AGXT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004760 L-serine:pyruvate transaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT supports the inherited serine:pyruvate transaminase activity of human AGXT. Reason: Human liver preparations show substantial flux through this reaction under quasi-physiological in-vitro conditions (PMID:10347152). This is a documented second substrate reaction, while the same paper's in-vivo gluconeogenesis experiment is in rabbit. The PTHR21152 PAINT cache places this function at PTN000475663; direct human evidence supports retention. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000475663 · PTN000475663 SUPPORTS TRANSFER The cached PTHR21152 PAINT table contains this term-specific IBD at PTN000475663. Independent human evidence supports the inherited annotation. The complete alignment/tree reconstruction was not re-performed; descendant donor count and human self-inclusion are not defects. Supporting Evidence: PMID:10347152 flux through serine dehydratase accounted for only traces, and that through SPT/AGT substantially contributed
GO:0006545 glycine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Glycine is synthesized directly by the glyoxylate-transaminating reaction of AGXT. Reason: The PAINT assertion at PTN000475663 agrees with human reaction kinetics (PMID:17696873): AGXT performs the amino-group transfer that makes glycine. This is direct catalytic participation, not merely a metabolite change following gene loss. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000475663 · PTN000475663 SUPPORTS TRANSFER The cached PTHR21152 PAINT table contains this term-specific IBD at PTN000475663. Independent human evidence supports the inherited annotation. The complete alignment/tree reconstruction was not re-performed; descendant donor count and human self-inclusion are not defects. Supporting Evidence: PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0009436 glyoxylate catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: AGXT directly consumes glyoxylate by transamination to glycine. Reason: The PAINT assertion at PTN000475663 is supported by human enzymology and the peroxisomal detoxification mechanism. Human AGXT among the descendant evidence is legitimate experimental grounding for ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000475663 · PTN000475663 SUPPORTS TRANSFER The cached PTHR21152 PAINT table contains this term-specific IBD at PTN000475663. Independent human evidence supports the inherited annotation. The complete alignment/tree reconstruction was not re-performed; descendant donor count and human self-inclusion are not defects. Supporting Evidence: PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0005777 peroxisome	IBA GO_REF:0000033	ACCEPT	Summary: Human AGXT functions in peroxisomes. Reason: PAINT places peroxisomal localization at PTN000475539. Human liver immunogold localization independently establishes this compartment. Species-dependent mitochondrial targeting in other mammals does not contradict the human peroxisomal pool (PMID:7813517). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000475539 · PTN000475539 SUPPORTS TRANSFER The cached PTHR21152 PAINT table contains this term-specific IBD at PTN000475539. Independent human evidence supports the inherited annotation. The complete alignment/tree reconstruction was not re-performed; descendant donor count and human self-inclusion are not defects. Supporting Evidence: PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0008453 L-alanine:glyoxylate transaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: The inherited alanine:glyoxylate transaminase activity is experimentally established in human AGXT. Reason: PAINT places this activity at PTN000475663. Purified human AGXT kinetics and the curated RHEA:24248 reaction directly support the annotation; no target-specific loss of catalytic function is evident. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000475663 · PTN000475663 SUPPORTS TRANSFER The cached PTHR21152 PAINT table contains this term-specific IBD at PTN000475663. Independent human evidence supports the inherited annotation. The complete alignment/tree reconstruction was not re-performed; descendant donor count and human self-inclusion are not defects. Supporting Evidence: PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0004760 L-serine:pyruvate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic mapping captures serine:pyruvate transamination. Reason: RHEA:22852 and EC:2.6.1.51 map the specific substrate reaction recorded in UniProt, supported by the human liver flux experiment in PMID:10347152. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:22852 SUPPORTS TRANSFER Proximate mapping recovered from WITH/FROM and checked against the cached UniProt reaction or location; independent human experimental evidence agrees. EC:2.6.1.51 SUPPORTS TRANSFER Proximate mapping recovered from WITH/FROM and checked against the cached UniProt reaction or location; independent human experimental evidence agrees. Supporting Evidence: file:human/AGXT/AGXT-uniprot.txt Reaction=L-serine + pyruvate = 3-hydroxypyruvate + L-alanine PMID:10347152 flux through serine dehydratase accounted for only traces, and that through SPT/AGT substantially contributed
