F7 encodes coagulation factor VII, a secreted, vitamin K-dependent plasma glycoprotein that circulates predominantly as a zymogen. Its activated form, factor VIIa, is a serine endopeptidase that binds tissue factor and cleaves factors IX and X to their active forms, initiating the extrinsic coagulation pathway. Tissue factor binding enhances protease activity, while calcium coordination and the gamma-carboxyglutamate-rich domain support assembly at phospholipid surfaces. The resulting extracellular, membrane-associated reactions feed thrombin generation and fibrin formation. Tissue-factor-bound factor VIIa also participates in context-dependent cell signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat hypoxia response does not yet resolve the human assertion. Reason: The actual Q8K3U6 donor GOA is IEP from PMID:9155722. Its positive abstract reports changes in rat coagulation during prolonged hypobaric hypoxia, including reduced FVII activity after eight weeks, with consumption during thrombosis considered. Complete original Methods/Results were not recovered. Preserve this observation without inferring oxygen sensing, dismissing the donor, or claiming that this particular response has been established for human F7. |
| GO:0002690 positive regulation of leukocyte chemotaxis | IDA PMID:17991872 TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced... | KEEP AS NON CORE | Summary: Retain context-dependent enhancement of human monocyte chemotaxis. Reason: The inspected Methods and Results of PMID:17991872 identify recombinant human FVIIa and primary human blood monocytes, alongside human fibroblasts and engineered porcine aortic endothelial cells. TF/FVIIa enhances PDGF-BB-directed migration, with PAR2 and Src/PLC perturbations supporting the signaling context. This is a measured cellular response, not evidence that FVIIa is itself a chemoattractant or kinase. Retain it as a contextual consequence of receptor-associated protease signaling rather than the principal coagulation role. Complete article and supplement access remains unavailable; the positive judgment uses the recovered original operative pages. Supporting Evidence: |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Specify serine-type endopeptidase activity. Reason: The rat donor assertion is IDA from PMID:12757778; its abstract reports recombinant rat FVII assayed in human FVII-deficient plasma and a TF-dependent chromogenic system, but the original Methods remain unavailable. Independently, human FVIIa peptide cleavage and inhibition were actually measured in PMID:34502392, and the current human protease-domain/EC record specifies serine endopeptidase chemistry. This supports the specific MF without treating a human expression host or human assay plasma as proof that the donor protein was human. Proposed replacements: serine-type endopeptidase activity |
| GO:0004252 serine-type endopeptidase activity | IDA PMID:24998411 MicroRNA-19b functions as potential anti-thrombotic protecto... | ACCEPT | Summary: Retain FVIIa serine endopeptidase activity and query the imported contribution qualifier. Reason: Activated FVIIa supplies the catalytic site. In the actual PMID:7797546 S-2288 Methods and Results associated with Figures 5β6, human FVIIa hydrolyzes the peptide without tissue factor; TF and calcium strongly enhance that activity. This establishes catalytic capacity of FVIIa itself, not efficient tissue-factor-independent physiological coagulation. The source PMID:24998411 remains abstract-only here, so its exact complex-level annotation rationale cannot be reconstructed. Retain the activity while asking the source curator to check contributes_to versus enables; neither the qualifier nor the source identifier is rewritten. |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the serine protease activity of activated FVII. Reason: Current target InterPro entries IPR001254, IPR012224 and IPR018114 and EC 3.4.21.21 support this chemistry, and the executed human FVIIa peptide assay in PMID:34502392 provides independent corroboration. Current ARBA00027237 conditions do not reproduce a match to current P08709 cross-references; that source-version limitation is retained without rejecting the independently supported combined assertion. The active protease is FVIIa, not every unprocessed FVII molecule. |
| GO:0004252 serine-type endopeptidase activity | TAS PMID:3037537 Nucleotide sequence of the gene coding for human factor VII,... | ACCEPT | Summary: Retain activated FVIIa serine endopeptidase activity. Reason: The complete PMID:3037537 original is a human gene-sequencing study; its account of FVIIa catalysis is background appropriate to the imported TAS evidence, not a new enzyme assay in that paper. Independent human biochemical evidence in PMID:8940045 supports the serine-protease role of the activated protein. The two alternative precursor leaders discussed in the sequence paper do not establish universal processing or functional equivalence of current natural products. |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain binding to the tissue-factor receptor/cofactor. Reason: Current rat Q8K3U6 GOA traces to PMID:18315926, whose abstract describes a rat EGF1 fusion binding cellular TF; complete original Methods are unavailable. Independently, the complete human study PMID:3455766 directly isolates human brain TF on a human plasma-FVII affinity column in a calcium-dependent interaction. This supports receptor binding rather than generic association; it does not by itself establish downstream PAR signaling. The paperβs FX-cleavage kinetics used bovine reagents and are not recast as human assays. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain calcium binding supporting FVII structure and assembly. Reason: All five cited InterPro entries are present in current P08709 and their actual mappings include calcium binding. The independently inspected human FVIIaβsoluble-TF structure deposition 1DAN contains calcium associated with the FVII light and heavy chains. This is a bound-metal structural observation in an active-site-inhibited preparation, not a measurement of catalytic activity or proof that the two precursor products have identical processing. |
