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monofunctional C1-tetrahydrofolate synthase, mitochondrial (formyltetrahydrofolate synthetase, MTHFD1L, FTHFSDC1)
Function:
- may provide missing metabolic reaction required to link the mitochondria & the cytoplasm in mammalian model of one-carbon folate metabolism in embryonic & transformed cells complementing enzymatic activities of MTHFD2
- one-carbon metabolism; tetrahydrofolate pathway
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
Kinetic parameters: KM=500 uM for THF monoglutamate KM=16 uM for THF triglutamate KM=3.6 uM for THF pentaglutamate
Structure:
- homodimer
- two major domains:
a) N-terminal inactive methylene-THF dehydrogenase & cyclohydrolase domain
b) active larger formyl-THF synthetase C-terminal domain
- tetrahydrofolate dehydrogenase/cyclohydrolase family tetrahydrofolate ligase family
Compartment: mitochondria
Alternative splicing: named isoforms=2
Expression:
- detected in most tissues
- highest expression found in placenta, thymus & brain
- low expression in liver & skeletal muscle
Pathology:
- up-regulated in colon adenocarcinoma
- may participate in the progression of colorectal cancer by conferring growth advantage
- polymorphism associated with late onset Alzheimer's disease ? [2]
Note:
- lacks methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) & ethenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activities
- an enzyme performing these two complementary activities has not been found in adult mitochondrial tissues
- MTHFD2, which performs these two activities, is found in developing tissues only
General
ligase or synthetase
mitochondrial protein
Properties
SIZE: entity length = 978 aa
MW = 106 kD
COMPARTMENT: mitochondria
MOTIF: Methylenetetrahydrofolate dehydrogenase & cyclohydrolase {31-348}
MOTIF: glycine-rich region {34-42}
Formyltetrahydrofolate synthetase {349-978}
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 423-430
Database Correlations
UniProt Q6UB35
PFAM correlations
Kegg hsa:2590
ENZYME 6.3.4.3
References
- UniProt :accession Q6UB35
- Yahoo News
http://news.yahoo.com/s/hsn/20100415/hl_hsn/newalzheimersgeneidentified