The imported human seed contains 243 original annotations and four recorded products (AR-B, AR-A/AR45, AR3/AR-V7 and AR4). Its source assertions, isoforms and qualifiers remain unchanged. The initial preflight covered AR and the HGNC-associated names DHTR, SBMA, AIS, NR3C4, SMAX1 and HUMARA, their gene/history directories, the task branch, and the complete open-PR inventory. No competing review was found. The baseline and machine-readable source inventory are retained under tmp/AR-initial/.
All 86 selected complete PMID abstracts and all 20 Reactome summaries were read. An abstract read does not establish that every experiment in the paper has been inspected. The original inventory preceded the Seed10 auxiliary import: its 73 missing records are now supplied by the exact normal-cache import, including the separately synchronized main-branch PMID:16461912. Existing caches were preserved. Richer staged copies, when consulted, are separate source views and do not replace canonical publication files.
The configured installed-client Falcon attempt with the perplexity-lite fallback terminated with a connection error after 4.68 seconds and produced no report. Its bounded receipt is tmp/AR-initial/deep-research-receipt.json. These are manual research notes; no provider-named research file was manufactured.
AR is a ligand-activated nuclear receptor whose DNA-binding, ligand-binding and transcriptional regulatory functions are supported by numerous target-specific studies. Binding to a coactivator does not make AR that coactivator's enzyme; association with an E3 ligase, deubiquitinase, kinase, phosphatase or chaperone does not transfer the partner's activity to AR. Reporter activation, direct molecular binding, proximity labeling, complex capture and native cellular localization require separate descriptions. Cancer-cell mutations, tagged constructs and isolated domains must not silently become claims about every wild-type product.
The Reactome summaries distinguish AR as receptor/cargo/substrate from its partners' catalytic steps. PKN1 phosphorylates histones, KDM4C/KDM1A demethylate chromatin, HSP90 hydrolyses ATP, and USP12/USP26 deubiquitinate AR. Those events can corroborate receptor-associated cellular pools without assigning those enzymatic functions to AR. The ligand, antagonist, coregulator and RUNX2 event summaries were also inspected individually.
The original author-uploaded paper was read through its experimental procedures, Results, figures and Discussion. Human AR N-terminal fragments were used for library probing and direct binding assays; full-length AR/ARA160 capture and mammalian two-hybrid experiments provide additional interaction evidence. The reporter experiments separate cell line, cofactor, ligand and receptor variant. Figure 6 tests estradiol-triggered AR activity, including wild-type AR and E708K/T877A variants. It does not turn AR into the estrogen receptor. A cellular response to estrogen and an estrogen-receptor signaling pathway annotation therefore need separate adjudication. ARA160's failure to bind the tested DNA probes is not a negative DNA-binding result for AR. The canonical cache remains abstract-only. PubMed record
The subsequently checked GO:0030520 definition describes estrogen-initiated signaling through an intracellular nuclear-family receptor; it does not explicitly restrict the receptor to ESR1/ESR2. Thus the term's name alone cannot exclude the observed estradiol-triggered AR context. The prospective assessment should retain this as a secondary ligand/cell/cofactor context, rather than replace it merely because AR is the receptor.
The original PMC article was accessed beyond its abstract. The Introduction, experimental procedures and early Results/Figures 1–3 were read directly; indexed original Results also exposed the p300 occupancy and colony-assay sections. These experiments use human prostate-cell systems, PSA/KLK2 readouts, chromatin immunoprecipitation and receptor/coregulator assays. Polymerase II occupancy is explicitly measured. The remaining later figure details and Discussion have not yet all been read because subsequent direct opens returned an access challenge. The seeded polymerase III assertion remains an open source-specific question until that scope is resolved. Neither a crystallographic/interaction title nor a missing abstract word is sufficient to reject it. The canonical abstract-only cache remains unchanged.
The complete cached Results/Discussion of the original signalosome study were read. The inspected experiments concern alpha1D-adrenergic receptor constructs, syntrophins/dystrophin-associated proteins, adrenergic ligand responses and vascular physiology. The abbreviation AR alone must not be interpreted as androgen receptor. However, the complete Methods and all participant tables have not yet been inspected, so this observation does not establish that the seeded AR experiment was misattributed. An author-uploaded original is a further access lead.
