The accepted intake preserves genuine source acquisitions and the unsuccessful provider attempt. The following manual-source notes record the biological assessment; no provider-authored report is fabricated.
2026-10-25 — Reviewed the 23 assigned database contexts only. The 15 experimental-source rows remain PENDING for the separate owner. All source fields, both natural products, INITIALIZED status and the seed description are preserved; no cores, NEW rows or publication quotations were authored.
Actual source work resolved 160 Reactome participant objects and four native P03951 chain entities. Peripheral receptor association is distinct from integral membrane topology. Disease reaction R-HSA-9673223 alters F9, not F11. Activation reactions distinguish the F11 substrate from the F12/F2 enzyme; FIX activation identifies F11 as the enzyme.
The current PANTHER geneinfo/immutable membership discrepancy remains explicit. A recovered family MSA does not establish target placement; target tree ancestry remains unverified. Positive human experimental evidence supports the biological judgments without inventing that missing proof.
PMID:89876 selected original pages support positive but contextual plasminogen/fibrin activity. Independent PMID:10823824 author-text Methods/Results support external platelet association. Complete PMID:15331420 main text became available through genuine normal acquisition after earlier failed routes; PMID:10899350 remains partial. Both genuine additions and all protected existing sources remain byte-exact. Reference proposals preserve actual availability separately from normal-cache metadata and bounded read scope.
Preparation correction: an initial private setup assertion attempted to read a runtime directory symlink as a regular file. It stopped before writing a candidate or changing any protected source. The corrected checker hashes the literal symlink target; all 228 preimages pass. No source restoration was performed.
Final specificity check: GO:0031638 zymogen activation is a current descendant of protein processing/proteolysis. The directly measured human FIX activation is work performed by FXIa, supporting refinement of the existing broad process row. The same-role exact-term comparator query returned four F12 assertions (three IDA); F2/F10 had no exact-term hit in that bounded query. That uneven annotation pattern was not represented as universal coverage. This is not a NEW annotation, and the contextual plasminogen descendant is not proposed as another core process. Final lane count: 6 ACCEPT, 13 MODIFY, 4 KEEP_AS_NON_CORE; 15 unassigned PENDING.
The human platelet-transcript study does not establish activity of a purified shorter splice product. Independent platelet-binding and deficient-plasma clotting experiments support coagulation and peripheral external-membrane association. Native plasma FXI, activated FXIa and the recombinant catalytic/A4 domains are kept separate. Self-binding is refined to homodimerization, while the engineered ecotin interaction remains non-core. The positive PCI report remains undecided because its full experiment could not be inspected.
The original purified-protein fibrinolysis experiments include meaningful contamination controls and are retained as positive, specialized non-core contexts; their concentrated and prolonged in vitro conditions do not establish physiological dominance. Urinary-vesicle proteomics includes an exact F11 target record but does not distinguish the current natural products. Public source locators and actual reading limits are collected in the source guide.
Both accepted source-indexed lanes are combined: 38 contexts, comprising 13 ACCEPT, 16 MODIFY, eight KEEP_AS_NON_CORE and one UNDECIDED. Earlier partial-lane counts describe their original checkpoints. All source objects and all 25 original reference identities/findings remain exact. Three genuine references are appended, giving 28 references. Shared PMID:89876 and PMID:10823824 assessments preserve separately labeled direct and database reading scopes; their original-availability flags agree. Both natural products, the seed description and INITIALIZED status remain unchanged pending core synthesis. There are no NEW annotations or publication quotations. Activated human FXI performs FIX zymogen activation; the role is distinct from F11 being a substrate during its own activation. No self-identical replacement remains. The source guide scopes its abstract-only cache statement to the nine original direct references, because the combined set includes separately acquired full texts.
Activated factor XIa directly converts factor IX to IXa by internal proteolysis. Human recombinant FXI was expressed in HEK293 cells, purified from conditioned medium and activated with FXIIa in PMID:22961984; removal or inhibition of activating FXIIa did not change FIX cleavage. Gel-resolved substrate/intermediate/product measurements and A3-domain perturbations distinguish actual bond cleavage from a requirement for FXI activation. The zymogen-activation process in the core means FXIa acting on FIX, not F11 being the substrate of another protease.
The protein forms a disulfide-linked homodimer, and activated subunits retain a heavy chain and catalytic light chain. The A4-domain structure and whole-protein solution measurements in PMID:17884987 support assembly and conformational change, but its proposed concerted two-site cleavage model is not made obligatory here. The later PMID:22961984 kinetic study supports sequential cleavage with release/rebinding while allowing some intermediate repositioning. The core does not require one FIX cleavage per FXIa subunit. Historical paper coordinates are not silently equated with precursor numbering.
The same catalytic unit has a soluble extracellular setting and a platelet-surface setting. Human platelet binding/competition and clotting experiments in PMID:10823824, together with the native target in Reactome R-HSA-158333, support peripheral external-surface association. F11 lacks a Gla domain: calcium dependence of the measured FIX reaction is not converted into an F11 calcium-binding or phospholipid-binding activity. Homodimerization and A3 substrate recognition are supporting features of the protease, not separate generic-binding cores.
The current 625- and 571-residue product objects remain distinct and unchanged. The shorter product's 109–162 deletion is not the signal peptide or activated-chain processing event. Its transcript evidence is not a purified-protein functional equivalence experiment. Specialized plasminogen activation and fibrinolysis remain positive non-core observations, bounded by the concentration/time and contamination controls in the selected original PMID:89876 pages; urinary vesicle detection does not become a core exosome function. The paired questions and experiments target these remaining product and physiological-context uncertainties.
The three broad blood-coagulation reviews now specify the intrinsic pathway. Its current definition explicitly includes activated FXI converting FIX to FIXa. Human recombinant FXIa directly cleaves FIX in the Experimental Procedures and Figure 2 of PMID:22961984(https://pmc.ncbi.nlm.nih.gov/articles/PMC3488089/); kaolin-activated clotting assays and Table III of PMID:10823824(https://doi.org/10.1074/jbc.M001890200) independently connect human FXI to that pathway. The current ontology path is GO:0007597 part_of GO:0072378 part_of GO:0007596. This does not exclude thrombin-mediated activation of FXI or establish equal activity of the shorter splice product.
Zymogen activation remains in the same catalytic core for the directly measured FIX reaction. Plasminogen activation is indeed its is_a descendant, but the retained non-core plasminogen contexts describe another substrate and specialized assay conditions. Substituting plasminogen activation for the FIX step would misdescribe the central reaction. No new annotation is proposed, and the two selected core processes are not ancestors of one another.
The ecotin and protein C inhibitor reviews retain their distinct evidence states. Engineered ecotin complexes provide positive direct association evidence; their nonphysiological reagent context bounds biological interpretation rather than invalidating binding. The SERPINA5 abstract is positive, but complete operative Methods and target-specific complex results remain unavailable, so that source-specific review remains UNDECIDED without denying the interaction. Neither inhibitor's activity is assigned to FXIa.
All seven extracellular-region contexts remain accepted. Current GO:0005615 is obsolete because it duplicates extracellular region, so its appearance as current in an older local cache is not grounds for refinement. A blood microparticle is a membrane microvesicle; soluble plasma purification alone does not establish that compartment. The independently supported external platelet-surface pool remains separately represented. No ontology or publication cache was edited.
The campaign's explicit instruction against new publication quotations is retained. Existing bare references and public assay locators identify the evidence; no verbatim-substring validation or new full-text access is claimed. Earlier journal entries describe their original checkpoints.