| GO:0005515 protein binding | IPI PMID:15522303 Dissecting and designing inhibitor selectivity determinants ... | MODIFY | Summary: Specify TF receptor binding represented in the human FVIIaβTF structure. Reason: The inspected primary deposition PDB:1O5D associated with PMID:15522303 contains human FVII light and heavy chains with tissue factor; the title foregrounding an inhibitor target does not make this a wrong-gene citation. It is structural complex evidence, not a signaling assay, and the article main text remains unavailable. Independent human physical-binding experiments in PMID:3455766 and PMID:8940045 support the specific TF receptor/cofactor interaction. Refine generic binding to signaling receptor binding, without assigning a signaling endpoint to the inhibitor-bound crystal. Proposed replacements: signaling receptor binding |
| GO:0005515 protein binding | IPI PMID:15664864 Design of selective phenylglycine amide tissue factor/factor... | MODIFY | Summary: Specify TF receptor binding in inhibitor-bound FVIIa complexes. Reason: PDB:1W0Y and PDB:1W2K associated with PMID:15664864 directly record the human FVIIaβTF complex. Their engineered chain boundaries, including the shortened light-chain construct, are retained; the inaccessible article is not treated as a full-length native-product signaling assay. Independent human TF binding in PMID:3455766 and PMID:8940045 supports the receptor-binding refinement. No direct receptor signaling is inferred from crystallographic membership alone. Proposed replacements: signaling receptor binding |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Specify the TF receptor association detected by cellular proximity ligation. Reason: The actual PMID:25241761 supplementary Tables S1/S7 identify the F7βF3 pair DI0178 in the HeLa proximity-ligation screen. Proximity supports the reported association but does not establish a purified binary interaction or the exact natural FVII product. Independent human physical-binding experiments in PMID:3455766 and PMID:8940045 establish the TF receptor/cofactor interaction and support the specific binding term. The screen itself is not presented as a signaling assay. Proposed replacements: signaling receptor binding |
| GO:0005515 protein binding | IPI PMID:3455766 Affinity purification of human tissue factor: interaction of... | MODIFY | Summary: Specify direct human FVII binding to the TF receptor/cofactor. Reason: The actual PMID:3455766 original reports calcium-dependent affinity binding between human plasma FVII and human brain tissue factor, with elution on calcium removal. This directly supports the TF receptor/cofactor interaction and the refinement from generic protein binding. The separate factor-X activation kinetics use bovine reagents and are not recast as human enzyme measurements or a receptor-signaling assay. Proposed replacements: signaling receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:8598903 The crystal structure of the complex of blood coagulation fa... | MODIFY | Summary: Specify the human FVIIaβTF receptor interaction. Reason: The primary PDB:1DAN deposition associated with PMID:8598903 resolves human FVIIa with soluble TF in an active-site-inhibited preparation. It provides structural complex and calcium-coordination evidence, not an executed catalytic or signaling measurement. The article main text remains unavailable. Human binding experiments in PMID:3455766 and PMID:8940045 independently support the receptor-binding refinement; inhibited structural preparations are kept distinct from those functional assays. Proposed replacements: signaling receptor binding |
| GO:0005515 protein binding | IPI PMID:8940045 Factor VII central. A novel mutation in the catalytic domain... | MODIFY | Summary: Specify experimentally measured human FVIIβTF receptor binding. Reason: The actual PMID:8940045 author original reports binding of recombinant human WT FVII to immobilized human TF residues 1β218, with gelatin controls and WT-versus-mutant affinity measurements. This directly supports binding to the TF receptor/cofactor. Its human Xa activation and TF-dependent functional assays are distinct from the physical-binding measurement and do not make TF the protease. The specific binding refinement does not require treating this study as a downstream cell-signaling experiment. Proposed replacements: signaling receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9414278 Factor VII deficiency caused by a structural variant N57D of... | MODIFY | Summary: Specify TF receptor binding demonstrated by WT human FVII. Reason: The actual PMID:9414278 author original tests human WT and engineered N57D/R79Q FVII preparations expressed in 293/COS-1 cells and WT binding to relipidated TF. This supports the TF receptor/cofactor interaction; mutant effects are not generalized to both natural F7 products. The coupled S-2222 assay