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: Cytoplasm is a broad but compatible location for a peroxisomal matrix enzyme. Reason: GO:0005737 includes subcellular structures outside the nucleus; it is not synonymous with soluble cytosol. Human peroxisomal localization therefore supports this broad assignment. The ARBA rule predicates were not recovered, so the rule-generation mechanism is unresolved rather than described as a default-localization error. The more precise matrix location is retained independently. Propagation Review Root cause: UNRESOLVED Sources checked: ARBA:ARBA00026971 UNRESOLVED Rule identifier recovered from WITH/FROM; its predicates and training evidence were not inspected. The annotation judgment rests on independent human evidence, not an asserted audit of rule internals. Supporting Evidence: PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005777 peroxisome	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt subcellular-location mapping identifies the human peroxisomal pool. Reason: UniProtKB-SubCell:SL-0204 agrees with direct human liver immunocytochemistry. The organelle-level mapping is correct and need not claim the finer matrix resolution of a different source. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0204 SUPPORTS TRANSFER Proximate mapping recovered from WITH/FROM and checked against the cached UniProt reaction or location; independent human experimental evidence agrees. Supporting Evidence: file:human/AGXT/AGXT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0008453 L-alanine:glyoxylate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic mapping identifies alanine:glyoxylate transamination. Reason: RHEA:24248 and EC:2.6.1.44 correspond to the experimentally supported reaction of glyoxylate and alanine to glycine and pyruvate. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:24248 SUPPORTS TRANSFER Proximate mapping recovered from WITH/FROM and checked against the cached UniProt reaction or location; independent human experimental evidence agrees. EC:2.6.1.44 SUPPORTS TRANSFER Proximate mapping recovered from WITH/FROM and checked against the cached UniProt reaction or location; independent human experimental evidence agrees. Supporting Evidence: file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0047635 L-alanine:oxo-acid transaminase activity	IEA GO_REF:0000117	MODIFY	Summary: The ARBA alanine/oxo-acid activity should be replaced by the characterized glyoxylate reaction. Reason: The current GO:0047635 definition describes L-alanine transfer to a generic 2-oxocarboxylate, yielding an L-alpha-amino acid. Human AGXT has a specifically measured glyoxylate-to-glycine reaction. GO:0008453 conveys that chemistry without assuming the two terms are a formal parent-child pair or that every oxo-acid acceptor is used. The reverse serine reaction is covered independently by GO:0004760. ARBA00092993 predicates remain uninspected. Propagation Review Root cause: UNRESOLVED Sources checked: ARBA:ARBA00092993 UNRESOLVED Rule identifier recovered from WITH/FROM; its predicates and training evidence were not inspected. The annotation judgment rests on independent human evidence, not an asserted audit of rule internals. Proposed replacements: L-alanine:glyoxylate transaminase activity Supporting Evidence: file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0005515 protein binding	IPI PMID:22529745 Molecular requirements for peroxisomal targeting of alanine-...	REMOVE	Summary: Human AGXT binds its peroxisomal cargo receptor PEX5 in a directly characterized complex. Reason: PMID:22529745 resolves the cargo-receptor interface using purified human proteins and crystallography. Generic protein binding is uninformative about AGXT's catalytic role, so remove that MF without denying the interaction. AGXT is the imported cargo; this binding does not establish that it performs the protein-import step. Supporting Evidence: PMID:22529745 we have determined the crystal structure of the respective cargo-receptor complex
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports binary interactions of AGXT with multiple proteins. Reason: The seeded IPI pairs and UniProt interaction list retain the screen provenance. The generic MF does not identify a specific activity of AGXT, so remove it as uninformative without declaring the pairs false or treating keratin partners as evidence of contamination. The complete pair-level experimental supplement was not separately reconstructed. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'
GO:0042802 identical protein binding	IPI PMID:12899834 Crystal structure of alanine:glyoxylate aminotransferase and...	MODIFY	Summary: The human AGXT structure supports homodimer formation. Reason: The source is a structure of normal human AGXT, and the IPI partner is the identical human P21549 protein. Refine the broader self-binding term to the experimentally established homodimerization activity, corroborated by the later human cargo-receptor structure. This refinement does not create a NEW annotation. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:12899834 crystal structure of normal human AGT complexed to the competitive inhibitor amino-oxyacetic acid PMID:22529745 forms an elongated Pex5p-(AGT)2-Pex5p assembly
GO:0042802 identical protein binding	IPI PMID:22529745 Molecular requirements for peroxisomal targeting of alanine-...	MODIFY	Summary: The human AGXT-PEX5 structure contains an AGXT homodimer. Reason: The two identical human AGXT chains form the dimer in the PEX5 cargo complex. The resolved stoichiometry supports the more informative homodimerization activity rather than only identical-protein binding. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:22529745 forms an elongated Pex5p-(AGT)2-Pex5p assembly
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: HuRI self-interaction supports AGXT self-association. Reason: The seeded partner is human P21549 itself. A binary interaction assay does not independently resolve oligomer stoichiometry, so retain its accurate self-binding scope; separate structural and biochemical annotations establish the homodimer. This is informative self-association, unlike a generic unspecified protein-binding term. Supporting Evidence: file:human/AGXT/AGXT-uniprot.txt SUBUNIT: Homodimer PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'
