AMT is the mitochondrial aminomethyltransferase (T-protein) of the glycine cleavage system. After GLDC decarboxylates glycine and loads its remaining aminomethyl group onto lipoylated GCSH, AMT transfers the one-carbon unit to tetrahydrofolate and releases ammonia, producing 5,10-methylenetetrahydrofolate and reduced lipoyl-GCSH. DLD subsequently reoxidizes the carrier. This matrix-localized enzyme directly couples glycine degradation to folate-mediated one-carbon metabolism. The mature human enzyme has a three-domain fold enclosing a folate-binding cavity. Biallelic pathogenic AMT variants cause glycine encephalopathy (nonketotic hyperglycinemia), with variable clinical severity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004047 aminomethyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved GcvT enzyme catalyzes the AMT reaction. Reason: The cached PTHR43757 PAINT table places GO:0004047 at IBD node PTN000354058, with human AMT among the experimental descendant sources. Human T-protein structure and mutational evidence support the inherited chemistry; there is no target-specific divergence from this reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000354058 SUPPORTS TRANSFER The local PAINT IBD record for this node carries GO:0004047 and includes human P48728 experimental evidence among its descendants. No extant-donor count or target self-evidence objection is warranted; the complete tree/MSA was not independently reconstructed. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. |
| GO:0019464 glycine decarboxylation via glycine cleavage system | IBA GO_REF:0000033 | ACCEPT | Summary: AMT catalyzes the folate-dependent step of glycine cleavage. Reason: PAINT IBD node PTN000354060 carries GO:0019464. AMT itself performs aminomethyl transfer and ammonia release after the GLDC reaction, so its participation follows from positive catalytic work rather than disease necessity alone. The term describes the multienzyme cleavage pathway; it does not assign the GLDC decarboxylase reaction to AMT. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000354060 SUPPORTS TRANSFER The local PAINT IBD record carries GO:0019464; the target enzyme directly performs the folate-dependent glycine-cleavage step. No extant-donor count or target self-evidence objection is warranted; the complete tree/MSA was not independently reconstructed. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. Reactome:R-HSA-5693977 the decarboxylated moiety from glycine decarboxylation attached to H protein (GCSH:SAMDLL) is further degraded by mitochondrial aminomethyltransferase (AMT, GCST, T protein) to ammonia (NH3) and GCSH with reduced lipoate. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited mitochondrial location agrees with human AMT evidence. Reason: The cached PAINT IBD node PTN000354060 carries mitochondrial localization, with target experimental evidence among its descendants. Human antibody localization and the mitochondrial glycine-cleavage reaction support the organelle-level assertion. Its original resolution is appropriate even though separate evidence places the reaction in the matrix. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000354060 SUPPORTS TRANSFER The local PAINT IBD record carries GO:0005739; human target evidence is legitimate grounding for inherited mitochondrial localization. No extant-donor count or target self-evidence objection is warranted; the complete tree/MSA was not independently reconstructed. Supporting Evidence: file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0004047 aminomethyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined mapping recovers the experimentally established aminomethyltransferase reaction. Reason: The source identifiers are InterPro:IPR006223, EC:2.1.2.10 and RHEA:16945. The live GO:0004047 definition and the cached UniProt reaction specify aminomethyl-lipoyl carrier plus tetrahydrofolate yielding reduced carrier, 5,10-methylene-THF and ammonium. This is the specific T-protein chemistry. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006223 SUPPORTS TRANSFER GcvT family assignment in the immutable UniProt record agrees with human T-protein chemistry. EC:2.1.2.10 SUPPORTS TRANSFER This enzyme classification identifies the specific aminomethyltransferase reaction. RHEA:16945 SUPPORTS TRANSFER The reaction cross-reference matches the live GO definition and immutable UniProt stoichiometry. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. file:human/AMT/AMT-uniprot.txt Xref=Rhea:RHEA:16945 |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt compartment mapping correctly retains mitochondrial localization. Reason: The proximate source is UniProtKB-SubCell:SL-0173. The curated UniProt mitochondrial location is independently supported by human HPA staining and the matrix-localized AMT reaction in Reactome. The mapping does not itself resolve a submitochondrial compartment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0173 SUPPORTS TRANSFER The source vocabulary maps the curated mitochondrial location at its original organelle resolution. Supporting Evidence: file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005960 glycine cleavage complex | IEA GO_REF:0000002 | ACCEPT | Summary: AMT supplies the T-protein catalytic component of the glycine cleavage system. Reason: The GcvT InterPro mapping agrees with the defined P/T/H/L glycine-cleavage system and the human Reactome pathway. Complex membership is a functional multienzyme-system assertion; it does not establish an invariant stoichiometry or assign the other components' catalytic activities to AMT. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006223 SUPPORTS TRANSFER The GcvT assignment is consistent with AMT being the T-protein component of the independently documented glycine-cleavage system. Supporting Evidence: file:human/AMT/AMT-uniprot.txt The glycine cleavage system is composed of four proteins: P, T, L and H. Reactome:R-HSA-6783984 The major pathway is via the glycine cleavage system, comprising dimeric P protein (GLDC), T protein (AMT, GCST), dimeric L protein (DLD) and H protein (GCSH) |
| GO:0006546 glycine catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: The automated glycine-catabolism assignment captures AMT catalytic participation. Reason: The InterPro and ARBA sources assign a broad but true core process. AMT transforms the glycine-derived carrier intermediate and supplies folate-bound one-carbon product; this is direct participation in glycine breakdown. The more specific cleavage-system term is already independently represented. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006223 SUPPORTS TRANSFER The GcvT family mapping agrees with the actual T-protein catabolic step. ARBA:ARBA00085463 UNRESOLVED The rule identifier is present in the source record; its complete condition set was not independently recovered. Positive target chemistry supports the annotation without treating the rule label as experimental evidence. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. Reactome:R-HSA-6783984 The major pathway is via the glycine cleavage system, comprising dimeric P protein (GLDC), T protein (AMT, GCST), dimeric L protein (DLD) and H protein (GCSH) |
| GO:0006546 glycine catabolic process | TAS Reactome:R-HSA-6783984 | ACCEPT | Summary: The curated human glycine-degradation pathway includes the AMT reaction. Reason: R-HSA-6783984 explicitly includes AMT/T-protein and the child reaction R-HSA-5693977. The latter identifies AMT as the catalyst converting carrier-bound glycine-derived aminomethyl groups into ammonia and folate-bound one-carbon product. This positive catalytic role supports the broad core process. Supporting Evidence: Reactome:R-HSA-6783984 The major pathway is via the glycine cleavage system, comprising dimeric P protein (GLDC), T protein (AMT, GCST), dimeric L protein (DLD) and H protein (GCSH) Reactome:R-HSA-5693977 the decarboxylated moiety from glycine decarboxylation attached to H protein (GCSH:SAMDLL) is further degraded by mitochondrial aminomethyltransferase (AMT, GCST, T protein) to ammonia (NH3) and GCSH with reduced lipoate. |
| GO:0004047 aminomethyltransferase activity | EXP PMID:16051266 Crystal structure of human T-protein of glycine cleavage sys... | ACCEPT | Summary: Human T-protein structural and biochemical evidence supports the specific enzyme activity. Reason: PMID:16051266 reports human T-protein structures and mutational analysis. The RCSB 1WSR/1WSV records independently identify human P48728 expressed in E. coli, distinguishing the enzyme species from its expression host. The local record is abstract-only; full kinetic conditions are not inferred from the structure or curator evidence code. The reaction itself is explicit and agrees with UniProt. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. PMID:16051266 crystal structures of human T-protein in free form and that bound to 5-methyltetrahydrofolate (5-CH3-H4folate) have been determined at 2.0 A and 2.6 A resolution, respectively. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence supports mitochondrial AMT. Reason: The directly inspected AMT HPA page reports supported mitochondrial localization with antibody HPA005566 in HeLa and Hep-G2; U2OS has no staining in the listed assay. It also reports an additional nucleoplasmic signal, so the evidence is not an exclusivity claim. This supports the seeded mitochondrion IDA at organelle resolution, not a microscopy-derived matrix assignment. Source: https://www.proteinatlas.org/ENSG00000145020-AMT/subcellular. Supporting Evidence: file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: The mitochondrial-proteome annotation agrees with independent human localization. Reason: PMID:34800366 describes quantitative fractionation, importomics and database/literature integration using human cell lines. Its cached full body was inspected, but the exact AMT supplement row was not independently recovered. The seeded HTP assertion is retained with curator deference because direct HPA mitochondrial staining and the independently modeled AMT reaction support this location. No AMT-specific abundance, peptide count or matrix resolution is inferred from the global MitoCoP total. Supporting Evidence: PMID:34800366 We defined a human mitochondrial high-confidence proteome (MitoCoP) of 1,134 protein-coding genes file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | IC PMID:16051266 Crystal structure of human T-protein of glycine cleavage sys... | ACCEPT | Summary: Mitochondrial location is a reasonable inference from the established AMT pathway. Reason: The original IC source links the glycine-cleavage process GO:0019464 to mitochondrion. This agrees with the human enzyme, the curated AMT location and direct HPA staining. The inference is retained at the original organelle level; it is not presented as localization measured in the crystal experiment. Supporting Evidence: file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. |
