F10 encodes factor X, a vitamin K-dependent plasma glycoprotein synthesized in the liver and secreted as a coagulation zymogen. Proteolytic activation produces factor Xa, a serine endopeptidase that converts prothrombin to thrombin. Its gamma-carboxyglutamate-rich domain supports calcium-dependent phospholipid association and assembly with factor Va in prothrombinase. Xa also participates in coagulation initiation and amplification by cleaving factor VII and the procofactors V and VIII. Beyond coagulation, Xa can cleave protease-activated receptor 2 (PAR2/F2RL1), eliciting barrier-protective responses in an endothelial-cell model; signaling outcomes depend on cellular context. Protein C inhibitor and protein Z-dependent proteinase inhibitor regulate Xa activity. F10 variants cause factor X deficiency, a bleeding disorder of variable severity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004252 serine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Reason: The human P00742 leaf PTN002542618 lies below the positive serine-endopeptidase IBD at PTN000669108 in PTHR24278; its ungapped MSA sequence exactly matches the 488-residue source sequence. No negative assertion intervenes. P00742 in the IBD evidence is valid experimental grounding on the target, not circularity. Human factor Xa hydrolyzes peptide substrates and activates prothrombin in the inspected assays. This activity belongs to activated Xa, not constitutively to the circulating factor X zymogen. |
| GO:0004252 serine-type endopeptidase activity | IDA PMID:17469850 Lipid-bound factor Xa regulates tissue factor activity. | ACCEPT | Summary: Activated factor X is a serine endopeptidase. Reason: PMID:17469850 reports factor X activation and active Xa in its abstract, but its full Methods were not recovered. Independent original experiments establish the activity: PMID:20427285 measures hydrolysis of Xa peptide substrates by explicitly human Xa, and PMID:6323392 uses human plasma factor X activated with Russellβs viper venom and detects cleavage of protein C inhibitor. These support the enzyme activity of processed Xa, not constitutive activity of the circulating zymogen or every RefSeq product. The broad catalytic term is appropriate. |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Reason: Current ARBA00027237 condition set 0 matches the target EGF/Gla domains and PTHR24278:SF28 classification. IPR001254/IPR018114 identify the S1 protease machinery, and EC 3.4.21.6 explicitly names coagulation factor Xa and prothrombin cleavage. Human Xa substrate hydrolysis and prothrombin activation corroborate the mapping. The source family includes inactive relatives, but the target itself has positive protease evidence; activation and processing remain required. |
| GO:0004252 serine-type endopeptidase activity | IMP PMID:12574802 Impaired prothrombinase activity of factor X Gly381Asp resul... | ACCEPT | Summary: The deficiency study supports the catalytic role of activated factor X. Reason: The verified PMID:12574802 abstract reports severe familial factor X deficiency associated with Gly381Asp, normal activation but absent amidolysis and strongly impaired prothrombinase activity. The full original remains unavailable, and Gly381 is retained as the paperβs coordinate rather than silently mapped to the current precursor. Independent human Xa biochemical experiments in PMID:20427285 and PMID:6323392 establish the annotated serine endopeptidase activity. Retain the curatorβs positive functional interpretation without claiming independent inspection of the patient assay controls. |
| GO:0004252 serine-type endopeptidase activity | TAS PMID:3011603 Isolation and characterization of human blood-coagulation fa... | ACCEPT | Summary: Human factor X supplies the active Xa serine-protease chain after processing. Reason: PMID:3011603 is a human factor X cDNA source, available here only as metadata and abstract; sequence characterization is not itself a new catalytic assay. Actual human Xa substrate-hydrolysis experiments in PMID:20427285 and PMID:6323392 independently support this established catalytic function. Preserve the TAS source while distinguishing precursor sequence from the processed active enzyme. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Reason: The actual InterPro Gla, calcium-binding EGF and conserved-site mappings fit P00742. The human Des[1β44] Xa structure independently reports bound calcium in the protease domain and partial EGF1 calcium occupancy; that engineered preparation lacks the Gla domain and therefore does not measure all native Gla sites. Calcium-dependent phospholipid/prothrombinase assays support the physiological importance of this binding facet without making the ions a separate catalytic activity. |
