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Information on EC 2.1.2.10 - aminomethyltransferase
for references in articles please use BRENDA:EC2.1.2.10
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EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.2 Hydroxymethyl-, formyl- and related transferases
2.1.2.10 aminomethyltransferase
IUBMB Comments
A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein .
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
- 2.1.2.10
- hyperglycinemia
-
nonketotic
-
photorespiratory
-
photorespiration
-
one-carbon
-
ketotic
- hydroxymethyltransferase
- lipoamide
- medicine
- h-protein
- dimethylglycine
Reaction Schemes
showSynonyms
aminomethyltransferase, glycine synthase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminomethyltransferase
Amt
GCVT
glycine synthase
-
-
-
-
synthase, glycine
-
-
-
-
T protein
-
-
-
-
T-protein
T-protein component of glycine cleavage complex
tetrahydrofolate aminomethyltransferase
-
-
-
-
Amt
-
-
-
-
T-protein
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
-
-
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
tetrahydrofolate is bound near the center of the tripartite enzyme, lipoic acid is bound adjacent to the tetrahydrofolate binding pocket
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
formation of a folate-binding cavity via the interaction of enzyme with H-protein
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
5-methyltetrahydrofolate is bound in a kinked shape with the pteridine group deeply buried into the hydrophobic pocket ant the glutamyl group pointed to the C-terminal side surface. R292 interacts through water molecules with the folate polyglutamate tail
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
T-protein recognition of lipoyl protein substrate and reaction mechanism, overview. The reversible transfer of the methylene group between the lipoate and tetrahydrofolate proceeds through the electron relay-assisted iminium intermediate formation
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C-N bond cleavage
-
-
-
-
methyl group transfer
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
MetaCyc
glycine biosynthesis II, glycine cleavage
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SYSTEMATIC NAME
IUBMB Comments
[protein]-S8-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-forming)
A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3].
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CAS REGISTRY NUMBER
COMMENTARY
37257-08-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
reduced H-protein + 5,10-methylene-tetrahydrofolate + NH4Cl
?
-
Substrates: -
Products: -
Products: -
?
reduced H-protein + 5,10-methylenetetrahydropteroyltetraglutamate + NH4Cl
?
-
Substrates: -
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
S-aminomethyldihydrolipoylprotein + tetrahydropteroyltetraglutamate
dihydrolipoylprotein + 5,10-methylenetetrahydropteroyltetraglutamate + NH3
-
Substrates: -
Products: better substrate than 5,10-methylenetetrahydrofolate, 6.5fold higher affinity for 5,10-methylenetetrahydropteroyltetraglutamate than for 5,10-methylenetetrahydrofolate
Products: better substrate than 5,10-methylenetetrahydrofolate, 6.5fold higher affinity for 5,10-methylenetetrahydropteroyltetraglutamate than for 5,10-methylenetetrahydrofolate
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: aminomethyl intermediate bound to the lipoate cofactor of H-protein
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: T-protein catalyzes the tetrahydrofolate-dependent step of the glycine cleavage reaction
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
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Substrates: tetrahydrofolate-dependent enzyme
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
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Substrates: folate-binding site: Lys-78, Lys-81 and Lys-352 are involved in binding, Lys-352 may serve as the primary binding site to alpha-carboxyl group of the first glutamate residue nearest the p-aminobenzoic acid ring of 5,10-methylenetetrahydrofolate and 5,10-methylenetetrahydropteroyltetraglutamate, Lys-81 may play a key role to hold the second glutamate residue through binding to its alpha-carboxyl group, 6.5fold higher affinity for 5,10-methylenetetrahydropteroyltetraglutamate than for 5,10-methylenetetrahydrofolate
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
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Substrates: decarboxylated glycine moiety attached to H-protein + tetrahydrofolate as substrates
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
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Substrates: strictly dependent on tetrahydrofolate
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: requires tetrahydrofolate
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: T-protein catalyzes the tetrahydrofolate-dependent step of the glycine cleavage reaction
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: tetrahydrofolate-dependent enzyme
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: important enzyme in glycine metabolism
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: decarboxylated glycine moiety attached to H-protein + tetrahydrofolate as substrates
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: T-protein participates in the formation of the one carbon unit and ammonia or the reverse reaction
Products: -
Products: -
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: glycine metabolism
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
r
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: component of the glycine cleavage system, T-protein is associated with H-protein forming a complex which is composed of one molecule of each of them
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is a component of the reversible glycine cleavage system which is composed of 4 protein components named as P-, H-, L- and T-protein
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: part of the glycine cleavage system
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: important enzyme in glycine metabolism
Products: -
Products: -
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
Substrates: glycine metabolism
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
Substrates: -
Products: -
Products: -
r
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Hyperglycinemia, Nonketotic
Glycine Cleavage System H Protein Is Essential for Embryonic Viability, Implying Additional Function Beyond the Glycine Cleavage System.
