AGPS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008609 alkylglycerone-phosphate synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: AGPS catalyzes the conserved ether-bond-forming reaction. Reason: PAINT places GO:0008609 at PTN000922550 in PTHR46568. The cached IBD is grounded by mouse, rat and human descendant annotations; human O00116 among the seeds is legitimate experimental grounding. Purified guinea-pig enzyme and recombinant human wild-type/mutant assays independently establish the conserved activity (PMID:8399344; PMID:9553082). No evidence of human catalytic loss challenges this node placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000922550 SUPPORTS TRANSFER Cached PTHR46568 IBD dated 2026-05-30 assigns GO:0008609 to this metazoan node; seeds MGI:MGI:2443065, RGD:620364 and UniProtKB:O00116. Human activity is independently assayed in PMID:9553082. Supporting Evidence: PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype. PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase, the second enzyme involved in ether phospholipid biosynthesis from dihydroxyacetone phosphate and responsible for glycero-ether bond formation, has been purified from guinea-pig liver.
GO:0005777 peroxisome	IBA GO_REF:0000033	ACCEPT	Summary: Peroxisomal localization is conserved and directly established for human AGPS. Reason: The PAINT peroxisome assertion at PTN000922550 is consistent with import of human precursor into purified peroxisomes (PMID:10415121) and patient-cell precursor/localization observations (PMID:9553082). These support the inherited localization rather than a default assignment from enzyme family membership. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000922550 SUPPORTS TRANSFER Cached IBD dated 2022-03-30 assigns GO:0005777 at this node from fly, rat and human descendants. The target is itself experimentally supported; donor count and target inclusion are not defects. Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro. PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence.
GO:0008610 lipid biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: AGPS directly catalyzes a step of lipid biosynthesis. Reason: The ether-bond-forming reaction is genuine participation in lipid biosynthesis. The broad PAINT process remains valid alongside the separately seeded ether-lipid child term. The cached IBD uses human O00116 as its descendant seed; that does not make the phylogenetic assertion circular (PMID:9553082). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000922550 SUPPORTS TRANSFER Cached GO:0008610 IBD dated 2022-03-30 has human O00116 as its experimental descendant seed. Human enzyme chemistry supports the process, with no target-specific divergence identified. Supporting Evidence: PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence. PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MODIFY	Summary: Refine catalytic activity to the experimentally established synthase reaction. Reason: The InterPro catalytic assertion is biologically correct but does not identify a reaction. Recombinant human AGPS activity in PMID:9553082 and the curated enzyme reaction resolve the acyl-to-alkyl exchange represented by GO:0008609. Refine this root molecular-function term to alkylglycerone-phosphate synthase activity. This is a precision correction to an existing assertion, not a new activity or a claim that the family mapping is false. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR004113 UNRESOLVED GOA identifies this InterPro source. The individual mapping rule was not independently reconstructed; human catalytic activity is corroborated by PMID:9553082. InterPro:IPR016164 UNRESOLVED GOA identifies this InterPro source. The individual mapping rule was not independently reconstructed; human catalytic activity is corroborated by PMID:9553082. Proposed replacements: alkylglycerone-phosphate synthase activity Supporting Evidence: PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0005777 peroxisome	IEA GO_REF:0000120	ACCEPT	Summary: Electronic peroxisome localization agrees with direct human import evidence. Reason: The combined ARBA and UniProt subcellular-location sources make a broad peroxisome assignment that is independently supported by import of human precursor into purified peroxisomes. Acceptance rests on this positive biology; ARBA rule predicates were not reconstructed (PMID:10415121). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028589 UNRESOLVED Rule identifier traced from GOA; its predicates and taxonomic scope were not independently inspected. UniProtKB-SubCell:SL-0204 SUPPORTS TRANSFER Cached human UniProt explicitly records Peroxisome, consistent with primary import evidence in PMID:10415121. Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro. file:human/AGPS/AGPS-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane
GO:0005778 peroxisomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: AGPS associates with the peroxisomal membrane. Reason: The SL-0203 mapping reflects the explicit peroxisomal-membrane entry in UniProt. Guinea-pig liver enzyme was extracted from a peroxisome-enriched membrane fraction, and the human disease study describes AGPS/GNPAT at the luminal membrane surface (PMID:8399344; PMID:21990100). Matrix access and membrane association are compatible compartments for this enzyme. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0203 SUPPORTS TRANSFER The cached UniProt localization maps Peroxisome membrane to this term. Its ortholog donor P97275 is guinea-pig AGPS, corroborated by PMID:8399344 and RCSB 4BBY. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase was solubilized from a membrane fraction prepared from an enriched peroxisome fraction with Triton X-100 and potassium chloride.
