Human factor IX is secreted as a zymogen. Activated FIXa supplies intrinsic-tenase protease chemistry, while FVIIIa supplies cofactor activity. This guide distinguishes performed FX activation from FIX being modified, transported or cleaved by another enzyme. The two natural products and source-specific experimental states remain separate. The campaign curation instructions govern reference-only support without new publication quotations.
PMID:2592373(https://pubmed.ncbi.nlm.nih.gov/2592373/), JBC 264:21257–21265, supplies the operative human FIX evidence. Selected original Materials, purification procedures, activity assays, Results and Figures 6–7 captions were recovered from the author-upload article. Normal and Nagoya FIX are purified from human plasma. The experiment activates FIX, then measures its conversion of bovine FX in the presence of human FVIII and cephalin; generated Xa cleaves the fluorogenic reporter. Thus FIXa performs FX zymogen activation, while upstream XIa/chymotrypsin/chymase activation and downstream reporter hydrolysis belong to other enzymes. The normal FXIa-activated comparator is distinct from the pathological Nagoya variant and experimental chymase/chymotrypsin rescue. Human FIX and FVIII, bovine FX and rabbit-brain cephalin are retained explicitly. This is not an intact-platelet assay. The immutable normal cache is abstract-only, while the external author-upload source supplied the inspected operative original passages. Only selected passages were saved and read, so full_text_unavailable: true continues to denote the lack of a complete recovered main-article export; it does not mean that only an abstract supported these decisions.
The current intrinsic-pathway definition explicitly includes IXa converting X to Xa. Zymogen activation is processing an inactive enzyme to its active form and lies below proteolysis. These support the broad coagulation/proteolysis refinements without inferring participation merely because FIX is needed or itself cleaved. Serine endopeptidase is the current more-specific catalytic term; no additional annotation is created.
PMID:20121197(https://doi.org/10.1021/jm901476x) was recovered only as selected reproduced original Results, structure caption and crystallization footnote, cross-checked against official citation metadata and PDB 3LC5. The text identifies human N-terminally truncated FIXa. The explicit fluorogenic footnote inspected is for uPA, so it is not reused as a FIXa protocol. The official main/PDF and supplement attempts did not supply complete Methods. PMID:20121198(https://doi.org/10.1021/jm901475e) remains abstract/primary-structure-citation access, with no detailed original assay reconstruction. PMID:12444082(https://doi.org/10.1074/jbc.M210722200) likewise remains abstract-only after bounded original-access attempts. Their experimental serine-protease assertions are retained with independent target-specific performed-step evidence from the Nagoya original, rather than rejected because of access limits.
PMID:8632006(https://doi.org/10.1074/jbc.271.7.3869) explicitly reports human G12R FIX, patient-plasma isolation and cofactor-dependent activity in its verified abstract. Previous genuine publisher failures are preserved; no complete original Methods are claimed. The valid NAS catalytic and IDA extracellular assertions are supported independently. The G12R mechanism is not extrapolated to the natural deletion product.
PMID:14722079(https://doi.org/10.1074/jbc.M314011200) is available as a complete Harvard author PDF. Selected Methods/Results and Tables I/III were read, including actual page pixels (printed 14339, 14340 and 14343). The preparation is a synthetic, fully gamma-carboxylated mature human FIX Gla1–47 peptide bound to Fab10C12. The model resolves residues 1–45 and six calcium ions. It directly establishes calcium coordination, allowing broad metal binding to be refined, without claiming physiological site occupancy or equivalence to full-length natural products. Comparative bovine-prothrombin/NMR columns in Table III are not treated as new human crystal observations.
PMID:9169594(https://doi.org/10.1042/bj3230629) has a verified positive abstract and actual selected publisher-indexed Results/captions on page 633 and Discussion on page 635. Normal FIX and propeptide variants differ in calcium-dependent conformation and activation. Complete Experimental/PDF access remains unavailable; the HTML challenge and BioC error responses are not original full text. Independent direct structural calcium evidence and human plasma purification support the retained calcium/extracellular annotations.