Hyperglycinemia, Nonketotic
Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia.
Hyperglycinemia, Nonketotic
Identification of the first reported splice site mutation (IVS7-1G-->A) in the aminomethyltransferase (T-protein) gene (AMT) of the glycine cleavage complex in 3 unrelated families with nonketotic hyperglycinemia.
Hyperglycinemia, Nonketotic
Identification of Two Novel Mutations in Aminomethyltransferase Gene in Cases of Glycine Encephalopathy.
Hyperglycinemia, Nonketotic
Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy.
Leukemia
Genomic organization of the dog dystroglycan gene DAG1 locus on chromosome 20q15.1-q15.2.
Leukemia, T-Cell
Genomic structures and sequences of two closely linked genes (AMT, TCTA) on dog chromosome 20q15.1-->q15.2.
Neoplasms
Proteomic analysis of the effect of retinoic acids on the human breast cancer cell line MCF-7.
Obesity
Obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats.
Propionic Acidemia
Inhibition of glycine synthase by branched-chain alpha-keto acids. A possible mechanism for abnormal glycine metabolism in ketotic hyperglycinemia.
Vitamin B 12 Deficiency
The vitamin B12-deficient rat as a possible model of ketotic hyperglycinemia.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.151
5,10-methylenetetrahydrofolate
-
N-terminal deletion mutant, His-tagged
0.0092
5,10-methylenetetrahydropteroyltetraglutamate
-
wild-type with His-tag
0.0108
5,10-methylenetetrahydropteroyltetraglutamate
-
mutant L6A, His-tagged
0.0174
5,10-methylenetetrahydropteroyltetraglutamate
-
mutant T4A, His-tagged
0.0382
5,10-methylenetetrahydropteroyltetraglutamate
-
N-terminal deletion mutant, His-tagged
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9.5
5,10-methylenetetrahydropteroyltetraglutamate
-
N-terminal deletion mutant, His-tagged
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
annotated as cysteine protease; cv. Lianshan 1
UniProt
brenda
recombinant enzyme, expressed in Escherichia coli BL21 (DE3)pLysS
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
enzyme AMT expression levels in obese and lean rats, effects of glycine on the expression levels, overview
brenda
-
the enzyme is present in large excess over the other proteins of the glycine cleavage system in leaves
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
-
T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction, shows a highly interacting intermolecular interface limited to a small area and the protein-bound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Arg292 of the T-protein is essential for complex assembly
malfunction
-
glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death, phenotypes, overview. Mutations in both GLDC and AMT genes are the main cause of glycine encephalopathy in Malaysian population
malfunction
-
enzyme mutations are responsible for 20% of nonketotic hyperglycinemia cases
malfunction
mutations S117L and R320H cause nonketotic hyperglycinemia (NKH). Analysis of mutations in the GLYCTK gene (encoding D-glycerate kinase, EC 2.7.1.165) causing glyceric aciduria. D-glyceric aciduria causes a blockage to the glycine cleavage enzyme system (GCS). The mutation S117L, a homozygous missense mutation in AMT c.350CNT, causes NKH, but no evidence is found that D-glyceric aciduria would cause nonketotic hyperglycinemia (NKH) as a secondary phenomenon. The p.Arg320His is included as the most common AMT mutation observed in NKH patients and when homozygous, is always observed in a severe phenotype
malfunction
mutation of AMT or GLDC, encoding the glycine cleavage system (GCS) components aminomethyltransferase and glycine decarboxylase, can cause malformations of the developing CNS (neural tube defects (NTDs) and ventriculomegaly) as well as a post-natal life-limiting neurometabolic disorder, non-ketotic hyperglycinemia. Null mutations of Gldc or Amt are compatible with embryonic survival despite the presence of NTDs. The loss of GCS activity in Gldc-deficient mice results in elevated glycine and a number of glycine derivatives in plasma and tissues, including liver and brain. Loss of function of the GCS components Gldc and Amt also results in lethal phenotypes, but null embryos survive to late-fetal stages and exhibit neural tube defects (NTDs) with varying penetrance
