F10 encodes the secreted factor X precursor. Proteolytic activation generates factor Xa, the serine protease that cleaves prothrombin in the calcium-, phospholipid- and factor Va-dependent prothrombinase system. The same gene therefore appears as a substrate in activation or maturation reactions and as the enzyme in later coagulation reactions. Those roles must be read from the actual participant and catalyst records.
The current UniProt P00742 source is 488 residues and has no alternative-products comment. Its annotated light chain is 41–179, heavy chain 183–488, activation peptide 183–234 and activated Xa heavy chain 235–488. Signal 1–31 and propeptide 32–40 are separate processing features. These are processed parts of one precursor, not splice-isoform identifiers. The separately captured NCBI locus records NP_001299603.1 (444 residues) and NP_001299604.1 (332 residues) do not establish their activity, maturation or localization.
The primary studies used purchased human plasma FX/Xa, recombinant FX constructs activated before assay, and deliberately Gla-deleted Xa preparations. None tests all natural products. The 2025 GGCX study uses FX-derived recognition segments in a fusion protein and labels its signal/propeptide split differently from current UniProt; that experimental boundary is retained literally rather than silently remapped.
Kamata et al., 1998 describe purchased human Xa beta-form and chymotrypsin-generated Des[1–44] Xa. Materials and Methods and the calcium-site/inhibitor Results support peptide-substrate hydrolysis, an active-site inhibitor complex and bound calcium. The preparation lacks the Gla domain, and EGF1 calcium occupancy is partial. It cannot establish the full complement of intact Gla-domain sites or native membrane binding. Residue labels from the paper are kept in its numbering system; no universal offset to the precursor is assumed.
Monteiro et al., 2008 distinguish human factor X zymogen binding from factor Xa binding to tick Ixolaris. The inspected Results and Methods include gel filtration, calorimetry, ELISA, surface plasmon resonance and factor X activation by FIXa/FVIIIa in calcium and PC/PS vesicles. Generated Xa is measured afterward. Thus positive zymogen binding is not evidence that uncleaved factor X performs proteolysis. HEK293-expressed coagulation constructs and High Five-produced Ixolaris are separate preparations.
Manithody et al., 2012 directly measure prothrombin activation using human plasma Xa, Va and prothrombin in a defined calcium/PC/PS system. Experimental Procedures, Results and Discussion also describe RVV-X activation of recombinant FX, full-length versus Gla-domainless preparations, PAR-2 reporter cleavage in EA.hy926 cells and permeability readouts. The lipid-vesicle assay supports peripheral membrane-associated Xa catalysis; it is not an intact-cell binding or transmembrane-topology assay. PAR-2 cleavage is a distinct substrate context. Controls reported as data not shown are not presented as inspected underlying data.
These primary passages were read from genuine full-text normal records. No figure pixels or supplements were inspected in this database assessment. The exact selected sections, rather than a claim to have read every paragraph, delimit the support.
The ER and Golgi annotations describe genuine precursor-processing pools. In Cao et al., 2025, selected Results and Methods show FX-derived propeptide/Gla recognition elements fused with TMG2 transmembrane/BRIL/GGCX segments. Human GGCX preparations were expressed using BacMam in HEK293S GnTI cells; Sf9 cells served virus production. The paper's FX segments are signal 1–21, propeptide 22–40 and Gla 41–85. Full-length functional carboxylation assays emphasized FIX, not natural full-length F10. F10 supplies the substrate segment and GGCX performs carboxylation.
Reactome independently models ER-luminal pro-factor X as GGCX substrate, transport to the Golgi, and cleavage by FURIN. ER/Golgi residence is retained as non-core biosynthetic context. It is not turned into F10 carboxylase, transport-motor or furin activity.
The actual PTHR24278 target leaf PTN002542618 has an exact 488-residue ungapped P00742 alignment. Its ancestor PTN000669108 has positive IBD assertions for serine-type endopeptidase activity and extracellular region; PTN009089245 has proteolysis. No target-path NOT was found. The target's presence in descendant experimental evidence is valid, and donor count is not used as a confidence score. Captured GOA and current IBD dates remain distinct versioned assertions.