GO:0008609 alkylglycerone-phosphate synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Reaction, EC and enzyme-family mappings capture the defining synthase activity. Reason: RHEA:36171 records the general acyl-DHAP/long-chain-alcohol exchange and RHEA:40659 its hexadecyl-substrate instance in the cached UniProt entry. These agree with the live GO:0008609 reaction and EC:2.5.1.26. Human wild-type and R419H assays support the chemistry; the InterPro rule itself was not independently re-evaluated (PMID:9553082). Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR025650 UNRESOLVED Source mapping identified; family membership is consistent with AGPS but rule internals were not inspected. RHEA:36171 SUPPORTS TRANSFER General ether-bond-forming reaction is explicitly present in human UniProt and matches GO:0008609. RHEA:40659 SUPPORTS TRANSFER Hexadecanoylglycerone-phosphate plus hexadecanol reaction is explicitly present in human UniProt and is within the term chemistry. EC:2.5.1.26 SUPPORTS TRANSFER Cached human enzyme EC assignment cites PMID:8399344 and PMID:9553082; the latter directly assays human AGPS. Supporting Evidence: PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0008610 lipid biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: AGPS catalysis is part of lipid biosynthesis. Reason: The InterPro-derived lipid-biosynthetic parent is accurate at its own breadth: AGPS builds the ether linkage of a lipid precursor. The seeded ether-lipid process provides greater specificity without making this broad source assertion an over-annotation (PMID:9553082). Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR025650 UNRESOLVED GOA mapping traced; rule internals were not inspected. The human catalytic step independently supports lipid biosynthesis. Supporting Evidence: PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence.
GO:0050660 flavin adenine dinucleotide binding	IEA GO_REF:0000002	ACCEPT	Summary: FAD is the catalytic cofactor of AGPS. Reason: The InterPro assignments agree with the UniProt cofactor record and the FAD-containing guinea-pig AGPS structure/mechanistic study (PMID:23112191; PDB 4BBY). GO:0050660 includes flavin adenine dinucleotide in different oxidation states; it is broader than the oxidized-FAD term GO:0071949, not an exact synonym. FAD binding does not imply that AGPS catalyzes a net oxidation-reduction reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR004113 UNRESOLVED Source identifier traced from GOA; its mapping internals were not inspected. Independent cofactor and ortholog structural evidence support the target binding function. InterPro:IPR006094 UNRESOLVED Source identifier traced from GOA; its mapping internals were not inspected. Independent cofactor and ortholog structural evidence support the target binding function. InterPro:IPR016164 UNRESOLVED Source identifier traced from GOA; its mapping internals were not inspected. Independent cofactor and ortholog structural evidence support the target binding function. InterPro:IPR036318 UNRESOLVED Source identifier traced from GOA; its mapping internals were not inspected. Independent cofactor and ortholog structural evidence support the target binding function. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692;
GO:0071949 FAD binding	IEA GO_REF:0000002	ACCEPT	Summary: AGPS binds oxidized FAD for catalysis. Reason: The IPR016166 binding-domain mapping is consistent with the cofactor record. The primary mechanistic study identifies oxidized flavin as catalytically competent and supports a covalent catalytic intermediate, rather than net substrate oxidation (PMID:23112191). FAD binding is integrated into the synthase core. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR016166 UNRESOLVED The InterPro source is traced but its mapping rule was not inspected; independent guinea-pig AGPS structure and mechanism support oxidized-FAD use (PMID:23112191). Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692;
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: The recorded AGPS–GORASP1 interaction has no resolved specific molecular function. Reason: This IPI assertion comes from the systematic human binary interactome map. GOA identifies GORASP1 (Q9BQQ3), also recorded in cached UniProt. The study framework and curated pair support considering an interaction, but no AGPS-specific adaptor, regulatory or catalytic function was established from the accessible source. Remove the uninformative generic protein-binding term without denying the reported interaction. The individual supplementary pair/variant record was not independently reconstructed. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt O00116; Q9BQQ3: GORASP1; NbExp=7; IntAct=EBI-2838732, EBI-2561458;
