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Information on EC 6.3.4.3 - formate-tetrahydrofolate ligase and Organism(s) Homo sapiens and UniProt Accession Q6UB35
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6.3.4.3 formate-tetrahydrofolate ligaseIUBMB Comments
In eukaryotes occurs as a trifunctional enzyme also having methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity.
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Word Map
- 6.3.4.3
-
trifunctional
-
one-carbon
- 5,10-methylenetetrahydrofolate
-
acetogens
- mthfr
- 5,10-methenyltetrahydrofolate
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homoacetogens
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folate-dependent
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acetogenesis
- cylindrosporum
- thermoaceticum
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folate-mediated
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1.5.1.5
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dehydrogenase-cyclohydrolase
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5,10-methenyl-thf
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5,10-methylene-thf
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biogas
- acetobacterium
- acidi-urici
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syntrophic
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
fthfs, formyltetrahydrofolate synthetase, c1-thf synthase, mthfd, 10-formyltetrahydrofolate synthetase, c1-tetrahydrofolate synthase, 10-formyl-thf synthetase, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase, methylenetetrahydrofolate dehydrogenase 1-like, n10-formyltetrahydrofolate synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
10-Formyltetrahydrofolate synthetase
C(1)-tetrahydrofolate synthase
-
a monofunctional 10-formyl-tetrahydrofolate synthetase lacking the 5,10-methylene-tetrahydrofolate dehydrogenase and 5,10-methenyl-tetrahydrofolate cyclohydrolase activities typically found in the trifunctional cytoplasmic proteins
FHS
-
-
-
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formate-tetrahydrofolate ligase
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-
-
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formate:tetrahydrofolate ligase (ADP-forming)
-
-
-
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Formyl-THF synthetase
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-
-
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Formyltetrahydrofolate synthetase
FTHFS
-
-
-
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methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase
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MTHFD1
Synthetase, formyl tetrahydrofolate
-
-
-
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Tetrahydrofolate formylase
-
-
-
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Tetrahydrofolic formylase
-
-
-
-
THFS
-
-
-
-
10-Formyltetrahydrofolate synthetase
-
-
-
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Formyltetrahydrofolate synthetase
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-
-
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MTHFD1
trifunctional enzyme consisting of methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, and formyltetrahydrofolate synthetase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
the enzyme is not trifunctional showing only 10-formyl-THS synthetase activity, enzyme evolutionary considerations
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
formylation
formylation
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
formate:tetrahydrofolate ligase (ADP-forming)
In eukaryotes occurs as a trifunctional enzyme also having methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity.
CAS REGISTRY NUMBER
COMMENTARY
9023-66-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + (6R,S)-tetrahydrofolate pteroylpentaglutamate
ADP + phosphate + 10-formyltetrahydrofolate pteroylpentaglutamate
-
-
-
-
?
ATP + (6R,S)-tetrahydrofolate pteroyltriglutamate
ADP + phosphate + 10-formyltetrahydrofolate pteroyltriglutamate
-
-
-
-
?
ATP + formate + (6R,S)-tetrahydrofolate monoglutamate
ADP + phosphate + 10-formyltetrahydrofolate monoglutamate
-
-
-
-
?
ATP + formate + tetrahydrofolate
?
-
two different physiological roles: 1. Functions anabolically in most organisms to activate formate via the forward reaction, and brings it into the one-carbon metabolic pool as N10-formyltetrahydrofolate, 2. In purine-fermenting bacteria the enzyme probably functions catabolically in the terminal step of the purine degradative pathway. This reaction may be responsible for ATP production in these organisms
-
-
?
formate + ATP + tetrahydrofolate
10-formyltetrahydrofolate + ADP + phosphate
synthetase activity of MTHFD1
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
trifuntional enzyme having 10-formyl-tetrahydrofolate synthetase, 5,10-methylene-tetrahydrofolate cyclohydrolase and 5,10-methylene-tetrahydrofolate dehydrogenase activity
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
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monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues
mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
-
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities
-
-
r
additional information
?
-
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
?
additional information
?
-
-
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
?
additional information
?
-
MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L directly interacts with the MAGE family member D1 (MAGED)
-
-
-
additional information
?
-
-
enzyme is involved in the folate-mediated one-carbon metabolism, overview
-
-
?
additional information
?
-
(MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + formate + tetrahydrofolate
?
-
two different physiological roles: 1. Functions anabolically in most organisms to activate formate via the forward reaction, and brings it into the one-carbon metabolic pool as N10-formyltetrahydrofolate, 2. In purine-fermenting bacteria the enzyme probably functions catabolically in the terminal step of the purine degradative pathway. This reaction may be responsible for ATP production in these organisms
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
formate + ATP + tetrahydrofolate
10-formyltetrahydrofolate + ADP + phosphate
synthetase activity of MTHFD1
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
-
-
-
?
