AGXT2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0042853 L-alanine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in L-alanine catabolism. AGXT2 uses L-alanine as the amino donor in its transaminase reactions (glyoxylate + L-alanine = glycine + pyruvate), consuming alanine, which is directly demonstrated experimentally for the human enzyme. Reason: Consistent with the biochemistry: L-alanine is the physiological amino donor in the alanine:glyoxylate transaminase reaction, so alanine is catabolised. There is also a directly-supported IDA annotation to the same term (PMID:20018850). Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Catalyzes the conversion of glyoxylate to glycine using alanine as the
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred mitochondrial localization/activity. AGXT2 carries a cleaved N-terminal mitochondrial transit peptide and its mitochondrial localization is directly demonstrated in human cells. Reason: Strongly corroborated by direct experimental evidence (PMID:20018850, PMID:24586340, PMID:31818439) and by the UniProt-annotated transit peptide; the enzyme acts within the mitochondrion. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0008453 L-alanine:glyoxylate transaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred alanine:glyoxylate transaminase activity (EC 2.6.1.44). This is the defining, namesake molecular function of AGXT2 and is directly demonstrated for the human enzyme. Reason: Core molecular function. Directly supported by IDA annotations (PMID:20018850, PMID:24586340) and by the UniProt catalytic-activity record; the IBA is at the correct level of specificity. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0009436 glyoxylate catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in glyoxylate catabolism. AGXT2 transaminates glyoxylate to glycine, consuming (detoxifying) glyoxylate. Reason: Consistent with the alanine:glyoxylate transaminase reaction; also supported by an IDA annotation to the same term (PMID:20018850). Note the dominant in vivo glyoxylate-to-glycine flux is peroxisomal (AGXT), but the AGXT2 reaction genuinely consumes glyoxylate. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to mitochondrion (transferred from rat ortholog Q64565 and UniProt subcellular-location mapping). Consistent with the experimentally established mitochondrial localization of human AGXT2. Reason: Correct localization, corroborated by multiple IDA/HTP annotations and the UniProt transit peptide. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005759 mitochondrial matrix	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning electronic annotation to mitochondrial matrix. As a soluble matrix aminotransferase imported via a cleaved transit peptide, matrix localization is the expected and correct sub-compartment. Reason: More specific than the mitochondrion annotation and biologically correct; Reactome also localizes the AGXT2 reaction to the mitochondrial matrix (Reactome:R-HSA-904864). Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0008453 L-alanine:glyoxylate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the core alanine:glyoxylate transaminase activity (EC 2.6.1.44, RHEA:24248), transferred from the rat ortholog. Redundant with the IBA/IDA/ISS annotations to the same term. Reason: Correct core molecular function, extensively supported experimentally. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt EC=2.6.1.44
GO:0016223 beta-alanine:pyruvate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to beta-alanine:pyruvate transaminase activity (EC 2.6.1.18), part of AGXT2's documented broad substrate specificity (transfers the amino group from beta-alanine to pyruvate). Inferred by similarity to the rat ortholog Q64565. Reason: A legitimate member of the multifunctional aminotransferase's substrate range as annotated in UniProt; not the core namesake activity but a valid enzymatic function. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Reaction=3-oxopropanoate + L-alanine = beta-alanine + pyruvate
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic annotation for pyridoxal 5'-phosphate binding. AGXT2 is a PLP-dependent class-III aminotransferase with a PLP Schiff-base lysine, so cofactor binding is required for catalysis. Reason: Correct cofactor-binding function; UniProt annotates PLP as the cofactor and a N6-(pyridoxal phosphate)lysine modified residue. Enabling/secondary to the transaminase catalytic activity. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt N6-(pyridoxal phosphate)lysine
GO:0047305 (R)-3-amino-2-methylpropionate:pyruvate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to (R)-3-amino-2-methylpropanoate (D-beta- aminoisobutyrate):pyruvate transaminase activity (EC 2.6.1.40). AGXT2 is identical to D-3-aminoisobutyrate-pyruvate aminotransferase and metabolises the D-isomer of beta-aminoisobutyrate. Reason: Correct; directly demonstrated for the human enzyme (IDA, PMID:24586340) and consistent with the UniProt catalytic-activity record. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt D-3-aminoisobutyrate-pyruvate aminotransferase