| GO:0005515 protein binding | IPI PMID:20427285 Basis for the specificity and activation of the serpin prote... | KEEP AS NON CORE | Summary: Human Xa binds and reacts with the serpin SERPINA10/ZPI. Reason: PMID:20427285 Experimental Procedures and Tables 1β3 measure inhibition and dissociation of complexes formed by explicitly human Xa with ZPI, with protein Z, calcium and phospholipid cofactors. Figure 4 is a modeled ternary Michaelis complex; the solved crystal contains ZPI and Gla-domainless protein Z, not Xa. This is positive inhibitorβenzyme association. No current specific inhibitor-binding MF was established by the ontology searches; protease binding would reverse the demonstrated partner role, and peptidase inhibitor activity belongs to ZPI. Retain generic binding as a supported non-core facet rather than a separate autonomous activity of F10. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI supports a screened F10 interaction currently curated to NOTCH2NLC. Reason: Current IntAct IM-25472 records identify human P00742βP0DPK4 in array, validated two-hybrid and prey-pooling assays. The original HuRI PSI archive records F10 ORF 11685 with partner ORF 55237 under historical Q7Z3S9-1 and ENSP00000462298.1 labels; these are retained as a version boundary, not asserted to be sequence-identical to current NOTCH2NLC. The assay is human-protein yeast two-hybrid with GAL4 fusions, not an assay of extracellular active Xa or all natural products. GO:0005112 requires a Notch surface receptor; NOTCH2NLC is a Notch N-terminal-like regulator, so name similarity does not justify that refinement. Retain the curated positive pair as non-core without inferring a Notch-signaling function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI reports F10 binding to ubiquilin-2. Reason: Original HuRI PSI records pair F10 P00742/ORF 11685 with UBQLN2 Q9UHD9/ORF 71001 in validated two-hybrid, array and prey-pooling assays; current IntAct retains the same pair. The human proteins are tested as GAL4 fusions in yeast, with partial sequence identification recorded. This does not establish mature Xa processing, an endogenous plasma interaction, or a role for F10 in proteostasis. The current partner record describes a ubiquitin-dependent degradation shuttle; the inspected evidence does not justify protein-folding chaperone binding merely from that role. No specific ubiquilin-binding MF was found. Retain the positive generic binding assertion as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:6323392 Mechanism of inhibition of activated protein C by protein C ... | KEEP AS NON CORE | Summary: Human Xa interacts with protein C inhibitor, SERPINA5. Reason: The original PMID:6323392 Methods (pp. 188β189) use human plasma factor X activated by Russellβs viper venom and specific Xa substrate assays. Table I reports inhibition kinetics; p. 193 additionally reports Xa-dependent inhibitor cleavage and a small approximately 94-kDa complex, with those gel data not shown. The prominent 102/88-kDa complexes concern activated protein C and are not transferred to Xa. This supports the binding context. No more specific inhibitor-binding MF was established; assigning inhibitor activity to Xa or protease binding to this inhibitor partner would invert the roles. Retain the generic binding as non-core. Supporting Evidence: |
| GO:0005543 phospholipid binding | IDA PMID:17469850 Lipid-bound factor Xa regulates tissue factor activity. | ACCEPT | Summary: Factor X/Xa binds phospholipid surfaces through its membrane-associated coagulation machinery. Reason: The PMID:17469850 abstract reports resonance-energy-transfer measurements of X and Xa binding to phospholipid vesicles; its complete Methods and reagent species remain unread. Independently, PMID:20427285 tests explicitly human Xa on phosphatidylserine/phosphatidylcholine vesicles and shows the strong loss of cofactor-accelerated inhibition with Gla-domainless Xa. These original functional comparisons support phospholipid association, without relabeling the protein Z light-scattering experiment as direct Xa binding. Retain broad phospholipid binding rather than infer exclusive specificity for a single lipid species. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Reason: The P00742 target descends from the positive extracellular-region IBD at PTN000669108, with exact 488-residue target MSA and no intervening NOT. Human plasma factor X/Xa and the inspected extracellular coagulation assays independently support this conserved location. The PAINT placement is assessed from the actual ancestral path, not the number of descendants in WITH/FROM. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Reason: Current ARBA00027128 set 24 matches P00742 through IPR000294, IPR012224 and PTHR24278:SF28. The current Gla-domain/superfamily mappings and UniProt SL-0243 explicitly support extracellular region. Human plasma factor X and activated Xa provide target-specific corroboration. This is the secreted protein location; the preceding ER/Golgi processing pools are reviewed separately. |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | ACCEPT | Summary: Factor X is an extracellular plasma protein. Reason: The author-uploaded original PMID:14718574 Table II explicitly lists P00742 in the literature and 2DEMS datasets. Its Data Sources and Methods describe human serum fractionation and mass-spectrometric identification. This directly supports the source context; individual F10 peptide sequences and splice-product resolution were not inspected. Independent human plasma purification in PMID:6323392 and PMID:6587384 corroborates extracellular factor X. The location does not exclude intracellular precursor biosynthesis. |