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: The recorded AGPS–GORASP1 interaction has no resolved specific molecular function. Reason: This IPI assertion comes from the population-variant interaction survey. GOA identifies GORASP1 (Q9BQQ3), also recorded in cached UniProt. The study framework and curated pair support considering an interaction, but no AGPS-specific adaptor, regulatory or catalytic function was established from the accessible source. Remove the uninformative generic protein-binding term without denying the reported interaction. The individual supplementary pair/variant record was not independently reconstructed. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt O00116; Q9BQQ3: GORASP1; NbExp=7; IntAct=EBI-2838732, EBI-2561458;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The recorded AGPS–GORASP1 interaction has no resolved specific molecular function. Reason: This IPI assertion comes from the HuRI binary interactome map. GOA identifies GORASP1 (Q9BQQ3), also recorded in cached UniProt. The study framework and curated pair support considering an interaction, but no AGPS-specific adaptor, regulatory or catalytic function was established from the accessible source. Remove the uninformative generic protein-binding term without denying the reported interaction. The individual supplementary pair/variant record was not independently reconstructed. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt O00116; Q9BQQ3: GORASP1; NbExp=7; IntAct=EBI-2838732, EBI-2561458;
GO:0008611 ether lipid biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: AGPS directly performs ether-lipid biosynthesis. Reason: UniPathway UPA00781 maps the documented ether-lipid pathway to GO:0008611. This is direct enzymatic participation: AGPS forms the ether-linked precursor, rather than merely being required for an unrelated phenotype (PMID:8399344; PMID:9553082). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniPathway:UPA00781 SUPPORTS TRANSFER The cached human UniProt pathway entry is ether lipid biosynthesis; purified ortholog and recombinant human enzyme studies establish the participating reaction. Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase, the second enzyme involved in ether phospholipid biosynthesis from dihydroxyacetone phosphate and responsible for glycero-ether bond formation, has been purified from guinea-pig liver. PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence.
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: The HPA peroxisome assignment is consistent with established human localization. Reason: The GO_REF:0000052 assertion records curated immunofluorescence localization. The underlying image was not independently re-scored, but peroxisome localization is corroborated by human precursor import and patient-cell studies. Retain the experimentally curated broad compartment without claiming an image-specific subcompartment (PMID:10415121; PMID:9553082). Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro. PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence.
GO:0005777 peroxisome	ISS GO_REF:0000024	ACCEPT	Summary: Guinea-pig AGPS localization supports the conserved peroxisomal compartment. Reason: The ISS donor P97275 is Cavia porcellus AGPS, verified through NCBI and RCSB 4BBY. Native guinea-pig enzyme purification from a peroxisome-enriched membrane fraction supports the donor compartment; human precursor import independently confirms target localization (PMID:8399344; PMID:10415121). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P97275 SUPPORTS TRANSFER Guinea-pig AGPS, not mouse. Native peroxisomal enrichment is reported in PMID:8399344; direct human peroxisomal import in PMID:10415121 corroborates transfer. The historical donor GO record itself was not reconstructed. Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase was solubilized from a membrane fraction prepared from an enriched peroxisome fraction with Triton X-100 and potassium chloride. PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro.
