1. C-1-tetrahydrofolate synthase, cytoplasmic
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: P11586 
Gene: MTHFD1 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Akar N, Akar E, Ozel D, Deda G, Sipahi T: Common mutations at the homocysteine metabolism pathway and pediatric stroke. Thromb Res. 2001 Apr 15;102(2):115-20. Pubmed
- Walkup AS, Appling DR: Enzymatic characterization of human mitochondrial C1-tetrahydrofolate synthase. Arch Biochem Biophys. 2005 Oct 15;442(2):196-205. Epub 2005 Aug 30. Pubmed
- Matakidou A, El Galta R, Rudd MF, Webb EL, Bridle H, Eisen T, Houlston RS: Prognostic significance of folate metabolism polymorphisms for lung cancer. Br J Cancer. 2007 Jul 16;97(2):247-52. Epub 2007 May 29. Pubmed
- Salmassi TM, Leadbetter JR: Analysis of genes of tetrahydrofolate-dependent metabolism from cultivated spirochaetes and the gut community of the termite Zootermopsis angusticollis. Microbiology. 2003 Sep;149(Pt 9):2529-37. Pubmed
- Prasannan P, Pike S, Peng K, Shane B, Appling DR: Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls. J Biol Chem. 2003 Oct 31;278(44):43178-87. Epub 2003 Aug 22. Pubmed
2. Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: P13995 
Gene: MTHFD2 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Salmassi TM, Leadbetter JR: Analysis of genes of tetrahydrofolate-dependent metabolism from cultivated spirochaetes and the gut community of the termite Zootermopsis angusticollis. Microbiology. 2003 Sep;149(Pt 9):2529-37. Pubmed
3. Aminomethyltransferase, mitochondrial
Pharmacological action: unknown
Actions: cofactor
The glycine cleavage system catalyzes the degradation of glycine
Organism class: human
UniProt ID: P48728 
Gene: AMT 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
- Masai E, Sasaki M, Minakawa Y, Abe T, Sonoki T, Miyauchi K, Katayama Y, Fukuda M: A novel tetrahydrofolate-dependent O-demethylase gene is essential for growth of Sphingomonas paucimobilis SYK-6 with syringate. J Bacteriol. 2004 May;186(9):2757-65. Pubmed
4. AMT protein
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q96IG6 
Gene: AMT 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Lee HH, Kim DJ, Ahn HJ, Ha JY, Suh SW: Crystal structure of T-protein of the glycine cleavage system. Cofactor binding, insights into H-protein recognition, and molecular basis for understanding nonketotic hyperglycinemia. J Biol Chem. 2004 Nov 26;279(48):50514-23. Epub 2004 Sep 7. Pubmed
- Masai E, Sasaki M, Minakawa Y, Abe T, Sonoki T, Miyauchi K, Katayama Y, Fukuda M: A novel tetrahydrofolate-dependent O-demethylase gene is essential for growth of Sphingomonas paucimobilis SYK-6 with syringate. J Bacteriol. 2004 May;186(9):2757-65. Pubmed
- Scrutton NS, Leys D: Crystal structure of DMGO provides a prototype for a new tetrahydrofolate-binding fold. Biochem Soc Trans. 2005 Aug;33(Pt 4):776-9. Pubmed
- Gangjee A, Kurup S, Namjoshi O: Dihydrofolate reductase as a target for chemotherapy in parasites. Curr Pharm Des. 2007;13(6):609-39. Pubmed
5. 10-formyltetrahydrofolate dehydrogenase
Pharmacological action: unknown
Actions: cofactor
10-formyltetrahydrofolate + NADP(+) + H(2)O = tetrahydrofolate + CO(2) + NADPH
Organism class: human
UniProt ID: O75891 
Gene: ALDH1L1 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Fu TF, Maras B, Barra D, Schirch V: A noncatalytic tetrahydrofolate tight binding site is on the small domain of 10-formyltetrahydrofolate dehydrogenase. Arch Biochem Biophys. 1999 Jul 15;367(2):161-6. Pubmed
- Krupenko SA, Wagner C: Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 1999 Dec 10;274(50):35777-84. Pubmed
- Krupenko SA, Vlasov AP, Wagner C: On the role of conserved histidine 106 in 10-formyltetrahydrofolate dehydrogenase catalysis: connection between hydrolase and dehydrogenase mechanisms. J Biol Chem. 2001 Jun 29;276(26):24030-7. Epub 2001 Apr 24. Pubmed