GO:0047635 L-alanine:oxo-acid transaminase activity	IEA GO_REF:0000116	ACCEPT	Summary: RHEA-mapping electronic annotation to the general L-alanine:oxo-acid transaminase activity, covering the several alanine-dependent transamination reactions catalysed by AGXT2 (e.g. with 2-oxobutanoate, oxaloacetate, methylarginines as acceptors/donors). Reason: A correct, if more general, grouping term consistent with AGXT2's broad alanine-dependent transaminase activity documented in UniProt. It captures the shared use of L-alanine/pyruvate as the amino donor/acceptor pair. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Reaction=oxaloacetate + L-alanine = L-aspartate + pyruvate
GO:0140385 amino acid transaminase activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning electronic annotation to the parent term amino acid transaminase activity. This is a broad grouping term encompassing AGXT2's transaminase activities. Reason: Correct but general; the more specific alanine:glyoxylate transaminase and other transaminase terms are the informative core annotations. Retained as a valid, non-core parent. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Multifunctional aminotransferase with a broad substrate
GO:0006545 glycine biosynthetic process	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	ACCEPT	Summary: Direct-assay involvement in glycine biosynthesis: AGXT2 forms glycine from glyoxylate by transamination (glyoxylate + L-alanine = glycine + pyruvate). Rodionov et al. characterized the human enzyme's function and localization. Reason: Correct; glycine is the product of the namesake reaction. UniProt's DR cross-reference uses the more specific child GO:0019265 "glycine biosynthetic process, by transamination of glyoxylate", which better captures the mechanism, but GO:0006545 is accurate. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Catalyzes the conversion of glyoxylate to glycine using alanine as the
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	ACCEPT	Summary: Direct experimental demonstration of alanine:glyoxylate transaminase activity for human AGXT2. Rodionov et al. cloned and expressed human AGXT2 and characterized its aminotransferase function. Reason: Core molecular function with direct experimental support in the human enzyme. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Multifunctional aminotransferase with a broad substrate specificity
GO:0042853 L-alanine catabolic process	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	ACCEPT	Summary: Direct-assay involvement in L-alanine catabolism, reflecting consumption of L-alanine as the amino donor in AGXT2 transaminase reactions. Reason: Consistent with the biochemistry of the alanine:glyoxylate transaminase reaction, where L-alanine is deaminated to pyruvate. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Catalyzes the conversion of glyoxylate to glycine using alanine as the
GO:0008453 L-alanine:glyoxylate transaminase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation of alanine:glyoxylate transaminase activity transferred from the rat ortholog Q64565. Redundant with the human IDA/IBA annotations to the same core term. Reason: Correct core molecular function; the human enzyme is directly demonstrated to have this activity, so the ISS is well supported. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt EC=2.6.1.44
GO:0016223 beta-alanine:pyruvate transaminase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation of beta-alanine:pyruvate transaminase activity (EC 2.6.1.18) transferred from the rat ortholog Q64565, part of AGXT2's broad substrate range. Reason: A documented reaction of the multifunctional enzyme (UniProt catalytic activity, by similarity); valid but non-core. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Beta-alanine-pyruvate aminotransferase
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial-proteome study assigning AGXT2 to the mitochondrion. Consistent with the directly established mitochondrial localization of the enzyme. Reason: Correct localization; corroborates the IDA localization annotations. Supporting Evidence: PMID:34800366 high-confidence human mitochondrial proteome
GO:0005739 mitochondrion	IDA PMID:31818439 Kidney and liver are the main organs of expression of a key ...	ACCEPT	Summary: Direct experimental localization of human AGXT2 to the mitochondrion by double immunofluorescence with an anti-mitochondrial antibody in human kidney/liver tissue. Reason: Direct experimental support for mitochondrial localization in native human tissue. Supporting Evidence: PMID:31818439 The double fluorescent staining revealed mitochondrial localization