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
-
monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues
mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
-
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities
-
-
r
additional information
?
-
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
?
additional information
?
-
-
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
?
additional information
?
-
MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L directly interacts with the MAGE family member D1 (MAGED)
-
-
-
additional information
?
-
-
enzyme is involved in the folate-mediated one-carbon metabolism, overview
-
-
?
additional information
?
-
(MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state kinetics, recombinant enzyme
-
0.04
ATP
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recombinant enzyme, 30°C, with substrate (6R,S)-tetrahydrofolate pteroyltriglutamate or (6R,S)-tetrahydrofolate pteroylpentaglutamate and formate
0.2
ATP
-
above, recombinant enzyme, 30°C, with substrate (6R,S)-tetrahydrofolate monoglutamate and formate
0.15
formate
-
recombinant enzyme, 30°C, with substrate (6R,S)-tetrahydrofolate pteroylpentaglutamate
0.44
formate
-
recombinant enzyme, 30°C, with substrate (6R,S)-tetrahydrofolate pteroyltriglutamate
11.8
formate
-
recombinant enzyme, 30°C, with substrate (6R,S)-tetrahydrofolate monoglutamate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the Kcat/Km tetrahydrofolate values are 0.03 s/M for the monoglutamate and 0.71 s/M for the pentaglutatmate substrates
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
100.2% activity of mutant R653Q after heating at 42°C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate
additional information
102% activity of wild type enzyme after heating at 42°C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate
additional information
57.4% activity of mutant R653Q, without adding of any cofactor, after heating at 42°C for 90 min, in 7.5% glycerol
additional information
72.3% activity of wild type enzyme, without adding of any cofactor, after heating at 42°C for 90 min, in 7.5% glycerol
additional information
80.5% activity of mutant R653Q after heating at 42°C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP
additional information
88.2% activity of wild type enzyme after heating at 42°C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP
additional information
enzyme knock-out cells are transfected with either wild type or R653Q mutant and their ability to synthesize purines is assessed by a 14C-formate incorporation assay, the cells expressing the R653Q variant incorporate only 74% of wild-type levels of formate into DNA, the R653Q protein appears to have a significant impact on cellular nucleotide metabolism
additional information
-
overexpression of MTHFD1L in HEK-292 cells stimulates colony formation indicating that expression of this gene confers a growth advantage
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
OSCC cell. The p53 pathway might contribute to the abnormal expression of MTHFD1L in OSCC
additional information
2fold increased expression of gene DKFZp586G1517 compared to normal colon tissue
additional information
MTHFD1L levels are higher in tumor tissue than in adjacent tissues, RNA analysis and immunohistochemic analysis, overview
additional information
MTHFD1L overexpression is present in solid cancers including esophageal cancer, stomach adenocarcinoma, bladder cancer, lung adenocarcinoma, breast cancer, colon adenocarcinoma, kidney renal cell carcinoma, and prostate adenocarcinoma
additional information
-
the cytoplasmatic MTHFD1 is ubiquitously expressed in all mammalian cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
mitochondrial isozyme, contains an N-terminal mitochondrial targeting sequence
MTHFD1L is a mitochondrial monofunctional enzyme with 10-CHO-THF synthase activity
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mitochondrial C1-THF synthase behaves as a peripheral membrane protein, tightly associated with the matrix side of the mitochondrial inner membrane
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the folate cycle is an important metabolic pathway that fulfills a number of cancer-specific nutrient demands. Folate (folic acid), or vitamin B9, is commonly found in Western diets and dietary supplements. A 1-carbon (1C) unit from serine is transferred to tetrahydrofolate (THF) by serine hydroxymethyl transferases (SHMTs) to form 5,10-methylenetetrahydrofolate (CH2-THF). The 1C unit is then transferred from one position of THF to another, thus creating the folate cycle. The folate cycle is composed of the cytoplasmic and mitochondrial compartments. The cytoplasmic compartment is carried out by methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), while the mitochondrial compartment is carried out by MTHFD2/2L and methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L). MTHFD1 is a cytoplasmic trifunctional enzyme with CH2-THF dehydrogenase (EC 1.5.1.5), 5,10-methenyl-tetrahydrofolate (CH+-THF, EC 3.5.4.9) cyclohydrolase, and 10-formyl-tetrahydrofolate (10-CHO-THF, EC 6.3.4.3) synthase activities
physiological function
malfunction
knockdown of MTHFD1L impedes hepatocellular carcinoma (HCC) proliferation through induction of oxidative stress and ROS-associated cell cycle delay. In the MTHFD1L-knockdown HCC cells, the levels of TCA cycle metabolic intermediates derived from pyruvate/acetyl-CoA, including citrate, cis-aconitate, and isocitrate, decrease
malfunction
knockdown of MTHFD1L suppresses cell proliferation, colony formation, and tumorigenesis, while it induces apoptosis in oral squamous cell carcinoma (OSCC). Mechanistically, a microarray analysis shows that MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. the suppression of MTHFD1L affects c-MYC expression and thereby inhibits tumor cell proliferation and induces apoptosis. MTHFD1L knockdown may affect JUN expression through MAGED and induce cell apoptosis of the tumor.