- Anguera MC, Field MS, Perry C, Ghandour H, Chiang EP, Selhub J, Shane B, Stover PJ: Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2006 Jul 7;281(27):18335-42. Epub 2006 Apr 20. Pubmed
- Oleinik NV, Krupenko NI, Reuland SN, Krupenko SA: Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation. Biochem Pharmacol. 2006 Jul 14;72(2):256-66. Epub 2006 Apr 25. Pubmed
6. Methionine synthase
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q99707 
Gene: MTR 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Hall DA, Jordan-Starck TC, Loo RO, Ludwig ML, Matthews RG: Interaction of flavodoxin with cobalamin-dependent methionine synthase. Biochemistry. 2000 Sep 5;39(35):10711-9. Pubmed
- Fowler B: The folate cycle and disease in humans. Kidney Int Suppl. 2001 Feb;78:S221-9. Pubmed
- Fu TF, di Salvo M, Schirch V: Enzymatic determination of homocysteine in cell extracts. Anal Biochem. 2001 Mar;290(2):359-65. Pubmed
- Jarrett JT, Choi CY, Matthews RG: Changes in protonation associated with substrate binding and Cob(I)alamin formation in cobalamin-dependent methionine synthase. Biochemistry. 1997 Dec 16;36(50):15739-48. Pubmed
- Jarrett JT, Hoover DM, Ludwig ML, Matthews RG: The mechanism of adenosylmethionine-dependent activation of methionine synthase: a rapid kinetic analysis of intermediates in reductive methylation of Cob(II)alamin enzyme. Biochemistry. 1998 Sep 8;37(36):12649-58. Pubmed
7. Formimidoyltransferase-cyclodeaminase
Pharmacological action: unknown
Actions: cofactor
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool
Organism class: human
UniProt ID: O95954 
Gene: FTCD 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Bashour AM, Bloom GS: 58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase. J Biol Chem. 1998 Jul 31;273(31):19612-7. Pubmed
- Cook RJ: Disruption of histidine catabolism in NEUT2 mice. Arch Biochem Biophys. 2001 Aug 15;392(2):226-32. Pubmed
- Kohls D, Croteau N, Mejia N, MacKenzie RE, Vrielink A: Crystallization and preliminary X-ray analysis of the formiminotransferase domain from the bifunctional enzyme formiminotransferase-cyclodeaminase. Acta Crystallogr D Biol Crystallogr. 1999 Jun;55(Pt 6):1206-8. Pubmed
- Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A: The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme. Structure. 2000 Jan 15;8(1):35-46. Pubmed
8. Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase
Pharmacological action: unknown
Actions: cofactor
10-formyltetrahydrofolate + 5-amino-1-(5- phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5- formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
Organism class: human
UniProt ID: P31939 
Gene: ATIC 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Wolan DW, Greasley SE, Wall MJ, Benkovic SJ, Wilson IA: Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site. Biochemistry. 2003 Sep 23;42(37):10904-14. Pubmed
- Bulock KG, Beardsley GP, Anderson KS: The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5’-monophosphate cyclohydrolase). A surprising lack of substrate channeling. J Biol Chem. 2002 Jun 21;277(25):22168-74. Epub 2002 Apr 10. Pubmed
9. Serine hydroxymethyltransferase, cytosolic
Pharmacological action: unknown
Actions: cofactor
Interconversion of serine and glycine
Organism class: human
UniProt ID: P34896 
Gene: SHMT1 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT: Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate. J Mol Biol. 2000 Feb 11;296(1):155-68. Pubmed
- Rao JV, Prakash V, Rao NA, Savithri HS: The role of Glu74 and Tyr82 in the reaction catalyzed by sheep liver cytosolic serine hydroxymethyltransferase. Eur J Biochem. 2000 Oct;267(19):5967-76. Pubmed
