FUCA1

Summary: Retain inherited alpha-L-fucosidase catalysis.

Reason: The actual PTHR10030 IBD is at AN0/PTN000003123, on the exact human AN252/PTN002467369 lineage. It is not restricted to a guessed metazoan node. Human FUCA1 is a legitimate experimental descendant source; the off-lineage fly NOT/IRD does not assert human loss. Human recombinant enzyme and patient fibroblast evidence independently support this core activity.

Summary: Retain directly assayed human FUCA1 catalysis.

Reason: The original paper explicitly prepared and characterized human FUCA1 as well as FUCA2. Its FUCA2-focused title does not invalidate the human FUCA1 assay. Infection-associated secretion and adhesion experiments are not transferred from FUCA2 to FUCA1; unread supplementary kinetic constants are not asserted.

Summary: Retain the electronically mapped catalytic activity.

Reason: The original combined electronic sources agree with the established human alpha-L-fucosidase reaction. Human FUCA1 was prepared and characterized alongside FUCA2 in PMID:19666478; the mouse knockout quotation retained here is corroborating cross-species evidence, not a human direct assay.

Summary: Retain the correct human fucosidase activity with explicit source scope.

Reason: The cited abstract surveys Drosophila fucosylated-glycan metabolism, so it is not a direct human enzyme assay. That does not establish a curator error or absence of relevant full-text discussion. Independent recombinant human FUCA1 characterization and human patient-cell activity support the same core activity.

Summary: Retain patient-cell support for the core catalytic activity.

Reason: The human fibroblast abstract reports low alpha-L-fucosidase activity with absent protein or abnormal precursor processing in fucosidosis cells. This supports catalytic identity. The active precursor and mature enzyme are processing states, not evidence of separate natural isoforms.

Summary: Retain the measured FUCA1–CIB1 interaction as non-core.

Reason: Three exact source-qualified IntAct records support this human pair in the HuRI yeast two-hybrid workflow, using a FUCA1 construct spanning residues 6–466. The positive assay does not establish an endogenous lysosomal complex, purified affinity or a specific adaptor function. Compartment expectations alone do not refute the recorded interaction.

Summary: Retain the measured FUCA1–MED10 interaction as non-core.

Reason: Three exact HuRI IntAct records support this pair in yeast two-hybrid assays. FUCA1 residues 6–466 were tested; MED10's nuclear role does not by itself disprove that assay. No physiological Mediator role or pair-specific orthogonal mammalian validation is inferred.

Summary: Retain the measured FUCA1–UBQLN2 interaction as non-core.

Reason: Five exact source-qualified HuRI records retain positive two-hybrid evidence for this pair with FUCA1 residues 6–466. This establishes a contextual association, not a new proteostasis function, native complex or purified binding constant.

Summary: Retain the extracellular pool as a secondary location.

Reason: The exact Reactome output member identifies human P04066 residues 32–466 in extracellular region, linked to the granule-release event. Human lymphoid pulse-chase evidence independently documents partial secretion in controls. This does not displace lysosomal hydrolysis as the core function or make FUCA1 an exocytosis catalyst.

Summary: Retain the more informative lysosomal lumen location.

Reason: The retained lysosomal lumen location reaches cytoplasm through the verified part_of/is_a path. Cytoplasm is therefore compatible with this organellar enzyme but less informative than its established compartment. TOO_GENERAL expresses that granularity, not a contradiction of PMID:4074382 or a demand for a separate cytosolic pool.

Summary: Retain lysosome as the core organelle location alongside lysosomal lumen.

Reason: PMID:9741689 measures lysosomal glycolipid turnover in human fibroblasts and the expected storage intermediate in fucosidosis cells. This supports the organelle-level experimental annotation; it does not resolve a sub-compartment. Lysosome remains an informative core location under the root-organelle policy, alongside the independently supported lysosomal lumen annotation. The bovine purified-enzyme experiment in the same paper is distinguished from these human-cell observations.

Summary: Retain the supported UniProt lysosome mapping alongside the lumen annotation.

Reason: The original UniProtKB-SubCell:SL-0158 mapping names the lysosome, consistent with human lysosomal substrate turnover and the explicit human FUCA1 catalyst in Reactome:R-HSA-5693807. Its organelle claim is sound. The root-organelle policy retains this informative location even when the existing lysosomal lumen annotation supplies finer resolution; no cytosolic pool is inferred.

Summary: The broad carbohydrate process is covered by retained fucose metabolism.

Reason: FUCA1 hydrolysis directly releases fucose. The retained fucose metabolic process is an official is_a descendant of hexose metabolism, then monosaccharide metabolism, then carbohydrate metabolism. It already supplies the informative coverage. Glycoprotein and glycoside catabolism are not asserted to be descendants of this term; no replacement or extra process annotation is needed here.

Summary: Retain inherited fucose metabolism as a direct catalytic role.

Reason: FUCA1 produces free fucose by hydrolysing fucosides. The literal IBD at AN0/PTN000003123 lies on the actual human lineage, with the original donor set and valid human descendant evidence. This does not assign FUCA1 the downstream kinase or other steps of fucose salvage.

Summary: Retain the assayed fucose-metabolism role.

