This authored guide records the 2026-11-11 reassessment of human HAAO (UniProtKB:P46952). It is not a provider-generated deep-research report. Falcon returned HTTP 403; the Perplexity-lite fallback returned HTTP 401 with insufficient quota. Manual primary-source reading and database checks therefore support this review. Existing publication caches and inherited supporting_text quotations remain unchanged.
All ten PMID identities and titles were checked against NCBI PubMed. Identity verification does not establish every claim attributed to a paper. The reading limits below govern individual annotation decisions. Source checks and retrieval provenance record the supporting observations.
| Source | Evidence read and usable conclusion | Limit |
|---|---|---|
| PMID:7514594(https://pubmed.ncbi.nlm.nih.gov/7514594/) | Abstract: human cDNA and active recombinant enzyme expressed in HEK293 cells. | Original localization methods were not inspected. The cytosol annotation is retained with curator deference and independent UniProt/Reactome support. |
| PMID:12007609(https://pubmed.ncbi.nlm.nih.gov/12007609/) | Abstract: purified recombinant human enzyme, Fe(II) requirement and zinc inhibition. | Full original methods were not accessible. The second inhibitory metal is not named in the abstract. Cellular zinc/cadmium-response claims remain UNDECIDED. |
| PMID:28375145(https://pmc.ncbi.nlm.nih.gov/articles/PMC8493610/) | Original Methods §§2.1–2.5 and Results §§3.1–3.4: human metal-binding structures and biophysical characterization. | The air-prepared crystal contains Fe(III), whereas Fe(II) is the catalytic cofactor. Bacterial mechanistic observations discussed in this paper are distinguished from human experiments. |
| PMID:28792876(https://pubmed.ncbi.nlm.nih.gov/28792876/) | Abstract and indexed original results: human HAAO variants, reduced catalytic activity and NAD deficiency. | Mouse gestational niacin rescue does not establish human therapeutic rescue. |
| PMID:2967497(https://pubmed.ncbi.nlm.nih.gov/2967497/) | Abstract: increased enzyme activity in human postmortem Huntington disease tissue. | PMC challenge, publisher 403 and unsuccessful alternative full-text access prevented original causal-evidence review. Neuronal homeostasis remains UNDECIDED. |
| UniProt P46952 and Reactome R-HSA-71218 | The catalytic reaction produces ACMS; subsequent spontaneous cyclization supplies quinolinate. Curated reaction/localization records place HAAO in cytosol. | Cytosol is established curated localization, not a newly inspected imaging result. Activity of the shorter alternative product was not established. |
The core is one Fe(II)-dependent dioxygenase activity. Quinolinate biosynthesis, NAD+ biosynthesis and tryptophan catabolism describe different pathway roles of that same catalytic step. Fresh QuickGO checks found all five core terms active and no directed is_a or part_of path between any pair of the three process terms.
The archived IntAct response contains 13 positive HAAO-target records. It is a bounded response, not proof that omitted interactions are absent. Source-paper identifiers and exact partner accessions were checked in the returned rows.
| PMID | Retained partner context | IMEx evidence | Decision |
|---|---|---|---|
| 16189514 | GAD1, Q99259 | IM-16520-414; two-hybrid pooling | KEEP_AS_NON_CORE |
| 25416956 | GAD1, Q8IVA8 | IM-23318-38393; validated two-hybrid | KEEP_AS_NON_CORE |
| 25416956 | GAD1, Q99259 | IM-23318-32712; validated two-hybrid | KEEP_AS_NON_CORE |
| 31515488 | GAD1, Q99259 | IM-27438-3932; two-hybrid array | KEEP_AS_NON_CORE |
| 32296183 | GAD1, Q99259 | IM-25472-131849 and associated screening records | KEEP_AS_NON_CORE |
| 21044950 | POT1, Q9NUX5 | EBI-11306959 and EBI-11312191; see below | KEEP_AS_NON_CORE |
Supported generic binding is retained under the ClinGen project instruction. These interactions do not establish a more specific molecular function. Both partner-accession contexts from PMID:25416956 are retained separately.
Updated IntAct records identify P46952/Q9NUX5 in PMID:21044950: EBI-11306959, BiFC in HTC75 (table S1); EBI-11312191, FLAG-HAAO/GST-POT1 pull-down in HEK293T (table S2; author score 1.31). Curators selected the S2 log2 threshold above 0.33 to reproduce the reported approximately 72% positive fraction. Original supplements remained inaccessible (403); these are curated records, not direct table inspection. No affinity, endogenous telomere function or specific molecular role is inferred.
Three judgments remain UNDECIDED: zinc response, cadmium response and neuronal homeostasis.
is_a/part_of path between these terms; this is not a claimed descendant-term refinement. Short definition excerpts are now quoted in the annotation, with the full definition retained in the source-evidence record.The literal QuickGO archive contains 35 current records. Its unchanged production-exporter projection exactly equals the 35-row downloaded TSV. The prior 35 TSV contexts and current 35 contexts share 32, yielding 38 retained review contexts. The older draft had only 34 authored rows; native seeding restored the second PMID:25416956 partner context and added three updated combined-source mappings.
The context audit maps every source record to its stored context, identifies the three historical-only mappings, preserves WITH/FROM grouping in the raw archive, and explicitly records the two obsolete-prefix label differences. There are no incoming extensions, isoform-qualified rows or negated rows. No NEW annotation is proposed.
The three historical-only mappings are explicitly marked retired: true because their exact source contexts were replaced in current GOA. They remain reviewed and traceable; the lifecycle flag does not reject the underlying catalytic, localization or pathway function.