malfunction
the elevation of oxidative stress through MTHFD1L knockdown or the use of methotrexate, an antifolate drug, sensitizes cancer cells to sorafenib, a targeted therapy for hepatocellular carcinoma
physiological function
the folate cycle, through transfer of a carbon unit between tetrahydrofolate and its derivatives in the cytoplasmic and mitochondrial compartments, produces other metabolites that are essential for cell growth, including nucleotides, methionine, and the antioxidant NADPH. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is the enzyme catalyzing the last step of the mitochondrial compartment generating formate, which subsequently can enter the cytoplasmic compartment. MTHFD1L plays critical roles in folate cycle maintenance and in support of cancer growth. MTHFD1L is transcriptionally activated by NRF2, a master regulator of redox homeostasis. MTHFD1L overexpression is closely associated with aggressive clinicopathological features of hepatocellular carcinoma (HCC) including the presence of tumor microsatellite formation, venous invasion, and more advanced tumor stages. MTHFD1L increased NADPH/NADP+ levels and reduced reactive oxygen species (ROS)
physiological function
the NAD-dependent methylenetetrahydrofolate dehydrogenase catalyzes the conversion of 10-formyltetrahydrofolate to formate in embryonic and adult mammalian mitochondria. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a folate cycle enzyme that is involved in the development of various diseases including cancer. Immunohistochemical staining and Kaplan-Meier survival analysis indicate that MTHFD1L upregulation is associated with a poor prognosis in oral squamous cell carcinoma (OSCC). MTHFD1L contributes to the production of NADPH, which is sufficient in combating oxidative stress in OSCC. MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. MTHFD1L directly interacts with the MAGE family member D1 (MAGED). MAGED enhances the phosphorylation of the JUN activator protein 1 (AP-1) transcription factor subunit and activates JUN. Regulation mechanism, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). C1TM_HUMAN
978
0
105790
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
107000
-
recombinant mitochondrial C1-THF synthase without the presequence but with the V5 epitope tag, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R653Q
additional information
R653Q
amino position 653 is located within the 10-formyltetrahydrofolate synthetase domain of the MTHFD1 protein affecting the supply of 10-formyltetrahydrofolate required for purine synthesis
R653Q
mutant enzyme has normal substrate affinity but a 36% reduction in half-life at 42°C, the mutation reduces the metabolic activity of MTHFD1 within cells: formate incorporation into DNA in murine Mthfd1 knockout cells transfected with Arg653Gln is reduced by 26%, compared to cells transfected with wild-type protein, the mutant may increase the risk for neural tube defects, under ideal storage and standard assay conditions, the synthetase activity of MTHFD1 is unaffected by the R653Q mutation
additional information
MTHFD1L-knockdown in cells is established by shRNA. Knockdown of MTHFD1L causes cell cycle delay
additional information
short hairpin RNA (shRNA)-induced MTHFD1L silencing, analysis of the effcets on the biological behavior of OSCC cells are assessed in vitro and in vivo, overview. Knockdown of MTHFD1L suppresses cell proliferation, colony formation, and tumorigenesis, while it induces apoptosis in oral squamous cell carcinoma (OSCC). Mechanistically, a microarray analysis shows that MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN
additional information
-
the recombinant protein product (short isoform) of the alternatively spliced short transcript of the mitochondrial isozyme is not enzymatically active
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
thermolability is reduced by magnesium adenosine triphosphate and eliminated by the substrate analog folate pentaglutamate, suggesting that folate status may modulate impact of the variant R653Q
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme is partially purified from HEK-293 cells by subcellular fractionation
recombinant maltose-binding protein fusion mitochondrial isozyme from Escherichia coli by metal affinity chromatography and gel filtration, the MBP-tag is cleaved off by TEV protease
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene DKFZp586G1517, DNA and amino acid sequence determination and analysis, overexpression of mitochondrial enzyme in HEK-293 cells, unlabeled or FLAG-tagged, stimulates cell growth
expression in Escherichia coli, localization of the interdomain region of the trifunctional enzyme by site-directed mutagenesis
-
expression of the mitochondrial isozyme as maltose-binding protein fusion protein in Escherichia coli, overexpression in yeast
-
the wild type and R653Q mutant pBKeDCS constructs are transformed into Escherichia coli BL21 DE3 to express the full-length protein
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
MTHFD1L is transcriptionally activated by NRF2, a master regulator of redox homeostasis. MTHFD1L is a transcription target of nuclear factor (erythroid-derived 2)-like 2 (NRF2), a transcription factor that acts as the central regulator for redox homeostasis. NRF2 expression is tightly regulated by kelch-like ECH-associated protein 1 (KEAP1), a negative regulator that targets NRF2 for proteosomal degradation
the expression of MTHFD1L is significantly affected by the mTORC1-4EBP1-eIF4E axis
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
MTHFD1L overexpression is closely associated with aggressive clinicopathological features of hepatocellular carcinoma (HCC) including the presence of tumor microsatellite formation, venous invasion, and more advanced tumor stages. The enzyme MTHFD1L is a potential target in cancer therapy. Inhibition of the folate cycle sensitizes HCC cells to sorafenib treatment in vitro and in vivo
medicine
MTHFD1L may be involved in OSCC progression via the c-MYC gene and p53 signaling and may serve as a target and orientation for tumor therapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schegg, K.M.; Welch jr., W.