| GO:0005576 extracellular region | TAS PMID:3011603 Isolation and characterization of human blood-coagulation fa... | ACCEPT | Summary: Mature human factor X is present in plasma. Reason: The source PMID:3011603 is a verified human cDNA study whose complete original was not recovered. Actual Methods in PMID:6587384 (p. 3701) and PMID:6323392 (p. 188) independently describe human plasma factor X purification. Retain the extracellular location, with biosynthetic processing and active Xa kept distinct from splice-product identity. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140686 | ACCEPT | Reason: The event assembles Va and Xa into membrane-associated prothrombinase. Its input Xa entity 140689 contains the human P00742 light and activated heavy chains with their own extracellular-region compartment. Thus extracellular Xa is a modeled reactant, not a location borrowed from Va or the event as a whole. The independent human prothrombinase assays retain the distinction between soluble Xa and phospholipid-associated complex. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140700 | ACCEPT | Reason: Reactome catalyst 140768 points to Xa entity 140689, whose P00742 chains themselves have extracellular-region location. Here Xa performs prothrombin cleavage; prothrombin is its substrate. Human Xa/prothrombin assays support this enzymatic setting without treating factor X activation as F10 autoprocessing. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140769 | ACCEPT | Reason: The factor VII activation event uses catalyst 140768, the extracellular Xa complex 140689 containing P00742 chains. This is a target-owned extracellular location and a modeled Xa catalytic role. The retained location does not independently validate every kinetic feature of factor VII activation or assign factor VII identity to F10. Supporting Evidence: Reactome:R-HSA-140769 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-158164 | ACCEPT | Reason: Native human factor X entity 140739 contains extracellular P00742 light chain 140687 and zymogen heavy chain 140738. In this event VIIIa:IXa activates factor X; F10 is the substrate, and Xa plus the activation peptide are products. The extracellular location is valid, while this route alone would not make F10 the enzyme performing its own activation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9015111 | ACCEPT | Reason: The inhibitor-binding model contains plasma-membrane Xa input 140649 and a product complex 9015108 that includes extracellular Xa entity 140689. The latter reaches P00742 light and activated heavy chains with their own extracellular-region compartment. This provides a literal target route as well as a membrane route; it does not establish measured translocation during inhibition. Independent human plasma Xa supports the broader extracellular location. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9668253 | ACCEPT | Reason: This disease event models enhanced factor X activation by a FIXa R384L-containing intrinsic-tenase complex. Native P00742 factor X 140739 is extracellular substrate and Xa/activation peptide are extracellular products. The variant is on FIX, not an F10 mutation; the target location remains sound without transferring the mutant mechanism to factor X. Supporting Evidence: Reactome:R-HSA-9668253 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9668365 | ACCEPT | Reason: The blocked activation event contains native human factor X 140739 as extracellular input. The defective FVIII-containing catalyst does not turn that P00742 substrate into a mutant F10 product. Retaining its own extracellular compartment neither claims successful activation nor attributes FVIII activity to F10. Supporting Evidence: Reactome:R-HSA-9668365 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9670874 | ACCEPT | Reason: The FIX-variant activation model retains native factor X 140739 as the extracellular substrate. Its P00742 chains have the requested location even though the modeled reaction fails. This is not evidence for an F10 variant or for F10 catalysis of its own activation. Supporting Evidence: Reactome:R-HSA-9670874 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9678434 | ACCEPT | Reason: The emicizumab:FIXa model has native extracellular factor X 140739 as input and Xa plus its activation peptide as outputs. Emicizumab supplies cofactor-like assistance to FIXa; F10 is cleaved in this step. The target-owned extracellular chains support the location independently of an invented F10 antibody-like role. Supporting Evidence: Reactome:R-HSA-9678434 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9769737 | ACCEPT | Reason: Extracellular Xa entity 140689 is the physical entity of catalyst 140768 in this factor V cleavage model. P00742 is