metabolism
-
aminomethyltransferase is a component of the T-protein, which is part of a multienzyme system composed of four proteins termed P-, H-, T-, and L-protein. T-protein/aminomethyltransferase degrades the aminomethyl moiety to ammonia and 5,10-methylentetrahydrofolate in the presence of tetrahydrofolate, leaving dihydrolipoate-bearing H-protein
metabolism
glycine catabolism is mediated primarily by the glycine cleavage system, which comprises four proteins: glycine dehydrogenase (decarboxylating) (GLDC), aminomethyltransferase (AMT), dihydrolipoyl dehydrogenase (DLD), and glycine cleavage system protein H (GCSH). GLDC, AMT, and DLD decompose a molecule of glycine into a molecule of carbon dioxide, ammonia, and a carbon unit with the aid of carrier protein GCSH. The phosphorylation modification induced by glycine-supply play important roles in the regulation of energy metabolism in tea roots and amino acid metabolism in tea leaves. In leaves, the glycine-supply changes the phosphorylation levels of glycine dehydrogenase, aminomethyltransferase, glutamine synthetase, and ferredoxin-dependent glutamate synthase, which accelerates the decomposition of glycine and enhances the ability of ammonia assimilation
metabolism
enzyme AMT acts specifically in the glycine cleavage system (GCS). The GCS shows decarboxylation of glycine by GLDC with transfer of the methylamine group to GCSH, followed by AMT mediated release of ammonia and transfer of the methylene group to tetrahydrofolate (THF), which enters the mitochondrial folate cycle that generates formate for transfer to the cytoplasm
physiological function
-
part of glycine cleavage system, serine metabolism
physiological function
-
aminomethyltransferase reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ammonia, 5,10-methylenetetrahydrofolate, and dihydrolipoate-bearing H-protein in the presence of tetrahydrofolate
physiological function
-
the enzyme is essential for photorespiration and one-carbon metabolism
physiological function
tea plants improve the enzyme activities of GLDC and AMT by dephosphorylation and phosphorylation, respectively, accelerating the decomposition of glycine
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
additional information
dimer
-
crystallization data, cloverleaf-like orientation of protomer around a central hole
dimer
-
crystallization data, cloverleaf-like orientation of protomer around a central hole
-
additional information
-
construction of low-resolution model and tertiary structure model
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphorylation of AMT on Ser173. In leaves, the glycine-supply changes the phosphorylation levels of glycine dehydrogenase, aminomethyltransferase, glutamine synthetase, and ferredoxin-dependent glutamate synthase, which accelerates the decomposition of glycine and enhances the ability of ammonia assimilation. The enzyme activity of AMT might be enhanced after phosphorylation modification, glycine enhances AMT phosphorylation
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
aminomethyltransferase/T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction, purified recombinant wild-type and mutant T-proteins, hanging drop vapor diffusion method, mixing of 22-25 mg/ml proteins, T-protein and H protein, with an equal volume of reservoir solution containing 0.095 M 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, pH 7.5, 0.19 M calcium chloride, 26.6% v/v PEG 400, and 5% v/v glycerol, at 15°C, 4-5 days to 2 weeks, soaking of the native crystals in mother liquid containing 1 mM (6S)-5-methyltetrahydrofolate at 15°C for 4 h, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement
-
apoform, tetrahydrofolate complex, folinic acid complex and lipoic acid complex of enzyme, homology model of human enzyme
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D96N
-
site-directed mutagenesis, both the glycine cleavage and synthesis activities are reduced to 34% compared to the wild-type enzyme
