AC   MF_00051;
DC   Protein; auto
TR   HAMAP; MF_00051; -; 1; level=0
XX
Names: SHMT
XX
case (<OC:Bacteria> and <FT:5=H>) or <OC:Methanomicrobia> or <OC:Halobacteria>
ID   GLYA
DE   RecName: Full=Serine hydroxymethyltransferase;
DE            Short=SHMT;
DE            Short=Serine methylase;
DE            EC=2.1.2.1;
GN   Name=glyA;
else case <OC:Bacteria> and <FT:5=T>
ID   MSHMT
DE   RecName: Full=2-methylserine hydroxymethyltransferase;
DE            Short=MSHMT;
DE            EC=2.1.2.7;
DE   AltName: Full=Alpha-methylserine hydroxymethyltransferase;
DE   AltName: Full=D-alanine 2-hydroxymethyltransferase;
GN   Name=mshmt;
else case <OC:Bacteria> and not <FT:5>
ID   GLYA
DE   RecName: Full=Probable serine hydroxymethyltransferase;
DE            Short=SHMT;
DE            Short=Serine methylase;
DE            EC=2.1.2.1;
GN   Name=glyA;
else
ID   GLYA
DE   RecName: Full=Serine hydroxymethyltransferase;
DE            Short=SHMT;
DE            Short=Serine methylase;
DE            EC=2.1.2.-;
GN   Name=glyA;
end case
XX
case <OC:Bacteria> and <FT:5=H>
CC   -!- FUNCTION: Catalyzes the reversible interconversion of serine and
CC       glycine with tetrahydrofolate (THF) serving as the one-carbon carrier.
CC       This reaction serves as the major source of one-carbon groups required
CC       for the biosynthesis of purines, thymidylate, methionine, and other
CC       important biomolecules. Also exhibits THF-independent aldolase activity
CC       toward beta-hydroxyamino acids, producing glycine and aldehydes, via a
CC       retro-aldol mechanism.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC         (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
else case <OC:Bacteria> and <FT:5=T>
CC   -!- FUNCTION: Catalyzes the reversible interconversion of alpha-methyl-L-
CC       serine to D-alanine with tetrahydrofolate (THF) serving as the one-
CC       carbon carrier.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + D-alanine + H2O
CC         = (6S)-5,6,7,8-tetrahydrofolate + 2-methylserine;
CC         Xref=Rhea:RHEA:10064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15636,
CC         ChEBI:CHEBI:57416, ChEBI:CHEBI:57453, ChEBI:CHEBI:58275; EC=2.1.2.7;
else case <OC:Bacteria> and not <FT:5>
CC   -!- FUNCTION: Catalyzes the reversible interconversion of serine and
CC       glycine with tetrahydrofolate (THF) serving as the one-carbon carrier.
CC       This reaction serves as the major source of one-carbon groups required
CC       for the biosynthesis of purines, thymidylate, methionine, and other
CC       important biomolecules.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC         (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
else case <OC:Methanomicrobia> or <OC:Halobacteria>
CC   -!- FUNCTION: Catalyzes the reversible interconversion of serine and
CC       glycine with tetrahydrofolate (THF) serving as the one-carbon carrier.
CC       Also exhibits THF-independent aldolase activity toward beta-
CC       hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol
CC       mechanism.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC         (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
else case <OC:Methanobacteria> or <OC:Methanococci> or <OC:Methanopyri> or <OC:Archaeoglobi>
CC   -!- FUNCTION: Catalyzes the reversible interconversion of serine and
CC       glycine with tetrahydromethanopterin (H4MPT) serving as the one-carbon
CC       carrier. Also exhibits a pteridine-independent aldolase activity toward
CC       beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-
CC       aldol mechanism.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,10-methylenetetrahydromethanopterin + glycine + H2O =
CC         5,6,7,8-tetrahydromethanopterin + L-serine; Xref=Rhea:RHEA:47104,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:33384, ChEBI:CHEBI:57305,
CC         ChEBI:CHEBI:57818, ChEBI:CHEBI:58103;
else
CC   -!- FUNCTION: Catalyzes the reversible interconversion of serine and
CC       glycine with a modified folate serving as the one-carbon carrier. Also
CC       exhibits a pteridine-independent aldolase activity toward beta-
CC       hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol
CC       mechanism.
end case
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
case <OC:Bacteria> or <OC:Methanomicrobia> or <OC:Halobacteria>
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
end case
case <FT:5=H>
CC   -!- PATHWAY: Amino-acid biosynthesis; glycine biosynthesis; glycine from L-
CC       serine: step 1/1.
end case
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the SHMT family.
