MTHFD1

MTHFD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A4I, 1DIA, 1DIB, 1DIG
Identifiers
Aliases	MTHFD1, MTHFC, MTHFD, C1-THF-Synthase, methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1, CIMAH
External IDs	OMIM: 172460; MGI: 1342005; HomoloGene: 55940; GeneCards: MTHFD1; OMA:MTHFD1 - orthologs
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 C3 Start 76,302,072 bp End 76,366,577 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver gastrocnemius muscle Achilles tendon adipose tissue ganglionic eminence subcutaneous adipose tissue caudate nucleus nucleus accumbens right coronary artery kidney Top expressed in Paneth cell primitive streak right lobe of liver left lobe of liver right kidney epiblast Epithelium of choroid plexus human kidney left lung right lung lobe More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding methylenetetrahydrofolate dehydrogenase (NADP+) activity methylenetetrahydrofolate dehydrogenase (NAD+) activity ligase activity methylenetetrahydrofolate dehydrogenase [NAD(P)+ activity] catalytic activity oxidoreductase activity ATP binding hydrolase activity protein binding formate-tetrahydrofolate ligase activity methenyltetrahydrofolate cyclohydrolase activity Cellular component membrane mitochondrion extracellular exosome cytoplasm cytosol Biological process purine nucleotide biosynthetic process transsulfuration neutrophil homeostasis one-carbon metabolic process serine family amino acid metabolic process embryonic neurocranium morphogenesis tetrahydrofolate interconversion histidine biosynthetic process cellular amino acid biosynthetic process somite development serine family amino acid biosynthetic process methionine biosynthetic process heart development methionine metabolic process neural tube closure folic acid metabolic process embryonic viscerocranium morphogenesis metabolism purine nucleobase biosynthetic process 10-formyltetrahydrofolate biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4522 108156 Ensembl n/a ENSMUSG00000021048 UniProt P11586 Q922D8 RefSeq (mRNA) NM_005956 NM_001364837 NM_138745 RefSeq (protein) NP_005947 NP_001351766 NP_620084 Location (UCSC) n/a Chr 12: 76.3 – 76.37 Mb PubMed search
Wikidata
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C-1-tetrahydrofolate synthase, cytoplasmic also known as C1-THF synthase is an enzyme that in humans is encoded by the MTHFD1 (methylenetetrahydrofolate dehydrogenase 1) gene.

Function

This gene encodes a protein that possesses three distinct enzymatic activities, methylenetetrahydrofolate dehydrogenase (1.5.1.5), methenyltetrahydrofolate cyclohydrolase (3.5.4.9) and formate–tetrahydrofolate ligase (6.3.4.3). 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. doi:10.1073/pnas.87.8.2916. PMC 53804. PMID 2183217.
• Peri KG, Belanger C, Mackenzie RE (1989). "Nucleotide sequence of the human NAD-dependent methylene tetrahydrofolate dehydrogenase-cyclohydrolase". Nucleic Acids Res. 17 (21): 8853. doi:10.1093/nar/17.21.8853. PMC 335047. PMID 2587219.
• MacKenzie RE, Mejia N, Yang XM (1989). "Methylenetetrahydrofolate dehydrogenases in normal and transformed mammalian cells". Adv. Enzyme Regul. 27: 31–9. doi:10.1016/0065-2571(88)90007-6. PMID 3074630.
• 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. doi:10.1016/S0969-2126(98)00019-7. PMID 9519408.
• 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. doi:10.1111/j.1399-0004.1998.tb02658.x. PMID 9611072.
• 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. doi:10.1021/bi992734y. PMID 10828945.
• 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. doi:10.1086/344213. PMC 385099. PMID 12384833.
• 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. PMC 139241. PMID 12477932.
• 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.
• 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. PMC 528928. PMID 15489334.
• 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.
• 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.
• 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. PMC 1276051. PMID 16236726.
• 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.
• 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. doi:10.1007/bf03347376. PMID 17114913.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.