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Formate--tetrahydrofolate ligase (EC 6.3.4.3) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymes participating in the transfer of one-carbon units, an essential element of 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 FTHFS, methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9).

In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyzes the dehydrogenase and cyclohydrolase activities. 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 FTHFS domain consist of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues [2].

The sequence of FTHFS is highly conserved in all forms of the enzyme. As signature patterns we selected two regions that are almost perfectly conserved. The first one is a glycine-rich segment located in the N-terminal part of FTHFS and which could be part of an ATP-binding domain [2]. The second pattern is located in the central section of FTHFS.

April 2006 / Patterns revised.

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

FTHFS_1, PS00721; Formate--tetrahydrofolate ligase signature 1  (PATTERN)

Consensus pattern: [GN]-[LIVMS]-K-G-[GST]-[AG]-[AST]-G-[GAS]-G-[YLHRKF] Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00721 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00721 • Scan Swiss-Prot/TrEMBL entries against PS00721 • view ligand binding statistics

Matching PDB structures: 1EG7 1FP7 1FPM 3DO6 ... [ALL]

FTHFS_2, PS00722; Formate--tetrahydrofolate ligase signature 2  (PATTERN)

Consensus pattern: V-[ASV]-[TS]-[IVLA]-[RQ]-[AGS]-[LIM]-[KER]-x-[HN]-[GAS]-[GLKD] Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00722 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00722 • Scan Swiss-Prot/TrEMBL entries against PS00722 • view ligand binding statistics

Matching PDB structures: 1EG7 1FP7 1FPM 3DO6 ... [ALL]

1	Authors	Shannon K.W., Rabinowitz J.C.
	Title	Isolation and characterization of the Saccharomyces cerevisiae MIS1 gene encoding mitochondrial C1-tetrahydrofolate synthase.
	Source	J. Biol. Chem. 263:7717-7725(1988).
	PubMed ID	2836393

2	Authors	Lovell C.R., Przybyla A., Ljungdahl L.G.
	Title	Primary structure of the thermostable formyltetrahydrofolate synthetase from Clostridium thermoaceticum.
	Source	Biochemistry 29:5687-5694(1990).
	PubMed ID	2200509

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