F7 encodes the circulating factor VII precursor. Activated FVIIa is a serine endopeptidase that works with tissue factor (TF) and calcium at extracellular membrane surfaces. Its cleavage of factors IX and X is distinct from the processing of FVII itself by other enzymes. The precursor also passes through ER and Golgi compartments during secretion; those transit pools do not make F7 a carboxylase, trafficking factor or furin-like processing enzyme.
The specific TF association is represented by signaling receptor binding (GO:0005102). TF is both receptor and coagulation cofactor. This term identifies binding to that partner; it does not require an inhibited crystal construct to signal. The independent human-FVIIa signaling study supplies a separate cellular context. No exact TF-specific binding term was established by the saved current searches, and generic heterodimerization would add a less informative stoichiometric description. Extrinsic coagulation, serine endopeptidase activity and zymogen activation describe the pathway and step performed by FVIIa; processing of FVII by Xa is a separate substrate relationship.
The complete original PMID:3455766, PNAS 83:299–302 was inspected as four official scan pages. Human brain TF was affinity-purified on human plasma-FVII resin, with calcium required for binding and its removal used for elution. This is direct evidence for the human TF–FVII interaction. The FX-cleavage kinetics on printed page 300 used bovine VIIa, TF and X. Those kinetics must not be described as an executed human-protein assay. The human affinity experiment also does not by itself establish downstream PAR signaling.
PMID:34502392(https://pmc.ncbi.nlm.nih.gov/articles/PMC8431025/), Results 2.3 and Methods 4.6–4.8, supplies independently inspected human FVIIa peptide-proteolysis evidence: human FVIIa and human TF were assayed with Boc-QAR-AMC in calcium-containing buffer, with Iripin-8 inhibition and complex formation examined. This is a peptide assay, not a direct FX-activation experiment or proof that the unactivated precursor has the same activity. The complete main text is available; selected operative text and captions were read, without figure pixels or supplementary inspection.
For PMID:8598903(https://doi.org/10.1038/380041a0), the full article remains unavailable. The actual 1DAN structural deposition was inspected through its molecule, summary and ligand records. It contains human FVIIa light and heavy chains, soluble human TF, an active-site inhibitor and calcium associated with FVII chains. This supports metal occupancy in that structure. It does not provide catalytic rates, a new residue-contact analysis or proof of equivalent activity of every precursor product. Current target InterPro mappings and EC 3.4.21.21 provide additional, explicitly curated enzyme/domain context.
The actual participant objects, rather than only reaction titles or catalyst locations, establish the modeled F7 compartments. R-HSA-140748 contains extracellular P08709 light/heavy chains 140749/140750 and their membrane-associated counterparts 140715/140724. R-HSA-140783 similarly distinguishes extracellular single-chain FVII 140771 from membrane-recruited FVII 140774. These extracellular proteins associate peripherally with the external membrane face; TF's transmembrane segment is not assigned to FVII.
R-HSA-159761 assigns gamma-carboxylation to GGCX and identifies the FVII precursor as substrate in ER lumen. R-HSA-159783 transports that cargo to Golgi lumen, and R-HSA-159868 assigns propeptide cleavage to furin. These are valid biosynthetic locations, distinct from the extracellular catalytic unit.
The native TF:FVIIa reactions R-HSA-9929051 and R-HSA-9822514 describe FVIIa-mediated FIX and FX activation. They support the performed zymogen-activation step and the extrinsic coagulation pathway. By contrast, R-HSA-140769 and R-HSA-9929060 assign FVII activation to FXa. The current 9929060 summation repeats an FX-release passage inconsistent with its event name and catalyst graph; the explicit participant graph supports the location without relying on that narrative.
Within R-HSA-9822522, FXa supplies the VIII-cleaving step in the larger TF:FVIIa:FXa complex. F7 membership is not an isolated FVIIa assay for VIII cleavage. TFPIβ and TFPIα/FV-intermediate/PROS1 routes likewise retain inhibitor and cofactor roles separately from FVIIa. These database models were actually traced, but their entire bibliographies were not independently reread.
The actual PTHR24278 v19 tree places human F7 at PTN002542619. Its ungapped alignment equals the displayed 466-residue protein. Positive extracellular, coagulation and protein-processing IBDs lie on that path, with no path NOT. Human self-WITH is legitimate experimental descendant grounding. The tree and MSA are exact earlier official captures because fresh requests timed out; their historical version is explicit, and no fresh successful geneinfo response is claimed.