PMID:19846852(https://doi.org/10.1056/NEJMoa0904377) is available as a complete author-repository PDF. Printed page 1672 was read in text and pixels: proband/control human plasma isolation, separate HEK293 WT/R338L expression and conditioned-medium clotting/anti-FIX controls. Selected page 1673 caption/text was also read. The native plasma, engineered mutant and current natural products are distinct.
PMID:2472424(https://www.jci.org/articles/view/114130) is available as the complete JCI PDF. Selected printed pages 113–115 and actual page 114/Table I pixels establish human hemophilia-B plasma clotting/antigen measurements and domain substitutions. These functional observations are distinguished from the independent purified FIXa-to-FX conversion used for intrinsic-pathway specificity. No whole-paper or full-figure read is claimed.
PMID:3857619(https://doi.org/10.1073/pnas.82.9.2847) and PMID:8295821(https://pubmed.ncbi.nlm.nih.gov/8295821/) explicitly describe human plasma preparations in verified abstracts, but complete originals were not recovered. The initial incorrect guessed PMC PDF route for 3857619 is preserved as a failed attempt; the subsequently observed citation PDF also returned non-PDF material. Positive independent plasma originals corroborate the extracellular assertions without inventing missing Methods or treating disease propeptide retention as normal processing.
PMID:14718574(https://doi.org/10.1074/mcp.M300127-MCP200) was read from selected original Data Sources and Methods and Table II text. P00740 occurs in the literature, 2DEMS and LCMS2 columns, not LCMS1. Saved excerpts are disjoint; complete-main availability and table-pixel inspection are not claimed. The compilation identifies plasma/serum FIX, not a unique natural product or cleavage state.
PMID:26157780(https://pubmed.ncbi.nlm.nih.gov/26157780/) has a complete cached original. Selected Methods/Results compare human FVIII A1, A2, A3 and C-domain preparations, using E. coli expression and GST pulldown with recombinant BeneFIX or standard human plasma. Preferential A2 association supports protein domain specific binding. The plasma Methods do not prove platelet provenance, and BeneFIX is not assumed activated. Pulldown binding is not relabeled as a tenase activity assay.
PMID:26414444(https://pubmed.ncbi.nlm.nih.gov/26414444/) has a complete cached original. Selected Methods/Results establish a glycosylated human FIX EGF acceptor bound to mouse XXYLT1. The literal Q3U4G3 partner is mouse XXYLT1 in the captured official record. E. coli-produced FIX fragment, enzymatic glycan preparation, HEK293T-produced/trimmed XXYLT1 and purified structural complex remain explicit. The resolved substrate interaction is retained as generic binding with a non-core disposition under the explicit campaign supported-binding exception. The literal enzyme-binding definition describes contact with an enzyme, but using it here would not identify an additional FIX function beyond being the glycan-bearing substrate. The relevant public locators are Results “Binary structure of XXYLT1 with acceptor Xyl-Glc-EGF” and Online Methods “Preparation of XXYLT1 acceptor substrate Xyl-Glc-EGF” and “Cloning, protein expression and purification of XXYLT1.” XXYLT1 catalyzes xylose transfer; FIX is the acceptor. No F9 glycosyltransferase/Notch-process annotation follows from this interaction, and the fragment is not equated with both natural products. Neither study's figures or supplements were newly inspected as pixels.
PMID:25037231(https://pubmed.ncbi.nlm.nih.gov/25037231/) original Methods use sequential extraction to enrich insoluble ECM from human colon, colorectal tumor, liver metastasis and normal liver. They allow incomplete separation of fractions. Additional file 2, sheets A and B, row 214 lists F9/P00740 with additional accession Q5FBE1 and 17 total unique peptides. Normal-colon patients 2/3 and both normal-liver pools are positive. The two sheets repeat the same source data. The raw annotations carry separate UBERON:0001155 and UBERON:0002107 anatomy contexts; both remain preserved despite seed collapse. The supported specialized location is retained as non-core, without a structural matrix function or unique natural-product claim.