GO:0005778 peroxisomal membrane	ISS GO_REF:0000024	ACCEPT	Summary: Peroxisomal membrane association is supported by the guinea-pig ortholog and human pathway context. Reason: P97275 is guinea-pig AGPS. The native enzyme required detergent/salt solubilization from a peroxisome-enriched membrane fraction (PMID:8399344). The human AGPS/GNPAT context places the enzyme at the luminal membrane surface (PMID:21990100). This supports membrane association without implying that AGPS is an integral transmembrane protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P97275 SUPPORTS TRANSFER Guinea-pig enzyme membrane extraction in PMID:8399344 supports the source compartment; human luminal-membrane pathway context corroborates transfer. The historical donor GO record was not separately reconstructed. Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase was solubilized from a membrane fraction prepared from an enriched peroxisome fraction with Triton X-100 and potassium chloride. file:human/AGPS/AGPS-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane
GO:0008609 alkylglycerone-phosphate synthase activity	IDA PMID:8399344 Ether lipid synthesis: purification and identification of al...	ACCEPT	Summary: Purified guinea-pig enzyme establishes the synthase reaction conserved in human AGPS. Reason: PMID:8399344 explicitly studies guinea-pig liver enzyme and reports extensive purification and positive activity. Preserve the original IDA source assertion while recording that organism scope. It establishes ortholog chemistry, and the human wild-type/mutant assays of PMID:9553082 independently establish the target activity; the annotation is not rejected from its nonhuman title. Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase, the second enzyme involved in ether phospholipid biosynthesis from dihydroxyacetone phosphate and responsible for glycero-ether bond formation, has been purified from guinea-pig liver. PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0005829 cytosol	TAS Reactome:R-HSA-9033232	KEEP AS NON CORE	Summary: Cytosolic AGPS is a precursor cargo for PEX7-dependent import. Reason: Reactome R-HSA-9033232 represents cytosolic recognition of PTS2-containing cargo by PEX7. Human AGPS has a cleavable PTS2 precursor (PMID:9553082; PMID:10415121), supporting this transient location. The core lipid-synthetic compartment is peroxisomal. Precursor presence in cytosol does not imply inactivity: processing did not increase enzyme activity in vitro. Supporting Evidence: PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence. PMID:10415121 Processing of alkyl-dihydroxyacetonephosphate synthase did not increase the activity of the enzyme.
GO:0005829 cytosol	TAS Reactome:R-HSA-9033514	KEEP AS NON CORE	Summary: The import reaction includes the cytosolic precursor stage. Reason: Reactome R-HSA-9033514 moves PEX7-bound cargo from cytosol to peroxisomal matrix. The cytosol annotation represents the source compartment of AGPS import rather than a demonstrated steady-state cytosolic lipid-synthesis pool. Human import/processing assays support the route, while showing that cleavage is not required to activate the precursor (PMID:10415121). Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro. PMID:10415121 Processing of alkyl-dihydroxyacetonephosphate synthase did not increase the activity of the enzyme.
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-9033514	ACCEPT	Summary: Human AGPS reaches the peroxisomal matrix through PTS2 import. Reason: The destination of Reactome R-HSA-9033514 is the matrix, matching direct import and processing of human precursor in purified peroxisomes (PMID:10415121). Matrix localization is compatible with catalytic association at the luminal membrane surface. AGPS is cargo in this event; the annotation does not establish an import-machine molecular function for AGPS. Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: Broad membrane association is consistent with AGPS biology. Reason: PMID:19946888 characterizes membrane preparations from the human YTS NK-like cell line and includes integral and associated proteins. The individual AGPS supplementary hit was not independently recovered, so the original HDA assertion is retained at its broad membrane resolution. Independent peroxisomal membrane extraction/localization evidence supports membrane association without assigning a more specific compartment to this particular assay (PMID:8399344). Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase was solubilized from a membrane fraction prepared from an enriched peroxisome fraction with Triton X-100 and potassium chloride.
