTRAAAVVGINSETIMKPASISEEELLNLINKL
  NNDDNVDGLLVQLPLPEHIDERRICNAVSPDKDVDGFHVINVGRMCLDQYSMLPATPWGV
  WEIIKRTGIPTLGKNVVVAGRSKNVGMPIAMLLHTDGAHERPGGDATVTISHRYTPKEQL
  KKHTILADIVISAAGIPNLITADMIKEGAAVIDVGINRVHDPVTAKPKLVGDVDFEGVRQ
  KAGYITPVPGGVGPMTVAMLMKNTIIAAKKVLRLEEREVLKSKELGVATN
• 3D-structure: PDB ID: 6JIB; Classification: Oxidoreductase; Method: X-ray diffraction; Resolution: 2.25 Å
• Function: Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency. .
• Uniprot ID: MTDC_HUMAN
• Ensembl ID: ENSG00000065911
• HGNC ID: HGNC:7434

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

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

H-mMnO2

Drug Sensitivity 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: Mitochondrial metabolism
• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Sensitive Drug: H-mMnO2
• 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: 1.76E-14; Fold-change: 5.67E-01; Z-score: 8.53E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki1/R cells; Liver; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO7was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

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

Sunitinib

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: Mitochondrial metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Sunitinib
• 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: 1.76E-14; Fold-change: 5.67E-01; Z-score: 8.53E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki1/R cells; Liver; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO5was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

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

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Sunitinib
• 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: 1.76E-14; Fold-change: 5.67E-01; Z-score: 8.53E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786O/R cells; Liver; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO4was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

References

• Ref 1: Engineered Biomimetic Nanovesicles Synergistically Remodel Folate-Nucleotide and gamma-Aminobutyric Acid Metabolism to Overcome Sunitinib-Resistant Renal Cell Carcinoma. ACS Nano. 2024 Oct 8;18(40):27487-27502.