Current ARBA matches are ARBA00027237 set 0 (serine endopeptidase), ARBA00027128 set 24 (extracellular), ARBA00028691 set 5 (ER lumen), ARBA00028705 sets 0/5 (Golgi lumen), and ARBA00092062 set 3 (positive TOR regulation). Actual domain, FunFam and taxonomic conditions were compared with the target; a matched rule does not by itself settle biological relevance.
The inspected InterPro Gla, calcium-binding EGF and S1-protease mappings are IPR000294, IPR001254, IPR001881, IPR012224, IPR018097, IPR018114 and IPR035972. The coagulation-protein family includes protein Z as a nonproteolytic exception; positive human Xa assays establish the target's enzymatic activity independently. EC 3.4.21.6 explicitly names activated factor Xa and prothrombin cleavage. UniProt SL-0243 maps secreted proteins to extracellular region. Current official GO definitions include membrane-associated proteins in plasma membrane; they do not require a transmembrane helix for this location.
Every route below reaches human P00742 through reference entity 140617, embedded in the captured target-chain records. Location is checked on the chain entity itself, not copied only from the reaction or another participant. Light/activated-heavy chains 140631/140642 are membrane-associated; 140687/140688 are extracellular. The zymogen heavy chain is 140738. ER and Golgi pro-light/heavy chains are separately represented. Released activation/propeptides are not used as a substitute for an available intact-chain route.
| Event | Location context | Representative target route |
|---|---|---|
| R-HSA-140686 | Extracellular | 140686 input → 140689 hasComponent → 140687 |
| R-HSA-140700 | Extracellular | 140700 catalystActivity → 140768 physicalEntity → 140689 hasComponent → 140687 |
| R-HSA-140769 | Extracellular | 140769 catalystActivity → 140768 physicalEntity → 140689 hasComponent → 140687 |
| R-HSA-158164 | Extracellular | 158164 input → 140739 hasComponent → 140687 |
| R-HSA-9015111 | Extracellular | 9015111 output → 9015108 hasComponent → 140689 hasComponent → 140687 |
| R-HSA-9668253 | Extracellular | 9668253 input → 140739 hasComponent → 140687 |
| R-HSA-9668365 | Extracellular | 9668365 input → 140739 hasComponent → 140687 |
| R-HSA-9670874 | Extracellular | 9670874 input → 140739 hasComponent → 140687 |
| R-HSA-9678434 | Extracellular | 9678434 input → 140739 hasComponent → 140687 |
| R-HSA-9769737 | Extracellular | 9769737 catalystActivity → 140768 physicalEntity → 140689 hasComponent → 140687 |
| R-HSA-9822512 | Extracellular | 9822512 output → 140689 hasComponent → 140687 |
| R-HSA-9822513 | Extracellular | 9822513 input → 140739 hasComponent → 140687 |
| R-HSA-9822514 | Extracellular | 9822514 input → 140739 hasComponent → 140687 |
| R-HSA-9823284 | Extracellular | 9823284 input → 140689 hasComponent → 140687 |
| R-HSA-9933742 | Extracellular | 9933742 input → 140689 hasComponent → 140687 |
| R-HSA-159757 | ER lumen | 159757 input → 159734 hasComponent → 159786 |
| R-HSA-159819 | ER lumen | 159819 input → 159754 hasComponent → 159810 |
| R-HSA-159733 | Golgi lumen | 159733 input → 159744 hasComponent → 159774 |
| R-HSA-159757 | Golgi lumen | 159757 output → 159744 hasComponent → 159774 |
| R-HSA-140664 | Plasma membrane | 140664 catalystActivity → 140663 physicalEntity → 140662 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-140686 | Plasma membrane | 140686 output → 140662 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9015111 | Plasma membrane | 9015111 input → 140649 hasComponent → 140631 |
| R-HSA-9015122 | Plasma membrane | 9015122 input → 140662 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9822512 | Plasma membrane | 9822512 input → 9822516 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9822513 | Plasma membrane | 9822513 output → 9822515 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9822514 | Plasma membrane | 9822514 output → 9822516 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9822522 | Plasma membrane | 9822522 catalystActivity → 9822518 activeUnit → 140649 hasComponent → 140631 |
| R-HSA-9822556 | Plasma membrane | 9822556 input → 9822516 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9929060 | Plasma membrane | 9929060 input → 9822515 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9931624 | Plasma membrane | 9931624 input → 9822516 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9932951 | Plasma membrane | 9932951 input → 140662 hasComponent → 140649 hasComponent → 140631 |
| R-HSA-9933742 | Plasma membrane | 9933742 output → 9930788 hasComponent → 140649 hasComponent → 140631 |
The disease events 9668253, 9668365 and 9670874 alter FIX/FVIII catalyst contexts while retaining native F10 substrate. Drug and serpin/TFPI events contain inhibited Xa; they do not assign inhibitor function to F10. Event 9015111 has membrane Xa input and an inhibitor-product branch containing extracellular Xa; these literal model states are retained without claiming measured translocation. All displayed target routes were recovered, while unrelated graph branches that returned rate-limit responses remain incomplete. The table describes model provenance, not newly inspected kinetic experiments for every event.