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	UNDECIDED	Summary: The mitochondrial proteomics annotation remains source-specific and unresolved. Reason: PMID:20833797 analyzes functional mitochondria isolated from human skeletal muscle. The local cache contains abstract and Discussion text but lacks the gene-level results and supplementary AGPS identification record; limited external Results text confirms functional preparation controls but does not resolve AGPS residence. Established peroxisomal localization neither demonstrates contamination nor excludes another pool. The mitochondrial assignment requires inspection of the actual AGPS peptide/fraction evidence and any localization validation. Supporting Evidence: PMID:20833797 We performed a phosphoproteomics study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphoproteins.
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-390427	ACCEPT	Summary: The ether-bond-forming reaction occurs on the luminal side of the peroxisome. Reason: Reactome R-HSA-390427 assigns AGPS its own ether-bond-forming reaction in the peroxisomal compartment. This is consistent with direct import and the AGPS/GNPAT luminal membrane context. The event summary describes the mature cleaved enzyme, but PMID:10415121 also demonstrates active precursor, so cleavage is not interpreted as obligatory activation. Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro. PMID:10415121 Processing of alkyl-dihydroxyacetonephosphate synthase did not increase the activity of the enzyme. Reactome:R-HSA-390427 Peroxisomal alkylglycerone phosphate synthase (AGPS) catalyzes the reaction of 1-palmitoylglycerone phosphate and hexadecanol to form O-hexadecylglycerone phosphate and palmitate.
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-75879	ACCEPT	Summary: The GNPAT-associated AGPS pool is peroxisomal. Reason: Reactome R-HSA-75879 describes GNPAT catalysis by a complex containing AGPS. It supports AGPS presence in the peroxisomal reaction compartment, consistent with import and luminal membrane association. The acyltransferase reaction belongs to GNPAT; AGPS performs the subsequent acyl/alkyl exchange. No GNPAT catalytic activity is assigned to AGPS. Supporting Evidence: Reactome:R-HSA-75879 The active form of the enzyme is one subunit of a heterotrimer with two molecules of the alkylglycerone phosphate synthase (AGPS) enzyme PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro.
GO:0008611 ether lipid biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: The guinea-pig ortholog supports conserved ether-lipid biosynthesis. Reason: P97275 is guinea-pig AGPS. Its native enzyme purification explicitly establishes the ether-bond-forming reaction in ether-phospholipid biosynthesis (PMID:8399344); human recombinant enzyme assays and disease-associated loss of activity corroborate the same participating step (PMID:9553082). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P97275 SUPPORTS TRANSFER Guinea-pig AGPS positive reaction evidence in PMID:8399344 and human biochemical corroboration in PMID:9553082 support the conserved process; historical donor GO metadata were not separately reconstructed. Supporting Evidence: PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase, the second enzyme involved in ether phospholipid biosynthesis from dihydroxyacetone phosphate and responsible for glycero-ether bond formation, has been purified from guinea-pig liver. PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0071949 FAD binding	ISS GO_REF:0000024	ACCEPT	Summary: Guinea-pig AGPS provides direct structural support for oxidized-FAD binding. Reason: The ISS donor is P97275 from Cavia porcellus. RCSB 4BBY explicitly maps this protein and bound FAD to the structural study PMID:23112191. That paper identifies catalytically competent oxidized flavin, consistent with the human UniProt cofactor transfer. This supports binding without turning the ether-forming reaction into an oxidoreductase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P97275 SUPPORTS TRANSFER Donor identity and FAD ligand independently verified in RCSB 4BBY, linked to PMID:23112191. Full primary Results/Discussion support the cofactor mechanism; this is positive donor evidence, although historical GO metadata were not reconstructed. Supporting Evidence: file:human/AGPS/AGPS-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692;
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	ACCEPT	Summary: The PEX14 membrane-complex study is compatible with AGPS membrane association. Reason: PMID:21525035 isolates native peroxisomal membrane assemblies from human Flp-In-293 cells. The accessible abstract does not expose the individual AGPS mass-spectrometry row, so the HDA source is retained with curator deference and independent membrane evidence (PMID:8399344; PMID:21990100). AGPS is not assigned the PEX14-specific tubulin binding or peroxisome-motility function. Supporting Evidence: PMID:21525035 We have established a procedure for isolating native peroxisomal membrane protein complexes from cultured human cells. PMID:8399344 Alkyl-dihydroxyacetone phosphate synthase was solubilized from a membrane fraction prepared from an enriched peroxisome fraction with Triton X-100 and potassium chloride.
