1.5.1.15: methylenetetrahydrofolate dehydrogenase (NAD+)

This is an abbreviated version!
For detailed information about methylenetetrahydrofolate dehydrogenase (NAD+), go to the full flat file.

Reaction

Synonyms

5,10-CH2-THF dehydrogenase, 5,10-methylenetetrahydrofolate reductase, bifunctional N5,N10-methylene-H4F dehydrogenase/N5,N10-methenyltetrahydrofolate cyclohydrolase, FolD, methenyltetrahydrofolate cyclohydrolase, methylenetetrahydrofolate dehydrogenase (NAD+-dependent), methylenetetrahydrofolate dehydrogenase-cyclohydrolase, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase, methylenetetrahydrofolate dehydrogenase/cyclohydrolase, methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase, methylenetetrahydrofolate reductase, methyleneTHF dehydrogenase, Mg2+-/phosphate-dependent dehydrogenase, Mg2+/NAD-dependent methylenetetrahydrofolate dehydrogenase, More, MSMEG_6596, MSMEG_6649, MTD, MTHFD2, MTHFD2L, MTHFR, MTHFR1, MTHFR2, NAD+-dependent methylene-H4F dehydrogenase, NAD-dependent dehydrogenase-cyclohydrolase, NADH-oxidizing methylenetetrahydrofolate reductase, NMDMC

ECTree

     1 Oxidoreductases

         1.5 Acting on the CH-NH group of donors

             1.5.1 With NAD⁺ or NADP⁺ as acceptor

                1.5.1.15 methylenetetrahydrofolate dehydrogenase (NAD+)

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Results	in table
9	Activating Compound
43	AA Sequence
6	Application
1	CAS Registry Number
21	Cloned(Commentary)
49	Cofactor
3	Crystallization (Commentary)
20595	Disease/ Diagnostics
1	Expression
10	General Information
1	General Stability
7	Inhibitors
13	kcat/KM [mM/s]
7	Ki Value [mM]
63	KM Value [mM]
59	Localization
21	Metals/Ions
28	Molecular Weight [Da]
149	Natural Substrates/ Products (Substrates)
100	Organism
1	Oxidation Stability
3	Pathway
23	PDB ID
4	pH Optimum
1	pH Range
1	pH Stability
24	Protein Variants
23	Purification (Commentary)
2	Reaction
3	Reaction Type
86	Reference
79	Source Tissue
101	Specific Activity [micromol/min/mg]
3	Storage Stability
183	Substrates and Products (Substrate)
28	Subunits
59	Synonyms
1	Systematic Name
4	Temperature Optimum [°C]
1	Temperature Stability [°C]
21	Turnover Number [1/s]

Reference

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Reference on EC 1.5.1.15 - methylenetetrahydrofolate dehydrogenase (NAD+)

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REF.

AUTHORS

TITLE

JOURNAL

VOL.

PAGES

YEAR

ORGANISM (UNIPROT)

PUBMED ID

SOURCE

392075

Moore, M.R.; O'Brien, W.E.; Ljungdahl, L.G.

Purification and characterisation of nicotinamide adenine dinucleotide-dependent methylenetetrahydrofolate dehydrogenase from Clostridium formicoaceticum

J. Biol. Chem.

249

5250-5253

1974

Saccharomyces cerevisiae, Gottschalkia acidurici, Clostridium formicaceticum, Mus musculus

4153026

brenda

392076

Ragsdale, S.W.; Ljungdahl, L.G.

Purification and properties of NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from Acetobacterium woodii

J. Biol. Chem.

259

3499-3503

1984

Acetobacterium woodii, Saccharomyces cerevisiae, Clostridium formicaceticum, Mus musculus

6608524

brenda

392077

Mejia, N.; Mackenzie, R.E.

NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells

J. Biol. Chem.

260

14616-14620

1985

Cricetulus griseus, Cricetus cricetus, Homo sapiens, Mesocricetus auratus, Mus musculus, Rattus norvegicus

3877056

brenda

392078

Mejia, N.; Rios-Orlandi, E.M.; Mackenzie, R.E.

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells. Purification and properties

J. Biol. Chem.

261

9509-9513

1986

Acetobacterium woodii, Clostridium formicaceticum, Mus musculus

3487546

brenda

392079

Mackenzie, R.E.; Mejia, N.; Yang, X.M.

Methylenetetrahydrofolate dehydrogenases in normal and transformed mammalian cells

Adv. Enzyme Regul.

27

31-39

1988

Saccharomyces cerevisiae, Homo sapiens, Mus musculus

3074630

brenda

392080

Mejia, N.; Mackenzie, R.E.

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase in transformed cells is a mitochondrial enzyme

Biochem. Biophys. Res. Commun.

