ALDH18A1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: PAINT places mitochondrial localization at ancestral node PTN000869169. Reason: The cached PTHR11063 PAINT IBD supports this inherited compartment, and human imaging and fractionation independently establish mitochondrial P5CS. The organelle-level assertion is valid at its original resolution; the target appearing among descendant evidence is expected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000869169 SUPPORTS TRANSFER Verified cached PAINT IBD for GO:0005739; human target localization supports inheritance without evidence of lineage-specific loss. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0004350 glutamate-5-semialdehyde dehydrogenase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT assigns the conserved glutamate-5-semialdehyde dehydrogenase activity at PTN000115463. Reason: The C-terminal P5CS domain reduces glutamyl phosphate using NADPH. GO:0004350 represents the reversible reaction, even though its definition displays the oxidative direction. Human biochemical evidence agrees with the ancestral activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000115463 SUPPORTS TRANSFER Cached PAINT IBD explicitly assigns GO:0004350; target experimental evidence is legitimate descendant grounding, not circular transfer. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro provides a root catalytic-activity annotation. Reason: P5CS catalysis is established, and the two resolved chemical activities provide more informative molecular functions than the root MF. This refines the broad assertion without rejecting the family mapping. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR005766 SUPPORTS TRANSFER The family mapping supports catalysis; human P5CS chemistry resolves the two enzymatic activities. Proposed replacements: glutamate 5-kinase activity glutamate-5-semialdehyde dehydrogenase activity Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0004349 glutamate 5-kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined sequence, reaction and enzyme-class mappings identify glutamate 5-kinase activity. Reason: The N-terminal domain phosphorylates glutamate with ATP, the first reaction in the P5CS pathway. The Rhea/EC mappings and human enzyme evidence converge on this exact activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:14877 SUPPORTS TRANSFER The cached UniProt catalytic reaction is glutamate phosphorylation, EC 2.7.2.11; this is one of the combined annotation sources. InterPro:IPR019797 SUPPORTS TRANSFER This source is listed in the combined row and agrees with the experimentally characterized kinase domain. Supporting Evidence: PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells. PMID:11092761 gamma-glutamyl kinase domain file:human/ALDH18A1/ALDH18A1-uniprot.txt Reaction=L-glutamate + ATP = L-glutamyl 5-phosphate + ADP;
GO:0004350 glutamate-5-semialdehyde dehydrogenase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined mappings identify the glutamyl-phosphate reductase reaction. Reason: The C-terminal activity converts glutamyl phosphate to glutamate semialdehyde using NADPH. The reversible GO reaction and EC 1.2.1.41 match this chemistry. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:19541 SUPPORTS TRANSFER The UniProt reaction/EC 1.2.1.41 assignment resolves the reductase chemistry represented by GO:0004350. InterPro:IPR000965 SUPPORTS TRANSFER This InterPro source is present in the combined mapping and consistent with the C-terminal enzyme activity. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: The kinase-domain mapping assigns ATP binding. Reason: ATP is a catalytic substrate of the glutamate 5-kinase reaction. Binding it is an integral property of the core enzyme, even though the integrated core is represented by the reaction term. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001057 SUPPORTS TRANSFER The mapped domain binds the ATP used for glutamate phosphorylation; target biochemistry supports the source assertion. Supporting Evidence: file:human/ALDH18A1/ALDH18A1-uniprot.txt Reaction=L-glutamate + ATP = L-glutamyl 5-phosphate + ADP; PMID:11092761 a bifunctional ATP- and NADPH-dependent mitochondrial enzyme
GO:0005737 cytoplasm	IEA GO_REF:0000002	ACCEPT	Summary: InterPro supplies the broad cytoplasm component. Reason: GO:0005737 includes subcellular structures other than the nucleus and plasma membrane, including mitochondria. It does not assert cytosolic residence. Human mitochondrial localization is compatible with this broad family-level location. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR005715 SUPPORTS TRANSFER The cytoplasm mapping is compatible with the actual GO definition and mitochondrial localization; no incorrect cytosol transfer is established. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping assigns mitochondrion. Reason: Human imaging, biochemical fractionation and the curated UniProt record support this core compartment. Preserve the source organelle resolution. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0173 SUPPORTS TRANSFER The cached UniProt mitochondrial location agrees with independent human localization experiments. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping assigns mitochondrial matrix. Reason: Human HeLa P5CS-APEX imaging and protease-protection experiments in PMID:32770108 support the matrix. The separate carbonate experiment supports non-integral topology; it is not evidence excluding all peripheral association. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0170 SUPPORTS TRANSFER The matrix vocabulary mapping is supported by the externally read Results/Figure 1 of PMID:32770108. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0008652 amino acid biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA assigns amino acid biosynthetic process. Reason: P5CS performs two chemical steps supplying proline and ornithine biosynthesis, so this broader biosynthetic assertion is correct and core. Its validity does not depend on excluding more specific process terms. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027355 UNRESOLVED The exact rule predicates were not recovered; the target process is independently supported by its demonstrated catalytic steps. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0016301 kinase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro assigns the broad kinase activity. Reason: The relevant kinase is a metabolite kinase that phosphorylates L-glutamate, not a protein kinase. Human enzymology and the reaction mapping resolve glutamate 5-kinase activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001057 SUPPORTS TRANSFER The kinase-domain assertion is sound; its substrate-specific molecular function is established. Proposed replacements: glutamate 5-kinase activity Supporting Evidence: PMID:11092761 gamma-glutamyl kinase domain file:human/ALDH18A1/ALDH18A1-uniprot.txt Reaction=L-glutamate + ATP = L-glutamyl 5-phosphate + ADP;
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro assigns the broad oxidoreductase activity. Reason: The resolved redox reaction is NADPH-dependent reduction of glutamyl phosphate to glutamate semialdehyde. GO:0004350 gives the appropriate specific reversible enzyme activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR015590 SUPPORTS TRANSFER The redox activity is supported, with substrate/reaction specificity established by the P5CS enzyme evidence. Proposed replacements: glutamate-5-semialdehyde dehydrogenase activity Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0055129 L-proline biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Combined mappings assign L-proline biosynthesis. Reason: P5CS executes glutamate phosphorylation and glutamyl-phosphate reduction upstream of P5C reduction to proline. This is actual catalytic participation, supported by human expression and disease-variant studies. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniPathway:UPA00098 SUPPORTS TRANSFER The proline pathway mapping matches the two P5CS reactions; multiple InterPro entries also contribute to the combined annotation. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: A human binary interaction map supplies generic protein binding. Reason: The source is a systematic interaction study and the annotation records pairs with AGTRAP and CMTM5. Generic protein binding does not identify a useful P5CS molecular function; remove the uninformative term without denying those interactions. The available source does not establish an adaptor or other replacement activity.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI supplies generic protein binding. Reason: The human binary-interaction mapping records COQ9 and DARS2 partners. The generic term adds no defined P5CS function, and association alone does not establish a specific replacement molecular function. This removal is not a claim that the pairs are false.
GO:0009266 response to temperature stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: The rat ortholog transfer originates in an enzyme temperature-stability study. Reason: The traced rat IDA source PMID:6131890 tests thermal inactivation in cell-free intestinal preparations, including detergent and stabilizing conditions. Its Results and Discussion address enzyme stability rather than a change in cellular or organismal state in response to temperature, as GO:0009266 requires. Transferring that physical lability as a human temperature-response process exceeds the demonstrated scope. PMID:32770108 studies starvation and oxidation and is not the donor experiment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:A0A8I6AAN3 SOURCE BAD Rat Aldh18a1 donor identified through ENSRNOP00000089847 and the MGI orthology GO graph; GO:0009266 IDA traces to PMID:6131890. The original full study measures cell-free thermal lability, not the cell/organism response specified by the term. Supporting Evidence: PMID:6131890 is susceptible to thermal inactivation in the presence of detergent.
