Summary: A one-carbon group transferase that transfers lipoamide-linked methylamine groups to tetrahydrofolate (TETRAHYDROFOLATES) to form methylenetetrahydrofolate and AMMONIA. It is one of four components of the glycine decarboxylase complex.

Top Publications

  1. Kure S, Kato K, Dinopoulos A, Gail C, DeGrauw T, Christodoulou J, et al. Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia. Hum Mutat. 2006;27:343-52 pubmed
    ..Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms. This study provides a comprehensive picture of the genetic background of NKH as it is known to date...
  2. Nanao K, Takada G, Takahashi E, Seki N, Komatsu Y, Okamura Ikeda K, et al. Structure and chromosomal localization of the aminomethyltransferase gene (AMT). Genomics. 1994;19:27-30 pubmed
    The gene for human aminomethyltransferase (AMT), also known as the T-protein of the glycine cleavage system, was isolated from a human placental cosmid library and examined by restriction mapping, polymerase chain reaction analysis, and ..
  3. Harada A, Kamimura N, Takeuchi K, Yu H, Masai E, Senda T. The crystal structure of a new O-demethylase from Sphingobium sp. strain SYK-6. FEBS J. 2017;284:1855-1867 pubmed publisher
  4. Ghrist A, Stauffer G. Characterization of the Escherichia coli gcvR gene encoding a negative regulator of gcv expression. J Bacteriol. 1995;177:4980-4 pubmed
    ..Models explaining how GcvR and GcvA might interact to regulate gcv expression are proposed. ..
  5. McNeil J, Zhang F, Taylor B, Sinclair D, Pearlman R, Bognar A. Cloning, and molecular characterization of the GCV1 gene encoding the glycine cleavage T-protein from Saccharomyces cerevisiae. Gene. 1997;186:13-20 pubmed
    ..Growth of shm1 shm2 mutants was stimulated by glycine, whereas glycine could not supplement the growth of the isogenic gcv1 strain. ..
  6. Okamura Ikeda K, Fujiwara K, Motokawa Y. The amino-terminal region of the Escherichia coli T-protein of the glycine cleavage system is essential for proper association with H-protein. Eur J Biochem. 1999;264:446-53 pubmed
    ..These results suggest that EH, when it interacts with ET, causes a change in conformation of ET and that the N-terminal region of ET is essential for the conformational change leading to the proper interaction with EH. ..
  7. Leeb T, Breen M, Brenig B. Genomic structures and sequences of two closely linked genes (AMT, TCTA) on dog chromosome 20q15.1-->q15.2. Cytogenet Cell Genet. 2000;89:98-100 pubmed
    ..The two genes represent the corresponding canine orthologs of human aminomethyltransferase (AMT) and the human T-cell leukemia translocation associated (TCTA) gene...
  8. Stauffer L, Stauffer G. Roles for GcvA-binding sites 3 and 2 and the Lrp-binding region in gcvT::lacZ expression in Escherichia coli. Microbiology. 1998;144 ( Pt 10):2865-72 pubmed
    ..Based on these results, a model for gcv regulation is presented in which Lrp plays a primarily structural role, by bending the DNA and GcvA functions as the activator protein. ..
  9. Kure S, Shinka T, Sakata Y, Osamu N, Takayanagi M, Tada K, et al. A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia. J Hum Genet. 1998;43:135-7 pubmed
    ..Familial analysis revealed that the 183delC and the D276H mutations were inherited from the father and the mother, respectively. This is the first report of T-protein gene mutation in Oriental patients with nonketotic hyperglycinemia. ..

More Information


  1. Stauffer L, Stauffer G. Spacing and orientation requirements of GcvA-binding sites 3 and 2 and the Lrp-binding region for gcvT::lacZ expression in Escherichia coli. Microbiology. 1998;144 ( Pt 5):1417-22 pubmed
    ..Because of the location of these target sites relative to the gcv promoter, it is also likely that DNA looping is required for this mechanism of regulation. ..
  2. Hayasaka K, Nanao K, Takada G, Okamura Ikeda K, Motokawa Y. Isolation and sequence determination of cDNA encoding human T-protein of the glycine cleavage system. Biochem Biophys Res Commun. 1993;192:766-71 pubmed
    ..RNA blot analysis of human liver transcripts and Southern blot analysis of human genomic DNA confirm that human T-protein is encoded by a single gene. ..
  3. Inaoka D, Takashima E, Osanai A, Shimizu H, Nara T, Aoki T, et al. Expression, purification and crystallization of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with orotate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005;61:875-8 pubmed
    ..87, b = 71.89, c = 123.27 A. The presence of two molecules in the asymmetric unit (2 x 34 kDa) gives a crystal volume per protein weight (VM) of 2.2 A3 Da(-1) and a solvent content of 44%. ..
  4. Vivekananda J, Beck C, Oliver D. Monoclonal antibodies as tools in membrane biochemistry. Identification and partial characterization of the dicarboxylate transporter from pea leaf mitochondria. J Biol Chem. 1988;263:4782-8 pubmed
    ..The techniques described should prove useful for identifying a number of membrane proteins that can be assayed in situ but are difficult to assay following dissolution of the membrane. ..
