Factor V is a secreted coagulation procofactor present in plasma and platelet alpha granules. Proteolytic activation produces factor Va, whose associated heavy and light chains bind factor Xa on negatively charged membrane surfaces and greatly enhance prothrombin conversion to thrombin. Factor Xa supplies the protease activity; Va supplies the cofactor activity that supports fibrin-clot formation. Activated protein C limits this activity by cleaving Va, and impaired inactivation of the Leiden variant prolongs thrombin generation. Factor V also has state-dependent anticoagulant activity: FV-short and protein S cooperate to enhance TFPIalpha-mediated inhibition of Xa, whereas intact factor V is less efficient and thrombin activation of FV-short removes this cofactor effect. FV-short is a splice-derived form, distinct from proteolytic FV intermediates and the heavy and light chains of Va. Factor V deficiency causes a bleeding disorder, while resistance to activated protein C can predispose to thrombosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005507 copper ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain measured copper binding as a supporting biochemical property. Reason: The actual IPR011707-to-GO mapping includes copper ion binding, but family membership alone is not decisive: its general description even excludes FV/FVIII from copper binding. The original human-plasma FV preparation in PMID:6490642 contained approximately one copper ion per protein by atomic absorption and emission spectroscopy after extensive dialysis, alongside bovine preparations and buffer/prothrombin controls. Retain this positive property without inferring oxidase activity or a demonstrated requirement for copper in FV cofactor function; the paper leaves its functional role unresolved. The preserved UniProt P12259 record also lists Cu-cation binding at displayed residues 1843 and 1845 and a copper keyword. Those two site assertions carry ECO:0000250 and are homology-based corroboration, not target-residue measurements from the human copper assay. |
| GO:0005515 protein binding | IPI PMID:2844223 Inactivation of human plasma kallikrein and factor XIa by pr... | UNDECIDED | Summary: The imported F5βSERPINA5 interaction could not be verified from the inaccessible original. Reason: PMID:2844223 reports inhibition and complexes of plasma kallikrein, factor XIa and activated protein C with protein C inhibitor in its verified abstract. The complete article was not recovered, so the abstract does not establish whether F5 was also tested. The UniProt F5 inhibition/heterodimer statements and the imported P05154 partner are preserved as source assertions, not treated as independent experimental confirmation. Neither a negative F5βPCI interaction result nor a replacement serpin-binding or heterodimerization function is inferred. This context remains unresolved pending the original target assay or clarification of its source mapping. UniProt specifically designates PMID:15140131 for activity regulation and heterodimer formation with SERPINA5. Its recovered publisher-indexed Methods and Results identify human APC, human PCI in transgenic-mouse plasma, APCβPCI immunoassay and residual APC activity; complete main text remains unavailable. Those positive experiments neither verify an F5βPCI interaction nor exclude an uninspected target assay. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain positive F5βOLR1 cellular co-association without assigning a receptor-ligand role. Reason: The author-labeled BioPlex 2.0 293T directed-edge table records OLR1 (GeneID 4973) as bait and F5 (GeneID 2153) as prey. Online Experimental Methods describe human ORFeome constructs with C-terminal HA-FLAG tags and anti-HA AP-MS. This supports the imported cellular association. GO:0005124 was considered, but its signaling-receptor-binding parent adds a receptor-ligand interpretation that this co-isolation alone does not establish. This is not a requirement that every binding paper measure downstream signaling: the unresolved point is whether F5 itself occupies that functional receptor-binding role rather than associating indirectly. Retain generic binding as non-core under the campaign supported-binding exception. No purified binary interface, uptake, plasma interaction, exact historical insert or processed F5 species is established. The explicitly labeled 2.0 directed table, not a generic v2 filename, identifies the assay direction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain positive F5βOLR1 cellular co-association without assigning a receptor-ligand role. Reason: The BioPlex 3.0 293T network contains P78380/OLR1 and P12259/F5 (pInt 0.99998471197731); the separate author directed-edge table identifies OLR1 bait and F5 prey. Direction is not inferred from network A/B ordering. The human ORFeome/OC, C-terminal FLAG-HA, anti-HA AP-MS experiment supports association, but not an established F5 receptor-ligand role for GO:0005124 or its GO:0005102 parent. Generic binding is retained as non-core under the campaign supported-binding exception. Binary contact, receptor response, physiological plasma binding and processing-state identity remain unresolved. The two BioPlex publications