D96N/Y188F
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
D97N
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
D97N/Y188F
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
K75E
-
mutant with 2.5fold increased Km-value for 5,10-methylenetetrahydrofolate and 8fold increased Km-value for 5,10-methylenetetrahydropteroyltetraglutamate
K81E
-
mutant with 3fold increased Km-value for 5,10-methylenetetrahydrofolate and 16fold increased Km-value for 5,10-methylenetetrahydropteroyltetraglutamate
L6A
-
in contrast to wild-type, quite susceptible to trypsinolysis, 4fold increase in Km-value for reduced H-protein
N113A
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
N113A/R223A
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
N113D
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
R223A
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
R223K
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
Y188F
-
site-directed mutagenesis, both the glycine cleavage and synthesis activities are reduced to 83% compared to the wild-type enzyme
E211K
-
polymorphism occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
H42R
-
present in many nonketotic hyperglycinemia affected members of an extended Israeli-Arab kindred
N145I
-
nonketotic hyperglycinemia, substitution of conserved N, patient has servere neonatal presentation and died in the newborn period
R265H
-
naturally occurring mutation in glycine encephalopathy patients and the Penan sub-population. Detection of four missense mutations (c.664C4T, c.688G4C, c.794G4A, c.826G4C) and one heterozygous deletion causing frameshift mutation (c.982delG) in AMT gene
R296H
-
mutation occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
R318R
-
polymorphism occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
R320H
S117L
naturally occuring mutation, a very rare homozygous missense mutation in AMT c.350CNT, that causes D-glyceric aciduria, but no evidence is found that D-glyceric aciduria would cause nonketotic hyperglycinemia (NKH) as a secondary phenomenon. The mutant enzyme shows 9% activity compared to wild-type. The expression of the p.Ser117Leu mutant shows a low residual enzyme activity of the glycine cleavage enzyme similar to that of the mock control
additional information
R320H
-
allele frequency of 7% for R320H of T-protein in 50 patients with enzymatic confirmation of their diagnostics of nonketotic hyperglycinemia
R320H
naturally occuring mutation that causes D-glyceric aciduria, the mutant enzyme shows 13% activity compared to wild-type. The expression of the p.Arg320Hisu mutant shows a low residual enzyme activity of the glycine cleavage enzyme similar to that of the mock control. The p.Arg320His is included as the most common AMT mutation observed in NKH patients and when homozygous, is always observed in a severe phenotype
additional information
-
N-terminal deletion of 7 amino acids, in contrast to wild-type, quite susceptible to trypsinolysis
additional information
-
allele frequency of 3% for T-protein splice site mutation IVS7-1G-A in 50 patients with enzymatic confirmation of their diagnostics of nonketotic hyperglycinemia, mutation with a one-base deletion 183delC
additional information
-
a subset of nonketotic hyperglycinemia cases is due to mutations in the gene for the T-protein
additional information
-
in 14 glycine encephalopathy patients from 13 families, six patients (43%) have biallelic mutations in the AMT gene, most of which are missense mutations and family-specific
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM Tris-HCl buffer, pH 8.0, 10 mM 2-mercaptoethanol, 50% v/v glycerol, at least 2 months, stable
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purification of recombinant enzyme, expressed in Escherichia coli BL21 (DE3)pLysS, and of mutants
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Amt gene is located on chromosome 3p21 and contains 9 exons spanning about 6 kb of genomic sequence
-
C-terminally His6-tagged T-protein wild-type and mutant enzymes expression in Escherichia coli strain BL21(DE3)pLysS
-
