GK

Summary: Both tested exon-18 forms possess glycerol kinase activity.

Reason: Their activity supports this assertion; the comparison does not resolve every natural product.

Summary: GK retains the ancestrally established glycerol kinase activity.

Reason: The exact human sequence descends from the inspected activity IBD at PTN000023392/AN0. Literal donors include legitimate human experimental evidence; no activity-loss assertion lies on this lineage. The independently established reaction corroborates inheritance.

Summary: The human GK preparation catalyzes glycerol phosphorylation.

Reason: The actual human enzyme assay supports this activity. Its coupled readout, declared isoform-1 template and engineered-construct limits are distinguished in the source evidence; PEP is not assigned as a GK substrate.

Summary: The combined electronic mapping matches the demonstrated GK reaction.

Reason: The supplied InterPro, EC and RHEA sources identify the same substrate-specific reaction as the human enzyme evidence. Retain this combined electronic assertion without counting its pipelines as independent experiments.

Summary: Human GK mutations reduce the measured glycerol kinase activity.

Reason: The original patient enzyme measurements support this IMP activity assertion. Historical variant numbering and clinical severity are not converted into normal product functions.

Summary: Human GK restores glycerol-kinase function in a deficient bacterial host.

Reason: The authentic abstract reports human GK complementation in a deficient bacterial host. This supports the existing NAS assertion without changing the protein species or claiming a modern product crosswalk.

Summary: GK catalyzes the annotated Reactome glycerol phosphorylation step.

Reason: The actual catalyst chain 75887 → 76115 → 3769055 → 55717 explicitly includes human GK. This is the enzyme performing glycerol phosphorylation, not a substrate or a candidate-only family assignment.

Summary: GK binds NR4A1 in a target-specific transcriptional inhibition context.

Reason: The validated GK–NR4A1 contact has targeted DNA-binding and reporter effects in the original study. Nuclear receptor binding therefore conveys supported functional context. It does not assign GK DNA binding, a new transcriptional process, physiological necessity or natural-product specificity. The original pair remains intact.

Proposed replacements: nuclear receptor binding

Summary: The positive BioPlex GK–GK2 association does not supply an informative GK molecular-function assertion.

Reason: The actual BioPlex association is retained, including the P32189-1 bait and Q14410 prey. Copurification does not establish a useful contact-dependent GK function or a functional heteromer. Remove the uninformative generic term without calling the pair false.

Summary: The U2OS GK–GK2 association is preserved without a class-only binding refinement.

Reason: The actual U2OS AP-MS edge is positive association evidence. It does not resolve binary binding, product specificity or a contact-dependent enzymatic role. The generic term is uninformative; no functional heteromer is inferred.

Summary: The nuclear assignment requires clarification.

Reason: The abstract describes perinuclear cytoplasm, whereas UniProt records nucleus. Unavailable imaging prevents resolving this discrepancy.

Summary: The propagated nuclear assignment remains unresolved.

Reason: This mapping inherits the same nucleus-versus-perinuclear discrepancy recorded on the experimental row; it supplies no independent imaging.

Summary: The actual MitoCoP data support GK as mitochondria associated.

Reason: Actual GK-specific group 4491 supports mitochondrial membership and is distinct from the mixed GK/GK3P group. Gene-level enrichment does not resolve a unique isoform or mitochondrial subcompartment.

Summary: GK has an inherited mitochondrial localization supported by human evidence.

Reason: The actual mitochondrial IBD is ancestral to the human sequence. Independent human evidence is compatible with this organelle assertion, without making every product exclusively mitochondrial or assigning matrix residence.

Summary: Exon-18-containing GK supports the outer-membrane assignment.

Reason: Predicted helix 532–552 lies within VSP_000771 (528–556), absent from products 1/4. Together with product-aware mitochondrial localization, this supports membrane association. Exact topology remains predicted.

Summary: GK has a product-dependent cytosolic pool.

Reason: Product-aware localization and the cytosolic reaction support this location. The ancestral cytosol IRD still limits canonical-product propagation.

Summary: The Reactome catalytic GK entity is explicitly placed in cytosol.

Reason: The actual catalyst entity is cytosolic. Its generic residue range does not establish every product’s localization; the independent product-aware evidence and ancestral cytosol IRD retain their distinct scope.