GO:0006565 L-serine catabolic process	IDA PMID:10347152 Flux of the L-serine metabolism in rabbit, human, and dog li...	ACCEPT	Summary: AGXT directly participates in L-serine breakdown through serine:pyruvate transamination. Reason: PMID:10347152 includes human liver preparations, where this reaction carries substantial flux under the tested in-vitro conditions. AGXT performs the reaction producing hydroxypyruvate; it is not merely necessary for another enzyme's process. Retain as a core substrate pathway alongside glyoxylate detoxification, without extending the rabbit-only in-vivo gluconeogenesis experiment to humans. Supporting Evidence: PMID:10347152 flux through serine dehydratase accounted for only traces, and that through SPT/AGT substantially contributed
GO:0005777 peroxisome	EXP PMID:23229545 Four of the most common mutations in primary hyperoxaluria t...	ACCEPT	Summary: The minor-allele variant study compares normal peroxisomal AGXT with mistargeted mutant proteins. Reason: The cached introduction and discussion document peroxisomal normal protein and altered partitioning of tested mutants in stably transformed CHO cells. Preserve the experimentally curated organelle-level assignment. The cache omits Methods/Results, so exact image-level comparisons are not claimed here; direct human liver localization independently corroborates the compartment. Supporting Evidence: PMID:23229545 the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005777 peroxisome	EXP PMID:24055001 Gly161 mutations associated with Primary Hyperoxaluria Type ...	ACCEPT	Summary: Peroxisomal AGXT is the normal context for the Gly161 variant study. Reason: The abstract describes recombinant and mammalian-cell experiments and cytosolic aggregation of Gly161 apo-variants. It does not reproduce the full wild-type localization assay. Retain the curator's peroxisome assignment, independently established in human liver, without using mutant aggregation alone as proof of wild-type localization. Supporting Evidence: PMID:24055001 inherited mutations on liver peroxisomal alanine:glyoxylate aminotransferase PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005777 peroxisome	EXP PMID:26149463 Misfolding caused by the pathogenic mutation G47R on the min...	ACCEPT	Summary: The G47R minor-allele study distinguishes peroxisomal intact protein from mitochondrial nicked protein. Reason: The abstract explicitly reports these two mutant protein pools and restoration of peroxisomal targeting with pyridoxine. This supports peroxisomal localization; it does not imply that all molecules of every AGXT allele are exclusively peroxisomal. Supporting Evidence: PMID:26149463 the intact and nicked forms have a peroxisomal and a mitochondrial localization, respectively
GO:0008453 L-alanine:glyoxylate transaminase activity	EXP PMID:23229545 Four of the most common mutations in primary hyperoxaluria t...	ACCEPT	Summary: The variant comparison measures retained alanine:glyoxylate catalytic activity. Reason: The accessible abstract and discussion report active G170R, I244T and F152I dimers and distinguish their localization defect from catalytic loss. The cache lacks detailed assay methods, so retain the curated activity with independent purified-human-enzyme corroboration. Supporting Evidence: PMID:23229545 the G170R, I244T, and F152I mutants are able to form dimers and are catalytically active PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0008453 L-alanine:glyoxylate transaminase activity	EXP PMID:24055001 Gly161 mutations associated with Primary Hyperoxaluria Type ...	ACCEPT	Summary: The Gly161 study biochemically characterizes purified human AGXT variants. Reason: The accessible abstract confirms recombinant biochemical analysis and explains loss through apo-protein aggregation and reduced stability. Retain the curated activity; exact substrate/assay details are not reconstructed from the abstract, while independent human kinetics establish the same chemistry. Supporting Evidence: PMID:24055001 biochemical analyses on the purified recombinant proteins PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0008453 L-alanine:glyoxylate transaminase activity	EXP PMID:26149463 Misfolding caused by the pathogenic mutation G47R on the min...	ACCEPT	Summary: Purified G47R-Mi retains substantial AGXT catalytic activity despite cellular folding defects. Reason: The abstract reports only a 2.5-fold reduction in variant kcat relative to the comparator and separates catalytic capacity from insolubility and targeting. Retain the core reaction rather than reading disease association as universal catalytic inactivity. Supporting Evidence: PMID:26149463 the recombinant purified G47R-Mi variant exhibits only a 2.5-fold reduction of its kcat
GO:0004760 L-serine:pyruvate transaminase activity	IDA PMID:10347152 Flux of the L-serine metabolism in rabbit, human, and dog li...	ACCEPT	Summary: Human liver flux experiments support serine:pyruvate transaminase activity. Reason: The cached abstract explicitly includes human liver and describes substantial SPT/AGT flux under quasi-physiological in-vitro conditions. It identifies peroxisomal enzyme in human and rabbit preparations and confines the in-vivo gluconeogenesis experiment to rabbit. This positive human catalytic evidence supports serine:pyruvate transamination without requiring an external full-text claim. Supporting Evidence: PMID:10347152 flux through serine dehydratase accounted for only traces, and that through SPT/AGT substantially contributed file:human/AGXT/AGXT-uniprot.txt Reaction=L-serine + pyruvate = 3-hydroxypyruvate + L-alanine