Subsequent targeted reading resolved the construct/TAP-purification methods, the complete Table 3 participant inventory and Figures 4–5. Those assays explicitly use adrenergic receptor constructs and identify their associated proteins; androgen receptor is not among the reported table participants. This now permits an experiment-specific attribution challenge, pending independent consultation, rather than a conclusion inferred from the title. Mouse antibody/aortic panels remain distinct from human receptor-expression experiments.
The actual cached original Introduction, SH2-domain/peptide assay methods, AR-specific Results and Discussion were read. Synthetic phosphorylated AR peptides were tested against recombinant SH2-domain preparations by fluorescence polarization. The report names selected interactions and affinities, including SRC-family, PI3K-regulatory, PLC, VAV and PTPN11 domains at particular AR phosphotyrosines. Numerous interactions are weak; the authors frame the set as binding potential rather than proof of endogenous recruitment. The complete partner-by-peptide supplementary matrix has not yet been read. A source-local domain-binding refinement may be justified for a directly inspected pair, but neither an uninspected pair nor the enzyme activity of its partner should be inferred from the general screen. PubMed record
The actual cached AR BioID Results and associated targeted confirmation passages were read. Tagged AR was studied in LAPC4 cells with ligand-dependent localization and functional checks; the work reports proximity-labeling sets in different hormone conditions. The narrative separately reports GFP-AR affinity-purification confirmation for selected partners, including KMT2A. That distinction matters for the eight seeded physical-interaction rows: the entire supplementary partner table and every reagent detail have not yet been inspected. Proximity or membership in a regulatory complex does not by itself establish a direct binary interface or a specific catalytic function for AR. PubMed record
The subsequently inspected plasmid and affinity-purification Methods explicitly identify human AR (NP_000035.2) in the BirA and GFP constructs. This resolves construct identity for those experiments, while leaving the unread partner-table boundary intact.
The entire canonical main text, including all Results, Discussion and Methods, has now been read. Recombinant human AR residues 1–558 and 330–448 were expressed in bacteria and purified; the tags were cleaved before the reported measurements. Both domains form droplets under the tested solution conditions, with the larger activation domain more prone to condensation. Concentration, salt, temperature and heavy-water effects were tested using microscopy, turbidity, NMR and solution measurements. These are direct domain-level self-condensation experiments, not a demonstration that every cellular AR punctum has the same physical behavior. The paper itself cautions against treating hexanediol disruption as uniquely diagnostic. Original identifier
The current GO:0140693 definition concerns bringing macromolecules together into a condensate and does not require those molecules to be different protein species. The directly measured self-condensation therefore informs the existing molecular-function assertion. The later full-receptor paper remains a distinct source with its own access limitations.
The full annotation map and independent consultation are still pending. These notes record actual reading and open questions; they do not claim completion of all 243 decisions.
The first complete prospective map covers all 243 source assertions without changing the seeded review. It proposes no NEW annotation. The receptor and condensate-scaffold functions are distinct parts of the compact core. Source-specific uncertainty is retained for uninspected screen pairs, narrow transferred locations/domains, the polymerase III assertion and the molecular-adaptor assertion. Coregulator refinements use positive results from the original cited paper; unrelated cofactor evidence is not silently relabeled as a screen result.
The current official definitions of coactivator binding and corepressor binding distinguish non-DNA-binding coregulators from DNA-binding transcription factors. FOXH1, SMAD1, FOXO1, FOXP1, ERG, ZBTB7A and HEYL therefore require the DNA-binding transcription-factor binding distinction. Binding a kinase, demethylase, ligase or phosphatase does not give AR that partner's catalytic activity. The SH2-domain binding refinement is limited to explicitly identified positive AR-phosphopeptide/SH2 pairs in the actual PMID:24728074 Results; unread matrix entries remain unresolved.
The independent source-identity consultation for PMID:18468998(https://pubmed.ncbi.nlm.nih.gov/18468998/) has now read the target-defining construct/TAP methods, complete Table 3 and signalosome Results. It corroborates the source-specific adrenergic-receptor attribution problem. The proposed removal concerns this one source assertion and does not deny that androgen receptor forms other complexes. This closes the earlier pending consultation described above.