XX
DR   Pfam; PF00464; SHMT; 1; trigger=no
DR   PROSITE; PS00096; SHMT; 1; trigger=no
DR   PIRSF; PIRSF000412; SHMT; 1; trigger=no
XX
case <FTTag:acetylation>
KW   Acetylation
end case
case <FT:5=H>
KW   Amino-acid biosynthesis
end case
KW   Cytoplasm
KW   One-carbon metabolism
KW   Pyridoxal phosphate
KW   Transferase
XX
case <FT:5=H>
GO   GO:0004372; F:glycine hydroxymethyltransferase activity
end case
GO   GO:0030170; F:pyridoxal phosphate binding
GO   GO:0006730; P:one-carbon metabolic process
case <FT:5=H>
GO   GO:0019264; P:glycine biosynthetic process from serine
end case
GO   GO:0005737; C:cytoplasm
XX
FT   From: GLYA_ECOLI (P0A825)
FT   BINDING         125..127
FT                   /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:57453"
FT   Optional; Condition: [GA]-H-[LIV]
FT   BINDING         355..357
FT                   /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:57453"
FT   Optional; Condition: [ST]-x-F
FT   BINDING         121
FT                   /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:57453"
FT   Optional; Condition: L
FT   BINDING         246
FT                   /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:57453"
FT   Optional; Condition: E
FT   SITE            228
FT                   /note="Plays an important role in substrate specificity"
FT   Condition: [HT]
FT   MOD_RES         229
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT   Condition: K
case <OC:Escherichia> or <OC:Shigella>
FT   MOD_RES         54
FT                   /note="N6-acetyllysine"
FT   Tag: acetylation; Condition: K
FT   MOD_RES         250
FT                   /note="N6-acetyllysine"
FT   Tag: acetylation; Condition: K
FT   MOD_RES         285
FT                   /note="N6-acetyllysine"
FT   Tag: acetylation; Condition: K
FT   MOD_RES         354
FT                   /note="N6-acetyllysine"
FT   Tag: acetylation; Condition: K
FT   MOD_RES         375
FT                   /note="N6-acetyllysine"
FT   Tag: acetylation; Condition: K
end case
XX
Size: 406-574;
Related: None;
Template: P0A825; D3DKC4; P9WGI9; P9WGI7; P39148; Q58992; Q46A52; Q9UWT5; O27433; B2DEU7;
Scope:
 Bacteria
 Archaea
Fusion:
 Nter: None
 Cter: None
Duplicate: in AGRFC, BORBR, BORPA, BURMA, BURP1, BURPS, BURL3, BURTA, COLP3,
 PECAS, HAHCH, MYCBO, MYCTU, PHOPR, PSE14, PSEAE, PSEF5, PSEPF, PSEPK, PSESM,
 PSEU2, CUPPJ, RALN1, RHILO, RHIME, RHOPA, RHORT, RUEPO, SULDN, VIBCH, VIBPA,
 VIBVU, VIBVY
Plasmid: None
Comments: The pteridine substrate used in this reaction by Archaea differs depending on the species.
 Methanomicrobia and Halobacteria appear to use tetrahydrofolate, whereas Methanobacteria and Methanococci
 use tetrahydromethanopterin, Sulfolobus solfataricus use tetrahydrosulfopterin, and hyperthermophiles use
 a modified folate (see PMID: 9783425 and references mentioned in template entries).
 M.tuberculosis possesses 2 SHMTs, one (O53441, Rv1093) binds 1 pyridoxal phosphate per homodimer
 whereas the other (O53615, Rv0070c) binds 1 pyridoxal phosphate per subunit like other characterized
 members of the SHMT family.
 Possible wrong start in ARCFU.
 Possible C-terminal problem in TREPA.
XX
# Revision 1.60 2023/11/28
//