GO:0031966 mitochondrial membrane	IEA GO_REF:0000107	UNDECIDED	Summary: The rat ortholog transfer carries a mitochondrial membrane location. Reason: PMID:6131890 genuinely retains rat intestinal P5CS activity in a particulate mitochondrial fraction and discusses possible inner-membrane or inner-surface association. Human matrix localization and carbonate release argue against integral insertion but do not exclude peripheral membrane association. The exact human membrane association and conservation of this rat preparation result remain unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:A0A8I6AAN3 UNRESOLVED The donor GO:0031966 IDA is linked to PMID:6131890. Rat biochemical fractionation is real; precise human membrane association is not resolved by the recovered studies. Supporting Evidence: PMID:6131890 The mitochondrial membrane fraction, freed of the soluble matrix and intermembrane space enzymes, retained all of the P5C-synthesizing activity.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence assigns mitochondrial localization. Reason: Retain the curated organelle-level imaging result, independently corroborated by human P5CS imaging in PMID:32770108. Microscopy at this evidence resolution is not by itself a matrix assignment. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005759 mitochondrial matrix	IDA PMID:32770108 Pyrroline-5-carboxylate synthase senses cellular stress and ...	ACCEPT	Summary: Human localization experiments place P5CS in the mitochondrial matrix. Reason: The externally recovered Results and Figure 1 of PMID:32770108 show HeLa P5CS-APEX matrix signal and an endogenous protease-protection profile like HSP60. Carbonate extraction further distinguishes P5CS from integral TOMM20. These assays directly support the matrix annotation. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: MitoCoP supplies a human mitochondrial proteomics annotation. Reason: The original study combines quantitative fractionation and profiling to define the human mitochondrial proteome. The seeded HTP target assignment is retained with curator deference and independent human P5CS localization support; the extracted article does not expose the target supplementary row. No matrix refinement is inferred from the organelle-level screen. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9837978	UNDECIDED	Summary: Reactome places the P5CS substrate entity in the mitochondrial inner membrane during LONP1 binding. Reason: The explicit Reactome compartment is a genuine assertion, not automatically an artifact of the reaction title. Its cached summary describes LONP1 substrates collectively and does not resolve the P5CS-specific localization assay. Human matrix/non-integral evidence permits peripheral association, so neither acceptance of this precise location nor its rejection is established. Rat intestinal fractionation in PMID:6131890 independently supports historical particulate association, but does not settle this human localization. Supporting Evidence: PMID:6131890 The mitochondrial membrane fraction, freed of the soluble matrix and intermembrane space enzymes, retained all of the P5C-synthesizing activity.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9838004	UNDECIDED	Summary: Reactome places P5CS in the mitochondrial inner membrane during LONP1-mediated degradation. Reason: The cached event documents LONP1 proteolysis and assigns substrate compartments but does not identify a P5CS-specific membrane-localization experiment. A matrix protein can interact peripherally with the inner membrane; the currently recovered evidence does not settle that location for human P5CS. Rat intestinal fractionation in PMID:6131890 independently supports historical particulate association, but does not settle this human localization. Supporting Evidence: PMID:6131890 The mitochondrial membrane fraction, freed of the soluble matrix and intermembrane space enzymes, retained all of the P5C-synthesizing activity.
GO:0004349 glutamate 5-kinase activity	IMP PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study supplies a glutamate 5-kinase mutant-phenotype annotation. Reason: The original publisher extract explicitly reports site-directed mutagenesis and enzyme assays of purified recombinant P5CS. The full kinetic figures were not recovered, so individual variant effects are not reconstructed here. The exact kinase activity is independently established and the curated experimental assertion is retained. Supporting Evidence: PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells. PMID:11092761 gamma-glutamyl kinase domain file:human/ALDH18A1/ALDH18A1-uniprot.txt Reaction=L-glutamate + ATP = L-glutamyl 5-phosphate + ADP;