  5. Applegarth D, Toone J. Glycine encephalopathy (nonketotic hyperglycinemia): comments and speculations. Am J Med Genet A. 2006;140:186-8 pubmed
  6. Lee H, Kim D, Ahn H, Ha J, Suh S. 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. 2004;279:50514-23 pubmed publisher
    ..T-protein, one of the four components of the glycine cleavage system,is a tetrahydrofolate dependent aminomethyltransferase. It catalyzes the transfer of the methylene carbon unit to tetrahydrofolate from the methylamine group ..
  7. Backofen B, Leeb T. Genomic organization of the murine aminomethyltransferase gene (Amt). DNA Seq. 2002;13:179-83 pubmed
    b>Aminomethyltransferase (Amt), also called glycine cleavage system T-protein is an important enzyme in glycine metabolism (EC Mutations in this gene in humans lead to nonketotic hyperglycinemia, a fatal Mendelian disease...
  8. Eisenhut M, Bauwe H, Hagemann M. Glycine accumulation is toxic for the cyanobacterium Synechocystis sp. strain PCC 6803, but can be compensated by supplementation with magnesium ions. FEMS Microbiol Lett. 2007;277:232-7 pubmed
    ..The toxic effect could be alleviated by addition of MgCl(2), suggesting that glycine might be toxic by reducing intracellular Mg(2+) ions, which are essential for many vital processes. ..
  9. Okamura Ikeda K, Hosaka H, Maita N, Fujiwara K, Yoshizawa A, Nakagawa A, et al. 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. 2010;285:18684-92 pubmed publisher
    b>Aminomethyltransferase, a component of the glycine cleavage system termed T-protein, reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ..
  10. Steiert P, Stauffer L, Stauffer G. The lpd gene product functions as the L protein in the Escherichia coli glycine cleavage enzyme system. J Bacteriol. 1990;172:6142-4 pubmed
    ..Enzyme levels were restored to normal under these growth conditions when the strain was transformed with a plasmid encoding a functional lpd gene. ..
  11. Okamura Ikeda K, Fujiwara K, Motokawa Y. Molecular cloning of a cDNA encoding chicken T-protein of the glycine cleavage system and expression of the functional protein in Escherichia coli. Effect of mRNA secondary structure in the translational initiation region on expression. J Biol Chem. 1992;267:18284-90 pubmed
    ..NH2-terminal amino acid sequence analysis (9 residues) revealed 100% identity with chicken T-protein determined chemically. The kinetic properties of the recombinant T-protein resembled those of the native chicken T-protein. ..
  12. Kochi H, Seino H, Ono K. Inhibition of glycine oxidation by pyruvate, alpha-ketoglutarate, and branched-chain alpha-keto acids in rat liver mitochondria: presence of interaction between the glycine cleavage system and alpha-keto acid dehydrogenase complexes. Arch Biochem Biophys. 1986;249:263-72 pubmed
  13. Lokanath N, 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 D Biol Crystallogr. 2004;60:1450-2 pubmed
    ..980, b = 95.708, c = 118.331 A. Assuming one homodimer per asymmetric unit gives a VM value of 2.4 A3 Da(-1) and a solvent content of 49.0%. ..
  14. Takatsuru Y, Eto K, Kaneko R, Masuda H, Shimokawa N, Koibuchi N, et al. Critical role of the astrocyte for functional remodeling in contralateral hemisphere of somatosensory cortex after stroke. J Neurosci. 2013;33:4683-92 pubmed publisher
    ..Our study has provided new insights into the mechanisms underlying synaptic remodeling after cerebral infarction, which contributes to the development of effective therapeutic approaches for patients after a stroke. ..
  15. Narisawa A, Komatsuzaki S, Kikuchi A, Niihori T, Aoki Y, Fujiwara K, et al. Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Hum Mol Genet. 2012;21:1496-503 pubmed publisher
    ..Overall, our findings suggest that loss-of-function mutations in GCS genes predispose to NTDs in mice and humans. These data highlight the importance of adequate function of mitochondrial folate metabolism in neural tube closure...
  16. Stauffer L, Ghrist A, Stauffer G. The Escherichia coli gcvT gene encoding the T-protein of the glycine cleavage enzyme system. DNA Seq. 1993;3:339-46 pubmed
    ..Single basepair changes were made in the promoter -10 and -35 sequences. These mutations significantly reduced expression from a gcvT-lacZ gene fusion. The gcvT gene is transcribed and translated in the same direction as the gcvH gene. ..
  17. Toone J, Applegarth D, Levy H, Coulter Mackie M, Lee G. Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH). Mol Genet Metab. 2003;79:272-80 pubmed
    ..The co-occurrence of the polymorphism E211K with the mutation R320H in patients with a severe phenotype is discussed...
  18. 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. 2003;278:10067-72 pubmed publisher
    ..The polyglutamyl tail of the folate substrate may be inserted into the bosom of the cavity leaving the pteridine ring near the entrance of the cavity in the context of the catalytic reaction...
