PROSITE documentation PDOC00616 [for PROSITE entry PS00767]
Tetrahydrofolate dehydrogenase/cyclohydrolase signatures


Enzymes that participate in the transfer of one-carbon units are involved in various biosynthetic pathways. In many of these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). Various reactions generate one-carbon derivatives of THF which can be interconverted between different oxidation states by formyltetrahydrofolate synthetase (EC, methylenetetrahydrofolate dehydrogenase (EC or EC and methenyltetrahydrofolate cyclohydrolase (EC

The dehydrogenase and cyclohydrolase activities are expressed by a variety of multifunctional enzymes:

  • Eukaryotic C-1-tetrahydrofolate synthase (C1-THF synthase), which catalyzes all three reactions described above. Two forms of C1-THF synthases are known [1], one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the dehydrogenase/cyclohydrolase domain is located in the N-terminal section of the 900 amino acids protein and consists of about 300 amino acid residues. The C1-THF synthases are NADP- dependent.
  • Eukaryotic mitochondrial bifunctional dehydrogenase/cyclohydrolase [2]. This is an homodimeric NAD-dependent enzyme of about 300 amino acid residues.
  • Bacterial folD [3]. FolD is an homodimeric bifunctional NADP-dependent enzyme of about 290 amino acid residues.

The sequence of the dehydrogenase/cyclohydrolase domain is highly conserved in all forms of the enzyme. As signature patterns we selected two conserved regions. The first one is located in the N-terminal part of these enzymes and contains three acidic residues. The second pattern is a highly conserved sequence of 9 amino acids which is located in the C-terminal section.

Last update:

December 2004 / Patterns and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

THF_DHG_CYH_2, PS00767; Tetrahydrofolate dehydrogenase/cyclohydrolase signature 2  (PATTERN)

THF_DHG_CYH_1, PS00766; Tetrahydrofolate dehydrogenase/cyclohydrolase signature 1  (PATTERN)


1AuthorsShannon K.W. Rabinowitz J.C.
TitleIsolation and characterization of the Saccharomyces cerevisiae MIS1 gene encoding mitochondrial C1-tetrahydrofolate synthase.
SourceJ. Biol. Chem. 263:7717-7725(1988).
PubMed ID2836393

2AuthorsBelanger C. MacKenzie R.E.
TitleIsolation and characterization of cDNA clones encoding the murine NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase.
SourceJ. Biol. Chem. 264:4837-4843(1989).
PubMed ID2647744

3Authorsd'Ari L. Rabinowitz J.C.
SourceJ. Biol. Chem. 266:23953-23958(1991).

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