PMID:32296183(https://pubmed.ncbi.nlm.nih.gov/32296183/) main Results, screening overview and Data availability, the original HuRI interaction file, and current IntAct publication records were inspected. Original records identify F10 ORF 11685, UBQLN2 ORF 71001 and partner ORF 55237, tested as GAL4 fusions in yeast. Three method records support each pair. ORF 55237 appears under historical Q7Z3S9-1 and ENSP00000462298.1 labels; current IntAct maps the source assertion to P0DPK4/NOTCH2NLC. These representations do not verify historical clone identity with the current sequence, nor native factor-X processing in the assay. Study-wide orthogonal validation is not claimed for these individual pairs.
The four binding assertions remain supported non-core associations. Xa's inhibitor partners do not confer inhibitor activity on Xa. GO:0005112 concerns binding a Notch surface receptor, whereas the inspected NOTCH2NLC record describes a N-terminal-like regulator. The UBQLN2 interaction does not establish protein-folding chaperone binding or a proteostasis function for F10. No more specific activity was justified by the inspected assays and ontology searches.
PMID:18612547(https://doi.org/10.1160/TH07-12-0722) has positive abstract findings in an Adriamycin-resistant MCF-7 context, including TF–VIIa–Xa-associated mTOR/p70S6K phosphorylation and rapamycin-sensitive migration. Complete Methods, active-Xa-specific causal controls and receptor attribution were not recovered. Both direct assertions remain UNDECIDED, consistently with the separate database TOR context; this does not deny the reported phenotype.
Normal publication files remain unchanged. Externally recovered originals are distinguished from abstract-only normal records in the reference assessments. Text inspection and actual image inspection are stated separately above. The complete migration/TOR article remains unavailable; its positive abstract is retained without resolving active-Xa-specific causality. No equivalence is inferred for all natural products or for historical clone accessions.
The core uses current serine-type endopeptidase activity, with prothrombin cleavage specified in its biological description. The former coagulation factor Xa activity term is obsolete. Calcium and phospholipid binding are retained as supporting facets rather than redundant catalytic units. The soluble extracellular pool and peripheral external membrane location have separate current location terms. No specific prothrombinase-complex identifier was established by the bounded ontology search.
For this synthesis, the human Xa preparation, crystallization and calcium-binding Results in PMID:9618463(https://doi.org/10.1073/pnas.95.12.6630) and the human plasma reagents/prothrombin-activation Methods and Results in PMID:22409427(https://doi.org/10.1021/bi300200p) were reread. No new figure pixels or supplements were inspected. The prior direct read of PMID:20427285(https://pmc.ncbi.nlm.nih.gov/articles/PMC2888451/) supplies the membrane-dependent inhibition and inhibitor-role scope. These data support activated Xa, not intrinsic activity of an uncleaved precursor or equivalence of all natural transcript products.
The campaign instructions explicitly retain supported generic binding as non-core when no specific replacement is established, and prohibit new publication quotations. They apply to the four retained interaction contexts; no new molecular role is inferred from association.