reports generated FXa, rather than direct FVIIa cleavage of that reporter, and does not itself establish receptor signaling. Proposed replacements: signaling receptor binding Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:36951360 Structural and functional characterization of novel F7 mutat... | ACCEPT | Summary: Retain extracellular localization of secreted human FVII. Reason: PMID:36951360 is accessible only as metadata and abstract, which reports secretion and functional characterization of human F7 variants; its specific construct and secretion controls remain uninspected. Independent actual human plasma purification in PMID:3455766 and WT human FVII recovered from conditioned medium in PMID:9414278 support the broad extracellular location. This does not assign a mutant-specific secretion defect to WT or establish equal secretion of every natural product. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the conserved extracellular functional pool. Reason: The actual v19 PTHR24278 tree places human PTN002542619 below extracellular-region IBD PTN000669108; the ungapped 466-residue target MSA equals the displayed P08709 sequence and there is no target-path NOT. Native human plasma FVII in PMID:3455766 and native extracellular Reactome entities independently support the location. Fresh family queries timed out, so the exact earlier official tree/MSA capture is used with its version boundary rather than claimed as a fresh response. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000669108 SUPPORTS TRANSFER Actual target path and positive extracellular-region IBD inspected; target self-WITH is legitimate descendant evidence, not circularity. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Retain secretion supported by independent components of the combined mapping. Reason: The source combines rat Q8K3U6, target GLA-domain mappings IPR000294/IPR035972, and official Secreted/SL-0243, which maps to extracellular region. The rat PMID:14724430 abstract provides a positive plasma-factor context but is not a read human localization assay. Native human plasma FVII used in the actually inspected PMID:3455766 and the explicit secreted mapping independently support the extracellular pool. |
| GO:0005576 extracellular region | TAS PMID:3037537 Nucleotide sequence of the gene coding for human factor VII,... | ACCEPT | Summary: Retain extracellular localization of FVII. Reason: The complete human sequence paper PMID:3037537 describes FVII as a secreted plasma zymogen; its TAS annotation is corroborated by direct purification of human plasma FVII in PMID:3455766 and secretion of WT human FVII in PMID:9414278. This broad extracellular location does not imply that the zymogen is already active or resolve processing of every alternative precursor. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140748 | ACCEPT | Summary: Retain the soluble extracellular FVIIa pool before TF recruitment. Reason: Reactome R-HSA-140748 input FVIIa complex 140751 contains native human P08709 light chain 140749 (61β212) and heavy chain 140750 (213β466), each explicitly extracellular. Their plasma-membrane output counterparts remain distinct. This location is also consistent with the human plasma preparation in PMID:3455766; it does not assign TFβs transmembrane topology to FVII. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140769 | ACCEPT | Summary: Retain extracellular FVII before and after activation. Reason: R-HSA-140769 contains native extracellular P08709 140771 (61β466) and its light/heavy products 140749/140750. FXa is the activating protease in this event; FVII is its substrate. The target objectsβ own compartments establish the location without claiming that F7 performs its own cleavage or inventing splice products. Supporting Evidence: Reactome:R-HSA-140769 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140783 | ACCEPT | Summary: Retain soluble extracellular FVII before receptor binding. Reason: R-HSA-140783 begins with extracellular native P08709 entity 140771 (61β466) and yields the membrane-associated TF:FVII complex with target 140774. The soluble input and recruited output are separately represented; the extracellular annotation is therefore supported by the target itself. Supporting Evidence: Reactome:R-HSA-140783 |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain ER-lumen localization during FVII biosynthesis. Reason: Current ARBA00028691 condition set 6 matches the actual human target through IPR000294, IPR001254 and Homo. Independent Reactome P08709 entities 159848 and 159722 are explicitly in the ER lumen during GGCX-dependent carboxylation. This is a biosynthetic precursor pool, not the principal extracellular protease context. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-159761 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-159761 | KEEP AS NON CORE | Summary: Retain the ER-lumen carboxylation substrate pool. Reason: R-HSA-159761 contains native human P08709 pro-factor VII 159848 and carboxylated product 159722, both residues 21β466 with their own ER-lumen compartment. GGCX performs gamma-carboxylation; FVII is the substrate. The valid biosynthetic location is retained as non-core rather than assigning carboxylase activity to F7. Supporting Evidence: Reactome:R-HSA-159761 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-159783 | KEEP AS NON CORE | Summary: Retain the ER-lumen pool before secretory transport. Reason: R-HSA-159783 has P08709 159722 (21β466) in the ER lumen and output 159767 in Golgi lumen. FVII is transported cargo. Its source-side location is valid but does not make F7 transport machinery or establish processing of both literal precursor products. Supporting Evidence: Reactome:R-HSA-159783 |