therefore represented in the enzyme, not only as an event output. Its chain-owned compartment supports extracellular region; the specific factor V intermediate pathway remains a Reactome-modeled context. Supporting Evidence: Reactome:R-HSA-9769737 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822512 | ACCEPT | Reason: The TF:FVIIa:FXa complex releases extracellular Xa 140689 in this event. Its P00742 light and activated heavy chains explicitly carry extracellular-region location. The input also contains membrane-associated Xa, so the two imported locations describe separate modeled states rather than contradictory gene identities. Supporting Evidence: Reactome:R-HSA-9822512 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822513 | ACCEPT | Reason: The TF:FVII activation event includes extracellular factor X 140739 and releases the P00742 activation peptide while forming a membrane complex containing Xa. The input zymogen chains, not merely the peptide output, support extracellular region. TF:FVII performs the activating step; F10 supplies the substrate. Supporting Evidence: Reactome:R-HSA-9822513 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822514 | ACCEPT | Reason: TF:FVIIa acts on extracellular factor X 140739 and produces a TF:FVIIa:FXa membrane complex plus activation peptide. Both native substrate chains explicitly map to human P00742 and extracellular region. This location judgment does not confuse the activating protease with the resulting Xa enzyme. Supporting Evidence: Reactome:R-HSA-9822514 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9823284 | ACCEPT | Reason: Extracellular Xa 140689 is captured by the SERPINC1/heparan-sulfate inhibitory system. Its own P00742 chains support the requested compartment. F10 is the inhibited protease in this event, not the antithrombin or heparan-sulfate catalyst/cofactor; independent human Xa assays support the physiological extracellular pool. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9933742 | ACCEPT | Reason: The event combines extracellular Xa 140689 with a factor Va intermediate to form a membrane-associated complex. P00742 input chains have extracellular-region location and product chains have the membrane-associated location. The location is retained without claiming that every intermediate has the same measured efficiency as mature prothrombinase. Supporting Evidence: Reactome:R-HSA-9933742 |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: Current ARBA00028691 set 5 matches the target Gla/S1 domains and Homo taxon. Reactome independently places pro-factor X chains in the ER lumen during GGCX-dependent carboxylation and export. The human FX propeptide/GlaβGGCX fusion structure supports substrate recognition in biosynthetic processing, not factor X catalysis of carboxylation. This is genuine transient biosynthetic residence, retained outside the mature Xa functional location. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-159757 | KEEP AS NON CORE | Reason: The transport event contains ER pro-factor X 159734 with P00742 pro-light chain 159786 and heavy chain 159776 explicitly in the ER lumen. The corresponding product is Golgi pro-factor X. This is supported precursor trafficking rather than an ER-localized mature Xa reaction, so the location is retained as non-core. Supporting Evidence: Reactome:R-HSA-159757 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-159819 | KEEP AS NON CORE | Reason: GGCX acts on ER-luminal pro-factor X 159754 to generate carboxylated pro-factor X 159734; their P00742 chains have their own ER-lumen compartment. F10 is the carboxylation substrate, while GGCX performs the chemistry. The inspected human FX propeptide/Gla fusion in a GGCX preparation supports recognition but is not a natural F10 isoform or autonomous F10 enzyme. Retain this biosynthetic residence as non-core. |
| GO:0005796 Golgi lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: Current ARBA00028705 matches P00742 through sets 0 and 5, using captured domain/FunFam and primate-lineage assignments. Reactome independently places pro-factor X and processed factor X chains in the Golgi lumen during secretion-associated maturation. This location is supported but describes biosynthetic passage rather than the principal extracellular Xa reaction. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-159733 Reactome:R-HSA-159757 |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-159733 | KEEP AS NON CORE | Reason: Furin cleaves Golgi pro-factor X 159744 to factor X 159785 and propeptide 159824. P00742 pro-light/heavy and processed light/heavy chains themselves carry Golgi-lumen location; the case does not rest only on the released peptide. FURIN is the processing protease and F10 its substrate. Retain the precursor/maturation location as non-core. Supporting Evidence: Reactome:R-HSA-159733 |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-159757 | KEEP AS NON CORE | Reason: The ER-to-Golgi transport event outputs pro-factor X 159744, containing P00742 pro-light chain 159774 and heavy chain 159846 with Golgi-lumen compartment. This supports a genuine secretory-pathway pool, not a separate Golgi Xa catalytic function. It is retained as non-core consistently with the ER side of this same transport event. Supporting Evidence: Reactome:R-HSA-159757 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140664 | ACCEPT | Reason: Prothrombinase catalyst 140663 points to FVa:FXa 140662, whose Xa complex 140649 contains P00742 light chain 140631 and activated heavy chain 140642 with their own plasma-membrane compartment. Human prothrombinase assays on phosphatidylcholine/phosphatidylserine vesicles support peripheral membrane-associated Xa catalysis. No transmembrane segment or constitutive membrane insertion is inferred. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140686 | ACCEPT | Reason: The prothrombinase assembly product 140662 contains membrane-associated Xa 140649 and its P00742 chains. The plasma-membrane location describes peripheral complex association, consistent with calcium/phospholipid-dependent human Xa assays, rather than an integral membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9015111 | ACCEPT | Reason: The Xa-inhibitor binding event directly includes membrane-associated Xa 140649 as input, with P00742 chain-owned plasma-membrane compartment. Inhibition does not erase the target identity or imply a transmembrane topology. A separate output branch also contains extracellular Xa; that mixed model is not taken as measured translocation. Supporting Evidence: Reactome:R-HSA-9015111 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9015122 | ACCEPT | Reason: The inhibitor event acts on FVa:FXa 140662 and preserves the P00742 membrane-associated chains through Xa 140649. This is inhibition of the membrane-associated coagulation enzyme, not evidence that the drug or Va location was projected onto an absent target. Supporting Evidence: Reactome:R-HSA-9015122 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822512 | ACCEPT | Reason: The TF:FVIIa:FXa input 9822516 contains membrane-associated Xa 140649 before Xa is released as extracellular entity 140689. The P00742 light and activated heavy chains explicitly carry plasma-membrane location in the input state. This supports the membrane-associated pool without equating all soluble and complex-bound states. Supporting Evidence: Reactome:R-HSA-9822512 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822513 | ACCEPT | Reason: The TF:FVII:FXa product 9822515 contains membrane-associated Xa 140649 and its P00742 chains. Here TF:FVII activates substrate factor X; the resulting Xa occupies the membrane complex. The location judgment is about this product state, not a claim that F10 catalyzes the preceding activation. Supporting Evidence: Reactome:R-HSA-9822513 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822514 | ACCEPT | Reason: The TF:FVIIa:FXa product 9822516 explicitly contains P00742 Xa chains through membrane entity 140649. The substrate factor X is extracellular, and activated Xa becomes part of the membrane complex. This is a supported processed-protein location, not an alternative splice product. Supporting Evidence: Reactome:R-HSA-9822514 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822522 | ACCEPT | Reason: The FVIII activation catalyst 9822518 identifies Xa 140649 as its active unit within TF:FVIIa:FXa. Its P00742 chains themselves have plasma-membrane location. The source therefore identifies F10-derived Xa in the catalytic complex, while avoiding assignment of FVIII substrate identity or transmembrane topology to F10. Supporting Evidence: Reactome:R-HSA-9822522 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822556 | ACCEPT | Reason: TFPIΞ² inhibits the TF:FVIIa:FXa complex containing membrane-associated P00742 Xa 140649. The target chains have the requested own compartment; this is not an inference from TFPIΞ² localization alone. Retain the location while distinguishing the inhibited protease from its inhibitor. Supporting Evidence: Reactome:R-HSA-9822556 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9929060 | ACCEPT | Reason: The TF:FVII:FXa input and TF:FVIIa:FXa output both contain membrane-associated P00742 Xa 140649; the modeled Xa catalyst is separately identified as 9933746. The target-owned location supports this membrane-bound enzymatic pool, without inferring that factor VII and factor X are the same protein. Supporting Evidence: Reactome:R-HSA-9929060 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9931624 | ACCEPT | Reason: The TFPIΞ±:factor V intermediate:PROS1 inhibitory assembly engages TF:FVIIa:FXa containing native P00742 Xa chains with plasma-membrane compartment. This is the location of the inhibited target enzyme, not a transferred PROS1 or inhibitor function. Supporting Evidence: Reactome:R-HSA-9931624 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9932951 | ACCEPT | Reason: The SERPINA10:PROZ inhibition model includes FVa:FXa 140662, reaching membrane Xa 140649 and P00742 chain entities 140631/140642. The target is the inhibited protease. The source does not assign PROZ cofactor or SERPINA10 inhibitor activity to F10. Supporting Evidence: Reactome:R-HSA-9932951 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9933742 | ACCEPT | Reason: The factor Va-intermediate:Xa product 9930788 contains membrane-associated Xa 140649 with P00742 chain-owned plasma-membrane location. This supports a processed Xa complex state, while the exact activity of that intermediate is distinct from mature prothrombinase assays. Supporting Evidence: Reactome:R-HSA-9933742 |