155

1-6

1988

Mus musculus

3261979

brenda

392081

Rios-Orlandi, E.M.; Mackenzie, R.E.

The activities of the NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells are kinetically independent

J. Biol. Chem.

263

4662-4667

1988

Mus musculus

3258307

brenda

392082

Belanger, C.; Mackenzie, R.E.

Isolation and characterization of cDNA clones encoding the murine NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase

J. Biol. Chem.

264

4837-4843

1989

Mus musculus

2647744

brenda

392083

Barlowe, C.K.; Appling, D.R.

Isolation and characterization of a novel eukaryotic monofunctional NAD+-dependent 5,10-methylenetetrahydrofolate dehydrogenase

Biochemistry

29

7089-7094

1990

Acetobacterium woodii, Saccharomyces cerevisiae, Clostridium formicaceticum, Homo sapiens, Rattus norvegicus, Saccharomyces cerevisiae KSY8

2223762

brenda

392084

Smith, G.K.; Banks, S.D.; Monaco, T.J.; Rigual, R.; Duch, D.S.; Mullin, R.J.; Huber, B.E.

Activity of an NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase in normal tissue, neoplastic cells, and oncogene-transformed cells

Arch. Biochem. Biophys.

283

367-371

1990

Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Fischer

2275549

brenda

392085

Peri, K.G.; Mackenzie, R.E.

NAD(+)-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase: detection of the mRNA in normal murine tissues and transcriptional regulation of the gene in cell lines

Biochim. Biophys. Acta

1171

281-287

1993

Homo sapiens, Mus musculus, Rattus norvegicus

8424951

brenda

392086

Price, B.D.; Laughon, A.

The isolation and characterization of a Drosophila gene encoding a putative NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase

Biochim. Biophys. Acta

1173

94-98

1993

Drosophila melanogaster, Homo sapiens, Mus musculus

8485162

brenda

392087

Yang, X.M.; Mackenzie, R.E.

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is the mammalian homolog of the mitochondrial enzyme encoded by the yeast MIS1 gene

Biochemistry

32

11118-11123

1993

Saccharomyces cerevisiae, Homo sapiens, Mus musculus

8218174

brenda

392088

Tremblay, G.B.; Sohi, S.S.; Retnakaran, A.; Mackenzie, R.E.

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is targeted to the cytoplasm in insect cell lines

FEBS Lett.

368

177-182

1995

Antheraea eucalypti, Choristoneura fumiferana, Drosophila melanogaster, Homo sapiens, Malacosoma disstria, Mus musculus, Spodoptera frugiperda

7615077

brenda

392089

Monzingo, A.F.; West, M.G.; Schelp, E.; Appling, D.R.; Robertus, J.D.

Crystallization of the NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from Saccharomyces cerevisiae

Proteins

26

481-482

1996

Acetobacterium woodii, Saccharomyces cerevisiae

8990502

brenda

392090

Appling, D.R.; West, M.G.

Monofunctional NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from Saccharomyces cerevisiae

Methods Enzymol.

281

178-188

1997

Acetobacterium woodii, Saccharomyces cerevisiae, Clostridium formicaceticum, Drosophila melanogaster, Homo sapiens, Mus musculus

9250982

brenda

392091

Mackenzie, R.E.

Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase

Methods Enzymol.

281

171-177

1997

Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae, Spodoptera frugiperda

9250981

brenda

392092

Di Pietro, E.; Sirois, J.; Trenblay, M.L.; Mackenzie, R.E.

Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is essential for embryonic development

Mol. Cell. Biol.

22

4158-4166

2002

Saccharomyces cerevisiae, Cricetulus griseus, Mus musculus

12024029

brenda

392093

Patel, H.; Christensen, K.E.; Mejia, N.; Mackenzie, R.E.

Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase

Arch. Biochem. Biophys.

403

145-148

2002

Drosophila melanogaster, Homo sapiens, Mus musculus

12061812

brenda

654447

Takeya, C.; Esumi, M.; Shiroishi, T.; Hishida, R.; Yamamoto, T.

Multiple single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase and its truncated pseudogene of 23 inbred strains of mice

Biochem. Biophys. Res. Commun.

312

480-486

2003

Mus musculus (Q9WU20), Mus musculus

14637162

brenda

654885

Di Pietro, E.; Wang, X.L.; MacKenzie, R.E.

The expression of mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase supports a role in rapid cell growth

Biochim. Biophys. Acta

1674

78-84

2004

Mus musculus (P18155)

15342116

brenda

655183

Saffroy, R.; Pham, P.; Chiappini, F.; Gross-Goupil, M.; Castera, L.; Azoulay, D.; Barrier, A.; Samuel, D.; Debuire, B.; Lemoine, A.