| GO:0005796 Golgi lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain Golgi-lumen localization during maturation. Reason: Current ARBA00028705 condition set 1 matches P08709 through IPR000152, IPR000294 and Primates. Independent native-human Reactome entities 159767/159808 occupy Golgi lumen during propeptide cleavage. This is a transient biosynthetic pool, retained separately from extracellular FVIIa function. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-159868 |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-159783 | KEEP AS NON CORE | Summary: Retain the Golgi-lumen cargo pool. Reason: In R-HSA-159783, output P08709 159767 (21β466) explicitly has Golgi-lumen compartment, distinct from ER input 159722. The gene product is cargo in this modeled trafficking step, not an executor of transport. Supporting Evidence: Reactome:R-HSA-159783 |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-159868 | KEEP AS NON CORE | Summary: Retain Golgi-lumen processing by furin. Reason: R-HSA-159868 models furin cleavage of P08709 159767 (21β466) into mature FVII 159808 (61β466) and propeptide 159847 (21β60), all explicitly in Golgi lumen. Furin is the catalyst. These are precursor-processing products, not additional alternative transcripts. Supporting Evidence: Reactome:R-HSA-159868 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140748 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 140748 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. TF recruits the activated light/heavy-chain enzyme. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-140783 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 140783 β 140775 β 140774 reaches P08709 target entities with their own plasma-membrane compartment. TF recruits mature single-chain FVII before activation. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822512 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9822512 β 9822516 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. FXa is released while TF-associated FVIIa remains assembled. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822513 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9822513 β 140775 β 140774 reaches P08709 target entities with their own plasma-membrane compartment. The event explicitly models the TF:FVII form in a low-activity activation route; that label is preserved rather than silently replaced by FVIIa. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822514 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9822514 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. TF-associated FVIIa performs FX activation in this model. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822522 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9822522 β 9822518 β 9822516 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. F7 is a component of TF:FVIIa:FXa; the event narrative assigns the VIII-cleaving step to FXa, not FVIIa. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9822556 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9822556 β 9822516 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. F7 remains in the surface complex targeted by TFPIΞ²; the inhibitorβs membrane anchor is not a transmembrane segment of FVII. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9929051 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9929051 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. TF-associated FVIIa performs FIX activation. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9929054 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9929054 β 9929061 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. FIXa release leaves the TF-associated FVIIa catalyst. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9929060 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9929060 β 9822515 β 140775 β 140774 and 9929060 β 9822516 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. FXa activates TF-bound FVII. The current summation repeats an FX-release passage inconsistent with the event name; the actual participant/catalyst graph, not that narrative, establishes this location. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9931624 | MODIFY | Summary: Specify peripheral association with the external plasma-membrane face. Reason: The actual native-human Reactome route 9931624 β 9822516 β 140734 β 140733 β 140715/140724 reaches P08709 target entities with their own plasma-membrane compartment. F7 belongs to the surface complex inhibited by TFPIΞ± with the modeled FV intermediate and PROS1; inhibitor/cofactor activities are not reassigned to F7. The secreted FVII/TF interaction and extracellular target topology support external-side association rather than integral-membrane FVII; the complete human TF-affinity experiment in PMID:3455766 independently confirms the interaction. Proposed replacements: external side of plasma membrane |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Specify the proteolytic activation step performed by FVIIa. Reason: The actual IPR001254/IPR018114 mappings and human protease activity support proteolysis, while native Reactome TF:FVIIa reactions specify cleavage of inactive factors IX and X into active enzymes. Zymogen activation captures that performed step more precisely. This is activation of FVIIa substrates, not F7βs own processing by FXa or furin. Proposed replacements: zymogen activation |