For PMID:21242980(https://pubmed.ncbi.nlm.nih.gov/21242980/), the actual AR/HDAC4 complex Results, SUMOylation Results and relevant reagent Methods were inspected. They report tagged and endogenous coimmunoprecipitation, in-vitro translated-protein capture, human-AR expression constructs, and SUMO acceptor-site tests. HDAC4 repression supports the binding-to-corepressor interpretation. Covalent SUMO conjugation, including denaturing capture, is not by itself evidence for a noncovalent AR–SUMO binding interface; that separate original assertion remains unresolved rather than denied.
For PMID:19345326(https://pubmed.ncbi.nlm.nih.gov/19345326/), actual targeted Results identify RNF6 in GST-AR C-terminal capture, reciprocal transfected-cell coimmunoprecipitation and endogenous prostate-cell assays. These support a genuine AR/RNF6 regulatory association. The separate RNF14/ARA54 experiment has not been fully located and inspected; the UniProt narrative does not substitute for that source-specific step.
For PMID:26175416(https://pubmed.ncbi.nlm.nih.gov/26175416/), targeted original Results and Discussion show AR–DNA-PKcs complex formation, persistence after ethidium bromide, AR-V7-containing complexes and receptor transcriptional regulation. These support binding to a transcriptional coactivator at the measured complex level. They do not establish an isolated binary interface or make AR a DNA-repair kinase. The complete paper, all animal experiments and all supplements were not independently reread here.
For PMID:23566155(https://pmc.ncbi.nlm.nih.gov/articles/PMC3668167/), actual reporter/coimmunoprecipitation/FRET Results, Figure 5 legend, relevant imaging Methods and the corresponding Discussion were read. Tagged AR and SKIP interact at SKIP-positive speckle-like structures in BHK cells; prostate-cell reporter experiments are a separate model. The authors caution about overexpression and do not claim every AR nuclear focus has the same compartment identity. The coactivator binding is supported; the specialized localization is retained as a secondary pool. Image pixels and videos were not inspected.
The live Human Protein Atlas AR subcellular page reports supported cytosolic localization with antibody HPA004733. The table supports the seeded cytosolic pool, without implying absence from the nucleus in other receptor/ligand states. Image pixels were not independently adjudicated.
An independent bounded consultation read the actual PMID:22722839(https://www.nature.com/articles/nature11125) AR/MLL-complex Results and the official supplement, Methods pages 37–39 and S16 caption page 63. It verified endogenous human VCaP AR coassociation/reverse immunoprecipitation for KMT2D, FOXA1, KMT2A and ASH2L. Those four specific rows can be retained as non-core associations; purified binary interfaces are not claimed. ERG's exact own-source panel remained unresolved because the figure/text distinguishes previously reported interactions, so that row remains uncertain. Q9UBL3 is ASH2L; it must not be mislabeled as KDM6A.
The earlier open-question bullet saying PMID:33978290's main body remained unread is historical: the complete main-text read is recorded in its later dedicated section above. The independent full 243-row consultation is still pending; the canonical annotation actions remain PENDING until that consultation is completed.
The independent all-243 prospective consultation passed before authoring. All 243 original source assertions and four product records are preserved. The authored map contains 121 ACCEPT, 46 MODIFY, 32 KEEP_AS_NON_CORE, 43 UNDECIDED and one REMOVE; there are no NEW annotations. The sole removal is the independently resolved PMID:18468998 adrenergic-receptor source attribution. Refinements use their own cited experiments, including eight directly inspected phosphopeptide/SH2 pairs. Two cores describe receptor-mediated transcription and experimentally supported condensate scaffolding. Each Reactome rationale identifies its distinct receptor/client/substrate context.
Uninspected pair tables, domain/interface experiments and narrow propagation claims remain uncertain. Positive but nonspecific associations remain non-core under the user-supplied ActionEnum: genericity alone does not meet its REMOVE criterion. Source availability flags describe the immutable normal cache; external primary reads and partial access are recorded separately above. The earlier pending-map and pending-consultation statements are historical, superseded by this completed prospective and authored assessment. Final retrospective consultation, schema/reference validation, rendering and history checks remain to be completed.
The independent prospective reviewer inspected the original PMID:17510388 Figure 4 caption and adjacent Results: DJ-1 overexpression increased AR reporter activity and knockdown decreased it without changing AR abundance. This supports a positive coregulatory interpretation beyond the direct-binding statement in the cached abstract. The primary locator is the original publisher article. The present author could not reopen that page and explicitly attributes the figure-level read to the independent consultation; no complete-paper read is claimed.