GO:0046487 glyoxylate metabolic process	IDA PMID:12777626 Primary hyperoxaluria type 1 in the Canary Islands: a confor...	ACCEPT	Summary: AGXT participates in glyoxylate metabolism by directly transaminating glyoxylate. Reason: The full study measures glyoxylate-dependent activity of recombinant normal and variant human AGXT, including substrate kinetics. The broad metabolic process is accurate at this source scope; the specific catabolic process is independently retained in the integrated core. Supporting Evidence: PMID:12777626 K m for glyoxylate was determined in the substrate range 0–2.5 mM
GO:0005777 peroxisome	IDA PMID:10960483 Functional synergism between the most common polymorphism in...	ACCEPT	Summary: The source discusses peroxisomal targeting and mutant mistargeting of human AGXT. Reason: The abstract mainly describes purified recombinant enzyme and refers to mistargeting in mammalian cells. It does not provide the full direct localization experiment. Defer to the curated peroxisome annotation because independent human immunogold evidence directly establishes it; do not infer localization of purified bacterial protein. Supporting Evidence: PMID:10960483 peroxisome-to-mitochondrion AGT mistargeting in mammalian cells PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005777 peroxisome	IDA PMID:12777626 Primary hyperoxaluria type 1 in the Canary Islands: a confor...	ACCEPT	Summary: Normal and variant human AGXT colocalize with a peroxisomal marker in the reported transfection system. Reason: The full PMID:12777626 study reports PMP70 colocalization in COS7 cells, including peroxisomal AGXT*LTM. Different mutant targeting outcomes in other cell systems do not invalidate this experiment. Supporting Evidence: PMID:12777626 colocalizing with the peroxisomal marker PMP70
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:10960483 Functional synergism between the most common polymorphism in...	ACCEPT	Summary: Purified recombinant human AGXT has alanine:glyoxylate transaminase activity. Reason: The source explicitly obtains correctly folded, dimeric and catalytically active normal human enzyme and tests variant effects. This directly supports the central catalytic activity. Supporting Evidence: PMID:10960483 normal human His-tagged AGT can be expressed at high levels in Escherichia coli and purified in a correctly folded, dimerized and catalytically active state
GO:0008453 L-alanine:glyoxylate transaminase activity	IMP PMID:12777626 Primary hyperoxaluria type 1 in the Canary Islands: a confor...	ACCEPT	Summary: Mutational and biochemical analysis supports the catalytic function of human AGXT. Reason: P11L/I244T protein loses soluble-cell-extract activity through aggregation, but soluble protein purified in suitable expression conditions retains activity. The source therefore supports the enzyme function without asserting that the variant is intrinsically catalytically dead. Its abstract reverses the P11L notation; the constructs in the full Methods explicitly specify P11L. Supporting Evidence: PMID:12777626 Purified wild-type GST-AGXT yielded 6,200 ± 1,500 μmol/h per mg
GO:0042803 protein homodimerization activity	IDA PMID:10960483 Functional synergism between the most common polymorphism in...	ACCEPT	Summary: Purified normal human AGXT forms an active dimer. Reason: Direct expression and purification establish the dimeric catalytic assembly. This is a structural feature of the core enzyme, integrated with its PLP-dependent chemistry rather than treated as a separate physiological role. Supporting Evidence: PMID:10960483 purified in a correctly folded, dimerized and catalytically active state
GO:0042803 protein homodimerization activity	IDA PMID:12777626 Primary hyperoxaluria type 1 in the Canary Islands: a confor...	ACCEPT	Summary: Human AGXT self-association and dimer formation are tested in the I244T study. Reason: The full source reports cross-linking, coimmunoprecipitation and two-hybrid analyses of normal and variant human AGXT. These support homodimerization; retained mutant dimerization does not guarantee solubility or normal activity. Supporting Evidence: PMID:12777626 Cross-linking of TnT products of all variants tested resulted in ≈90-kDa bands, consistent with functional dimerization
GO:0005829 cytosol	TAS Reactome:R-HSA-9033235	KEEP AS NON CORE	Summary: Reactome represents AGXT cargo before import into the peroxisomal matrix. Reason: R-HSA-9033235 explicitly models the cytosolic input and matrix destination of PEX5 cargo. The cytosolic precursor context is credible and non-core relative to the mature enzyme's matrix function; it does not establish a major steady-state cytosolic metabolic pool. Supporting Evidence: Reactome:R-HSA-9033235 the cargo protein is released into the peroxisomal matrix while PEX5S or PEX5L remains in the membrane
GO:0005829 cytosol	TAS Reactome:R-HSA-9033236	KEEP AS NON CORE	Summary: The PEX5 cargo-docking event represents a pre-import cytosolic AGXT pool. Reason: R-HSA-9033236 places PEX5-bound cargo at the docking/translocation module. Retain this pathway-stage location as non-core; PEX5 and the membrane apparatus execute import, while AGXT is their cargo. Supporting Evidence: Reactome:R-HSA-9033236 PEX5S or PEX5L bound to cargo proteins containing PTS1 interacts with the Docking and Translocation Module
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:16971151 Consequences of missense mutations for dimerization and turn...	ACCEPT	Summary: Human AGXT activity is measured across a missense-variant series. Reason: The source expresses human variants in bacterial and reticulocyte systems and compares activity, dimerization and turnover. This supports the normal catalytic function while showing that variant-specific defects can affect several properties. Supporting Evidence: PMID:16971151 We have investigated their effects on enzyme activity, dimerization, aggregation, and turnover.