| GO:0006508 proteolysis | IBA GO_REF:0000033 | MODIFY | Summary: Refine proteolysis to activation-related protein processing across the supported substrate classes. Reason: The verified PAINT target path and positive ancestral proteolysis assertion remain valid; target self-WITH is legitimate experimental grounding. GO:0016485 describes maturation by peptide-bond cleavage and is a strict descendant of proteolysis. Unlike the narrower inactive-enzyme term GO:0031638, it accommodates the documented activation substrates beyond zymogens: human Xa converts prothrombin to thrombin and cleaves the PAR2 reporter associated with endothelial barrier protection in PMID:22409427; curated target-specific reactions also assign Xa cleavage of factor VII and maturation of factor V/VIII procofactors. Xa performs these cleavages rather than merely being processed itself. The source-defined factor V intermediate remains an intermediate, and factor VIII-inactivating cleavage at other sites is not reclassified as maturation. Use the single inclusive processing term without also adding its zymogen-activation child. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN009089245 SUPPORTS TRANSFER The broad source assignment is supported; the target experiments permit a more specific performed-step term. Proposed replacements: protein processing Supporting Evidence: GO_REF:0000033 Reactome:R-HSA-140769 Reactome:R-HSA-9769737 Reactome:R-HSA-9822522 |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Refine proteolysis to activation-related protein processing across the supported substrate classes. Reason: The InterPro S1-protease domain and active-site mappings remain valid, but the target evidence supports a more specific processing role. GO:0016485 describes maturation by peptide-bond cleavage and is a strict descendant of proteolysis. Unlike the narrower inactive-enzyme term GO:0031638, it accommodates the documented activation substrates beyond zymogens: human Xa converts prothrombin to thrombin and cleaves the PAR2 reporter associated with endothelial barrier protection in PMID:22409427; curated target-specific reactions also assign Xa cleavage of factor VII and maturation of factor V/VIII procofactors. Xa performs these cleavages rather than merely being processed itself. The source-defined factor V intermediate remains an intermediate, and factor VIII-inactivating cleavage at other sites is not reclassified as maturation. Use the single inclusive processing term without also adding its zymogen-activation child. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR001254 SUPPORTS TRANSFER The broad source assignment is supported; the target experiments permit a more specific performed-step term. InterPro:IPR018114 SUPPORTS TRANSFER The broad source assignment is supported; the target experiments permit a more specific performed-step term. Proposed replacements: protein processing Supporting Evidence: GO_REF:0000002 Reactome:R-HSA-140769 Reactome:R-HSA-9769737 Reactome:R-HSA-9822522 |
| GO:0007596 blood coagulation | IC PMID:17469850 Lipid-bound factor Xa regulates tissue factor activity. | ACCEPT | Summary: Activated factor X executes a proteolytic step in blood coagulation. Reason: The imported IC from serine endopeptidase activity is biologically supported by Xaβs coagulation role, not by protease activity alone. PMID:22409427 independently measures prothrombin activation by Xa with human factor Va and human prothrombin on calcium-containing PC/PS vesicles, reading generated thrombin with S2238 (Prothrombin activation Methods; Figure 1). This supplies an executed coagulation step. The zymogenβs activation by upstream proteases is a separate substrate role; the present conclusion concerns the catalytic Xa product. PMID:17469850 itself remains abstract-only in this review. |
| GO:0007596 blood coagulation | IEA GO_REF:0000002 | ACCEPT | Reason: IPR012224 identifies the vitamin-K-dependent coagulation-protein family and maps to blood coagulation. The family label alone would not establish enzymatic activity for every member, but human Xa directly activates prothrombin in a factor Va/calcium/phospholipid system. Thus F10-derived Xa performs a coagulation step rather than merely being necessary as an uncleaved precursor. |