All 243 decisions are now recorded and the review status is COMPLETE, including the 43 explicitly unresolved assertions. Initial schema validation caught an invalid propagation metadata field; it was corrected to the supported source_label field without changing any original assertion or action. Validation then passed with 21 documented advisories: 20 positive generic associations retained as non-core under the explicit user ActionEnum, and one source-specific enzyme-binding action difference (two experimentally supported refinements versus an unresolved electronic inference). These advisories do not justify inventing interfaces or overriding source-specific uncertainty. Final rendering, literal-evidence checks and retrospective independent consultation are recorded in the session history.
The first published review and its validation counts above are historical. This follow-up preserves all 243 original assertions, all four alternative products, the original source references and qualifiers, and both core functions. Twelve existing positive protein-binding rows now use a more informative partner-class term: HIF1A and FOXA1 use RNA polymerase II-specific DNA-binding transcription factor binding; MDM2, RNF6 and Siah2 use ubiquitin protein ligase binding; BRG1 uses ATPase binding; KMT2D and the two KMT2A assertions use histone methyltransferase binding; USP26, FKBP52 and KDM5D use enzyme binding. Each refinement rests on the same paper as the original assertion. A positive co-immunoprecipitation or complex-association assay can support a binding class without resolving an isolated binary interface. It does not assign the partner's catalytic activity to AR.
The original ARA160 study, PMID10428808 was read at the Methods, Results around Figure6 and figure-legend level. In DU145 cells, wild-type AR with ARA70 responded to 10nM estradiol, whereas ARA160 had only a marginal effect in that setting. In PC3 cells, wild-type AR with ARA160 showed a modest estradiol response. These positive wild-type results are distinct from the E708K negative and T877A positive estradiol responses in the subsequent panels. The assays use transfected receptor/cofactor combinations and reporters; they do not establish a universal native estrogen response. Figure text and legends were inspected, without a new pixel-level analysis. The normal cache remains abstract-only.
The actual Figure6 wild-type AR experiments show estradiol-responsive reporter activation in PC3 with ARA160 and in DU145 with ARA70; E708K and T877A were tested separately.
The current GO:0030520 definition does not restrict the initiating intracellular nuclear-family receptor to ESR1 or ESR2. Retaining the two existing estrogen-related annotations as non-core therefore reflects the actual contextual wild-type result. The distinct estrogen-response-element IBA remains uncertain: its exact PTN001182563 IBD is available, but target-to-node topology and intended experimental scope were not reconstructed.
The original HIF1 study, PMID17426252, Cross Talk Results and Figure6A legend, report reciprocal endogenous AR/HIF1alpha co-immunoprecipitation in LNCaP cells after 20h at 1% oxygen with 10nM DHT. This is physical-association evidence separate from the promoter ChIP experiment. A preliminary private locator incorrectly said Figure6B; the independent source consultation corrected it to Figure6A before authorship.
The original Figure6A reciprocal immunoprecipitation identifies endogenous AR and HIF1alpha in the same complex in hypoxic, DHT-treated LNCaP cells; the promoter ChIP is a separate assay.
The FKBP52 study, PMID21730179 supports Hsp90/FKBP52/AR coassociation and MJC13-sensitive receptor release. Independent targeted Results/Figure3 and main Methods reading resolves co-IP in LNCaP, LAPC4 and22Rv1 cells. FKBP52 is a peptidyl-prolyl isomerase, but its catalytic requirement for this regulatory association is not asserted. The proposed direct AR BF3 contact was not established. Membership in the Hsp90 complex alone would not justify protein-folding chaperone binding by AR.
The RNF6 evidence is the actual GST-AR capture and reciprocal/endogenous co-IP in PMID19345326. Siah2 co-IP, AF2 capture and domain/mutant mapping in PMID23518348 support the E3-partner class while preserving the original mouse Siah2 accession Q06986. In both cases AR is the regulated substrate, not the ligase. MDM2, USP26 and KDM5D positive target associations are explicit in the respective complete cached abstracts; their full protocols were not silently treated as read.
The MLL-complex study, PMID22722839 supports endogenous VCaP coassociation/reverse IP for KMT2D, KMT2A, FOXA1 and ASH2L through actual main Results and the independently inspected supplement. The exact own-source ERG panel remains unresolved. PMID33640491 independently confirms KMT2A by GFP-AR affinity purification beyond its BioID result; other uninspected proximity-table pairs remain uncertain. The BRG1 source, PMID18487222 explicitly identifies the associated ATPase in antagonist-treated cells; it does not resolve the separate p300 and PolIII claims.
