MTHFD1

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
File:PBB Protein MTHFD1 image.jpg PDB rendering based on 1a4i.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1a4i​, 1dia​, 1dib​, 1dig​
Identifiers
Symbols	MTHFD1 ; MTHFC; MTHFD
External IDs	Template:OMIM5 Template:MGI HomoloGene: 55940
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE MTHFD1 202309 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase, also known as MTHFD1, is a human gene.

This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain.

Further reading

• Schild D, Brake AJ, Kiefer MC; et al. (1990). "Cloning of three human multifunctional de novo purine biosynthetic genes by functional complementation of yeast mutations". Proc. Natl. Acad. Sci. U.S.A. 87 (8): 2916–20. PMID 2183217.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Peri KG, Belanger C, Mackenzie RE (1989). "Nucleotide sequence of the human NAD-dependent methylene tetrahydrofolate dehydrogenase-cyclohydrolase". Nucleic Acids Res. 17 (21): 8853. PMID 2587219.CS1 maint: Multiple names: authors list (link)
• Rozen R, Barton D, Du J; et al. (1989). "Chromosomal localization of the gene for the human trifunctional enzyme, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase". Am. J. Hum. Genet. 44 (6): 781–6. PMID 2786332.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hum DW, Bell AW, Rozen R, MacKenzie RE (1988). "Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase". J. Biol. Chem. 263 (31): 15946–50. PMID 3053686.CS1 maint: Multiple names: authors list (link)
• MacKenzie RE, Mejia N, Yang XM (1989). "Methylenetetrahydrofolate dehydrogenases in normal and transformed mammalian cells". Adv. Enzyme Regul. 27: 31–9. PMID 3074630.CS1 maint: Multiple names: authors list (link)
• Shannon KW, Rabinowitz JC (1986). "Purification and characterization of a mitochondrial isozyme of C1-tetrahydrofolate synthase from Saccharomyces cerevisiae". J. Biol. Chem. 261 (26): 12266–71. PMID 3528153.
• Mejia NR, MacKenzie RE (1985). "NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells". J. Biol. Chem. 260 (27): 14616–20. PMID 3877056.
• Allaire M, Li Y, MacKenzie RE, Cygler M (1998). "The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution". Structure. 6 (2): 173–82. PMID 9519408.CS1 maint: Multiple names: authors list (link)
• Hol FA, van der Put NM, Geurds MP; et al. (1998). "Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects". Clin. Genet. 53 (2): 119–25. PMID 9611072.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Schmidt A, Wu H, MacKenzie RE; et al. (2000). "Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase". Biochemistry. 39 (21): 6325–35. PMID 10828945.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Brody LC, Conley M, Cox C; et al. (2003). "A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group". Am. J. Hum. Genet. 71 (5): 1207–15. PMID 12384833.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gevaert K, Goethals M, Martens L; et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Parle-McDermott A, Mills JL, Kirke PN; et al. (2005). "MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae". Am. J. Med. Genet. A. 132 (4): 365–8. doi:10.1002/ajmg.a.30354. PMID 15633187.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Parle-McDermott A, Pangilinan F, Mills JL; et al. (2005). "A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss". Mol. Hum. Reprod. 11 (7): 477–80. doi:10.1093/molehr/gah204. PMID 16123074.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH (2005). "Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans". Proc. Natl. Acad. Sci. U.S.A. 102 (44): 16025–30. doi:10.1073/pnas.0504285102. PMID 16236726.CS1 maint: Multiple names: authors list (link)
• De Marco P, Merello E, Calevo MG; et al. (2006). "Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958G>A polymorphism for neural tube defect risk". J. Hum. Genet. 51 (2): 98–103. doi:10.1007/s10038-005-0329-6. PMID 16315005.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sun J, Xu Y, Zhu Y, Lu H (2007). "Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in Type 2 diabetes mellitus". J. Endocrinol. Invest. 29 (9): 814–20. PMID 17114913.CS1 maint: Multiple names: authors list (link)
• Ewing RM, Chu P, Elisma F; et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMID 17353931.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)