are related releases, not independent reconstitutions. Absence from inspected HCT116 files is not negative binding evidence or cell-line exclusivity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:6323392 Mechanism of inhibition of activated protein C by protein C ... | UNDECIDED | Summary: The complete cited article does not resolve the imported F5βSERPINA5 binding assertion. Reason: The complete PMID:6323392 original, pages 187β195, was read. Its Methods purify human protein C, PCI and proteases, and its Results demonstrate APCβPCI complexes and inhibition of thrombin, Xa, trypsin and chymotrypsin. F5 is mentioned as an APC substrate/cofactor in the background; an F5βPCI binding assay was not found in the executed experiments. This creates a source-specific citation question, not evidence that F5 cannot bind PCI. The sourceβs P05154 partner and UniProt heterodimer/inhibition assertions are retained pending clarification; no serpin-binding or heterodimerization refinement is made from those assertions alone. UniProt specifically designates PMID:15140131 for activity regulation and heterodimer formation with SERPINA5. Its recovered publisher-indexed Methods and Results identify human APC, human PCI in transgenic-mouse plasma, APCβPCI immunoassay and residual APC activity; complete main text remains unavailable. Those positive experiments neither verify an F5βPCI interaction nor exclude an uninspected target assay. |
| GO:0005515 protein binding | IPI PMID:9556620 Protein C inhibitor secreted from activated platelets effici... | UNDECIDED | Summary: The recovered original distinguishes F5 platelet localization from the APCβPCI interaction being measured. Reason: In PMID:9556620, Preparation of Proteins and Immunoelectron Microscopic Analysis identify human PCI/protein C reagents and anti-F5 used as a localization control. Results report F5 labeling in platelet alpha granules and on activated platelet membranes/canalicular structures, with the latter data not shown. The complex-formation and inhibition experiments instead measure APC with PCI. These positive F5 location observations are retained, but colocalization does not establish an F5βPCI heterodimer. Only selected original author-upload passages were recovered, so the imported P05154 interaction remains unresolved rather than being rejected or refined solely from the UniProt claim. UniProt specifically designates PMID:15140131 for activity regulation and heterodimer formation with SERPINA5. Its recovered publisher-indexed Methods and Results identify human APC, human PCI in transgenic-mouse plasma, APCβPCI immunoassay and residual APC activity; complete main text remains unavailable. Those positive experiments neither verify an F5βPCI interaction nor exclude an uninspected target assay. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the conserved extracellular functional pool. Reason: The exact human P12259/PTN002554984 sequence lies below extracellular-region IBD PTN009099846 in the actual PANTHER v19 PTHR24543 tree; the aligned 2224 residues match the displayed protein and there is no target-path NOT. This broad ancestral location is compatible with the more distant secreted donors, including RS1/O15537, without transferring their distinct activities. Native human plasma FV and extracellular FVa cofactor assays independently support the location. Current PTHR46806 and the v19 PTHR24543 placement are retained as different source versions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN009099846 SUPPORTS TRANSFER Actual target ancestry and positive IBD were inspected; donor count and self-WITH are not treated as weaknesses. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Retain secretion supported by the combined source record. Reason: The captured multi-source assertion includes official Secreted/SL-0243, which maps to extracellular region, and verified mouse F5/O88783 and rat F5/A0A0G2K3W2 orthologs. Current ARBA00027128 conditions do not reproduce a match to the current P12259 cross-references, so that historical rule assignment is not claimed as a current successful rule match. The independent subcellular mapping, actual human plasma FV preparation and modeled native extracellular entities support the location despite that version boundary. |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | ACCEPT | Summary: F5 is positively identified in the human circulating plasma/serum protein compilation. Reason: PMID:14718574 Table II identifies P12259 as coagulation factor V, with presence in the literature, LCMS1 and LCMS2 sources and no entry in 2DEMS. The recovered Data Sources and Methods describe the human serum/plasma datasets and sequence-based consolidation. This target-specific positive record supports extracellular region, consistent with the circulating cofactor pool; it does not resolve intact precursor versus active chains or every locus transcript. Selected original Methods and table text were accessible, but the entire original was not recovered and no table pixels were inspected. Supporting Evidence: |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140686 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-140686 participant graph establishes