ARSA

Summary: Retain inherited aryl-sulfate hydrolysis as a non-core assay activity.

Reason: The inherited aryl-sulfate hydrolysis assertion is independently consistent with human synthetic-substrate assays. Retain as non-core diagnostic-substrate activity; do not claim the PAINT ancestral placement was inspected or challenge its donor list.

Summary: Accept the physiological cerebroside-sulfatase reaction.

Reason: RHEA:21300/EC:3.1.6.8 match direct sulfatide hydrolysis and the core activity.

Summary: Accept the lysosomal enzyme location.

Reason: Mature enzyme location independently supported by expression/trafficking and the direct human Reactome catalyst model.

Summary: Retain ER localization during enzyme maturation as non-core.

Reason: ER transit and formylglycine maturation; distinguish from mature lipid-hydrolysis location.

Summary: Retain the source-reported ARSA–TRIP13 interaction as non-core.

Reason: The primary HuRI portal exposes the ARSA–TRIP13 pair under Yu-11, matching this source. This corroborates the curator-established interaction, but establishes neither an endogenous complex nor an additional specific molecular function. The gene-level portal record does not resolve the original construct or isoform details; the exact source partner identifier is preserved. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: Retain the source-reported ARSA–TRIP13 interaction as non-core.

Reason: The primary HuRI portal exposes the ARSA–TRIP13 pair under HI-II-14, matching this source. This corroborates the curator-established interaction, but establishes neither an endogenous complex nor an additional specific molecular function. The gene-level portal record does not resolve the original construct or isoform details; the exact source partner identifier is preserved. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: The source-specific ARSA–TRIP13 perturbation experiment remains unresolved.

Reason: The cached source describes disease-associated interaction perturbations, and the curator explicitly assigns the ARSA–TRIP13 interaction. The inspected primary portal lists this pair for other datasets but did not expose its Sahni-15 source record. Variant/construct details and the exact experiment remain unread. Preserve the positive annotation as UNDECIDED; missing accessible source detail is not evidence of a false interaction.

Summary: Retain the reported ARSA–TRIP13 interaction without an isoform-specific functional claim.

Reason: The primary HuRI portal exposes the ARSA–TRIP13 pair under Yang-16, matching this source. This corroborates the curator-established interaction, but establishes neither an endogenous complex nor an additional specific molecular function. The gene-level portal record does not resolve the original construct or isoform details; the exact source partner identifier is preserved. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:O60826 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: Retain the real synthetic aryl-sulfate assay activity as non-core.

Reason: The complete original letter reports both natural sulfatide UPLC-MS/MS and synthetic-substrate colorimetric comparison. Real aryl-sulfate activity is non-core; GO:0004065 is a sibling of GO:0004098, not its ancestor.

Summary: Generalize the sulfated-glycolipid catabolic role to glycosphingolipid breakdown.

Reason: The original Results, Table III and Discussion describe sulfated SM4s, SM3 and SB1a in ASA-deficient mouse kidneys. The current ganglioside term requires sialylated substrates, whereas these experiments concern sulfate-containing glycosphingolipids. GO:0046479 captures the supported catabolic role without conflating the chemistries. The mouse experimental provenance and original IDA source are retained; this refines an existing assertion.

Proposed replacements: glycosphingolipid catabolic process

Summary: Accept the inferred endolysosomal activity site with its IC scope explicit.

Reason: Retain curator inference for an acid hydrolase. The displayed experiments assay cathepsins and acid phosphatase, not direct ARSA imaging; inferential scope is explicit.

Summary: Accept cerebroside-sulfatase activity measured against unmodified sulfatide.

Reason: Natural sulfatide assay explicitly described in cached abstract; full paper not read.

Summary: Retain the established sphingolipid catabolic role with the assay scope qualified.

Reason: Core catabolic process is established by ARSA sulfatide catalysis. The original paper assays 4-nitrocatechol sulfate activity and provides physiological background, not direct natural-lipid turnover. Preserve IDA provenance without overstating that assay.

Summary: Retain the established cerebroside-sulfatase activity assessed through MLD mutants.

Reason: Retain curator-established core enzyme activity; cached mutant-expression abstract supports functional relevance but the substrate-specific full methods remain unread.

Summary: Retain the ER maturation compartment as non-core.

Reason: Cached abstract and Discussion describe ARSA translocation and active-site maturation in ER; maturation location is non-core.

Summary: Retain the modeled extracellular ARSA pool as a non-core location.

Reason: The previously inspected Reactome output set R-HSA-6806184 explicitly models both mature ARSA chains, 19–444 and 448–507, in the extracellular pool after azurophil-granule exocytosis. This is a contextual secretory pool, distinct from the acidic compartment where the mature enzyme performs its principal substrate hydrolysis, and is therefore retained as non-core. Reading the source hierarchy checks the actual TAS assertion; it is not independent experimental replication. No extracellular catalytic activity or ARSA-driven degranulation is inferred.

Summary: Retain the modeled azurophil-granule ARSA pool as a non-core location.

Reason: The previously inspected Reactome input set R-HSA-6798742 explicitly models both mature ARSA chains, 19–444 and 448–507, as azurophil-granule lumen cargo. This supplies a modeled storage/release context in addition to the established lysosomal catalytic compartment, so the location is retained as non-core. The source hierarchy verifies the TAS membership claim without independently validating its underlying target experiment. Cargo membership does not establish that ARSA performs degranulation, and dominant lysosomal localization does not exclude this granule pool.