  19. Piper M, Hong S, Ball G, Dawes I. Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae. J Biol Chem. 2000;275:30987-95 pubmed
    ..When glycine is in excess, 5, 10-CH(2)-H(4)folate is decreased, and the regulation loop shifts the balance of generation of one-carbon units into the mitochondrion. ..
  20. Stauffer L, Stauffer G. Role for the leucine-responsive regulatory protein (Lrp) as a structural protein in regulating the Escherichia coli gcvTHP operon. Microbiology. 1999;145 ( Pt 3):569-76 pubmed
    ..The results are consistent with Lrp playing primarily a structural role in gcv regulation, although they do not completely rule out the possibility that Lrp also interacts with another gcv-regulatory protein or with RNA polymerase. ..
  21. Orun O, Koch M, Kan B, Svergun D, Petoukhov M, Sayers Z. Structural characterization of T-protein of the Escherichia coli glycine cleavage system by X-ray small angle scattering. Cell Mol Biol (Noisy-le-grand). 2003;49 Online Pub:OL453-9 pubmed
    ..A low resolution model of the protein was constructed ab initio and tentative models of the tertiary structure were built using prediction methods constrained by the scattering data. ..
  22. 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. 1999;274:17471-7 pubmed
  23. Toone J, Applegarth D, Coulter Mackie M, James E. 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. 2001;72:322-5 pubmed
    ..allele frequencies of 5% for R515S of P-protein (glycine decarboxylase) and 7% for R320H of T-protein (aminomethyltransferase)...
  24. Okamura Ikeda K, Hosaka H, Yoshimura M, Yamashita E, Toma S, Nakagawa A, et al. 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. 2005;351:1146-59 pubmed
    ..A clever mechanism of recruiting the aminomethyl lipoate arm to the reaction site seems to function as a way of avoiding the release of toxic formaldehyde...
  25. Hiraga K, Kochi H, Hayasaka K, Kikuchi G, Nyhan W. Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein. J Clin Invest. 1981;68:525-34 pubmed
    ..The content of H-protein in the liver of the patient was approximately 35% of that of control human liver. ..
  26. Hong S, Piper M, Sinclair D, Dawes I. Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae is mediated by a tetrahydrofolate-responsive protein binding to a glycine regulatory region including a core 5'-CTTCTT-3' motif. J Biol Chem. 1999;274:10523-32 pubmed
    ..Tetrahydrofolate or a derivative may act as a ligand for the transcription factor controlling expression of one-carbon metabolism genes. ..
  27. Pardal Fernández J, Carrascosa Romero M, de Cabo de la Vega C, Iniesta López I, Gil Pons E, Martínez Gutiérrez A. Atypical glycine encephalopathy in an extremely low birth weight infant: description of a new mutation and clinical and electroencephalographic analysis. Epileptic Disord. 2009;11:48-53 pubmed publisher
    ..Genetic analysis showed a non-previously described mutation affecting a consensus splice site (IVS2-1G > C 3) in the AMT gene encoding the T protein of the glycine cleavage system. ..
  28. Fujiwara K, Okamura Ikeda K, Motokawa Y. cDNA sequence, in vitro synthesis, and intramitochondrial lipoylation of H-protein of the glycine cleavage system. J Biol Chem. 1990;265:17463-7 pubmed
  29. Kure S, Mandel H, Rolland M, Sakata Y, Shinka T, Drugan A, et al. A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia. Hum Genet. 1998;102:430-4 pubmed
    ..The availability of DNA testing facilitates the prenatal diagnosis of NKH and the identification of carriers, which is necessary for genetic counseling in the affected families. ..
  30. Vallée M, Guay F, Beaudry D, Matte J, Blouin R, Laforest J, et al. Effects of breed, parity, and folic Acid supplement on the expression of folate metabolism genes in endometrial and embryonic tissues from sows in early pregnancy. Biol Reprod. 2002;67:1259-67 pubmed
  31. Nanao K, Okamura Ikeda K, Motokawa Y, Danks D, Baumgartner E, Takada G, et al. Identification of the mutations in the T-protein gene causing typical and atypical nonketotic hyperglycinemia. Hum Genet. 1994;93:655-8 pubmed
    ..coli. The mutation occurring in more conservative amino acid residues thus results in more deleterious damage to the T-protein, and gives the severe clinical phenotype, viz., typical NKH. ..
  32. Stauffer L, Stauffer G. Characterization of the gcv control region from Escherichia coli. J Bacteriol. 1994;176:6159-64 pubmed
    ..The results suggest that the gcv regulatory region is complex, with numerous cis-acting sites that are required for normal gcv expression. ..
  33. Jourdan A, Stauffer G. GcvA-mediated activation of gcvT-lacZ expression involves the carboxy-terminal domain of the alpha subunit of RNA polymerase. FEMS Microbiol Lett. 1999;181:307-12 pubmed
    ..Amino acid residues in the alphaCTD important for GcvA-dependent activation, however, have no effect on GcvA-mediated repression of the operon. ..