GO:0047305 (R)-3-amino-2-methylpropionate:pyruvate transaminase activity	IDA PMID:24586340 Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms ...	ACCEPT	Summary: Direct experimental demonstration that human AGXT2 metabolises beta-aminoisobutyrate (D-BAIB), the prototypic AGXT2 substrate, via (R)-3-amino-2-methylpropanoate:pyruvate transaminase activity (EC 2.6.1.40). Kittel et al. assayed AGXT2 activity using BAIB as substrate in HEK cells overexpressing the human enzyme, and the p.Val140Ile variant significantly reduced BAIB degradation. Reason: Directly supported enzymatic activity of the human enzyme; BAIB is described as a prototypic AGXT2 substrate. Supporting Evidence: PMID:24586340 prototypic substrate of AGXT2 PMID:24586340 significant reduction of enzyme activity was observed
GO:0005739 mitochondrion	IDA PMID:24586340 Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms ...	ACCEPT	Summary: Direct experimental localization of human AGXT2 to the mitochondrion by immunofluorescence with MitoTracker co-staining in HEK cells overexpressing the enzyme. Reason: Direct experimental support; consistent with all other localization evidence. Supporting Evidence: PMID:24586340 AGXT2 was localized to mitochondria in both cell lines
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:24586340 Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms ...	ACCEPT	Summary: Direct experimental demonstration of alanine:glyoxylate transaminase activity in human AGXT2. Kittel et al. measured AGXT2 enzyme activity using pyruvate and glyoxylate as amino-group acceptor and PLP as cofactor, and showed the p.Val140Ile variant reduces this activity. Reason: Core molecular function with direct human experimental support. Supporting Evidence: PMID:24586340 1 mM sodium pyruvate and 1 mM sodium glyoxylate as amino group acceptor
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-904864	ACCEPT	Summary: Reactome traceable-author statement localizing the AGXT2 transamination reaction to the mitochondrial matrix. Consistent with the enzyme being a soluble matrix aminotransferase. Reason: Correct sub-compartment; the mature enzyme is imported into the mitochondrial matrix via its cleaved transit peptide. Supporting Evidence: Reactome:R-HSA-904864 Mitochondrial AGXT2 (alanine-glyoxylate transaminase 2) catalyzes the irreversible reaction of glyoxylate and alanine to form glycine and pyruvate
GO:0005739 mitochondrion	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	ACCEPT	Summary: Direct experimental demonstration of mitochondrial localization of human AGXT2 by confocal microscopy, with delineation of a 41-amino-acid N-terminal mitochondrial cleavage sequence by N-terminal sequencing of the mature protein. Reason: Foundational, direct experimental evidence for mitochondrial localization of the human enzyme. Supporting Evidence: PMID:20018850 Mitochondrial localization of human AGXT2 was demonstrated by
GO:0009436 glyoxylate catabolic process	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	ACCEPT	Summary: Direct-assay involvement in glyoxylate catabolism: AGXT2 converts glyoxylate to glycine, consuming glyoxylate. Reason: Correct; the reaction detoxifies glyoxylate by transamination. The IBA annotation to the same term is likewise accepted. Supporting Evidence: file:human/AGXT2/AGXT2-uniprot.txt Catalyzes the conversion of glyoxylate to glycine using alanine as the
GO:0045429 positive regulation of nitric oxide biosynthetic process	IDA PMID:20018850 Human alanine-glyoxylate aminotransferase 2 lowers asymmetri...	KEEP AS NON CORE	Summary: Direct-assay finding that human AGXT2 overexpression lowers ADMA (an endogenous inhibitor of NO synthase) and thereby protects endothelial cells from ADMA-mediated inhibition of nitric oxide production. This links AGXT2 methylarginine metabolism to positive regulation of NO biosynthesis. Reason: Well supported physiologically, but this is a downstream regulatory consequence of AGXT2's methylarginine-transaminase activity (via lowering ADMA), not a direct enzymatic core function. Retain as a non-core biological-process annotation. Supporting Evidence: PMID:20018850 protected endothelial cells from PMID:20018850 decreased ADMA levels and improved endothelial NO production

Gene Description

Existing Annotations Review

Core Functions

Mitochondrial PLP-dependent aminotransferase that transaminates glyoxylate to glycine using L-alanine as amino donor (alanine:glyoxylate transaminase, EC 2.6.1.44), contributing to glyoxylate detoxification.

Transaminates D-beta-aminoisobutyrate (a pyrimidine-catabolism end product) with pyruvate ((R)-3-amino-2-methylpropanoate:pyruvate transaminase, EC 2.6.1.40); AGXT2 activity is the main determinant of urinary beta-aminoisobutyrate excretion.

Broad-specificity amino acid transaminase that also metabolises the endogenous NO-synthase inhibitors ADMA and SDMA and other amino-acid substrates, using L-alanine/pyruvate as the amino donor/acceptor pair; requires pyridoxal 5'-phosphate as cofactor.

References

📚 Additional Documentation

Notes

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