Summary: Detected in an extracellular-vesicle proteome, but the detection does not establish that this protein is an EV constituent.

Reason: Soluble lysosomal sulfatase. Secreted or lumenal protein (UniProt). MISEV2018 (PMID:30637094) category 5 allows such proteins onto EVs through specific or promiscuous (proteoglycan, lipid) receptors on the EV surface, but asks that their identification be backed by evidence of that association. A bulk EV proteome cannot separate surface binding from co-isolation, and this protein's annotations record no experimental proteoglycan, heparin or lipid binding, and its own review keeps no experimental cell-surface or plasma-membrane pool. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.)

Summary: Retain ER-lumen ARSA maturation by SUMF1 as a non-core location.

Reason: Live Reactome substrate and product sets include ARSA in ER lumen; SUMF1 is the catalyst, ARSA its substrate. Retain maturation location as non-core.

Summary: Retain ER-lumen transit of ARSA cargo as non-core.

Reason: Reactome explicitly models active ARSA:Ca2+ as ER-luminal cargo transported by M6PR. Non-core transit location.

Summary: Accept the lysosomal-lumen site of sulfatide hydrolysis.

Reason: Target-specific cached reaction describes saposin-B-mediated sulfatide hydrolysis by ARSA in lysosomal lumen.

Summary: Accept lysosomal-lumen delivery of active ARSA.

Reason: Reactome explicitly models active ARSA:Ca2+ arriving in lysosomal lumen; mature enzyme destination.

Summary: Accept lysosomal-lumen ARSA catalysis of SM3 desulfation.

Reason: Live Reactome event names active ARSA:Ca2+ as lysosomal catalyst of SM3 desulfation.

Summary: Accept calcium binding as part of the catalytic machinery.

Reason: Cached original abstract directly identifies calcium in endogenous human placental ARSA active site. This supports the catalytic cofactor annotation, not a distinct calcium-signaling function.

Summary: Accept sulfuric ester hydrolysis as an umbrella description of the core catalytic activity.

Reason: GO:0008484 is a true parent of the physiological cerebroside-sulfatase activity, so this existing broad assertion represents the same core chemistry rather than an additional core function. In contrast, sibling GO:0004065 specifies phenol-sulfate hydrolysis and is retained as a non-core synthetic-substrate activity. The original main text and Figure 4 include ARSA expressed in Cos7 cells in sulfatase-activity measurements. Substrate-specific Methods are delegated to an unread supplement; preserve this source-specific broad IDA assertion without substituting a narrower assay claim from another paper. The LOW_QUALITY reference assessment records the correction to loading-control panels associated with Figure 2; it does not establish that Figure 4 ARSA activity or sulfuric ester hydrolysis is invalid. The core summary uses only the specific GO:0004098 term.

Summary: Retain aryl-sulfate activity as a non-core assay function.

Reason: Retain non-core aryl-sulfate activity in light of direct synthetic-substrate assays; old cloning abstract does not specify substrate, so do not invent its exact assay.

Summary: Accept the M6P-dependent lysosomal targeting of human ARSA.

Reason: Original abstract explicitly reports human ARSA expression in monkey/baby-hamster cells and M6P-dependent delivery to dense lysosomes.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:O75360 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: Retain the source-reported ARSA–VENTX interaction as non-core.

Reason: Exact ARSA–VENTX pair is displayed as HI-III in the neighboring-network interaction table on the primary TRIP13 portal page. This closes the reported pair for PMID32296183; retain non-core, without inferring a specific regulatory activity or native-cell complex. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:P28069 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:P50995 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q12951-2 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q13554-3 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: Retain the source-reported ARSA–TRIP13 interaction as non-core.

Reason: The primary HuRI portal exposes the ARSA–TRIP13 pair under HI-III, matching this source. This corroborates the curator-established interaction, but establishes neither an endogenous complex nor an additional specific molecular function. The gene-level portal record does not resolve the original construct or isoform details; the exact source partner identifier is preserved. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q16512 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q6P5X5 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q96D98 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: Retain the source-reported ARSA–RHOXF2 interaction as non-core.

Reason: Exact ARSA–RHOXF2 pair is displayed as HI-III in the neighboring-network interaction table on the primary TRIP13 portal page. This closes the reported pair for PMID32296183; retain non-core, without inferring a specific regulatory activity or native-cell complex. The reported pair is adjudicated at the existing generic binding scope. Its physiological purpose and a narrower molecular-function assignment remain unresolved; those separate limits do not make the reported pair itself undecided. Non-core retention is a curation judgment from the inspected positive source record, not an action logically forced by an instruction conflict.

Summary: The exact source-specific interaction record remains unresolved.

Reason: The curator-established HuRI interaction with UniProtKB:Q9H0I2 is preserved. The shipped UniProt aggregation lists the partner, but the exact HI-III pair/construct record and assay controls were not exposed in the inspected material. This is a source-specific evidence limit, not evidence of absence or artifact. No directness, physiological complex or isoform-specific activity is inferred.

Summary: Accept the endolysosomal activity inference with its GO:0030149 supporting entity.

Reason: Retain the curator inference that an acid hydrolase acts in the endolysosome lumen, preserving supporting entity GO:0030149. The inspected paper measures cathepsins and acid phosphatase in NRK, HeLa and MCF7 contexts; direct ARSA imaging is not claimed. The cached ARSA GO-CAM activity explicitly carries this IC occurs_in association.