GO:0004350 glutamate-5-semialdehyde dehydrogenase activity	IMP PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study supplies a glutamate-5-semialdehyde dehydrogenase annotation. Reason: The C-terminal redox reaction is independently supported by human P5CS enzymology. The publisher extract establishes recombinant enzyme assays, but the unavailable detailed figures prevent a variant-by-variant judgment. Retaining this activity does not assert that every SPG9 variant impairs both domains equally. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0006592 L-ornithine biosynthetic process	IMP PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study annotates participation in ornithine biosynthesis. Reason: P5CS catalytically produces glutamate semialdehyde/P5C, which supplies the ornithine aminotransferase route. This positive reaction mechanism, together with human loss-of-function evidence, supports the core process without requiring that P5CS catalyze the terminal ornithine-forming reaction. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0019240 L-citrulline biosynthetic process	IMP PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	KEEP AS NON CORE	Summary: The SPG9 study links P5CS to citrulline biosynthesis. Reason: P5CS executes the upstream glutamate-to-P5C chemistry in the glutamate-to-ornithine-to-citrulline route. Thus participation can be valid even though OTC catalyzes citrulline formation. Retain this context-dependent intestinal precursor-supply process as non-core; the full original SPG9 physiological measurements remain inaccessible, and human pathway support also comes from PMID:11092761. Supporting Evidence: PMID:11092761 The short isoform has high activity in the gut, where it participates in arginine biosynthesis and is inhibited by ornithine.
GO:0042802 identical protein binding	IDA PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study assigns P5CS self-association. Reason: P5CS homomerization is an established property of its catalytic assemblies, corroborated by human mutant/wild-type interaction experiments in PMID:26320891 and multimerization-dependent organization in PMID:32770108. Retain the source IDA with this independent support without inferring a single obligatory native oligomer stoichiometry. Supporting Evidence: PMID:26320891 stable and able to interact with wild-type P5CS but showed an altered sub-mitochondrial distribution.
GO:0055129 L-proline biosynthetic process	IMP PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study assigns L-proline biosynthesis. Reason: P5CS executes the two reactions producing the P5C precursor used by proline reductases. Human expression and loss-of-function studies establish that catalytic role; the retained IMP does not require inventing details of the unavailable source kinetic figures. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells.
GO:0005739 mitochondrion	IDA PMID:26297558 ALDH18A1 gene mutations cause dominant spastic paraplegia SP...	ACCEPT	Summary: The SPG9 study supplies mitochondrial localization. Reason: Human mitochondrial P5CS localization is independently established by imaging and fractionation. Retain the source IDA at the organelle level with curator deference; detailed localization panels from this letter were not recovered. Supporting Evidence: PMID:32770108 We found that P5CS localizes in mitochondria in rod- and ring-like patterns
GO:0005739 mitochondrion	IDA PMID:26320891 Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrr...	ACCEPT	Summary: Patient fibroblasts and heterologous expression support mitochondrial P5CS localization. Reason: PMID:26320891 reports an altered sub-mitochondrial distribution of Arg138Trp P5CS in affected fibroblasts and expression experiments. This supports the organelle location while distinguishing changed intramitochondrial organization from loss of mitochondrial import. Supporting Evidence: PMID:26320891 stable and able to interact with wild-type P5CS but showed an altered sub-mitochondrial distribution.
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	UNDECIDED	Summary: A HeLa mRNA-interactome capture study supplies an RNA-binding annotation. Reason: The source uses covalent UV crosslinking and biochemical/statistical criteria to identify RNA-binding proteins. The target-specific ALDH18A1 result and its supplementary evidence were not recovered from the abstract-only cache or external search. Preserve uncertainty without treating a metabolic enzyme as contamination or asserting a characterized RNA-binding role. Supporting Evidence: PMID:22658674 Employing two complementary protocols for covalent UV crosslinking of RBPs to RNA
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-508040	UNDECIDED	Summary: The P5CS catalytic Reactome event explicitly describes inner-membrane association. Reason: R-HSA-508040 states that P5CS is associated with the inner mitochondrial membrane and cites mammalian isoform enzymology. The historical rat fractionation source supports a particulate association, while human matrix and carbonate assays exclude integral topology more clearly than peripheral association. The precise human membrane relationship remains unresolved; matrix localization alone does not overturn this event. Supporting Evidence: PMID:6131890 The mitochondrial membrane fraction, freed of the soluble matrix and intermembrane space enzymes, retained all of the P5C-synthesizing activity.