All 86 PMID assessments now state the inspected target result and its limits rather than using cache-title agreement as the basis of VERIFIED. A complete abstract can establish a plainly stated positive target result; it is not a claim that all original Methods, figures or isoforms were read. References with unresolved pair, isoform or mechanistic claims remain UNVERIFIED even when other results in that paper are positive. PMID18468998 remains MISCITED based on the actual adrenergic construct, purification and participant-table audit. The seven GO method records remain UNVERIFIED; twenty Reactome assessments retain their individually read event-summary scopes. Normal publication bytes and availability metadata were not changed.
The biological summary now includes the polymorphic N-terminal CAG/polyglutamine tract, androgen-insensitivity loss-of-function and expansion-associated spinal and bulbar muscular atrophy, using the unchanged UniProt P10275 record. Androgen recognition is explicit within the nuclear steroid receptor core. A second core describes condensation as a receptor-assembly mode, separating purified human activation-domain fragments from the separate full-receptor evidence. Neither a new core nor a new annotation is added.
The current totals are 121 ACCEPT, 58 MODIFY, 20 KEEP_AS_NON_CORE, 43 UNDECIDED and one REMOVE, with no NEW. Eight positive generic-binding rows remain non-core and unverified specific pairs remain uncertain. This follows the explicit user-supplied ActionEnum: REMOVE means an assertion is unlikely to be correct on the combined evidence. That criterion takes precedence over the annotation-reviewer skill's generic-binding removal default. Lack of specificity alone does not make a true interaction false, and an unread relevant experiment does not justify its removal. The same precedence will be stated in the pull-request response. Prospective independent consultation has passed; final validation and the authored-delta consultation are recorded in the new follow-up history.
Availability correction after the final source audit: the immutable PMID19345326 record uses legacy content_type: full_text_xml and contains the actual Results and Methods, so its authored full_text_unavailable flags are false. Absence of the newer Boolean is not evidence that the body is unavailable. The other three legacy AR records lacking that Boolean (PMID12958311, PMID17108144 and PMID21730179) are explicitly abstract_only; their flags remain true. The original published flags and the first follow-up peer snapshots are preserved. No source text or biological decision changed.
This entry supersedes the earlier conclusion that the absence of ESR1/ESR2 names from the GO:0030520 definition was sufficient reason to retain that pathway annotation. The current definition and parent describe an estrogen-binding event at an intracellular nuclear-family receptor followed by regulation of a cellular process. The wording does not impose an ESR1/ESR2-only restriction, but this observation alone does not establish that a particular reporter experiment represents the intended pathway.
I reopened the original ARA160 paper, specifically the Plasmids and Transfection and Reporter Gene Assays Methods, estradiol Results, Figure 6 legend and related Discussion. The positive wild-type AR results remain: estradiol-responsive MMTV reporters in DU145 cells with ARA70 and PC-3 cells with ARA160. E708K and T877A were separate tests. These experiments measure transactivation under specified receptor/cofactor conditions; they do not by themselves resolve the initiating ligand-receptor mechanism or the annotation's more specific pathway interpretation. This is an evidence-scope distinction, not a requirement that every signaling annotation must have a purified ligand-binding experiment. No new pixel-level quantification or supplement analysis was performed, and the normal publication cache remains abstract-only.
The GO:0030520 row is therefore UNDECIDED, preserving its original IDA assertion and all positive evidence while making this mapping uncertainty explicit. The separately supported GO:0071391 cellular response to estrogen stimulus remains KEEP_AS_NON_CORE with its existing wild-type, cell and cofactor limits. This does not assert that AR cannot participate in estrogen signaling, reintroduce the reviewer's withdrawn mutant-only account, or reject the observed response. No other annotation, core, product, reference or supporting attachment changes. Both published history records and all source caches remain unchanged.
Current totals after this single pathway change are 121 ACCEPT, 58 MODIFY, 19 KEEP_AS_NON_CORE, 44 UNDECIDED and one REMOVE, with no NEW. Validation, rendering and history validation pass. The same nine advisories concern eight retained source-specific generic interactions and one evidence-specific enzyme-binding distinction; those unchanged decisions follow the explicit user criteria described above.