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MGP004778

UniProt Annotations

Entry Information
Gene Namemethylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like
Protein EntryC1TM_HUMAN
UniProt IDQ6UB35
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q6UB35-1; Sequence=Displayed; Name=2; IsoId=Q6UB35-2; Sequence=VSP_034565, VSP_034566;
Biophysicochemical PropertiesKinetic parameters: KM=500 uM for THF monoglutamate {ECO:0000269|PubMed:16171773}; KM=16 uM for THF triglutamate {ECO:0000269|PubMed:16171773}; KM=3.6 uM for THF pentaglutamate {ECO:0000269|PubMed:16171773};
Catalytic ActivityATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
CautionThis enzyme lacks methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) and 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, was found in developing tissues only. {ECO:0000305}.
CautionWas originally thought to be a trifunctional enzyme but only a formyltetrahydrofolate synthetase activity was detected and not a dehydrogenase/cyclohydrogenase activity. {ECO:0000305|PubMed:12937168}.
DomainThis monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain.
FunctionMay provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2. {ECO:0000250}.
InteractionP49662:CASP4; NbExp=1; IntAct=EBI-1046835, EBI-1057327; Q9Y5V3:MAGED1; NbExp=1; IntAct=EBI-1046835, EBI-716006; Q9P2S5:WDR8; NbExp=1; IntAct=EBI-1046835, EBI-1054904;
MiscellaneousMay participate in the progression of colorectal cancer by conferring growth advantage. Could be a new molecular target for cancer therapy.
PathwayOne-carbon metabolism; tetrahydrofolate interconversion.
Sequence CautionSequence=AAH08629.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB15009.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityIn the C-terminal section; belongs to the formate-- tetrahydrofolate ligase family. {ECO:0000305}.
SimilarityIn the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. {ECO:0000305}.
Subcellular LocationMitochondrion {ECO:0000269|PubMed:12937168}.
SubunitHomodimer. {ECO:0000269|PubMed:16171773}.
Tissue SpecificityDetected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma. {ECO:0000269|PubMed:12937168, ECO:0000269|PubMed:15013446}.
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