GO:0042803 protein homodimerization activity	IDA PMID:16971151 Consequences of missense mutations for dimerization and turn...	ACCEPT	Summary: The human variant series experimentally assays AGXT dimerization. Reason: Dimerization defects occur for many, but not all, tested variants, with PLP-dependent improvement in one case. This directly supports the normal homodimeric assembly without asserting a uniform mutant mechanism. Supporting Evidence: PMID:16971151 Dimerization failure was a frequent observation (13/15) except for G41V and D183N.
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-389684	ACCEPT	Summary: The Reactome glyoxylate-transamination event places active AGXT in the peroxisomal matrix. Reason: The reaction model agrees with direct matrix localization in normal human liver. Matrix localization is the catalytic compartment, distinct from the import-precursor cytosol. Supporting Evidence: Reactome:R-HSA-389684 Alanine-glyoxylate transaminase (AGXT) catalyzes the irreversible reaction of glyoxylate and alanine to form glycine and pyruvate PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-9033235	ACCEPT	Summary: The PEX5 cargo-translocation model terminates in the peroxisomal matrix. Reason: R-HSA-9033235 explicitly releases cargo into the matrix. Independent AGXT immunogold localization confirms the mature enzyme at this destination. Supporting Evidence: Reactome:R-HSA-9033235 the cargo protein is released into the peroxisomal matrix PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:18492492 Reactions of human liver peroxisomal alanine:glyoxylate amin...	ACCEPT	Summary: The human AGXT substrate study retains the main alanine:glyoxylate transamination reaction. Reason: The abstract explicitly compares side-reaction kinetics with physiological L-alanine transamination. This agrees with the independently measured forward/reverse human AGXT reaction; the additional substrate reactions do not negate the main activity. Supporting Evidence: PMID:18492492 the physiological transaminase reaction with L-alanine PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0008483 transaminase activity	IDA PMID:18492492 Reactions of human liver peroxisomal alanine:glyoxylate amin...	MODIFY	Summary: The broad transaminase term is refined to the established alanine:glyoxylate reaction. Reason: PMID:18492492 explicitly compares its additional substrate chemistry with the physiological L-alanine transaminase reaction. The specific alanine:glyoxylate activity is already annotated from this same source and is independently established by human AGXT kinetics in PMID:17696873. GO:0008483 describes amino-group transfer without identifying the cysteine substrate or beta-elimination chemistry, so GO:0008453 is the informative refinement. The directly observed cysteine reactions remain documented in their own non-core process annotation and substrate-scope question; this replacement does not deny them. Proposed replacements: L-alanine:glyoxylate transaminase activity Supporting Evidence: PMID:18492492 the physiological transaminase reaction with L-alanine PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0016597 amino acid binding	IDA PMID:18492492 Reactions of human liver peroxisomal alanine:glyoxylate amin...	ACCEPT	Summary: Kinetic and spectroscopic experiments show binding of amino-acid substrates to human AGXT. Reason: The source reports measured cysteine/alanine/serine binding affinities and reaction intermediates; docking energies provide additional calculations rather than the sole basis. Binding amino-acid substrates is part of the enzyme's catalytic substrate recognition, so this supported MF is retained as core. A separate binding-only core unit would duplicate the integrated catalytic function. Supporting Evidence: PMID:18492492 L-cysteine binds to AGT with a binding affinity 30- and 200-fold higher than that of L-alanine and L-serine, respectively.