this location: 140692 contains P12259 light chain 140690 (1574β2224) and heavy chain 140691 (29β737), each with its own extracellular compartment. The membrane-associated output is distinguished from these soluble input components. FVa is the FXa cofactor in prothrombinase, not its proteolytic subunit. Supporting Evidence: Reactome:R-HSA-140686 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140696 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-140696 participant graph establishes this location: Input 140697 is native P12259 29β2224 in extracellular region; extracellular outputs include the processed heavy/light chains and activation-peptide material. Thrombin performs the cleavage of the F5 procofactor; the location does not assign self-proteolysis to F5. Supporting Evidence: Reactome:R-HSA-140696 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-141026 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-141026 participant graph establishes this location: The target branches include extracellular P12259 cleavage products 5605103 (535β737) and 5605104 (29β534), together with light chain 140690. APC is the catalyst and FVa its substrate; these processed fragments do not define new splice products. Supporting Evidence: Reactome:R-HSA-141026 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-481007 participant graph establishes this location: The input granule-content set contains P12259 entity 141766, whereas output 481033 contains extracellular P12259 140697 (29β2224). This is secretion of platelet cargo, not evidence that F5 executes vesicle exocytosis. Supporting Evidence: Reactome:R-HSA-481007 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5591040 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-5591040 participant graph establishes this location: The current APC-inactivation route contains extracellular P12259 products 5605101 (29β334), 5605102 (335β534) and light chain 140690. APC performs the cleavage; target product compartments, rather than the catalyst compartment, establish the location. Supporting Evidence: Reactome:R-HSA-5591040 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9769737 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9769737 participant graph establishes this location: Input 140697 is extracellular P12259 29β2224; the output includes 9930787 (738β1046), heavy chain 140691 and 9930782 (1047β2224). FXa is the catalyst and the F5 intermediate is a processed cofactor, not an alternative transcript. Supporting Evidence: Reactome:R-HSA-9769737 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9930440 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9930440 participant graph establishes this location: The actual target route contains APC-resistant I387T and R334T variants, including modified P12259 entities 9930487 and 9930471 in extracellular region. These disease-model entities are not silently relabeled wild type. Independent native extracellular FV evidence supports the same location for the gene product, without transferring resistance to normal FV. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9930452 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9930452 participant graph establishes this location: The actual target set contains the A540V and R534Q heavy-chain variants 9930406 and 9930427, each P12259 29β737 with an explicit extracellular compartment. The disease-model scope is retained. Native human plasma FV independently supports extracellular location; APC resistance is not generalized to wild type. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9930790 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9930790 participant graph establishes this location: The thrombin-processing route contains extracellular native P12259 140697 and products 9930787, 9930782 and 140691. The source models partial F5 activation by another protease, not intrinsic F5 enzyme activity. Supporting Evidence: Reactome:R-HSA-9930790 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9930792 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9930792 participant graph establishes this location: The input intermediate 9930795 contains extracellular heavy chain 140691 and P12259 1047β2224 entity 9930782; outputs include 9933750 (1047β1573) and the extracellular mature chains. Thrombin performs the final processing step; the released fragment and assembled cofactor retain separate identities. Supporting Evidence: Reactome:R-HSA-9930792 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9931624 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9931624 participant graph establishes this location: The inhibitory-complex route 9931650β9931610β9930795 reaches P12259 intermediate chains 140691 and 9930782 with their own extracellular compartments. F5 is a cofactor-containing component of the TFPIΞ±/PROS1 assembly; TFPIΞ± supplies protease inhibition. The explicitly modeled processed intermediate is not equated with FV-short splicing. Supporting Evidence: Reactome:R-HSA-9931624 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9931628 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9931628 participant graph establishes this location: The plasma assembly 9931610 contains