The effect of nordihydroguaiaretic acid and related lignans on formyltetrahydrofolate synthetase and carboxylesterase
Biochim. Biophys. Acta
788
167-180
1984
Bos taurus, Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus
Buttlaire, D.H.
Purification and properties of formyltetrahydrofolate synthetase
Methods Enzymol.
66
585-599
1980
Clostridium acidi-urici, Clostridium cylindrosporum, Escherichia coli, Gallus gallus, Homo sapiens, Micrococcus aerogenes, Moorella thermoacetica, Neurospora crassa, Oryctolagus cuniculus, Ovis aries, Pigeon, Pisum sativum, Priestia megaterium, Proteus vulgaris, Saccharomyces cerevisiae, Spinacia oleracea, Veillonella parvula
Hum, D.W.; MacKenzie, R.E.
Expression of active domains of a human folate-dependent trifunctional enzyme in Escherichia coli
Protein Eng.
4
493-500
1991
Homo sapiens
Hol, F.A.; van der Put, N.M.; Geurds, M.P.; Heil, S.G.; Trijbels, F.J.; Hamel, B.C.; Mariman, E.C.; Blom, H.J.
Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects
Clin. Genet.
53
119-125
1998
Homo sapiens
Prasannan, P.; Pike, S.; Peng, K.; Shane, B.; Appling, D.R.
Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls
J. Biol. Chem.
278
43178-43187
2003
Homo sapiens (Q6UB35), Homo sapiens
Walkup, A.S.; Appling, D.R.
Enzymatic characterization of human mitochondrial C1-tetrahydrofolate synthase
Arch. Biochem. Biophys.
442
196-205
2005
Homo sapiens
Sugiura, T.; Nagano, Y.; Inoue, T.; Hirotani, K.
A novel mitochondrial C1-tetrahydrofolate synthetase is upregulated in human colon adenocarcinoma
Biochem. Biophys. Res. Commun.
315
204-211
2004
Homo sapiens (Q6UB35), Homo sapiens
Parle-McDermott, A.; Kirke, P.N.; Mills, J.L.; Molloy, A.M.; Cox, C.; OLeary, V.B.; Pangilinan, F.; Conley, M.; Cleary, L.; Brody, L.C.; Scott, J.M.
Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population
Eur. J. Hum. Genet.
14
768-772
2006
Homo sapiens (P11586)
Prasannan, P.; Appling, D.R.
Human mitochondrial C(1)-tetrahydrofolate synthase: Submitochondrial localization of the full-length enzyme and characterization of a short isoform
Arch. Biochem. Biophys.
481
86-93
2008
Homo sapiens, Rattus norvegicus
Slopien, R.; Jasniewicz, K.; Meczekalski, B.; Warenik-Szymankiewicz, A.; Lianeri, M.; Jagodzinski, P.P.
Polymorphic variants of genes encoding MTHFR, MTR, and MTHFD1 and the risk of depression in postmenopausal women in Poland
Maturitas
61
252-255
2008
Homo sapiens
Christensen, K.E.; Rohlicek, C.V.; Andelfinger, G.U.; Michaud, J.; Bigras, J.L.; Richter, A.; Mackenzie, R.E.; Rozen, R.
The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects
Hum. Mutat.
30
212-220
2009
Homo sapiens (P11586)
Christensen, K.E.; Mackenzie, R.E.
Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases
Vitam. Horm.
79
393-410
2008
Homo sapiens, Saccharomyces cerevisiae (P07245), Saccharomyces cerevisiae (P09440)
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