aminomethyltransferase

アミノメチルトランスフェラーゼ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/10/29 04:36:32」(JST)

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AMT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WSR, 1WSV
Identifiers
Aliases	AMT, aminomethyltransferase, GCE, GCST, GCVT, NKH
External IDs	MGI: 3646700 HomoloGene: 409 GeneCards: AMT
Gene location (Human) Chr. Chromosome 3 (human) Band 3p21.31 Start 49,416,775 bp End 49,422,753 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9|9 F1 Start 108,296,853 bp End 108,302,302 bp
Gene ontology Molecular function • transferase activity • transaminase activity • aminomethyltransferase activity Cellular component • mitochondrial matrix • nucleoplasm • mitochondrion Biological process • methylation • glycine catabolic process • glycine decarboxylation via glycine cleavage system Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	275	434437
Ensembl	ENSG00000145020	ENSMUSG00000032607
UniProt	P48728	Q8CFA2
RefSeq (mRNA)	NM_000481 NM_001164710 NM_001164711 NM_001164712	NM_001013814
RefSeq (protein)	NP_000472 NP_001158182 NP_001158183 NP_001158184	NP_001013836
Location (UCSC)	Chr 3: 49.42 – 49.42 Mb	Chr 3: 108.3 – 108.3 Mb
PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Aminomethyltransferase
Identifiers
EC number	2.1.2.10
CAS number	37257-08-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Aminomethyltransferase
Crystallographic structure of human AMT.
Identifiers
Symbol	AMT
Entrez	275
HUGO	AMT 473 AMT
OMIM	238310
PDB	1WSR
RefSeq	NM_000481
UniProt	P48728
Other data
EC number	2.1.2.10
Locus	Chr. 3 p21.2-21.1

Aminomethyltransferase is an enzyme that catabolizes the creation of methylenetetrahydrofolate. It is part of the glycine decarboxylase complex.

Structure

The gene is about 6 kb in length and consists of nine exons. The 5′-flanking region of the gene lacks typical TATAA sequence but has a single defined transcription initiation site detected by the primer extension method. Two putative glucocorticoid-responsive elements and a putative thyroid hormone-responsive element are present. The AMT gene has been localized to 3p21.2-p21.1 by fluorescence in situ hybridization. The 1209 base pair open reading frame encodes 403 amino acid precursor protein, and the deduced amino acid sequence of the mature peptide shows 90 and 68% homology to that of bovine and chicken counterpart, respectively.

The protein encoded by this gene has its crystal structure resolved at 2 Angstroms. The most recent model contains two monomers related by a non-crystallographic 2-fold axis, 1176 water molecules, and 11 molecules sulfate ions in an asymmetric unit. Several dimeric interactions are observed among the residues on the N-terminal loop, on α-helix D, and the flank on either side of β-strand 8 of the two monomers.

Function

The protein encoded by AMT catalyzes the release of ammonia and the transfer of a methylene carbon unit to a tetrahydrofolate moiety. The aminomethyl intermediate is the product of the decarboxylation of glycine catalyzed by P-protein. In the reverse reaction, T-protein catalyzes the formation of the H-protein-bound aminomethyl lipoate intermediate from 5,10-CH2-H4folate, ammonia, and reduced H-protein via an ordered Ter Bi mechanism, in which reduced H-protein is the first substrate to bind followed by 5,10-CH2-H4folate and ammonia.