GO:0005777 peroxisome	IDA PMID:10415121 In vitro processing of the human alkyl-dihydroxyacetonephosp...	ACCEPT	Summary: Human precursor import directly supports peroxisomal localization. Reason: PMID:10415121 explicitly assays the human AGPS precursor, produced in vitro or in E. coli. Processing uses a guinea-pig liver organellar fraction enriched in mitochondria, lysosomes and peroxisomes; a separate experiment demonstrates import and processing in purified peroxisomes, whose species is not stated in the accessible abstract. This supports peroxisomal targeting of the human protein in vitro, without claiming an intact human-cell localization experiment. Processing did not increase catalytic activity, and the cysteine processing protease was not identified by the later TYSND1 name. Supporting Evidence: PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro.
GO:0008609 alkylglycerone-phosphate synthase activity	IDA PMID:10415121 In vitro processing of the human alkyl-dihydroxyacetonephosp...	ACCEPT	Summary: Both precursor and processed human AGPS retain synthase activity. Reason: PMID:10415121 measures enzyme activity while investigating precursor processing and finds no increase after cleavage. This supports the synthase activity and prevents conflating targeting-sequence removal with enzyme activation. Human recombinant wild-type/mutant data provide independent catalytic corroboration (PMID:9553082). Supporting Evidence: PMID:10415121 Processing of alkyl-dihydroxyacetonephosphate synthase did not increase the activity of the enzyme. PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0005777 peroxisome	IDA PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome...	ACCEPT	Summary: Patient-cell observations support intraperoxisomal AGPS localization. Reason: PMID:9553082 reports instability when import is defective and precursor retention in a patient with isolated PTS1-import deficiency, consistent with a PTS2 enzyme inside peroxisomes. The latter is explicitly a localization interpretation in the abstract, independently strengthened by the purified-peroxisome import experiment of PMID:10415121. Supporting Evidence: PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence. PMID:10415121 exogenously added pre-alkyl-dihydroxyacetonephosphate synthase was imported and processed in purified peroxisomes in vitro.
GO:0008609 alkylglycerone-phosphate synthase activity	IDA PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome...	ACCEPT	Summary: Human wild-type and R419H enzyme assays establish AGPS catalytic activity. Reason: PMID:9553082 reports active recombinant human wild-type AGPS and inactive R419H protein, together with substrate protection against chemical inactivation. These are direct positive biochemical evidence for the synthase activity; the patient phenotype is corroborative rather than the sole basis for this molecular function. Supporting Evidence: PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.
GO:0008610 lipid biosynthetic process	IDA PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome...	ACCEPT	Summary: Human AGPS catalysis participates directly in lipid biosynthesis. Reason: PMID:9553082 connects active human enzyme, loss-of-activity variants and ether-phospholipid biosynthesis. The broad lipid-biosynthetic term is true for this enzymatic step. The separately seeded ether-lipid term supplies process specificity without requiring a duplicate replacement or treating the broad assertion as incorrect. Supporting Evidence: PMID:9553082 Alkyl-dihydroxyacetonephosphate synthase, a peroxisomal enzyme playing a key role in the biosynthesis of ether phospholipids, contains the peroxisomal targeting signal type 2 in a N-terminal cleavable presequence. PMID:9553082 Expression of a recombinant protein carrying this mutation in Escherichia coli yielded an inactive enzyme, whereas a comparable control recombinant enzyme was active, providing further proof that this substitution is responsible for the inactivity of the enzyme and the phenotype.

Gene Description

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