- Heil SG, Van der Put NM, Waas ET, den Heijer M, Trijbels FJ, Blom HJ: Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab. 2001 Jun;73(2):164-72. Pubmed
- Ravanel S, Cherest H, Jabrin S, Grunwald D, Surdin-Kerjan Y, Douce R, Rebeille F: Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15360-5. Pubmed
- Li R, Moore M, King J: Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol. 2003 Mar;44(3):233-41. Pubmed
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
10. Serine hydroxymethyltransferase, mitochondrial
Pharmacological action: unknown
Actions: cofactor
Interconversion of serine and glycine
Organism class: human
UniProt ID: P34897 
Gene: SHMT2 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Heil SG, Van der Put NM, Waas ET, den Heijer M, Trijbels FJ, Blom HJ: Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab. 2001 Jun;73(2):164-72. Pubmed
- Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D’Aguanno S, Bossa F: l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. Eur J Biochem. 2001 Dec;268(24):6508-25. Pubmed
- Li R, Moore M, King J: Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol. 2003 Mar;44(3):233-41. Pubmed
- Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS: Structure-function relationship in serine hydroxymethyltransferase. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):24-9. Pubmed
- Angelaccio S, Chiaraluce R, Consalvi V, Buchenau B, Giangiacomo L, Bossa F, Contestabile R: Catalytic and thermodynamic properties of tetrahydromethanopterin-dependent serine hydroxymethyltransferase from Methanococcus jannaschii. J Biol Chem. 2003 Oct 24;278(43):41789-97. Epub 2003 Aug 5. Pubmed
11. Methylenetetrahydrofolate reductase
Pharmacological action: unknown
Actions: cofactor
Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co- substrate for homocysteine remethylation to methionine
Organism class: human
UniProt ID: P42898 
Gene: MTHFR 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Ubbink JB, Christianson A, Bester MJ, Van Allen MI, Venter PA, Delport R, Blom HJ, van der Merwe A, Potgieter H, Vermaak WJ: Folate status, homocysteine metabolism, and methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of pregnancy complicated by neural tube defects. Metabolism. 1999 Feb;48(2):269-74. Pubmed
- Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, Knook DL, Westendorp RG, Slagboom EP: Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet. 1999 Feb-Mar;7(2):197-204. Pubmed
- Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, Yang F, Bullemer FE, Rasmussen R, Graham KJ: Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis. 1999 Mar;143(1):163-70. Pubmed
- Holmes ZR, Regan L, Chilcott I, Cohen H: The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol. 1999 Apr;105(1):98-101. Pubmed
- Larsson J, Hultberg B, Hillarp A: Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand. 2000 Jun;78(3):340-3. Pubmed
12. Serine hydroxymethyltransferase 2
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q53ET4 
Protein Sequence: FASTA
Gene Sequence: FASTA
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
- Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF: Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin-Characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Jul 30;. Pubmed
13. SHMT2 protein
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5BJF5 
Gene: SHMT2 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
14. Hypothetical protein DKFZp686P09201
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5HYG8 
Gene: DKFZp686P09201 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
15. 5,10-methylenetetrahydrofolate reductase
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q5SNW5 
Gene: MTHFR 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