Mouse P70375/MGI:109325 and zebrafish Q504H3 donor identities and current GO assertions were checked. The mouse FVII knockout abstract reports fatal bleeding with relatively normal development, distinct from tissue-factor knockout. The zebrafish source concerns hepsin/FSAP and FVII/coagulation experiments. Their complete originals were not recovered. Independent human interaction/chemistry and native target models support the conserved coagulation assignment without transferring uninspected donor assay details or developmental phenotypes.
The rat ortholog Q8K3U6 supplies many context-dependent assertions. Those donor references were traced individually:
| Source | Actually available evidence | Boundary for human F7 |
|---|---|---|
| 12757778 | Abstract: recombinant rat FVII in HEK293 cells and deficient-plasma/TF assays | Human host or plasma does not make the protein human; independent human chemistry supports the broad enzyme role. |
| 18315926 | Abstract: rat EGF1 fusion binding cellular TF | Human affinity-purification evidence supports TF binding independently. |
| 3379837 | Complete original; dietary vitamin-K deficiency and rat FVII clot-based assays, sex/time dependence | Positive biosynthetic response, corroborated by human GGCX/FVII context; not FVII carboxylase activity. |
| 26855512 | Complete original; CO2 pneumoperitoneum with varied pressure/duration and reperfusion | FVII rose only in the 12-mmHg one-hour group; CO2, pressure and procedure were not isolated. |
| 14724430 | Abstract: FVII changes after major hepatectomy as a protein-production marker | No regenerative step performed by FVII is established by the available text. |
| 4307182 | Bibliographic record only | The rat vesicle assay and exact topology remain unread. |
| 9155722, 2607889, 11880553, 15670042 | Abstracts: hypoxia, daily rhythm, fat gavage and cholesterol responses | The historical donor experiments remain source-limited; independent human/mouse rhythmic-activity evidence is described below. Rhythm does not imply that FVII is an autonomous oscillator. |
| 18336749, 21382270, 20838740, 2821645, 7493602 | Abstracts: thyroid-axis, estrogen/genistein and growth-hormone interventions | Antigen, expression and activity endpoints differ; none is automatically a hormone-binding mechanism. |
| 10901669, 22309505 | Abstracts: dioxin-related and astaxanthin-associated changes | Exposure/model-specific responses are retained without asserting their conservation or disproving the donor observations. |
Full originals for the abstract-only donor entries were not recovered after bounded attempts. Except for the independently corroborated rhythmic-activity context below, unresolved human response assertions remain undecided; the available positive donor observations are not grounds for removal. The PMID:18612547(https://pubmed.ncbi.nlm.nih.gov/18612547/) human cancer-cell abstract similarly reports TF–FVIIa–Xa-associated mTOR signaling, but unread full Methods prevent attribution of the individual enzyme requirements. A current matching ARBA rule does not resolve that boundary.
The literal UniProt products A/P08709-1 and B/P08709-2 remain distinct: displayed A is 466 residues; B is 444 residues with deletion of displayed positions 22–43. Signal 1–20, propeptide 21–60 and activated light/heavy chains 61–212/213–466 describe processing of the displayed precursor. They are not new splice products and are not silently transferred to B. Separate RefSeq/Ensembl models also remain distinct from tested preparations.
Actual current ARBA condition sets match the target for stress, ER, Golgi, body-fluid levels and TOR. The current ARBA00027237 protease rule does not reproduce a target match; independent InterPro, EC and human assay evidence supports the combined protease annotation despite that version boundary. SL-0243 explicitly maps secretion to extracellular region.
Reference full_text_unavailable flags describe actual original-main availability, including recovered external originals. They do not simply copy normal-cache metadata. Conversely, an available complete main does not imply that every paragraph, figure pixel or supplement was inspected. Exact selected reading and access failures remain in the private evidence ledger; immutable machine source and publication bytes are preserved.