intermediate 9930795 and its native P12259 chains 140691/9930782, explicitly extracellular. The event concerns TFPIΞ±, PROS1 and a proteolytic F5 intermediate. Mention of FV-short in the source narrative does not create an alternative-product object or establish equivalence to that intermediate. Supporting Evidence: Reactome:R-HSA-9931628 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9933742 | ACCEPT | Summary: Retain the target-specific extracellular location. Reason: The inspected Reactome R-HSA-9933742 participant graph establishes this location: The soluble input intermediate includes extracellular P12259 chains 140691 and 9930782; the output carries their membrane-associated counterparts. Retain the extracellular pool while treating membrane recruitment as a separate context of cofactor assembly. Supporting Evidence: Reactome:R-HSA-9933742 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-203973 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 203973 input 5694337β5694339β5694523β5694244 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; SAR1 drives budding. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-203973 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-204008 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 204008 coat-recruitment complexes through 5694523β5694244 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; SEC13/SEC31 and associated factors form the coat. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-204008 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5694417 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 5694417 SEC16-associated complex through 5694523β5694244 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; SEC16/TFG organize the exit site. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-5694417 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5694431 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 5694431 output 5694243β5694189 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; LMAN1:MCFD2 is the cargo receptor. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-5694431 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5694522 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 5694522 inner-coat/cargo assembly through 5694244 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; SAR1 and SEC23/SEC24 perform coat assembly. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-5694522 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5694527 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during biosynthetic transport. Reason: The actual Reactome route 5694527 cargo-receptor complex through 5694244 reaches human P12259 entity 5689447 (29β2224), whose own compartment is ER lumen. FV is soluble glycosylated cargo associated with its receptor; SAR1 supplies GTPase activity. This is a valid transit pool, retained as non-core rather than converted into a transport or GTPase function of F5. Supporting Evidence: Reactome:R-HSA-5694527 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Retain the modeled ER-lumen substrate pool. Reason: Reactome R-HSA-8952289 reaches native P12259 5689447 through substrate set 8956956 and phosphorylated P12259 8956960 through product set 8956996; both target entities have their own ER-lumen compartment. FAM20C performs phosphorylation, while F5 is the secretory substrate. Retain this biosynthetic context as non-core. The inspected general FAM20C Methods/Results do not independently establish an F5-specific intracellular imaging assay or kinase activity of F5. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140664 | MODIFY | Summary: Specify the peripheral external face of the plasma membrane. Reason: The actual Reactome route 140664 catalyst 140663β140662β140661 reaches P12259 heavy/light entities 140653 (29β737) and 140660 (1574β2224), explicitly assigned to plasma membrane. In this reaction FVa supports FXa-mediated prothrombin cleavage; it is not the serine protease. The target-owned Reactome compartment models a native human processed-F5 surface pool. PMID:9556620 independently reports F5 on activated human platelet membranes/canalicular surfaces, explicitly as data not shown; PMID:9252393 tests human FV-containing prothrombinase on synthetic PC/PS membranes. The native-cell context and modeled extracellular reaction support the external face, whose definition includes peripheral proteins. The vesicle assay alone is not localization microscopy. These native/processed-cofactor sources differ from the engineered FV-short/QQ synthetic-lipid experiments used for the anticoagulant core, to which no native-cell location is assigned. No membrane insertion or cytoplasmic-face pool is inferred. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140686 | MODIFY | Summary: Specify the peripheral external face of the plasma membrane. Reason: The actual Reactome route 140686 output 140662β140661 reaches P12259 heavy/light entities 140653 (29β737) and 140660 (1574β2224), explicitly assigned to plasma membrane. In this reaction FVa is recruited with FXa to the phospholipid surface. The target-owned Reactome compartment models a native human processed-F5 surface pool. PMID:9556620 independently reports F5 on activated human platelet membranes/canalicular surfaces, explicitly as data not shown; PMID:9252393 tests human FV-containing prothrombinase on synthetic PC/PS membranes. The native-cell context and modeled extracellular reaction support the external face, whose definition includes peripheral proteins. The vesicle assay alone is not localization microscopy. These native/processed-cofactor sources differ from the engineered FV-short/QQ synthetic-lipid experiments used for the anticoagulant core, to which no native-cell location is assigned. No membrane insertion or cytoplasmic-face pool is inferred. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9015122 | MODIFY | Summary: Specify the peripheral external face of the plasma membrane. Reason: The actual Reactome route 9015122 inhibitor-associated prothrombinaseβ140662β140661 reaches P12259 heavy/light entities 140653 (29β737) and 140660 (1574β2224), explicitly assigned to plasma membrane. In this reaction the drugs inhibit FXa, not an F5 protease active site. The target-owned Reactome compartment models a native human processed-F5 surface pool. PMID:9556620 independently reports F5 on activated human platelet membranes/canalicular surfaces, explicitly as data not shown; PMID:9252393 tests human FV-containing prothrombinase on synthetic PC/PS membranes. The native-cell context and modeled extracellular reaction support the external face, whose definition includes peripheral proteins. The vesicle assay alone is not localization microscopy. These native/processed-cofactor sources differ from the engineered FV-short/QQ synthetic-lipid experiments used for the anticoagulant core, to which no native-cell location is assigned. No membrane insertion or cytoplasmic-face pool is inferred. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9932951 | MODIFY | Summary: Specify the peripheral external face of the plasma membrane. Reason: The actual Reactome route 9932951 SERPINA10:PROZ-associated prothrombinaseβ140662β140661 reaches P12259 heavy/light entities 140653 (29β737) and 140660 (1574β2224), explicitly assigned to plasma membrane. In this reaction SERPINA10 traps FXa; FVa remains a cofactor component. The target-owned Reactome compartment models a native human processed-F5 surface pool. PMID:9556620 independently reports F5 on activated human platelet membranes/canalicular surfaces, explicitly as data not shown; PMID:9252393 tests human FV-containing prothrombinase on synthetic PC/PS membranes. The native-cell context and modeled extracellular reaction support the external face, whose definition includes peripheral proteins. The vesicle assay alone is not localization microscopy. These native/processed-cofactor sources differ from the engineered FV-short/QQ synthetic-lipid experiments used for the anticoagulant core, to which no native-cell location is assigned. No membrane insertion or cytoplasmic-face pool is inferred. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9933742 | MODIFY | Summary: Specify the peripheral external face of the plasma membrane. Reason: The actual Reactome route 9933742 output 9930788β9930784 reaches P12259 entities 140653 (29β737) and 9930793 (1047β2224), explicitly assigned to plasma membrane. In this reaction the partially processed F5 cofactor associates with FXa without being equated with fully processed FVa. The target-owned Reactome compartment models a native human processed-F5 surface pool. PMID:9556620 independently reports F5 on activated human platelet membranes/canalicular surfaces, explicitly as data not shown; PMID:9252393 tests human FV-containing prothrombinase on synthetic PC/PS membranes. The native-cell context and modeled extracellular reaction support the external face, whose definition includes peripheral proteins. The vesicle assay alone is not localization microscopy. These native/processed-cofactor sources differ from the engineered FV-short/QQ synthetic-lipid experiments used for the anticoagulant core, to which no native-cell location is assigned. No membrane insertion or cytoplasmic-face pool is inferred. Proposed replacements: external side of plasma membrane |
| GO:0007596 blood coagulation | IBA GO_REF:0000033 | MODIFY | Summary: Specify participation in fibrin clot formation. Reason: Human P12259/PTN002554984 descends from the actual coagulation IBD at PTN002815661 in v19 PTHR24543, supported by mouse F5 and zebrafish f5. The inherited coagulation role is valid. Native human FV in PMID:9252393 supplies the cofactor activity for FXa-dependent prothrombin activation, giving a concrete step in fibrin clot formation. The actual mouse platelet experiments and zebrafish plasma/vascular assays corroborate this conserved role; they do not make F5 a protease. Refine the broad process to the clot-formation term rather than question the IBD placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002815661 SUPPORTS TRANSFER Positive GO:0007596 IBD and exact target path verified; more specific target-supported process refinement, not a propagation failure. Proposed replacements: blood coagulation, fibrin clot formation |