PMID:23533145(https://pubmed.ncbi.nlm.nih.gov/23533145/) original Methods describe EPS-urine pools from 12 low-grade PCa and 12 biopsy-negative patients, differential ultracentrifugation with DTT/sucrose wash, duplicate MS and MaxQuant FDR below 1%. Genuine BioStudies Supplemental Table 2, row 564, identifies sole P00740/F9 with 3/3 unique peptides in the PCa analyses and 0/0 in the NC analyses. This positive specialized location is non-core. A precursor/light/heavy-chain name in the table is not a processing-state identification; topology, exosomal function and universal disease specificity remain unestablished. An older HTML response named .xlsx is excluded, with its failed-load provenance retained.
PMID:34502392(https://pubmed.ncbi.nlm.nih.gov/34502392/) independently measures direct peptide hydrolysis by human FIXa and its inhibition by Iripin-8. The selected original Methods specify 200 nM FIXa, a 250 μM Boc-G(OBzl)GR-AMC reporter and a calcium-containing buffer. The plasma clotting effects are not uniquely attributable to FIXa, and this peptide assay is not described as an FX-conversion experiment. Complete main text is available; the reading was restricted to the operative target Methods and Results, without new figure or supplement inspection.
PMID:22961984(https://pubmed.ncbi.nlm.nih.gov/22961984/) examines purified human FIX as an FXIa substrate. The selected Methods and Results use gel densitometry to resolve sequential cleavage, intermediate FIXα and calcium-dependent binding. Discussion of alternative coupled reporters is not treated as an experiment executed in that comparison. PMID:39880037(https://pubmed.ncbi.nlm.nih.gov/39880037/) examines GGCX-dependent modification using engineered human FIX-derived structural fusions, radiocarboxylation assays and separate full-length FIX secretion/carboxylation experiments in human cells. GGCX performs that chemistry. Sf9 baculovirus generation, human-cell expression and the engineered FIX–TMG2/BRIL–GGCX structure are kept separate. Both complete original main texts are available, but only the specified operative sections were read; no new pixels or supplements were inspected.
The actual PTHR24278 version-19 tree and alignment place the exact 461-residue human sequence at PTN002542616. Positive ancestral serine-endopeptidase/extracellular assertions at PTN000669108 and coagulation/zymogen-activation assertions at PTN000667592 lie on its path. A further positive proteolysis IBD is distinguished from the imported contexts; no path NOT was found. Human self-WITH is valid descendant grounding, and donor count is not an evidence-quality proxy. The IBD file and tree have explicitly retained source versions rather than an assumed synchronous release.
The mouse donor P16294/MGI:88384 has actual peptidase IDA and coagulation IMP assertions to PMID:15178576(https://pubmed.ncbi.nlm.nih.gov/15178576/). Its author-uploaded original was accessible, and selected original passages were captured. Selected Methods, Results and Table 1 compare wild-type mouse, FIX knockout and engineered human-FIX knock-in plasma in a human FIX-deficient-plasma clotting assay. The human T148A/R333Q construct, mouse/human sequence junction, human-protein infusion and AAV rescue are distinct. This is positive functional evidence, but not an isolated mouse peptide-cleavage assay. The normal cache remains abstract-only; the accessible author page, selected captures and absence of a complete recovered export are recorded separately.
Actual current InterPro target membership, GO mappings, ARBA condition sets, Secreted/SL-0243, the official GO reference registry and EC 3.4.21.22 were read. ARBA00043315/00028854/00028691/00028705/00087425 match current target conditions. Current ARBA00027237 and00027128 do not; independent IPR/EC/subcellular evidence remains available within the combined source. No current rule match is presented as a new experiment or proof of all products.
