Search
C-1-tetrahydrofolate synthase, cytoplasmic; C1-THF synthase; includes: methylenetetrahydrofolate dehydrogenase; methenyltetrahydrofolate cyclohydrolase; formyltetrahydrofolate synthetase (MTHFD1, MTHFC, MTHFD)
Function:
- one-carbon metabolism; tetrahydrofolate interconversion
- trifunctional enzyme
5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH
5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate
ATP + formate + tetrahydrofolate = ADP +phosphate + 10-formyltetrahydrofolate
Structure:
- two major domains:
a) an N-terminal part containing the methylene-THF dehydrogenase & cyclohydrolase activities
b) a larger C-terminal part containing formyl-THF synthetase activity
- tetrahydrofolate dehydrogenase/cyclohydrolase family tetrahydrofolate ligase family
Compartment: cytoplasm
Expression: ubiquitous
Pathology:
- defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects
- genetic defects in MTHFD1 may affect the risk of spina bifida via the maternal rather than the embryonic genotype
- genetic variation in MTHFD1 could be associated with susceptibility to colorectal carcinoma
General
mitochondrial protein
N-methyltransferase
oxidoreductase
phosphoprotein
Properties
SIZE: entity length = 935 aa
MW = 102 kD
COMPARTMENT: cytoplasm
MOTIF: Methylenetetrahydrofolate dehydrogenase and cyclohydrolase {2-305}
MOTIF: alanine residue {2}
Substrate binding {52-56}
Substrate binding {99-101}
cofactor-binding site [172-174]
COFACTOR-BOUND: NADP
cofactor-binding site [197-197]
COFACTOR-BOUND: NADP
Substrate binding {272-276}
Formyltetrahydrofolate synthetase {306-935}
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 380-387
Thr phosphorylation site {T786}
Database Correlations
OMIM correlations
MORBIDMAP 172460
UniProt P11586
PFAM correlations
Entrez Gene 4522
Kegg hsa:4522
ENZYME correlations
References
UniProt :accession P11586