Selected publisher-indexed original pages 135–136 and 139–140 were recovered and read, including Cell Lines, Monocytes, Chemotaxis Assay, Reagents, signaling Methods and Figures 4–5 captions/Results. Recombinant human FVIIa was tested in primary human monocytes and fibroblasts and porcine aortic endothelial cells expressing human TF/PDGFRβ. The PDGFR phosphorylation experiments are in that engineered PAE context. These support context-dependent migration/signaling, not FVIIa kinase activity or all-product equivalence. Full PDF/supplement access failed; no figure pixels or complete-main reading claimed. https://doi.org/10.1161/ATVBAHA.107.155754
PubMed/Europe PMC identity and publisher abstract verified. The abstract reports miR-19b regulation of TF expression and procoagulant activity in endothelial cells, but complete original Methods/Results were not recovered. Specific FVII/FX reagent identity and the original projected complex/catalytic assays remain unverified. Central FVIIa biology is retained using independently inspected human biochemical and structural sources, without pretending this article was read in full. https://doi.org/10.1016/j.yjmcc.2014.06.017
All five official PMC original page images (PNAS pp. 5158–5162) were viewed and read, including Methods, sequence Results and Figures 1–2. This is human genomic sequencing and alternative-leader evidence; enzyme-function statements are background appropriate to TAS. Historical HepG2 cDNA/transcript accounts do not establish identical processing or function of every current natural product. The normal publication cache is abstract-only despite complete external original access. https://pmc.ncbi.nlm.nih.gov/articles/PMC298813/
The journal article remains unavailable beyond metadata/abstract, but the actual primary PDB 1O5D entry, polymer entities and author/software-defined assembly were inspected. This structure belongs to PMID:15522303 and includes human P08709 light/heavy chains and human P13726 TF, despite the uPA-focused title. FVII chain sequences match displayed residues 61–212 and 213–466. This is structural association in an inhibitor study, not autonomous inhibitor activity, an executed turnover assay or proof of both natural products. https://doi.org/10.1016/j.jmb.2004.09.032 ; https://www.rcsb.org/structure/1O5D
Journal metadata/abstract and primary PDB 1W0Y/1W2K entries, polymer sequences and assemblies were inspected. They contain human FVIIa and TF with inhibitor ligands; the deposited heavy chain matches displayed 213–466 and the shortened 142-residue light sequence matches 61–202. Structural association is positive while full article Methods remain inaccessible. No natural-product equivalence, uninhibited catalytic measurement or FVII inhibitor function is inferred. https://doi.org/10.1016/j.bmcl.2004.10.092 ; https://www.rcsb.org/structure/1W0Y ; https://www.rcsb.org/structure/1W2K
Actual official ACS Supporting Information was recovered. Supplementary Figures 1–2 captions describe competition and negative/positive controls and thresholds; Table S1 page 6 lists F7–F3 among the 557 positive interactions, and Table S7 page 85 identifies paired-antibody catalog DI0178. Both target table pages were visually inspected. The abstract identifies the endogenous HeLa PLA setting. This supports cellular proximity, not purified binary affinity or product/cleavage-state resolution. Complete journal main text remains unavailable; the supplementary PDF is not misrepresented as the article body. https://doi.org/10.1021/pr5002737 ; https://acs.figshare.com/articles/journal_contribution/2228524
The actual author-upload article main text was accessible through its indexed rendering. Experimental Procedures (Proteins, General Methods, Tissue Factor Binding Assay, FVII Activation), Results and Figure 4 caption were read. Human WT FVII and TF1–218 give saturable binding with gelatin controls; F328S has lower affinity. Human Xa-mediated FVII activation and clotting comparisons distinguish substrate activation from FVIIa catalysis. Mature-protein residue numbering is preserved. No figure pixels or new simulation analysis; normal cache remains abstract-only. https://doi.org/10.1074/jbc.271.48.30685 ; https://www.researchgate.net/publication/14267239
Actual author-upload main text was accessible through an indexed rendering. Materials/Methods, WT/N57D/R79Q expression and TF-binding Results, Figures 3–5 captions and relevant Discussion were read. Human FVII in 293/COS-1 conditioned medium binds relipidated TF; mock-medium controls and WT comparisons are explicit. S-2222 is a coupled downstream FXa readout, not direct FVIIa amidolysis. Historical mature numbering and unverified current precursor-product assignment remain bounded. No figure pixels; normal cache remains abstract-only. https://pubmed.ncbi.nlm.nih.gov/9414278/ ; https://www.researchgate.net/publication/13816530
PubMed/Europe PMC identity and abstract were read; publisher main text was inaccessible. The abstract reports human F7 variant expression, secretion and functional assays, but exact constructs/controls/current-product mapping remain uninspected. Broad extracellular location is independently corroborated by actual human plasma and conditioned-medium studies, without manufacturing details from this paper. https://doi.org/10.1111/bjh.18768
PubMed/Europe PMC original abstract explicitly includes TF–FVIIa activation of human FIX; the FIXa-focused title is not evidence of wrong-gene attribution. Bounded publisher/author routes did not recover complete operative Methods/Results. FVII reagent species/construct and detailed activation conditions remain unresolved. Independent human FVII biochemical work supports the general extrinsic-coagulation role, not an invented read of this article. https://doi.org/10.1074/jbc.271.7.3869
Actual full original Methods and the original supplementary workbook were inspected. Additional file 2, sheets A Complete MS Data Set and B Matrisome, row 281, identifies F7/P08709 with a P08709|P08709-2|B4DPM2 group; peptides are positive in normal-liver pools and one liver-metastasis patient. Sequential extraction/insoluble ECM-enrichment and LC–MS/MS are described with fractionation controls. The result is a contextual fraction observation, not isoform-specific localization or demonstrated structural ECM function; possible co-isolation is not proven contamination. https://pmc.ncbi.nlm.nih.gov/articles/PMC4223627/
The 3455766 reading includes Methods, Table 1 and Figure 1 on all four original pages. For 1DAN, the independent sequence/assembly examination maps FVII chains to displayed 61–212 and 213–466 and retains the two deposited soluble-TF segments; no new interface analysis was performed. For 18612547, identifier/abstract verification coexists with unresolved FVIIa-specific attribution in both the direct migration/TOR contexts and the database TOR context. The combined reference retains both labeled assessments.