Summary: The carbohydrate-metabolism parent adds no information beyond the retained glycerol pathway.

Reason: The official ontology places the accepted glycerol catabolic process beneath carbohydrate metabolic process. This generic parent provides no additional pathway role in the inspected GK evidence. The mapping is true; the decision concerns informativeness, not incorrect chemistry or an inferred glucose-kinase activity.

Summary: Glycerol metabolism is covered more precisely by the retained catabolic entry step.

Reason: GK consumes glycerol in its phosphorylation reaction, already captured by glycerol catabolic process. No additional glycerol reaction is established. The ancestral PTN000023394/AN364 IBD remains valid; the broader term adds no distinct role.

Summary: The retained glycerol-catabolic term specifies this metabolic role.

Reason: Direct enzymology establishes glycerol phosphorylation; the gene-identification study supplies genetic context. Existing glycerol catabolism already captures the supported role, so the broader term is too general regardless of its experimental evidence code.

Summary: The generic glycerol-3-phosphate metabolic parent is already covered by its retained biosynthesis.

Reason: Existing accepted glycerol-3-phosphate biosynthetic-process rows identify GK’s actual role, and the current ontology places that process beneath this parent. The broader mapping supplies no additional consumption or alternative metabolic function. Preserve its evidence while marking the term too general, without a duplicate replacement.

Summary: The retained triglyceride-biosynthetic term specifies the inherited pathway role.

Reason: GK supplies a precursor for triglyceride synthesis; this review establishes no separate triglyceride-degradation role. The PTN000023394 IBD remains valid. The biosynthetic descendant therefore captures the supported process more precisely.

Summary: Triglyceride biosynthesis specifies the supported pathway contribution.

Reason: The pathway supports precursor production; the patient study establishes enzyme deficiency and glycerol excess, not triglyceride flux. Retain the more precise biosynthetic term rather than this broad parent, using the same criterion across evidence codes.

Summary: The kinase parent adds no term-level coverage beyond glycerol kinase activity.

Reason: The official ontology makes glycerol kinase activity a descendant of kinase activity. Existing accepted glycerol-kinase rows already capture the informative substrate-specific function. This electronic parent is true but adds no useful independent activity; its source evidence and original machine context remain valid, and no duplicate replacement is proposed.

Summary: The alcohol-acceptor phosphotransferase parent is already covered by glycerol kinase activity.

Reason: GK’s specific phosphate transfer to glycerol entails this official parent, and that substrate-specific activity is already retained in multiple existing rows. The broad InterPro assertion is biologically sound but does not distinguish another GK function. Mark the term too general without rejecting its mapping evidence or duplicating the existing specific annotation.

Summary: GK catalyzes a precursor-forming reaction within triglyceride biosynthesis.

Reason: The pathway explicitly includes the GK catalyst event. Production of glycerol-3-phosphate is biochemical participation in triglyceride biosynthesis; downstream enzymes perform esterification. This is an existing assertion, not a new process inferred from necessity.

Summary: GK catalyzes the entry step of glycerol catabolism.

Reason: The inherited UniPathway mapping agrees with the substrate-consuming GK step. Retain glycerol catabolic entry without requiring every resulting metabolite to undergo complete oxidation.

Summary: GK’s inherited activity directly forms glycerol-3-phosphate.

Reason: The inspected biosynthesis IBD is ancestral to human GK. Its literal donor set includes valid target evidence, and the normal reaction directly produces the named metabolite.

Summary: The recombinant GK reaction produces glycerol-3-phosphate.

Reason: The assigned phosphorylation reaction supports the existing biosynthetic process. The coupled assay does not establish cellular lipid flux or a separate PEP reaction.

Summary: Loss of GK activity impairs the glycerol-phosphorylation route to glycerol-3-phosphate.

Reason: The measured activity defect supports impaired GK function. Independent reaction evidence supplies the product-forming mechanism; this does not claim a patient intracellular product-pool measurement.

Summary: GK was identified in the urinary extracellular-vesicle proteomic preparation.

Reason: The study-specific urinary-vesicle target identification supports this contextual location. Preserve the literal urine restriction; one peptide does not resolve a modern isoform or establish a GK-specific vesicle mechanism.