- Siva A, De Lange M, Clayton D, Monteith S, Spector T, Brown MJ: The heritability of plasma homocysteine, and the influence of genetic variation in the homocysteine methylation pathway. QJM. 2007 Aug;100(8):495-9. Epub 2007 Jul 17. Pubmed
- Leopardi P, Marcon F, Caiola S, Cafolla A, Siniscalchi E, Zijno A, Crebelli R: Effects of folic acid deficiency and MTHFR C677T polymorphism on spontaneous and radiation-induced micronuclei in human lymphocytes. Mutagenesis. 2006 Sep;21(5):327-33. Epub 2006 Sep 1. Pubmed
- Ott K, Vogelsang H, Marton N, Becker K, Lordick F, Kobl M, Schuhmacher C, Novotny A, Mueller J, Fink U, Ulm K, Siewert JR, Hofler H, Keller G: The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer. Int J Cancer. 2006 Dec 15;119(12):2885-94. Pubmed
16. SHMT2 protein
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q8N1A5 
Gene: SHMT2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Prabhu V, Chatson KB, Lui H, Abrams GD, King J: Effects of sulfanilamide and methotrexate on 13C fluxes through the glycine decarboxylase/serine hydroxymethyltransferase enzyme system in arabidopsis. Plant Physiol. 1998 Jan;116(1):137-44. Pubmed
- Heil SG, Van der Put NM, Waas ET, den Heijer M, Trijbels FJ, Blom HJ: Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects? Mol Genet Metab. 2001 Jun;73(2):164-72. Pubmed
- Rajaram V, Bhavani BS, Kaul P, Prakash V, Appaji Rao N, Savithri HS, Murthy MR: Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory. FEBS J. 2007 Aug;274(16):4148-60. Epub 2007 Jul 25. Pubmed
- Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D’Aguanno S, Bossa F: l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. Eur J Biochem. 2001 Dec;268(24):6508-25. Pubmed
- Vatsyayan R, Roy U: Molecular cloning and biochemical characterization of Leishmania donovani serine hydroxymethyltransferase. Protein Expr Purif. 2007 Apr;52(2):433-40. Epub 2006 Oct 26. Pubmed
17. Methionyl-tRNA formyltransferase, mitochondrial
Pharmacological action: unknown
Actions: cofactor
Formylates methionyl-tRNA in mitochondria. A single tRNA(Met) gene gives rise to both an initiator and an elongator species via an unknown mechanism
Organism class: human
UniProt ID: Q96DP5 
Gene: MTFMT 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Li Y, Holmes WB, Appling DR, RajBhandary UL: Initiation of protein synthesis in Saccharomyces cerevisiae mitochondria without formylation of the initiator tRNA. J Bacteriol. 2000 May;182(10):2886-92. Pubmed
18. Methylenetetrahydrofolate reductase intermediate form
Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q9NY62 
Gene: MTHFR 
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Dilley A, Hooper WC, El-Jamil M, Renshaw M, Wenger NK, Evatt BL: Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C—>T677) and cystathione beta-synthase (CBS G—>A919, CBS T—>c833) are not associated with myocardial infarction in African Americans. Thromb Res. 2001 Jul 15;103(2):109-15. Pubmed
- Huang L, Zhang J, Hayakawa T, Tsuge H: Assays of methylenetetrahydrofolate reductase and methionine synthase activities by monitoring 5-methyltetrahydrofolate and tetrahydrofolate using high-performance liquid chromatography with fluorescence detection. Anal Biochem. 2001 Dec 15;299(2):253-9. Pubmed
- Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, Knook DL, Westendorp RG, Slagboom EP: Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet. 1999 Feb-Mar;7(2):197-204. Pubmed
- Tsai AW, Cushman M, Tsai MY, Heckbert SR, Rosamond WD, Aleksic N, Yanez ND, Psaty BM, Folsom AR: Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE). Am J Hematol. 2003 Mar;72(3):192-200. Pubmed
- Larsson J, Hultberg B, Hillarp A: Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand. 2000 Jun;78(3):340-3. Pubmed
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