The core uses serine-type endopeptidase activity, extrinsic coagulation and zymogen activation. Positive regulation of blood coagulation (GO:0030194) is also represented, retaining the accepted coagulation-promoting effect. Current is_a/part_of closures show no ancestor/descendant redundancy among these three process facets. The TF–FVIIa assembly is represented by serine-type peptidase complex (GO:1905286), whose definition and narrow TF–FVII synonym fit the inspected target composition. FVIIa supplies the catalytic site; tissue factor binding and calcium-dependent surface assembly support the same unit. The accepted receptor-binding observations remain intact without making each inhibited structure or proximity assay a signaling experiment.
The synthesis inspected the human-reagent, activation, binding and activity passages of PMID:8940045(https://doi.org/10.1074/jbc.271.48.30685), especially Methods and Figures 2–4 with their accompanying Results. Human WT FVII binds soluble TF1–218 and gains clotting activity after human Xa activation; the F328S mutant retains measurable TF binding despite profound catalytic impairment. No new figure pixels or supplements were read. The distinct human peptide assay in PMID:34502392(https://pmc.ncbi.nlm.nih.gov/articles/PMC8431025/) and the human-versus-bovine boundary of PMID:3455766(https://pmc.ncbi.nlm.nih.gov/articles/PMC322845/) remain as described above. The inspected native Reactome models assign the FIX/FX cleavage step to TF:FVIIa and identify F7's own extracellular and membrane-associated chains; they are source models rather than additional primary assays.
The two open questions concern precursor-specific maturation and the attribution of cell signaling within TF:FVIIa:FXa assemblies. Comparing sequence-verified A and B products requires direct processing and active-site measurements. Separating FVIIa from FXa signaling requires both protease-specific controls and direct receptor-cleavage endpoints. Neither comparison presumes equivalence of the two precursors or a resolved FVIIa-specific TOR mechanism.
PMID:7797546(https://doi.org/10.1074/jbc.270.26.15523), S-2288 assay Methods and Results/Figures 5–6, directly measures human FVIIa peptide hydrolysis without TF. TF and calcium enhance that activity. This supports FVIIa as the catalytic gene product while keeping efficient physiological substrate recognition in its TF/cofactor context. The actual publisher-indexed original was read at those named passages; complete article export and figure pixels were not recovered. Calcium measurements in this paper also distinguish native, Gla-domainless and active-site-blocked preparations and their stability. Neither the peptide assay nor a crystal ion count establishes universal physiological calcium occupancy.
The inherited BHF-UCL assertion from PMID:24998411 retains its literal contributes_to qualifier. Its complete original remains inaccessible, so a bounded SUSPECTED/CHECK query asks whether that source-specific complex projection should instead use enables. This is not a confirmed source error. PMID:34502392 includes TF in its peptide assay and is not cited as a no-TF control.
GO:1905286 applies to the catalytic complex, not a new localization pool. In the actual Reactome TF:FVIIa object 140734, component 140704 is human TF/P13726; component 140733 contains P08709 light 61–212 and heavy 213–466 plus calcium. The inhibited 1DAN deposition independently records human FVII light/heavy chains and two soluble-TF segments. Its four polymer entities are not four distinct gene products, and the inhibited preparation is not an executed turnover assay.
Human FIX/P00740 and FX/P00742 are the structured substrate identities. They designate gene products without asserting an untested splice product or equating precursor and activated forms. TF binding and calcium coordination remain essential supporting molecular facets of the same coagulation unit; the single-function core schema is not populated with duplicate units merely to repeat those interactions. The specific accepted annotations retain their molecular detail.