The MTHFR 677C > T polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis

Carcinogenesis

25

1443-1448

2004

Homo sapiens

15033905

brenda

656129

Patel, H.; Pietro, E.D.; MacKenzie, R.E.

Mammalian fibroblasts lacking mitochondrial NAD+-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase are glycine auxotrophs

J. Biol. Chem.

278

19436-19441

2003

Mus musculus

12646567

brenda

671588

Patel, H.; Di Pietro, E.; Mejia, N.; MacKenzie, R.E.

NAD- and NADP-dependent mitochondrially targeted methylenetetrahydrofolate dehydrogenase-cyclohydrolases can rescue mthfd2 null fibroblasts

Arch. Biochem. Biophys.

442

133-139

2005

Mus musculus

16150419

brenda

674480

Christensen, K.E.; Mirza, I.A.; Berghuis, A.M.; Mackenzie, R.E.

Magnesium and phosphate ions enable NAD binding to methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase

J. Biol. Chem.

280

34316-34323

2005

Homo sapiens (P13995), Homo sapiens

16100107

brenda

726831

Buchenau, B.; Thauer, R.K.

Tetrahydrofolate-specific enzymes in Methanosarcina barkeri and growth dependence of this methanogenic archaeon on folic acid or p-aminobenzoic acid

Arch. Microbiol.

182

313-325

2004

Methanosarcina barkeri (Q46A53), Methanosarcina barkeri DSM 804 (Q46A53)

15349715

brenda

756334

Shin, M.; Momb, J.; Appling, D.R.

Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase

Cancer Metab.

5

11

2017

Homo sapiens (P13995), Homo sapiens (Q9H903)

29225823

brenda

756337

Gustafsson, R.; Jemth, A.S.; Gustafsson, N.M.; Faernegardh, K.; Loseva, O.; Wiita, E.; Bonagas, N.; Dahllund, L.; Llona-Minguez, S.; Haeggblad, M.; Henriksson, M.; Andersson, Y.; Homan, E.; Helleday, T.; Stenmark, P.

Crystal structure of the emerging cancer target MTHFD2 in complex with a substrate-based inhibitor

Cancer Res.

77

937-948

2017

Homo sapiens (P13995)

27899380

brenda

757773

Hitzel, J.; Lee, E.; Zhang, Y.; Bibli, S.I.; Li, X.; Zukunft, S.; Pflueger, B.; Hu, J.; Schuermann, C.; Vasconez, A.E.; Oo, J.A.; Kratzer, A.; Kumar, S.; Rezende, F.; Josipovic, I.; Thomas, D.; Giral, H.; Schreiber, Y.; Geisslinger, G.; Fork, C.; Yang, X.; Sigala, F.; Romanoski, C.E.; Kroll, J.; Jo, H.; Lan, L.a.n.d.

Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells

Nat. Commun.

9

2292

2018

Homo sapiens (P13995)

29895827

brenda

760434

Zuo, C.; Jolly, A.L.; Nikolova, A.P.; Satzer, D.I.; Cao, S.; Sanchez, J.S.; Ballou, D.P.; Trimmer, E.E.

A role for glutamine 183 in the folate oxidative half-reaction of methylenetetrahydrofolate reductase from Escherichia coli

Arch. Biochem. Biophys.

642

63-74

2018

Escherichia coli

29407039

brenda

765009

Sah, S.; Lahry, K.; Talwar, C.; Singh, S.; Varshney, U.

Monomeric NADH-oxidizing methylenetetrahydrofolate reductases from Mycobacterium smegmatis lack flavin coenzyme

J. Bacteriol.

202

e00709-19

2020

no activity by Mycobacterium smegmatis MSMEG_6664, no activity by Mycobacterium smegmatis MSMEI_6484, Mycolicibacterium smegmatis (A0R6M0), Mycolicibacterium smegmatis (A0R6S0), Mycolicibacterium smegmatis, Mycolicibacterium smegmatis ATCC 700084 (A0R6M0), Mycolicibacterium smegmatis ATCC 700084 (A0R6S0)

32253341

brenda

765840

Yue, L.; Pei, Y.; Zhong, L.; Yang, H.; Wang, Y.; Zhang, W.; Chen, N.; Zhu, Q.; Gao, J.; Zhi, M.; Wen, B.; Zhang, S.; Xiang, J.; Wei, Q.; Liang, H.; Cao, S.; Lou, H.; Chen, Z.; Han, J.

Mthfd2 modulates mitochondrial function and DNA repair to maintain the pluripotency of mouse stem cells

Stem Cell Reports

15

529-545

2020

Mus musculus (P18155), Mus musculus

32679066

brenda

Entries 1 - 20 of 32

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