Clinical significance

Mutations in the AMT gene are associated with Glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), which is an inborn error of glycine metabolism defined by deficient activity of the glycine cleavage enzyme and, as a consequence, accumulation of large quantities of glycine in all body tissues including the brain. The majority of glycine encephalopathy presents in the neonatal period (85% as the neonatal severe form and 15% as the neonatal attenuated form). Of those presenting in infancy, 50% have the infantile attenuated form and 50% have the infantile severe form. Overall, 20% of all children presenting as either neonates or infants have a less severe outcome, defined as developmental quotient greater than 20. A minority of patients have mild or atypical forms of glycine encephalopathy. The neonatal form manifests in the first hours to days of life with progressive lethargy, hypotonia, and myoclonic jerks leading to apnea and often death. Surviving infants have profound intellectual disability and intractable seizures. The infantile form is characterized by hypotonia, developmental delay, and seizures. The atypical forms range from milder disease, with onset from late infancy to adulthood, to rapidly progressing and severe disease with late onset. Glycine encephalopathy is suspected in individuals with elevated glycine concentration in blood and CSF. An increase in CSF glycine concentration together with an increased CSF-to-plasma glycine ratio suggests the diagnosis. Enzymatic confirmation of the diagnosis relies on measurement of glycine cleavage system (GCS) enzyme activity in liver obtained by open biopsy or autopsy. The majority of affected individuals have no detectable enzyme activity. The three genes in which biallelic mutations are known to cause glycine encephalopathy are: GLDC (encoding the P-protein component of the GCS complex and accounting for 70%-75% of disease), AMT (accounting for ~20% of disease), and GCSH (encoding the H-protein component of the GCS complex and accounting for <1% of disease). About 5% of individuals with enzyme-proven glycine encephalopathy do not have a mutation in any of these three genes and have a variant form of glycine encephalopathy.

External links

• aminomethyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human AMT genome location and AMT gene details page in the UCSC Genome Browser.

English Journal

• Mutation analysis of GLDC, AMT and GCSH in cataract captive-bred vervet monkeys (Chlorocebus aethiops).

• Chauke CG1, Magwebu ZE1,2, Sharma JR3, Arieff Z3, Seier JV1.
• Journal of medical primatology.J Med Primatol.2016 Jun 21. doi: 10.1111/jmp.12219. [Epub ahead of print]
• BACKGROUND: Non-ketotic hyperglycinaemia (NKH) is an autosomal recessive inborn error of glycine metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms.METHODS: This study describes the first screening of NKH in cataract captive-bred vervet monkeys (Chlo
• PMID 27325422

• A novel AMT gene mutation in a newborn with nonketotic hyperglycinemia and early myoclonic encephalopathy.

• Belcastro V1, Barbarini M2, Barca S3, Mauro I2.
• European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.Eur J Paediatr Neurol.2016 Jan;20(1):192-5. doi: 10.1016/j.ejpn.2015.08.008. Epub 2015 Sep 5.
• Early myoclonic encephalopathy (EME) presents in neonatal period with erratic or fragmentary myoclonus and a burst-suppression electroencephalography (EEG) pattern. Nonketotic hyperglycinemia (NKH) is the most common metabolic cause of EME and genetic testing confirms the diagnosis of NKH in around
• PMID 26371980

• Two novel missense mutations in nonketotic hyperglycinemia.

• Yilmaz BS1, Kor D2, Ceylaner S3, Mert GG4, Incecik F4, Kartal E2, Mungan NO2.
• Journal of child neurology.J Child Neurol.2015 May;30(6):789-92. doi: 10.1177/0883073814535499. Epub 2014 May 16.
• Nonketotic hyperglycinemia (OMIM no. 605899) is an autosomal recessively inherited glycine encephalopathy, caused by a deficiency in the mitochondrial glycine cleavage system. Here we report 2 neonates who were admitted to the hospital with complaints of respiratory failure and myoclonic seizures wi
• PMID 24838951

Japanese Journal

• Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy

• Journal of human genetics 59(11), 593-597, 2014-11
• NAID 40020269636

• 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

• JOURNAL OF BIOLOGICAL CHEMISTRY 285(24), 18684-18692, 2010
• NAID 80021098396

• Structure and chromosomal localization of the aminomethyltransferase gene (AMT)

• Genomics 19, 27-30, 1994
• NAID 80007419926

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aminomethyltransferase