GO:0019448 L-cysteine catabolic process	IDA PMID:18492492 Reactions of human liver peroxisomal alanine:glyoxylate amin...	KEEP AS NON CORE	Summary: Purified human AGXT directly processes L-cysteine in vitro. Reason: Product and coenzyme analyses identify both beta-elimination and half-transamination of L-cysteine, so AGXT directly performs cysteine-breakdown chemistry rather than merely binding or inhibiting another enzyme. This positive catalytic participation supports retention of the existing process at its in-vitro scope instead of marking the process unsupported. Half-transamination turnover is 200-fold below alanine and 60-fold below serine; physiological human cysteine flux remains unresolved, so the activity is non-core. Supporting Evidence: PMID:18492492 the occurrence of both beta-elimination and half-transamination of L-cysteine together with the pyruvate transamination
GO:0042853 L-alanine catabolic process	IDA PMID:18492492 Reactions of human liver peroxisomal alanine:glyoxylate amin...	ACCEPT	Summary: AGXT directly converts L-alanine to pyruvate during glyoxylate transamination. Reason: L-alanine breakdown is the amino-donor half of the core reaction, not a downstream perturbation phenotype. This source's enzyme assay is consistent with that reaction, independently defined by human kinetics and UniProt. Retain the process as core without claiming AGXT dominates total hepatic alanine disposal. Supporting Evidence: PMID:18492492 the physiological transaminase reaction with L-alanine file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:17696873 Human wild-type alanine:glyoxylate aminotransferase and its ...	ACCEPT	Summary: Human wild-type AGXT kinetics establish the glyoxylate-to-glycine reaction. Reason: Forward/reverse steady-state and half-reaction measurements support glyoxylate detoxification by alanine-dependent transamination. The G82E variant analysis is a mechanistic comparison rather than the only evidence for wild-type function. Supporting Evidence: PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0030170 pyridoxal phosphate binding	IDA PMID:17696873 Human wild-type alanine:glyoxylate aminotransferase and its ...	ACCEPT	Summary: PLP binding and its catalytic-cycle behavior are measured for normal and G82E human AGXT. Reason: The abstract explicitly compares the variant with wild type for two PLP molecules per dimer and cofactor affinity. PLP is the core catalytic cofactor; its binding is integrated with transaminase activity rather than presented as an independent biological role. Supporting Evidence: PMID:17696873 Although, like the wild-type, the G82E variant is able to bind 2 mol PLP/dimer
GO:0042853 L-alanine catabolic process	IDA PMID:17696873 Human wild-type alanine:glyoxylate aminotransferase and its ...	ACCEPT	Summary: AGXT directly converts L-alanine to pyruvate during glyoxylate transamination. Reason: L-alanine breakdown is the amino-donor half of the core reaction, not a downstream perturbation phenotype. This source's enzyme assay is consistent with that reaction, independently defined by human kinetics and UniProt. Retain the process as core without claiming AGXT dominates total hepatic alanine disposal. Supporting Evidence: PMID:17696873 the steady-state kinetic parameters of the forward and reverse reactions file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0008483 transaminase activity	IDA PMID:20133649 Molecular defects of the glycine 41 variants of alanine glyo...	MODIFY	Summary: The G41 variant study supports the established catalytic function of human AGXT. Reason: The cached PMID:20133649 abstract identifies human alanine:glyoxylate aminotransferase and reports altered catalytic efficiency of G41 variants, but it does not state the assay substrate concentrations or full reaction scheme. The specific alanine/glyoxylate chemistry is independently established by the cached kinetic study PMID:17696873 and the UniProt reaction. This combined evidence supports refinement to GO:0008453 without presenting an externally read Results passage as cached evidence. Proposed replacements: L-alanine:glyoxylate transaminase activity Supporting Evidence: PMID:20133649 reduced coenzyme binding affinity, and catalytic efficiency PMID:17696873 the pre-steady-state kinetics of the half-reactions of the PLP form of AGT with L-alanine or glycine and the PMP (pyridoxamine 5'-phosphate) form with pyruvate or glyoxylate have been measured. file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0030170 pyridoxal phosphate binding	IDA PMID:20133649 Molecular defects of the glycine 41 variants of alanine glyo...	ACCEPT	Summary: The G41 study compares PLP binding in normal and mutant human AGXT. Reason: The primary Results describe two PLP molecules per dimer and quantitative cofactor-affinity changes. The abstract corroborates reduced coenzyme binding affinity in variants. Retain the core cofactor-binding property. Supporting Evidence: PMID:20133649 reduced coenzyme binding affinity