Reason: The original study includes human FUCA1 enzyme characterization on fucoside substrates, supporting direct fucose metabolism. Its distinct FUCA2 infection experiments do not define FUCA1's physiological role.

Summary: Retain electronically inferred fucose metabolism.

Reason: Release of fucose is a direct product of the established fucosidase reaction. The electronic assertion is biologically appropriate without claiming that FUCA1 performs all downstream fucose-utilization steps.

Summary: Retain inherited glycoside catabolism.

Reason: Cleavage of alpha-L-fucosides directly performs glycoside breakdown. The literal positive AN0/PTN000003123 IBD is on the actual human lineage and includes valid human experimental grounding. Glycoprotein and glycolipid catabolism describe related substrate contexts but are not typed descendants of this term in the retained ontology response.

Summary: Retain direct glycoside-catabolism evidence.

Reason: Human FUCA1 was experimentally characterized on fucoside substrates in the cited original article. Its substrate hydrolysis supports the existing process term without importing the separate FUCA2 host–pathogen phenotype.

Summary: Retain the glycoside-catabolism electronic annotation.

Reason: The established alpha-L-fucoside hydrolase reaction directly breaks a glycosidic substrate. This is a catalytic role, not an inference from a disease phenotype or from being a substrate of another enzyme.

Summary: Retain glycolipid catabolism with the bovine donor and human-cell evidence distinguished.

Reason: The exact donor Q2KIM0 is bovine FUCA1; its corresponding IDA annotation cites PMID:9741689. That paper's Materials identify bovine kidney fucosidase, and its purified-enzyme experiment removes fucose from the isolated linear intermediate after NAGA action. Human fucosidosis fibroblasts independently accumulate that intermediate. The intact branched A glycolipid is a poor fucosidase substrate; a human purified-enzyme experiment is not claimed.

Summary: Retain azurophil granule localization as a specialized cellular context.

Reason: The electronic assertion is corroborated by the exact human P04066 granule-lumen member of the Reactome input set. This is a specialized lysosome-related compartment; cargo localization does not establish that FUCA1 performs the vesicle fusion or exocytosis step.

Summary: Retain the modeled neutrophil granule cargo location.

Reason: The original event input set contains FUCA1 member R-HSA-6798773, human P04066 residues 32–466 in azurophil granule lumen; the separate FUCA2 member is not substituted for it. This is a curator-modeled cargo location, not a newly measured secretion mechanism.

Summary: Retain lysosomal lumen as the core catalytic compartment.

Reason: The original human reaction identifies the FUCA1 tetramer as the catalyst for defucosylation in lysosomal lumen. The exact complex contains the modeled mature FUCA1 chain, consistent with human enzyme processing and the established lysosomal degradation role.

Summary: Retain the urinary-exosome detection with its original urine scope.

Reason: The authentic original Table 1 lists FUCA1 with Pep 1 and ID 1. This is positive proteomic detection with limited peptide support, not an exosome-specific catalytic mechanism. The original QuickGO response (annotation UniProtKB:P04066!58678521) contains extensions[0].connectedXrefs[0] with relation part_of, db UBERON and id 0001088. The public source-evidence file preserves that exact object under original_contexts[23] and its normalized BFO:0000050 urine extension under machine_contexts.restored_extensions; the 16-column GOA export has no extension column.

Summary: Retain FUCA1 detection in the EPS-urine exosome preparation as a non-core location.

Reason: The recovered original supplementary Table 2 (SI Table 2, row 197) identifies P04066/FUCA1 with five unique peptides in each of four analysis columns; FUCA2 is a separate entry. These are duplicate analyses of two pooled clinical groups, not four independent donors. This supports the curated preparation-level HDA location. The article cautions that soluble or contaminating proteins may accompany such isolates; the finding does not establish vesicle topology, cell of origin, an exosome-biogenesis function or disease-specific differential expression.

Summary: Infer participation in lysosomal glycoprotein catabolism from human fucosidase catalysis and its established substrate context.

Reason: This is an authored IC inference from alpha-L-fucosidase activity (GO:0004560) in the lysosomal lumen (GO:0043202). PMID:19666478 explicitly characterizes human FUCA1 enzymatic activity; the human Reactome:R-HSA-5693807 reaction identifies FUCA1 as the catalyst removing fucose from an N-glycoprotein substrate. FUCA1 itself performs the hydrolytic step, rather than being cargo or merely required for another enzyme to act. Human patient fibroblast activity/processing evidence in PMID:4074382 supports the enzyme identity. The source combination supports process participation but is not presented as a direct human glycoprotein-turnover IMP assay; the mouse storage experiments in PMID:27491075 are separate corroboration. The official term includes breakdown of glycan-bearing proteins and has a protein-catabolic parent. Same-role human lysosomal hydrolases MAN2B1 and GLB1 carry the term, including an IC MAN2B1 annotation inferred from its glycosidase activity. Retained ontology ancestry shows that this term is neither an ancestor nor a descendant of the existing fucose, glycoside or glycolipid process terms; the broad carbohydrate-metabolism row is independently TOO_GENERAL. No local GO-CAM index entry for FUCA1 was found. The earlier human IMP row based on a mouse study remains retired in the inherited archive; this separately attributed IC proposal does not revive that evidence claim.