| GO:0007596 blood coagulation | TAS PMID:9252393 Increased tissue factor-initiated prothrombin activation as ... | MODIFY | Summary: Human factor V supplies prothrombinase cofactor work in the fibrin-clot-forming coagulation cascade. Reason: The complete PMID:9252393 article was recovered. Materials and Methods (p.20722) compare F5 purified from normal human plasma with Leiden F5 from homozygous patients in a reconstituted TF-initiated human coagulation system on phospholipid vesicles. Results and Figure 1 (p.20723) show thrombin generation and altered APC-mediated control; immunoblot analyses track activation/inactivation of the F5 cofactor. F5 contributes cofactor activity to Xa-mediated prothrombin conversion, rather than acting as the protease or merely being an activation substrate. GO:0072378 is the current more-specific blood-coagulation descendant covering this protein-activation cascade and its regulation; it does not mean F5 polymerizes fibrin itself. Normal and disease preparations remain distinct, and the purified-system readout is not represented as an in-vivo clotting experiment. Proposed replacements: blood coagulation, fibrin clot formation Supporting Evidence: |
| GO:0008015 blood circulation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the broad circulation phenotype as non-core. Reason: The actual GO:0008015 IBD at PTN002815661 lies on the verified human target path and cites mouse F5/MGI:88382. Current donor assertions trace to mouse knockout/low-plasma-FV rescue papers PMID:8900278 and PMID:10669158. Their accessible abstracts positively report embryonic vascular/perinatal bleeding and rescue contexts; complete Methods were unavailable. Retain the curated conserved association as a broader physiological consequence of hemostasis, without inventing blood-pumping activity or dismissing the annotation from abstract-only access. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002815661 SUPPORTS TRANSFER Positive circulation IBD is inherited; donor original access is abstract-only and the process is retained contextually. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The original NK-cell membrane-proteomics target record remains unavailable. Reason: PMID:19946888 describes membrane fractions of the human NK-like YTS cell line in its verified abstract, including extraction of peripheral proteins and MS identification. The original target table/peptides for F5 were not recovered; the saved publisher supplement request failed and the inspected Figshare search returned no record. Independent evidence that F5 can associate with platelet surfaces does not verify this particular NK-cell screen. Preserve the imported membrane assertion and HDA source without inferring an integral membrane topology, declaring contamination, or rejecting it from abstract absence. The broad membrane term is less precise than the established platelet-associated pool, but TOO_GENERAL would not resolve whether the unavailable NK-cell target identification supports this distinct source context. UNDECIDED therefore remains the source-specific decision; no more specific NK-cell location is asserted. Supporting Evidence: |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain COPII-vesicle cargo localization as non-core. Reason: Current ARBA00027486 condition set 5 matches the two actual P12259 FunFam cross-references and Haplorrhini. Those FunFam names mention factor VIII, but target membership was checked directly rather than inferred from the name. The independent Reactome route contains P12259 5689792 in a COPII-coated vesicle. FV is transported cargo, not a coat component or transport catalyst. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-203973 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-203973 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 203973 output 5694329β5694272β5694271 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here budding releases cargo-containing vesicles. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-203973 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-5694409 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 5694409 RAB1-exchange complexes through 5694330β5694329 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here TRAPPC supplies RAB1 exchange activity. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-5694409 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-5694418 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 5694418 output 5694332β5694330 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here RAB1/USO1 and Golgi factors mediate docking. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-5694418 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-5694439 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 5694439 output 5694334β5694329 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here coat-associated TRAPPC/RAB1 machinery mediates tethering. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-5694439 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-5694441 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 5694441 output 5694326β5694272 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here CSNK1D phosphorylates SEC23. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-5694441 |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | TAS Reactome:R-HSA-5694446 | KEEP AS NON CORE | Summary: Retain the modeled COPII cargo pool. Reason: The actual Reactome route 5694446 input 5694326β5694272 reaches glycosylated FV/FVIII set 5694193 and its F5 member 5689792 (P12259 29β2224), whose own compartment is COPII-coated ER-to-Golgi transport vesicle. Here SNAREs supply the fusion machinery. Keep this transit localization as non-core; FV is cargo and is not assigned the reaction machineryβs molecular activity. Supporting Evidence: Reactome:R-HSA-5694446 |
