Search by BoMiProt ID - Bomi4275


Primary Information

BoMiProt ID Bomi4275
Protein Name Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Organism Bos taurus
Uniprot IdQ0P5C2
Milk FractionWhey
Ref Sequence Id NP_001069223.1
Aminoacid Length 350
Molecular Weight 37767
Fasta Sequence https://www.uniprot.org/uniprot/Q0P5C2.fasta
Gene Name MTHFD2
Gene Id 517539
Protein Existence Status reviewed

Secondary Information

Protein Function involved in mitochondrial folate one-carbon metabolism ,dehydrogenase activity,confers redox homeostasis.participate in the production of formyltetrahydrofolate for the synthesis of formylmethionyl transfer RNA required for the initiation of protein synthesis.
Biochemical Properties NAD dependent enzyme. performs two main reactions in the one-carbon metabolism(Folate metabolism): the 5,10-methylene-THF (CH2-THF) dehydrogenase and 5,10-methenyl-THF (CH+-THF) cyclohydrolase. A one-carbon unit (1C) from serine is transferred to tetrahydrofolate (THF) by serine hydroxymethyl transferases (SHMTs) to form 5,10-methylenetetrahydrofolate (methylene-THF/CH2-THF). The 1C unit is then transferred among different forms of THFs, thus enabling the folate cycle.
PTMs Acetylation, Isopeptide bond formation, Ubl conjugation
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Phosphorylation
na
Predicted Disorder Regions NA
DisProt Annotation
TM Helix Prediction No TM helices
Significance of PTMs MTHFD2 is hyperacetylated and lysine 88 is the critical acetylated site.deacetylation of MTHFD2 by SIRT3 leads to increase enzymatic activity and upregulates cellular NADPH levels.Cisplatin is able to inhibit SIRT3 expression and increase acetylation of MTHFD2 which results in decrease NADPH levels and upregulate ROS levels.Cisplatin-induced acetylated K88 MTHFD2 is sufficient to inhibit its enzymatic activity and downregulate NADPH levels in colorectal cancer cells.
Bibliography 1.Zhu Z, Leung GKK. More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy? Front Oncol. 2020 Apr 28;10:658. doi: 10.3389/fonc.2020.00658. PMID: 32411609; PMCID: PMC7199629. 2.Wan X, Wang C, Huang Z, Zhou D, Xiang S, Qi Q, Chen X, Arbely E, Liu CY, Du P, Yu W. Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell. Cell Death Dis. 2020 Aug 6;11(8):649. doi: 10.1038/s41419-020-02825-y. PMID: 32811824; PMCID: PMC7434776.