In PMID:22409427(https://pmc.ncbi.nlm.nih.gov/articles/PMC3314109/), Experimental Procedures (PAR2–alkaline-phosphatase reporter and permeability assays), Results (PAR2 cleavage and signaling) and Discussion establish Xa acting on a receptor substrate in EA.hy926 cells. Released reporter activity measures cleavage, while albumin flux after thrombin challenge measures barrier protection. Variant effects discriminate this substrate recognition from prothrombinase activity. Anti-PAR2/anti-PAR1 blockade and the reported optimal protective concentration are data not shown, not newly inspected panels. Gla-deleted Xa retains the reported PAR2 and protective activity; the Gla requirement for prothrombinase is not universalized to signaling. This bounded human-cell experiment supports the added catalytic prose, not a broad new inflammatory, migration or TOR annotation.
The curated factor VII, factor V and factor VIII reactions assign Xa an enzyme role. VII/V events reach catalyst 140768 and soluble Xa 140689; the VIII event's catalyst 9822518 explicitly names Xa 140649 as active unit within TF–VIIa–Xa. FVa intermediates retain part of the inhibitory B domain, and the VIII summary also describes inactivating cleavages at other sites. Thus the description records participation in initiation/amplification without assigning every cleavage to complete activation. These are verified curated models, not new readings of each cited kinetic original.
The two broad proteolysis mappings are now refined to protein processing, GO:0016485, whose current definition covers maturation through peptide-bond cleavage. It is a strict descendant of proteolysis and the direct parent of zymogen activation. The broader processing term retains Xa’s performed activation of enzyme precursors, procofactors and the PAR2 receptor without calling procofactors or receptors enzymes. The factor V activation intermediate remains an intermediate; the different factor VIII-inactivating cleavages are not relabeled maturation. No parent/child pair or NEW annotation is added. The single existing protease core and its bounded substrate descriptions are unchanged.
The authoritative QuickGO API record for GO:0005615, retrieved on 2026-10-25, explicitly reports isObsolete: true, the label “obsolete extracellular space,” and explains that it represents the same concept as GO:0005576. See also the public QuickGO term page. Thus GO:0005615 is not a current, more-specific replacement for the accepted extracellular-region assertions. Two older repository lookups at the reviewed commit are stale relative to this official current record: cache/ontologies/go.tsv, line 834 records False with a 2026-03-21 fetched date, while cache/go/terms.csv, line 1598 retains the old label with a 2026-05-08 retrieval date. These cached bytes are preserved, not repaired in this gene revision. This conclusion uses the official ontology response, not another gene review or an inferred obsoletion date.
The UniProt P00742 record, CC FUNCTION, TISSUE SPECIFICITY, PTM and DISEASE, supports the added liver/plasma, Gla-dependent calcium association and variable bleeding-disorder summary. This is curated-record evidence, not a claim to have newly read all of its cited disease or signaling papers. The primary 22409427 experiment, rather than a blanket inflammatory label, defines the signaling scope used here.
Author availability flags refer to whether the complete original was accessible, independently of cache metadata. The recovered 6323392 PDF covers pages 187–195; the four official 6587384 images cover its complete main pages 3699–3702. Both flags are false, while their normal caches remain untouched and abstract-only. For 14718574, selected author-rendered Methods and Table II/P00742 rows are positive evidence, but the saved disjoint excerpts do not establish complete-main availability; its flag remains true. All actual earlier text/pixel reading scopes above remain in force.
ARBA00092062 condition set 3 is a verified matching provenance path, not an independent causal experiment. The positive Adr-MCF-7 mTOR report in PMID:18612547(https://doi.org/10.1160/TH07-12-0722) is retained. Missing operative controls leave its source-specific attribution unresolved; absence of a curated UniProt TOR sentence is not contradictory evidence. The 22409427 endothelial PAR2 result does not establish mTOR regulation in that distinct cancer-cell system.
The TOR row remains UNDECIDED. Its imported GO_REF:0000117 and ARBA00092062 identifiers remain unchanged, and the reason still distinguishes a matching rule from causal experimental support. Only the redundant method citation is removed from supported_by; the positive PMID:18612547 evidence remains. The rule is neither treated as its own biological validation nor declared false from incomplete original access.
The complete-original availability convention is unchanged. PMID:6323392 has a complete nine-page original PDF and PMID:6587384 has all four original main-page images, whereas PMID:14718574 has selected, disjoint author-rendered Methods/table excerpts without established complete-main availability. These are different access outcomes, not different meanings of the flag. Normal-cache metadata remains immutable and actual reading boundaries remain stated separately.