| GO:0031091 platelet alpha granule | IBA GO_REF:0000033 | MODIFY | Summary: Specify the platelet alpha-granule lumen. Reason: The actual positive alpha-granule IBD at PTN002815661 lies on the exact human P12259 target path and is grounded in mouse F5/MGI:88382. PMID:12816857 establishes the mouse platelet pool by transplant, functional activity and immunoblot experiments; it does not prove identical human biosynthetic origin. Independently, human PMID:9556620 quantifies intragranular F5 immunogold, and Reactome entity 141766 explicitly places native P12259 in alpha-granule lumen. Refine the retained location to that interior compartment without asserting F5 is a granule membrane component. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002815661 SUPPORTS TRANSFER Valid positive GO:0031091 IBD; the finer target-supported lumen location is not a node-placement objection. Proposed replacements: platelet alpha granule lumen |
| GO:0031091 platelet alpha granule | IEA GO_REF:0000107 | MODIFY | Summary: Specify the platelet alpha-granule lumen. Reason: The literal ENSMUSP00000083204 donor is mouse F5/O88783. Its GO:0031091 IDA traces to PMID:12816857, whose actually read transplant, gel-filtered platelet, clotting and immunoblot experiments support mouse platelet FV. Human granule immunogold in PMID:9556620 and the explicit P12259 lumen entity 141766 independently support refinement to platelet alpha-granule lumen. Human uptake and mouse synthesis are not equated. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O88783 SUPPORTS TRANSFER Actual mouse F5 identity and experimental source verified; finer human compartment supported independently. Proposed replacements: platelet alpha granule lumen |
| GO:0031093 platelet alpha granule lumen | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the target-supported granule-lumen prediction. Reason: ARBA00084788 condition set 3 matches both captured P12259 FunFam memberships and Haplorrhini. The ruleβs predicted lumen location is independently supported by human F5 intragranular immunogold in PMID:9556620 and native P12259 141766 in Reactomeβs alpha-granule lumen. No protease-inhibitor activity or biosynthetic route is inferred from that location. |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: Retain native F5 in platelet alpha-granule lumen. Reason: In Reactome R-HSA-481007 the input content set 481003 has member 141766, explicitly human P12259 29β2224 with its own GO:0031093 compartment. The output is extracellular P12259 140697. Human immunogold measurements in PMID:9556620 independently support intragranular F5. This is storage/release of a clotting cofactor, not F5-catalyzed exocytosis. |
| GO:0032571 response to vitamin K | IEA GO_REF:0000107 | UNDECIDED | Summary: Leave the conserved vitamin-K response unresolved. Reason: The actual ENSRNOP00000072800 donor is rat F5/A0A0G2K3W2; its positive response-to-vitamin-K IEP cites PMID:658784. The original publisher abstract reports modest FV reductions after warfarin or biliary fistula and restoration after vitamin K1. This is compatible with the current broad response definition, but full Methods/Results and the basis for transfer to human F5 were not available. Do not recast it as vitamin-K-dependent F5 gamma-carboxylation, nor remove the positive rat observation merely because F5 is not a conventional vitamin-K-dependent coagulation factor. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:A0A0G2K3W2 UNRESOLVED Rat F5 identity and IEP/PMID:658784 are verified; full donor experiment and target conservation remain unresolved. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the modeled ERGIC association as non-core transit. Reason: Current ARBA00092682 condition set 1 matches the two actual target FunFam entries and Primates. Reactome independently assigns P12259 cargo entity 5689793 itself to ERGIC membrane within the cargo/receptor assembly. Retain this modeled peripheral cargo association as non-core; it is not a transmembrane topology claim or evidence that F5 drives membrane fusion. