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Information on EC 6.3.4.3 - formate-tetrahydrofolate ligase and Organism(s) Mus musculus and UniProt Accession Q922D8

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EC Tree
     6 Ligases
         6.3 Forming carbon-nitrogen bonds
             6.3.4 Other carbon-nitrogen ligases
                6.3.4.3 formate-tetrahydrofolate ligase
IUBMB 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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This record set is specific for:
Mus musculus
UNIPROT: Q922D8
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The taxonomic range for the selected organisms is: Mus musculus
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, formate-tetrahydrofolate ligase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10-Formyltetrahydrofolate synthetase
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10-formylTHF synthetase
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Formyltetrahydrofolate synthetase
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methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase enzyme
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10-Formyltetrahydrofolate synthetase
FHS
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formate-tetrahydrofolate ligase
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formate:tetrahydrofolate ligase (ADP-forming)
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Formyl-THF synthetase
Formyltetrahydrofolate synthetase
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FTHFS
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-
-
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MTHFD1
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Synthetase, formyl tetrahydrofolate
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Tetrahydrofolate formylase
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Tetrahydrofolic formylase
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THFS
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
formylation
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-
-
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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 hide
9023-66-9
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
additional information
?
-
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MTHFD1 is a cytoplasmic enzyme with 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, and 10-formyltetrahydrofolate synthetase activities
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
flow of one-carbon units through cytoplasmic and mitochondrial folate pathways, overview
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r
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
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-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Heminordihydroguaiaretic acid
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nordihydroguaiaretic acid
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Norisoguaiacin
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
mitochondrial isozyme activity in different cell lines, overview
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
DCS, complete gene and exon 27; gene mthfd1 encodes the cytosolic isozyme which is a trifunctional methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase enzyme DCS, a mitochondrial monofunctional 10-formyltetrahydrofolate synthetase isozyme is encoded by a different gene
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the MTHFD1L transcript is detected at all stages of mouse embryogenesis examined. MTHFD1L is expressed ubiquitously throughout the embryo but with localized regions of higher expression. The spatial pattern of MTHFD1L expression is virtually indistinguishable from that of MTHFD2 and cytoplasmic C1-THF synthase MTHFD1 in embryonic day 9.5 mouse embryos
Manually annotated by BRENDA team
embryonic fibroblast cell line
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
additional information
isozyme expression analysis and growth rates of cell lines, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
trifunctional cytosolic isozyme
Manually annotated by BRENDA team
mitochondrial monofunctional isozyme
Manually annotated by BRENDA team
MTHFD1L enzyme is present in mitochondria from normal embryonic tissues and embryonic fibroblast cell lines, and embryonic mitochondria possess the ability to synthesize formate from glycine. Greater than 75% of 1-C units entering the cytoplasmic methyl cycle are mitochondrially derived
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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complete loss of synthetase activity is incompatible with life. Embryos die shortly after 10.5 days gestation, and are developmentally delayed or abnormal. Female synthetase-deficient mice have decreased neutrophil counts during pregnancy and increased incidence of developmental defects in embryos. Synthetase deficiency may lead to pregnancy complications through decreased purine synthesis and reduced cellular proliferation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
C1TC_MOUSE
935
0
101200
Swiss-Prot
Mitochondrion (Reliability: 5)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K386E
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the mutation completely abrogates synthetase activity
R653Q
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the mutation reduces metabolic activity in cells by about 26%
additional information
construction of a DCS disruption knockout mutant fibroblast SF6 cell line lacking the cytoplasmic isozyme but expressing active mitochondrial isozyme from a disruption mutant embryonic stem cell line
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis
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
Manually annotated by BRENDA team
Christensen, K.E.; Patel, H.; Kuzmanov, U.; Mejia, N.R.; MacKenzie, R.E.
Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria
J. Biol. Chem.
280
7597-7602
2005
Mus musculus (Q922D8)
Manually annotated by BRENDA team
Pike, S.T.; Rajendra, R.; Artzt, K.; Appling, D.R.
Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos
J. Biol. Chem.
285
4612-4620
2010
Mus musculus (Q3V3R1), Mus musculus
Manually annotated by BRENDA team
Christensen, K.E.; Deng, L.; Leung, K.Y.; Arning, E.; Bottiglieri, T.; Malysheva, O.V.; Caudill, M.A.; Krupenko, N.I.; Greene, N.D.; Jerome-Majewska, L.; MacKenzie, R.E.; Rozen, R.
A novel mouse model for genetic variation in 10-formyltetrahydrofolate synthetase exhibits disturbed purine synthesis with impacts on pregnancy and embryonic development
Hum. Mol. Genet.
22
3705-3719
2013
Mus musculus
Manually annotated by BRENDA team