| GO:0004047 aminomethyltransferase activity | IMP PMID:16051266 Crystal structure of human T-protein of glycine cleavage sys... | ACCEPT | Summary: Human T-protein mutational analysis supports aminomethyltransferase activity. Reason: The primary abstract explicitly reports structural and mutational analysis of the folate-binding region. UniProt attributes loss of activity for precursor Asp129 substitutions to this paper; the abstract uses mature-protein Asp101/Arg292, corresponding to precursor Asp129/Arg320 after the 28-residue targeting segment. These records support the specific catalytic assertion, while the full assay protocol and each disease-variant activity were not independently read. Supporting Evidence: PMID:16051266 Structural and mutational analyses demonstrated that Arg292 interacts through water molecules with the folate polyglutamate tail file:human/AMT/AMT-uniprot.txt D->A,N: Loss of aminomethyltransferase activity. |
| GO:0019464 glycine decarboxylation via glycine cleavage system | IMP PMID:16051266 Crystal structure of human T-protein of glycine cleavage sys... | ACCEPT | Summary: AMT catalytic impairment disrupts the glycine-cleavage reaction. Reason: The human T-protein performs aminomethyl transfer within the glycine-cleavage pathway, and the source combines structural and mutational analyses relevant to that reaction. Its direct catalytic step establishes participation; the disease phenotype is corroboration rather than the sole argument. Patient-liver T-protein deficiency in PMID:9600239 provides independent human evidence without implying that the 2005 crystal assay was an intact-cell flux measurement. Supporting Evidence: PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. PMID:9600239 Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-5693977 | ACCEPT | Summary: Reactome explicitly places the human AMT catalyst in the mitochondrial matrix. Reason: The live R-HSA-5693977 record lists AMT [mitochondrial matrix] as its catalyst and places the carrier substrate and folate reaction participants in that compartment. The cached summary independently describes the reaction but omits the participant compartment fields; the exact primary-page access receipt is in the notes. This supports the original TAS matrix annotation without attributing matrix resolution to HPA or proteomic measurements. Supporting Evidence: Reactome:R-HSA-5693977 the decarboxylated moiety from glycine decarboxylation attached to H protein (GCSH:SAMDLL) is further degraded by mitochondrial aminomethyltransferase (AMT, GCST, T protein) to ammonia (NH3) and GCSH with reduced lipoate. file:human/AMT/AMT-notes.md The live R-HSA-5693977 Catalyst Activity field reads: aminomethyltransferase activity of AMT [mitochondrial matrix]. |
| GO:0005739 mitochondrion | TAS PMID:8188235 Structure and chromosomal localization of the aminomethyltra... | ACCEPT | Summary: The historical TAS mitochondrial assertion agrees with independent localization evidence. Reason: PMID:8188235 is a human placental-library genomic and chromosomal mapping study. Its accessible abstract identifies T-protein but does not explicitly describe a mitochondrial-localization assay; the earlier review overstated that abstract. Retain the curator's TAS assertion because independent HPA staining and UniProt support mitochondria, while keeping the original full-text statement and the listed 1994 erratum content unresolved. Supporting Evidence: file:human/AMT/AMT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006546 glycine catabolic process | TAS PMID:9600239 A missense mutation (His42Arg) in the T-protein gene from a ... | ACCEPT | Summary: Human T-protein deficiency supports AMT's role in glycine catabolism. Reason: PMID:9600239 measures deficient T-protein activity in a liver specimen from one affected individual and reports H42R segregation in the kindred. This supports the human catabolic pathway in combination with the established aminomethyltransferase chemistry. The abstract does not independently demonstrate the isolated H42R enzyme's kinetic defect, so association and the patient-tissue enzyme measurement are distinguished. Supporting Evidence: PMID:9600239 Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. PMID:16051266 catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein. |
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