GO:0042803 protein homodimerization activity	IDA PMID:20133649 Molecular defects of the glycine 41 variants of alanine glyo...	ACCEPT	Summary: Biophysical analysis supports stable normal AGXT dimers and altered mutant dimer-monomer equilibria. Reason: The primary Results use cross-linking and size-exclusion chromatography; normal major/minor proteins remain dimeric over the tested concentration range. The effects differ between apo and holo variants, so avoid a universal claim that every G41 mutant fails to dimerize. Supporting Evidence: PMID:20133649 increasing the dimer-monomer equilibrium dissociation constant
GO:0005777 peroxisome	IDA PMID:9053548 Immunocytochemical localization of peroxisomal proteins in h...	ACCEPT	Summary: The source describes human liver immunolabelling of AGXT among peroxisomal proteins. Reason: The abstract confirms the tissue, AGXT inclusion and protein-A gold methodology, but does not reproduce AGXT-specific images. Retain the reliable curator's peroxisomal annotation with independent direct human matrix localization rather than treating the methods-focused abstract as negative evidence. Supporting Evidence: PMID:9053548 The sample preparation and immunocytochemical methods for investigating the presence and subcellular localization of peroxisomal proteins (catalase, the three beta-oxidation enzymes, alanine : glyoxylate aminotransferase and a peroxisomal membrane protein) in human liver biopsies are described. PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005782 peroxisomal matrix	IDA PMID:3418107 Immunocytochemical localization of human hepatic alanine: gl...	ACCEPT	Summary: Human liver immunogold microscopy localizes AGXT throughout the peroxisomal matrix. Reason: The abstract directly reports normal controls and randomly dispersed matrix labelling without obvious membrane association. This is precise positive compartment evidence. Supporting Evidence: PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0006545 glycine biosynthetic process	IDA PMID:22198249 The N-terminal extension is essential for the formation of t...	ACCEPT	Summary: AGXT synthesizes glycine through its main transamination reaction. Reason: The source compares full-length and truncated enzyme activity. Glycine production is directly supported by the independently characterized reaction, not inferred from kidney disease alone. Supporting Evidence: PMID:22198249 The purified soluble fraction showed reduced affinity for PLP and greatly reduced catalytic activity. PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0008453 L-alanine:glyoxylate transaminase activity	IDA PMID:22198249 The N-terminal extension is essential for the formation of t...	ACCEPT	Summary: The N-terminal-deletion study compares catalytic activity with full-length AGXT. Reason: The soluble truncated enzyme has markedly reduced activity and PLP affinity despite remaining dimeric. This supports the normal catalytic function without equating any dimeric state with full activity. Supporting Evidence: PMID:22198249 The purified soluble fraction showed reduced affinity for PLP and greatly reduced catalytic activity. PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0009436 glyoxylate catabolic process	IDA PMID:22198249 The N-terminal extension is essential for the formation of t...	ACCEPT	Summary: AGXT directly catabolizes glyoxylate by converting it to glycine. Reason: The source assayed enzyme activity following N-terminal deletion. The process follows the measured reaction chemistry, independently established in human kinetics; the disease phenotype is not the sole basis. Supporting Evidence: PMID:22198249 The purified soluble fraction showed reduced affinity for PLP and greatly reduced catalytic activity. PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0042853 L-alanine catabolic process	IDA PMID:22198249 The N-terminal extension is essential for the formation of t...	ACCEPT	Summary: AGXT directly converts L-alanine to pyruvate during glyoxylate transamination. Reason: L-alanine breakdown is the amino-donor half of the core reaction, not a downstream perturbation phenotype. This source's enzyme assay is consistent with that reaction, independently defined by human kinetics and UniProt. Retain the process as core without claiming AGXT dominates total hepatic alanine disposal. Supporting Evidence: PMID:22198249 The purified soluble fraction showed reduced affinity for PLP and greatly reduced catalytic activity. file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0005782 peroxisomal matrix	IDA PMID:22198249 The N-terminal extension is essential for the formation of t...	ACCEPT	Summary: The N-terminal-deletion study reports peroxisomal targeting of the truncated human enzyme. Reason: The abstract describes catalytically inactive intraperoxisomal aggregates but does not resolve every ultrastructural detail. Preserve the curated matrix assignment, corroborated directly by normal-human-liver immunogold localization; do not infer that deletion abolishes dimerization or peroxisomal import. Supporting Evidence: PMID:22198249 the truncated construct was normally targeted to peroxisomes PMID:3418107 immunoreactive AGT protein was confined to peroxisomes, where it was randomly dispersed throughout the peroxisomal matrix
GO:0005777 peroxisome	IDA PMID:7813517 Evolution of alanine:glyoxylate aminotransferase 1 peroxisom...	ACCEPT	Summary: Comparative immunoelectron microscopy explicitly places human AGXT in the peroxisomal group. Reason: The abstract names human among type I species, in which all or nearly all AGXT is peroxisomal. The documented distribution differs among mammals and must not be transferred wholesale from rodent or carnivore localization. Supporting Evidence: PMID:7813517 Type I animals include the human PMID:7813517 all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes
GO:0030170 pyridoxal phosphate binding	IMP PMID:15802217 Overexpression of human alanine:glyoxylate aminotransferase ...	ACCEPT	Summary: Apoenzyme reconstitution and variant comparison demonstrate PLP binding. Reason: The source measures PLP-dependent reconstitution of recombinant human AGXT and assigns lower minor-allele affinity to I340M. Successful refolding without PLP is compatible with an essential catalytic-cofactor role. Supporting Evidence: PMID:15802217 K(M)s for PLP were determined by reconstitution of the apoenzyme
GO:0042803 protein homodimerization activity	IDA PMID:12899834 Crystal structure of alanine:glyoxylate aminotransferase and...	ACCEPT	Summary: Structural analysis supports the human AGXT homodimer. Reason: The abstract identifies normal human AGXT structure and quaternary conformation; its homodimer interpretation is independently confirmed by the later AGXT-PEX5 structure. Retain the curated homodimerization function without extending mutant-specific effects to all alleles. Supporting Evidence: PMID:12899834 in terms of AGT tertiary and quaternary conformation PMID:22529745 forms an elongated Pex5p-(AGT)2-Pex5p assembly
GO:0046487 glyoxylate metabolic process	IMP PMID:3709805 Peroxisomal alanine:glyoxylate aminotransferase deficiency i...	ACCEPT	Summary: AGXT-deficient human liver links its catalytic loss to glyoxylate metabolism. Reason: The patient/control study measures a profound loss of peroxisomal AGXT activity. Independent reaction chemistry establishes that AGXT itself performs a glyoxylate-metabolizing step, so this IMP process assignment is more than a necessity-only inference. Supporting Evidence: PMID:3709805 there was a complete absence of peroxisomal alanine:glyoxylate aminotransferase file:human/AGXT/AGXT-uniprot.txt Reaction=glyoxylate + L-alanine = glycine + pyruvate
GO:0005515 protein binding	IPI PMID:15911627 Peroxisomal import of human alanine:glyoxylate aminotransfer...	REMOVE	Summary: Human AGXT interacts with human PEX5 as a peroxisomal cargo. Reason: The abstract directly reports mammalian-cell two-hybrid interaction and construct-localization studies. Remove generic protein binding as uninformative without denying the interaction or assigning PEX5's import function to the cargo. Its proposed requirement for a separate adaptor is qualified by later direct reconstitution and structural evidence in PMID:22529745. Supporting Evidence: PMID:15911627 human AGT interacts with human Pex5p in mammalian cells, but not yeast cells
GO:0005777 peroxisome	IDA PMID:3709805 Peroxisomal alanine:glyoxylate aminotransferase deficiency i...	ACCEPT	Summary: Human liver fractionation establishes a peroxisomal AGXT pool. Reason: The source compares normal and PH1 liver fractions and reports loss of peroxisomal activity in the patient. This directly supports the normal organelle localization without claiming finer compartment resolution from fractionation alone. Supporting Evidence: PMID:3709805 Detailed subcellular fractionation of one of the hyperoxaluric livers, compared with a control liver
GO:0008453 L-alanine:glyoxylate transaminase activity	TAS PMID:2363689 Human peroxisomal L-alanine: glyoxylate aminotransferase. Ev...	ACCEPT	Summary: The early human AGXT cDNA study identifies the peroxisomal aminotransferase. Reason: This TAS assignment is consistent with the paper's identified enzyme and subsequent direct human kinetics. The early evolutionary targeting hypothesis is not treated as a complete explanation of all disease mistargeting mechanisms. Supporting Evidence: PMID:2363689 human hepatic peroxisomal L-alanine: glyoxylate aminotransferase 1 PMID:17696873 the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification
GO:0005777 peroxisome	IDA PMID:1703535 Identification of mutations associated with peroxisome-to-mi...	ACCEPT	Summary: The patient and control comparison establishes normally peroxisomal human AGXT and allele-dependent mitochondrial diversion. Reason: The abstract describes controls and notes a small mitochondrial proportion even for one minor-allele homozygote. Retain the normal peroxisomal localization without asserting absolute exclusion from mitochondria for every allele. Supporting Evidence: PMID:1703535 the normally peroxisomal enzyme alanine/glyoxylate aminotransferase (AGT)

Gene Description

Existing Annotations Review

Core Functions

PLP-dependent, homodimeric alanine:glyoxylate transaminase converts glyoxylate and L-alanine to glycine and pyruvate in the peroxisomal matrix, limiting glyoxylate availability for oxalate formation. Amino-acid substrate binding supplies recognition within this catalytic cycle.

PLP-dependent serine:pyruvate transaminase converts L-serine and pyruvate to hydroxypyruvate and L-alanine in liver peroxisomes. This reaction contributes substantially to serine breakdown in human liver preparations under the tested quasi-physiological in-vitro conditions.

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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