cloning and sequencing of the Amt gene with 9 closely spaced exons that are contained within about 5 kb of genomic DNA, encoding a protein of 403 amino acids, cis-acting promoter is likely to be very short, Amt gene may be localized on chromosome 9F
-
gene AMT, genotyping in 14 glycine encephalopathy patients from 13 families from Malaysia, six patients (43%) have biallelic mutations in the AMT gene
-
gene AMT, located on chromosome 3p21.3, DNA and amino acid sequence determination and analysis. The AMT gene is located on chromosome 3p21.3 and the GLYCTK gene on 3p21.1. The possibility of a microdeletion is considered given the homozygosity for a mutation in both genes in a non-consanguineous family, but a comparative microarray does not identify a copy number variation in any exon of either gene
transfection to Leishmania infantum and Leishmania major
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats. Both mRNA and protein expression of aminomethyltransferase (AMT) and glycine dehydrogenase, decarboxylating (GLDC) are increased in the livers of obese versus lean rats
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
-
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
-
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
-
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
a subset of nonketotic hyperglycinemia cases is due to mutations in the gene for the T-protein
medicine
-
strategy for molecular investigation of patients with nonketotic hyperglycinemia: defective glycine cleavage enzyme system, composed of P-, H-, T- and L-protein, 15% of patients have a T-protein defect
medicine
-
identification of several mutations and polymorphisms occurring in patients with glycine encephalopathy, NKH, and methods for their PCR-restriction enzyme analysis
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bourguignon, J.; Neuburger, M.; Douce, R.
Resolution and characterization of the glycine-cleavage reaction in pea leaf mitochondria. Properties of the forward reaction catalysed by glycine decarboxylase and serine hydroxymethyltransferase
Biochem. J.
255
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1988
Lathyrus oleraceus
brenda
Motokawa, Y.; Kikuchi, G.
Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components
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164
624-633
1974
Rattus norvegicus
brenda
Okamura-Ikeda, K.; Fujiwara, K.; Motokawa, Y.
Purification and characterization of chicken liver T-protein, a component of the glycine cleavage system
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257
135-139
1982
Gallus gallus
brenda
Toone, J.R.; Applegarth, D.A.; Coulter-Mackie, M.B.; James, E.R.
Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): A strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH)
Mol. Genet. Metab.
72
322-325
2001
Homo sapiens
brenda
Backofen, B.; Leeb, T.
Genomic organization of the murine aminomethyltransferase gene (Amt)
DNA Seq.
13
179-183
2002
Homo sapiens, Mus musculus
brenda
Okamura-Ikeda, K.; Fujiwara, K.; Motokawa, Y.
Identification of the folate binding sites on the Escherichia coli T-protein of the glycine cleavage system
J. Biol. Chem.
274
17471-17477
1999
Escherichia coli
brenda
Lokanath, N.K.; Kuroishi, C.; Okazaki, N.; Kunishima, N.
Purification, crystallization and preliminary crystallographic analysis of the glycine-cleavage system component T-protein from Pyrococcus horikoshii OT3
Acta Crystallogr. Sect. D
60
1450-1452
2004
Pyrococcus horikoshii, Pyrococcus horikoshii OT-3
brenda
Orun, O.; Koch, M.H.; Kan, B.; Svergun, D.I.; Petoukhov, M.V.; Sayers, Z.
Structural characterization of T-protein of the Escherichia coli glycine cleavage system by X-ray small angle scattering
Cell. Mol. Biol.
49
453-459
2003
Escherichia coli
-
brenda
Okamura-Ikeda, K.; Kameoka, N.; Fujiwara, K.; Motokawa, Y.
Probing the H-protein-induced conformational change and the function of the N-terminal region of Escherichia coli T-protein of the glycine cleavage system by limited proteolysis
J. Biol. Chem.
278
10067-10072
2003
Escherichia coli
brenda
Lee, H.H.; Kim do, J.; Ahn, H.J.; Ha, J.Y.; Suh, S.W.
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.