GO:0004349 glutamate 5-kinase activity	IDA PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: Human R84Q expression experiments support the glutamate 5-kinase function. Reason: The source places R84Q in the kinase domain and reports reduced activity of both human splice forms in mammalian cells. This is consistent with the established ATP-dependent glutamate phosphorylation step. The accessible abstract reports coupled P5CS activity rather than a complete isolated-domain kinetic analysis. Supporting Evidence: PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells. PMID:11092761 gamma-glutamyl kinase domain file:human/ALDH18A1/ALDH18A1-uniprot.txt Reaction=L-glutamate + ATP = L-glutamyl 5-phosphate + ADP;
GO:0004350 glutamate-5-semialdehyde dehydrogenase activity	IDA PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: Human P5CS experiments support the glutamyl-phosphate reductase function. Reason: The source identifies a bifunctional ATP/NADPH-dependent enzyme converting glutamate to P5C, consistent with the C-terminal reductase reaction. Retain the curated IDA in light of established human chemistry; the R84Q coupled-activity defect does not on its own localize the lesion to the reductase domain. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0006536 glutamate metabolic process	IMP PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: Human P5CS deficiency is annotated to glutamate metabolism. Reason: P5CS directly modifies glutamate through phosphorylation and reduction. This is a true core metabolic assertion, not merely a downstream phenotype, and remains valid alongside the more specific amino-acid biosynthetic processes. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0006592 L-ornithine biosynthetic process	IMP PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: Human P5CS deficiency supports ornithine biosynthesis. Reason: The source documents reduced ornithine in the affected siblings, while P5CS chemistry directly supplies the semialdehyde/P5C substrate for ornithine formation. The mechanistic participation supports the process beyond the deficiency phenotype alone. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0019240 L-citrulline biosynthetic process	IMP PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	KEEP AS NON CORE	Summary: P5CS deficiency is associated with reduced citrulline synthesis. Reason: The source describes the intestinal short-isoform pathway and hypocitrullinemia. P5CS performs precursor-forming chemistry within the glutamate-derived citrulline route, with OAT and OTC executing later reactions. Retain this tissue/pathway-dependent process as non-core rather than claiming that an upstream catalyst cannot participate. Supporting Evidence: PMID:11092761 The short isoform has high activity in the gut, where it participates in arginine biosynthesis and is inhibited by ornithine.
GO:0006592 L-ornithine biosynthetic process	IMP PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: A duplicated seeded row retains the supported ornithine-biosynthesis assertion. Reason: This seeded entry duplicates the other PMID:11092761 IMP assertion; the GOA file has two ornithine-biosynthesis rows, and this is not independent evidence. The source row is preserved. P5CS supplies glutamate semialdehyde/P5C by catalysis, and the human deficiency study documents the expected ornithine phenotype. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine.
GO:0055129 L-proline biosynthetic process	IMP PMID:11092761 Hyperammonemia with reduced ornithine, citrulline, arginine ...	ACCEPT	Summary: The human deficiency study supports proline biosynthesis. Reason: P5CS directly produces the P5C precursor, and R84Q reduces expressed enzyme activity together with a patient hypoprolinemia phenotype. This combines a known performed reaction with perturbation evidence for the core pathway. Supporting Evidence: PMID:11092761 catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. PMID:11092761 dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells.
GO:0055129 L-proline biosynthetic process	TAS PMID:8761662 Database cloning human delta 1-pyrroline-5-carboxylate synth...	ACCEPT	Summary: The original human cDNA paper attributes P5CS to the first two proline-biosynthetic reactions. Reason: The primary abstract identifies a human bifunctional enzyme and describes glutamate-to-semialdehyde conversion. This TAS process is consistent with later expression/complementation and human enzyme studies; cloning is not represented as an isolated-domain kinetic assay. Supporting Evidence: PMID:8761662 This cDNA, as its plant counterpart, encodes a bifunctional enzyme, with both gamma-glutamyl kinase (gamma-GK) and gamma-glutamyl phosphate reductase (gamma-GPR) activities

Gene Description

Existing Annotations Review

Core Functions

The N-terminal glutamate 5-kinase domain phosphorylates L-glutamate using ATP, initiating the mitochondrial glutamate-to-P5C route that supplies proline and ornithine synthesis. Homomeric P5CS assemblies organize this bifunctional enzyme.

References

Suggested Questions for Experts

📚 Additional Documentation

Notes

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