{PDOC00595}
{PS00721; FTHFS_1}
{PS00722; FTHFS_2}
{BEGIN}
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* Formate--tetrahydrofolate ligase signatures *
***********************************************

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.

-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.

-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.

-Last update: April 2006 / Patterns revised.

[ 1] Shannon K.W., Rabinowitz J.C.
     "Isolation and characterization of the Saccharomyces cerevisiae MIS1
     gene encoding mitochondrial C1-tetrahydrofolate synthase."
     J. Biol. Chem. 263:7717-7725(1988).
     PubMed=2836393
[ 2] Lovell C.R., Przybyla A., Ljungdahl L.G.
     "Primary structure of the thermostable formyltetrahydrofolate
     synthetase from Clostridium thermoaceticum."
     Biochemistry 29:5687-5694(1990).
     PubMed=2200509

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