The complete PMID:15604416 publisher article in the University of Ferrara repository was read at main Methods, Results, Discussion and captions, printed pp. 646–649. Thirteen healthy men were sampled at 8 AM and 2 PM; FVII-dependent activity was higher in the morning. Mice were sampled across light/dark, restricted-feeding/fasting and constant-darkness conditions. FVII rhythmic activity persisted in constant darkness, distinguishing an endogenous rhythm from a light/dark-associated daily fluctuation. The assay measured generated FXa in FVII-depleted plasma, not FVIIa hydrolysis of the fluorescent reporter. No figure pixels or online supplement were inspected. Human two-time-point sampling alone does not establish an endogenous circadian oscillator. These results corroborate a non-core rhythmic-activity context, while the original rat PMID:2607889 remains available only as an abstract.
Response-term definitions allow changes in expression or activity; they do not require each coagulation protein to be a hormone receptor, environmental sensor or driver of the entire treatment outcome. The remaining hypoxia, hormone, nutrient and exposure annotations are unresolved because of their particular donor-access and human-transfer boundaries. The complete CO2-pneumoperitoneum experiment does not isolate gas from pressure/procedure. In contrast, dietary vitamin-K experiments plus the human GGCX/FVII biosynthetic model connect vitamin K to production of functional FVII. F7 remains the carboxylation substrate, not the modifying enzyme.
For animal organ regeneration, the available PMID:14724430 abstract uses FVII recovery after hepatectomy as an indicator of hepatic protein production. It does not identify a regenerative step performed by FVII. The full original remains inaccessible; this supports explicit uncertainty rather than a negative conclusion about uninspected experiments. The cancer-cell TF–FVIIa–FXa mTOR/migration source likewise remains unresolved at individual-protease attribution. No statement here converts publication inaccessibility into an experimental contradiction.
The full_text_unavailable field consistently describes the retained publication-cache record here. The caches for PMID:3037537, PMID:3455766, PMID:8940045, PMID:9414278, PMID:3379837, PMID:26855512 and PMID:15604416 are abstract-only, so their flags are true. This does not retract external source access: the official five-page PMID:3037537 and four-page PMID:3455766 scans were read; PMID:3379837 and PMID:15604416 complete deposited PDFs and PMID:26855512 complete PMC main were accessible with the stated selected reading; PMID:8940045 and PMID:9414278 author-upload indexed main text was accessible at the saved selected Methods/Results/caption scope. Full-cache availability, complete-original access and actual selected reading are separate statements. All normal bytes and their own metadata are unchanged.
For PMID:7797546, the publisher's original article (DOI), the inspected Methods subsection on S-2288 amidolytic activity specifies the TF/FVIIa/calcium reaction mixtures and that phospholipid enters only with TF. The Results subsection on calcium and TF effects and the Figure 5 caption explicitly compare FVIIa without TF with TF-added mixtures in EDTA. Figure 6A describes calcium enhancement without TF; Figure 6B includes TF. These selected publisher text and caption passages establish basal peptide hydrolysis and strong cofactor enhancement, not autonomous physiological coagulation. Direct PDF retrieval attempts failed; no complete article export or new figure-pixel inspection is claimed. The PMID:24998411 source-specific rationale remains unread, so the inherited qualifier is unchanged and the query remains SUSPECTED/CHECK and NOT_REPORTED. Merely recording that query does not send it to ARUK-UCL; no export or external notification has been performed.
TF receptor binding and calcium coordination remain accepted essential facets of the single FVIIa catalytic unit. Their physical-binding and structural evidence does not imply that each binding assay tested downstream signaling. Removing the now-unused PMID:17991872 support from seven TF-binding reviews leaves the source-specific structures/proximity observations and independent human binding assays explicit. That reference remains where it supports the distinct original signaling context. Separate redundant binding cores and automatic non-core downgrades are not warranted by the absence of an additional structured MF slot.
The current GO:0030194 definition covers processes that activate or increase the frequency, rate or extent of coagulation. FVIIa's performed FIX/FX activation provides that positive contribution as well as its extrinsic-pathway step; the retained term is not a claim that FVIIa senses a regulatory signal or that the unactivated precursor performs proteolysis. The checked typed ancestry does not make this term an ancestor or descendant of the other two core process terms. The rat source's incomplete Methods and independent human/model evidence remain labeled.
The ClinGen campaign curation instructions explicitly prohibit new publication quotations while requiring verified identifiers, access limits and precise locators. No new quotation is introduced; reference-only support is not described as verbatim-substring validation. The source guide is an ordinary authored evidence guide linked from the gene notes, not a fabricated deep-research provider output.