279
50514-50523
2004
Thermotoga maritima
brenda
Okamura-Ikeda, K.; Hosaka, H.; Yoshimura, M.; Yamashita, E.; Toma, S.; Nakagawa, A.; Fujiwara, K.; Motokawa, Y.; Taniguchi, H.
Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia
J. Mol. Biol.
351
1146-1159
2005
Homo sapiens (P48728)
brenda
Toone, J.R.; Applegarth, D.A.; Levy, H.L.; Coulter-Mackie, M.B.; Lee, G.
Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH)
Mol. Genet. Metab.
79
272-280
2003
Homo sapiens
brenda
Lokanath, N.K.; Kuroishi, C.; Okazaki, N.; Kunishima, N.
Crystal structure of a component of glycine cleavage system: T-protein from Pyrococcus horikoshii OT3 at 1.5 A resolution
Proteins
58
769-773
2005
Pyrococcus horikoshii, Pyrococcus horikoshii OT-3
brenda
Mueller, M.; Papadopoulou, B.
Stage-specific expression of the glycine cleavage complex subunits in Leishmania infantum
Mol. Biochem. Parasitol.
170
17-27
2010
Leishmania infantum, Leishmania major
brenda
Kikuchi, G.; Motokawa, Y.; Yoshida, T.; Hiraga, K.
Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia
Proc. Jpn. Acad. Ser. B Phys. Biol. Sci.
84
246-263
2008
Escherichia coli, Homo sapiens, Lathyrus oleraceus
brenda
Okamura-Ikeda, K.; Hosaka, H.; Maita, N.; Fujiwara, K.; Yoshizawa, A.C.; Nakagawa, A.; Taniguchi, H.
Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system: implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism
J. Biol. Chem.
285
18684-18692
2010
Escherichia coli
brenda
Azize, N.A.; Ngah, W.Z.; Othman, Z.; Md Desa, N.; Chin, C.B.; Md Yunus, Z.; Mohan, A.; Hean, T.S.; Syed Zakaria, S.Z.; Lock-Hock, N.
Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy
J. Hum. Genet.
59
593-597
2014
Homo sapiens
brenda
Gencpinar, P.; Cavusoglu, D.; Oezbeyler, O.e.; Kaya, O.O.; Baydan, F.; Olgac Dundar, N.
Nonketotic hyperglycinemia novel mutation in the aminomethyl transferase gene. Case report
Arch. Argent. Pediatr.
114
e142-e146
2016
Homo sapiens
brenda
Timm, S.; Giese, J.; Engel, N.; Wittmiss, M.; Florian, A.; Fernie, A.R.; Bauwe, H.
T-protein is present in large excess over the other proteins of the glycine cleavage system in leaves of Arabidopsis
Planta
247
41-51
2018
Arabidopsis thaliana
brenda
Swanson, M.A.; Garcia, S.M.; Spector, E.; Kronquist, K.; Creadon-Swindell, G.; Walter, M.; Christensen, E.; Van Hove, J.L.K.; Sass, J.O.
D-Glyceric aciduria does not cause nonketotic hyperglycinemia a historic co-occurrence
Mol. Genet. Metab.
121
80-82
2017
Homo sapiens (P48728)
brenda
Simmons, R.M.; McKnight, S.M.; Edwards, A.K.; Wu, G.; Satterfield, M.C.
Obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats
Amino Acids
52
1413-1423
2020
Rattus norvegicus (Q5XI85)
brenda
Li, Y.; Fan, K.; Shen, J.; Wang, Y.; Jeyaraj, A.; Hu, S.; Chen, X.; Ding, Z.; Li, X.
Glycine-induced phosphorylation plays a pivotal role in energy metabolism in roots and amino acid metabolism in leaves of tea plant
Foods
12
334
2023
Camellia sinensis var. sinensis (A0A4S4DI93)
brenda
Leung, K.Y.; De Castro, S.C.P.; Galea, G.L.; Copp, A.J.; Greene, N.D.E.
Glycine cleavage system H protein is essential for embryonic viability, implying additional function beyond the glycine cleavage system
Front. Genet.
12
625120
2021
Mus musculus (Q8CFA2)
brenda
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