The current native-human target routes were traced through actual participant, complex, catalyst, active-unit and regulator records, including each P00740 entity's own coordinates and compartment. This source-model reading does not claim independent full-text review of every event bibliography.
R-HSA-9673231 contains a bounded nomenclature discrepancy. Its labels use N43L/N43Q/N43W/N46S, while the same entities' replacement records specify arginine at43/46 and the current P00740 sequence has R at both positions. The query concerns those labels and summation only. It neither disputes the ER compartment nor changes the immutable source, gene identity or evidence code.
The source-provided P00740-1 (461 residues) and P00740-2 (423 residues, deletion 93–130) remain literal, separate objects. Displayed-product processing features are not transferred automatically to the deletion product. Synthetic Gla peptides, glycosylated EGF fragments, truncated inhibitor structures, engineered R338L/G12R/Nagoya/propeptide variants and processed FIXa are not interchangeable natural products. Historical mature-protein numbering is retained within each source rather than globally shifted.
Reference flags describe actual original availability separately from immutable normal-cache full_text_available metadata and the precise material read. In the direct-original lane, seven references have a complete main available (three recovered PDFs and four complete cached originals); the other nine retain an unavailable flag with partial/abstract scope. All normal bytes remain unchanged. Exact private capture hashes, line/block/page locators and helper extraction provenance are in the evidence ledger; public links above are source locators, not claims that every linked page was fetched afresh. No additional normal publication was required by this lane.
Database reference assessments separately record complete-main availability for the direct human FIXa peptide assay and the FXIa/GGCX studies, and selected-only access for the mouse donor article. Shared PMID:2592373 remains unavailable as a complete export; PMID:14722079 has a complete PDF. Their merged notes preserve both independent reading scopes, including direct-lane page pixels versus database text-only inspection. The official Nagoya article page range is 21257–21265; the database note’s former 21263 endpoint is corrected explicitly in the private integration delta, with no biological change.
The core combines serine-type endopeptidase activity with the performed FX activation step of intrinsic coagulation. FIXa performs the cleavage; FVIIIa enhances it. Independent direct peptide hydrolysis in PMID:34502392(https://pubmed.ncbi.nlm.nih.gov/34502392/) supports an enabled enzyme activity rather than only an accessory contribution. The human pathway substrate is F10/P00742; the separate Nagoya-paper reconstruction uses bovine FX. Upstream processing of FIX itself is not the reason for assigning zymogen activation.
Calcium coordination and peripheral membrane association are integrated structural and assembly properties. The bounded recent exact tenase-complex ontology query returned no identifier; the assembly is described in prose without inventing a GO complex. Biosynthetic compartments, matrix/exosome detections and engineered variants do not become additional core functions. The natural 423-residue product is not assumed equivalent to the displayed 461-residue precursor or its activated chains.
The synthesis used the operative peptide assay in PMID:34502392 (Results 2.3 and Methods 4.5–4.6), the Materials, purification and coupled activity assay plus Results/Figures 6–7 in PMID:2592373, and the Gla-domain Methods, structural Results and Table I in PMID:14722079. Earlier source assessments retain their precise reading and availability limits. No new figure-pixel, whole-paper or supplement inspection is claimed by this feedback pass.
The current official GO:0007597 definition was checked again and explicitly includes the performed FIXa-to-FXa step; the existing intrinsic-coagulation replacement and core therefore remain unchanged. This does not require every experimental FIXa activation route to reproduce the entire contact cascade. Calcium coordination and Gla-dependent lipid association remain supporting properties of the single catalytic assembly unit. The existing product-comparison experiment already tests matched calcium/phospholipid conditions; no separate binding core or new process assertion is required by this bounded feedback.
The full_text_unavailable flags for PMID:14722079, PMID:19846852, PMID:2472424 are true because their immutable normal caches are abstract-only. Complete external original availability and the precise previously documented reading scopes remain unchanged in reference_review.review_notes. Cache contents, external availability and actual reading are separate records; this metadata correction changes no annotation decision, citation identity or biological conclusion.