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-5694446 |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-5694446 | KEEP AS NON CORE | Summary: Retain receptor-associated F5 at the ERGIC membrane. Reason: The actual output route R-HSA-5694446β5694253β5694255β5694192 reaches human P12259 5689793 (29β2224), whose own compartment is ERGIC membrane. This target annotation is not merely copied from the outer SNARE complex. FV remains soluble receptor-associated cargo during transport; SNAREs perform fusion. Retain the modeled association as non-core without inferring membrane insertion or an autonomous trafficking function. Supporting Evidence: Reactome:R-HSA-5694446 |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: The author-deposited human CSF proteomics data positively identify F5 in vesicle-enriched fractions. Reason: The official PRIDE project PXD000608 explicitly links PMID:24769233 and human CSF pools. Its deposited MaxQuant proteinGroups table identifies P12259 as the majority accession of the F5 group, with 52 and 44 peptides in exo_A/exo_G and 9 and 15 in the corresponding soluble-fraction labels sn_B/sn_H. The group includes additional sequence identifiers, so the numbers are author protein-group calls, not unique current-product or cleavage-state assignments. The deposited design and search parameters support this positive fraction-associated detection. The main article was not recovered completely and PRIDE omits sample-processing details; no vesicle lumen/surface topology, neuronal origin or F5-specific vesicle function is inferred. Retain the supported specialized location as non-core. The original CSF anatomy extension remains in raw GOA rather than being invented as a seeded field. Supporting Evidence: |
| GO:0061133 endopeptidase activator activity | IDA PMID:9252393 Increased tissue factor-initiated prothrombin activation as ... | NEW | Summary: Factor Va performs nonenzymatic cofactor work that increases factor Xa-dependent prothrombin activation. Reason: Human normal and Leiden plasma FV preparations in the reconstituted coagulation system of PMID:9252393 support Xa-dependent prothrombin activation on PC/PS membranes, measured by thrombin activity and protein-cleavage analysis. The established human Xa/Va assembly is independently represented by Reactome 140686 and its prothrombinase reaction 140664. Activated Va supplies the binding/cofactor contribution that enhances the endopeptidase; Xa supplies proteolysis. This matches the current GO:0061133 definition and is not inferred merely from FV necessity or from FV being cleaved. Same-role FVIII, tissue factor and thrombomodulin annotation records were checked and do not carry this exact MF; their absence is not treated as an overlooked consensus. The new assertion rests on the target biochemical role, with no autonomous protease or universal splice-product claim. |
| GO:0030195 negative regulation of blood coagulation | IDA PMID:30046712 Factor V-short and protein S as synergistic tissue factor pa... | NEW | Summary: FV-short provides an experimentally tested, state-dependent anticoagulant cofactor contribution. Reason: PMID:30046712 directly measures synergistic enhancement of TFPIalpha-mediated Xa inhibition by FV-short and protein S in purified-component S2765 assays and suppression of plasma thrombin generation with antibody and cleavage controls. Intact human plasma-derived or recombinant FV is less efficient; thrombin cleavage removes the FV-short synergistic effect. F5 therefore performs cofactor work in the inhibitory assembly rather than merely being necessary or serving as an APC substrate. TFPIalpha supplies the direct inhibitory contact. Recombinant FV-short, cleavage-resistant R709Q/R1545Q QQ, intact FV and proteolytic Reactome intermediates remain distinct; no natural-product equivalence or universal anticoagulant activity is asserted. This regulatory process is not an is_a/part_of ancestor or descendant of retained coagulation/clot-formation terms. Same-role anticoagulant cofactors and the production GO-CAM APC-input models were inspected: those substrate models do not themselves support this separate TFPIalpha cofactor assertion. |
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Download this section (compressed HTML)Q: How do the abundance and cleavage state of native full-length FV, FV-short and proteolytic FV intermediates determine the balance between Xa cofactor activity and TFPIalpha cofactor activity on human platelet and endothelial surfaces?
Q: Does the OLR1-associated F5 detected in cellular interaction screens represent an intact precursor, a processed species or an indirect complex, and what functional consequence follows from that association?
Experiment: Resolve native human FV species by sequence-specific mass spectrometry and cleavage-sensitive immunoblotting, then compare defined preparations in matched Xa/prothrombin and TFPIalpha/protein-S inhibition assays. Include omission controls, matched phospholipid surfaces and direct cleavage measurements so that cofactor enhancement is separated from protease turnover and product loss.
Hypothesis: The exposed B-domain region and proteolytic state govern the relative procoagulant and TFPIalpha-cofactor activities; activity cannot be inferred from F5 antigen concentration alone.
Experiment: Reconstitute OLR1 association using sequence-verified F5 preparations and purified receptor, alongside receptor-null and rescue cells. Identify the bound F5 species and test binding separately from uptake or signaling, retaining indirect-association controls for the original AP-MS observations.
Hypothesis: OLR1 association depends on a particular F5 state or an additional cellular partner, rather than establishing equivalent receptor binding by every F5 product.
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