| GO:0007596 blood coagulation | TAS PMID:6587384 Characterization of a cDNA coding for human factor X. | ACCEPT | Summary: Factor Xa contributes directly to thrombin generation in coagulation. Reason: The full scanned PMID:6587384 original identifies human liver cDNA and plasma factor X, while its description of coagulation chemistry is background rather than a newly performed thrombin-generation experiment. Independent PMID:22409427 provides the measured XaβVa prothrombinase step with human coagulation reagents and phospholipid vesicles. Retain the broad TAS blood-coagulation assertion without equating the precursorβs processing with an autonomous activation reaction or claiming a clot endpoint from the cDNA study. |
| GO:0009897 external side of plasma membrane | IC PMID:17469850 Lipid-bound factor Xa regulates tissue factor activity. | ACCEPT | Summary: Xa can associate peripherally with the extracellular face of the plasma membrane. Reason: GO:0009897 includes proteins peripherally associated with the extracellular leaflet; it does not require an integral membrane segment. The imported inference from phospholipid binding is consistent with extracellular plasma factor X/Xa and the lipid-associated Xa reactions supported by PMID:20427285 and PMID:22409427. The inspected assays use synthetic phospholipid vesicles and, separately, extracellular Xa acting on a cell-surface PAR-2 reporter; they are not presented as direct intact-cell Xa localization microscopy. Retain the established physiological membrane context while distinguishing it from soluble plasma and intracellular biosynthetic locations. |
| GO:0030335 positive regulation of cell migration | TAS PMID:18612547 Formation of tissue factor-factor VIIa-factor Xa complex ind... | UNDECIDED | Summary: The reported breast-cancer migration effect requires source-level assay verification. Reason: The PMID:18612547 abstract positively reports enhanced migration after TFβFVIIaβXa complex formation in human Adr-MCF-7 cells and reduced migration with rapamycin. Full Methods, Xa reagent identity and the experiments separating active Xaβs contribution from other complex components were not recovered. The abstract presents PAR1/2 mediation as probable. These access limits prevent a firm source-specific judgment about the F10 contribution; they do not contradict the reported phenotype or establish that Xa cannot regulate migration. Supporting Evidence: |
| GO:0032008 positive regulation of TOR signaling | IDA PMID:18612547 Formation of tissue factor-factor VIIa-factor Xa complex ind... | UNDECIDED | Summary: The positive mTOR response is reported, but the Xa-specific causal assay remains unread. Reason: PMID:18612547 reports mTOR and p70 S6 kinase phosphorylation after TFβFVIIaβXa complex formation in Adr-MCF-7 cells. The complete original and controls defining Xaβs active contribution remain unavailable after bounded publisher and repository searches. Retain an undecided judgment for this direct source rather than infer a kinase activity for F10, universal mTOR regulation, or absence of the reported response. Independent endothelial PAR-2 cleavage experiments do not by themselves resolve this breast-cancer mTOR context. Supporting Evidence: |
| GO:0032008 positive regulation of TOR signaling | IEA GO_REF:0000117 | UNDECIDED | Reason: ARBA00092062 matches P00742 through FunFam condition set 3 and the primate taxon. This establishes the rule provenance, not an independent experiment demonstrating TOR regulation. PMID:18612547 positively reports TFβFVIIaβXa-associated mTOR/p70S6K phosphorylation and rapamycin-sensitive migration in Adr-MCF-7 cells. Its complete operative Methods/Results remain unavailable, leaving active-Xa requirement, reagent preparation and attribution within the signaling assembly unresolved. The abstract describes PAR1/2 mediation as probable. Retain UNDECIDED rather than discard this positive report or infer a false propagated claim from the absence of a UniProt TOR sentence. Neither rule matching nor the abstract resolves the missing causal controls. Supporting Evidence: |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which independently verified natural F10 transcripts produce secreted, correctly processed proteins, and how do their calcium binding, phospholipid association and prothrombin-cleaving activities differ?
Q: In which cellular settings does active factor Xa itself drive migration or TOR signaling, and how can that contribution be distinguished from other components of the tissue-factorβVIIa complex and from receptor-specific cleavage effects?
Experiment: Express sequence-verified F10 transcript products in a matched system and identify the secreted chains, activation sites and gamma-carboxylation state by protein analysis. Compare zymogen and experimentally activated preparations for calcium/phospholipid binding and prothrombin activation with controlled factor Va, calcium and lipid concentrations; normalize to active enzyme concentration.
Experiment: Compare purified factor X, active Xa and catalytically inactive Xa in defined cell systems while independently controlling tissue factor and VIIa. Combine receptor-specific perturbations with direct receptor-cleavage measurements, TOR-pathway readouts and migration assays to separate Xa proteolysis from parallel signaling by the other complex components.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)