GPT encodes cytosolic alanine aminotransferase ALT1, a homodimeric pyridoxal 5'-phosphate-dependent enzyme. It catalyzes reversible transamination of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate, linking alanine turnover with glucose and amino-acid metabolism. Human liver protein has been purified and characterized, and ALT1 is detected in tissues including liver and kidney. Alanine breakdown supplies pyruvate for further metabolism, while reverse flux can produce alanine. ALT1 can also be detected in plasma and extracellular vesicle preparations; these observations do not establish secretion as its defining physiological function. The related mitochondrial enzyme is encoded by GPT2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004021 L-alanine:2-oxoglutarate transaminase activity | IDA PMID:11863375 cDNA cloning, genomic structure, chromosomal mapping, and fu... | ACCEPT | Summary: Alanine:2-oxoglutarate transamination is the defining native enzyme activity. Reason: Native human ALT activity is directly established by isoform-specific biochemical characterization in PMID:19360321. The original PMID:11863375 chiefly reports the cloned GPT2 enzyme; this does not invalidate the correctly assigned activity of human GPT, independently established by purified liver protein in PMID:1931970. Do not infer wrong-gene curation from an abstract emphasizing its paralog. Supporting Evidence: PMID:11863375 Alanine aminotransferase (ALT) catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate PMID:19360321 ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different Km and kcat values |
| GO:0004021 L-alanine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Alanine:2-oxoglutarate transamination is the defining native enzyme activity. Reason: Native human ALT activity is directly established by isoform-specific biochemical characterization in PMID:19360321. The original PMID:11863375 chiefly reports the cloned GPT2 enzyme; this does not invalidate the correctly assigned activity of human GPT, independently established by purified liver protein in PMID:1931970. Do not infer wrong-gene curation from an abstract emphasizing its paralog. Supporting Evidence: PMID:11863375 Alanine aminotransferase (ALT) catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate PMID:19360321 ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different Km and kcat values |
| GO:0004021 L-alanine:2-oxoglutarate transaminase activity | NAS PMID:1931970 Complete amino acid sequence of human liver cytosolic alanin... | ACCEPT | Summary: Alanine:2-oxoglutarate transamination is the defining native enzyme activity. Reason: Native human ALT activity is directly established by isoform-specific biochemical characterization in PMID:19360321. The original PMID:11863375 chiefly reports the cloned GPT2 enzyme; this does not invalidate the correctly assigned activity of human GPT, independently established by purified liver protein in PMID:1931970. Do not infer wrong-gene curation from an abstract emphasizing its paralog. Supporting Evidence: PMID:11863375 Alanine aminotransferase (ALT) catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate PMID:19360321 ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different Km and kcat values |
| GO:0005576 extracellular region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ALT1 is detectable extracellularly in human plasma. Reason: PMID:19360321 independently immunoprecipitates and detects both ALT isoenzymes in plasma. Retain the location as contextual; detection can reflect release from tissues and does not identify an extracellular catalytic or secretory function. Supporting Evidence: PMID:19360321 both ALT1 and 2 were immunoprecipitated from human plasma |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Refine the broad cytoplasmic location to the supported cytosol. Reason: Human liver purification and human hepatocyte fractionation support cytosolic ALT1, already represented by the more precise rows. The reported additional ER fraction does not alter the core cytosolic assignment or establish an ER-specific enzyme function. Proposed replacements: cytosol Supporting Evidence: PMID:19360321 ALT1 was only localised to the cytosol and ER, with no detection in mitochondria. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: The mature ALT1 enzyme acts in the cytosol. Reason: Human hepatocyte fractionation in PMID:19360321 and purified cytosolic liver enzyme in PMID:1931970 independently support the curated compartment. Reactome forward/reverse records describe the same reversible reaction rather than separate localization experiments. Supporting Evidence: PMID:19360321 ALT1 was only localised to the cytosol and ER, with no detection in mitochondria. PMID:1931970 human liver cytosolic alanine aminotransferase |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70523 | ACCEPT | Summary: The mature ALT1 enzyme acts in the cytosol. Reason: Human hepatocyte fractionation in PMID:19360321 and purified cytosolic liver enzyme in PMID:1931970 independently support the curated compartment. Reactome forward/reverse records describe the same reversible reaction rather than separate localization experiments. Supporting Evidence: PMID:19360321 ALT1 was only localised to the cytosol and ER, with no detection in mitochondria. PMID:1931970 human liver cytosolic alanine aminotransferase |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70524 | ACCEPT | Summary: The mature ALT1 enzyme acts in the cytosol. Reason: Human hepatocyte fractionation in PMID:19360321 and purified cytosolic liver enzyme in PMID:1931970 independently support the curated compartment. Reactome forward/reverse records describe the same reversible reaction rather than separate localization experiments. Supporting Evidence: PMID:19360321 ALT1 was only localised to the cytosol and ER, with no detection in mitochondria. PMID:1931970 human liver cytosolic alanine aminotransferase |
| GO:0008483 transaminase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine general transaminase activity to alanine aminotransferase. Reason: Both canonical human enzymes have directly measured alanine/pyruvate transamination. The existing GO:0004021 term is the supported precise descendant; the general chemistry is true. Proposed replacements: L-alanine:2-oxoglutarate transaminase activity Supporting Evidence: PMID:19360321 ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different Km and kcat values |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: PLP is the catalytic cofactor of this alanine aminotransferase. Reason: The class-I aminotransferase family and curated cofactor assignment support PLP dependence. Human GPT2 structure PDB 3IHJ, described by Reactome, contains PLP; human GPT sequence/biochemistry supports the homologous cofactor mechanism. This is enzyme cofactor chemistry, not a second independent physiological function. Supporting Evidence: file:human/GPT/GPT-uniprot.txt Name=pyridoxal 5'-phosphate Reactome:R-HSA-507749 one molecule of pyridoxal phosphate associated with each monomer |
| GO:0042853 L-alanine catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Alanine transamination directly executes alanine catabolism. Reason: The alanine-to-pyruvate direction is measured in native human enzyme assays and represented by the curated reaction. Reversibility and alanine synthesis in other conditions do not invalidate this direct catabolic role. Supporting Evidence: PMID:19360321 ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different Km and kcat values PMID:11863375 Alanine aminotransferase (ALT) catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Retain the curated detection in human urinary exosome preparations. Reason: The original human urinary-vesicle proteomic study supports a contextual compartment observation. Its abstract describes the large-scale assay but not the target-specific peptide table; accept the curator assignment conservatively without claiming that every peptide was independently inspected or that ALT1 has a dedicated vesicle function. No contamination claim is inferred from its usual cytosolic location. Supporting Evidence: PMID:19056867 we used LC-MS/MS to profile the proteome of human urinary exosomes. |
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