| GO:0006950 response to stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the broad hemostatic response context as non-core. Reason: Current ARBA00026300 condition set 175 matches three actual target FunFam memberships. The broad stress-response term is compatible with tissue-factor-triggered hemostasis but is less informative than the defined catalytic cascade. Retain it as a contextual response, without using the rule to infer every specific hypoxic, hormonal or metabolic response proposed elsewhere. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-9822514 |
| GO:0007596 blood coagulation | IBA GO_REF:0000033 | MODIFY | Summary: Specify the tissue-factor-initiated coagulation pathway. Reason: The exact human target lies below the actual blood-coagulation IBD PTN002800588. Current donor annotations include mouse P70375/MGI:109325 knockout evidence and zebrafish Q504H3; their complete originals were not recovered. Human target self-WITH remains valid grounding. The inspected TF-binding experiment and native TF:FVIIa activation models independently support the more specific extrinsic-pathway role, without transferring developmental phenotypes or treating the donor count as evidence quality. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002800588 SUPPORTS TRANSFER Positive coagulation IBD and exact target descent inspected. Broad inheritance is sound; independent target evidence supports the finer pathway term. Proposed replacements: blood coagulation, extrinsic pathway Supporting Evidence: GO_REF:0000033 Reactome:R-HSA-9929051 Reactome:R-HSA-9822514 |
| GO:0007596 blood coagulation | IDA PMID:24998411 MicroRNA-19b functions as potential anti-thrombotic protecto... | MODIFY | Summary: Specify FVIIa participation in the extrinsic coagulation pathway. Reason: TF-associated FVIIa performs the initiating proteolytic step of the extrinsic pathway. PMID:24998411 remains abstract-only and its TF-dependent procoagulant assay cannot be assigned a detailed FVII reagent scope here. Independent human FVII biochemical evidence in PMID:8940045 and PMID:9414278 supports the performed coagulation role. The current extrinsic-pathway term is a typed specialization of blood coagulation; the refinement does not claim that FVII is the downstream thrombin or fibrin substrate. Proposed replacements: blood coagulation, extrinsic pathway |
| GO:0007596 blood coagulation | IDA PMID:8632006 Structural integrity of the gamma-carboxyglutamic acid domai... | MODIFY | Summary: Specify the extrinsic pathway role of TF-associated FVIIa. Reason: The original PMID:8632006 abstract explicitly includes TF/FVIIa activation of human FIX and compares the G12R FIX variant, despite the title emphasizing FIXaβFVIIIa binding. Full operative Methods remain unavailable after bounded retrieval attempts, so no unverified FVII reagent species, concentration or product is asserted. The imported coagulation role is independently supported by actual human FVII WT biochemical studies PMID:8940045 and PMID:9414278 and is more precisely represented by the extrinsic pathway. This does not transfer FIXa/FVIIIa cofactor activity to FVII. Proposed replacements: blood coagulation, extrinsic pathway |
| GO:0007596 blood coagulation | IEA GO_REF:0000002 | MODIFY | Summary: Specify the extrinsic coagulation pathway. Reason: Current P08709 contains IPR012224 with the blood-coagulation mapping. Human FVII binding to TF and the explicit native-human TF:FVIIa reactions activating FIX and FX support the more informative tissue-factor-initiated pathway. This is participation by the FVIIa protease, not merely the consumption of a zymogen. Proposed replacements: blood coagulation, extrinsic pathway |
| GO:0007596 blood coagulation | TAS PMID:3037537 Nucleotide sequence of the gene coding for human factor VII,... | MODIFY | Summary: Specify the extrinsic coagulation pathway. Reason: The complete PMID:3037537 sequence paper describes the FVIIaβTF pathway as established background, consistent with the imported TAS evidence. Independent human FVII biochemical studies PMID:8940045 and PMID:9414278 support the coagulation role. GO:0007598 specifies the TF-initiated pathway in which activated FVIIa performs proteolysis, without treating the genomic sequencing experiment as a new catalytic assay or asserting equal activity of the two precursor products. Proposed replacements: blood coagulation, extrinsic pathway |
| GO:0007623 circadian rhythm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain rhythmic FVII activity as a non-core physiological context. Reason: The rat donor PMID:2607889 positively reports a roughly 24-hour FVII coagulant-activity rhythm, although its complete original remains unavailable. Independent complete PMID:15604416 Methods/Results (pp. 646β648) measure human FVII-dependent FXa generation in 13 healthy men at 8 AM and 2 PM, with higher morning activity, and demonstrate persistence of a FVII activity rhythm in mice kept in constant darkness. Human two-time-point sampling alone does not prove an endogenous circadian oscillator; the mouse experiment supplies that conserved rhythm context. GO:0007623 includes recurrent biological activity and does not require FVII to be a clock component. Retain this context outside the core coagulation function. |
| GO:0008236 serine-type peptidase activity | TAS PMID:3037537 Nucleotide sequence of the gene coding for human factor VII,... | MODIFY | Summary: Specify serine-type endopeptidase activity of FVIIa. Reason: The broader serine-type peptidase term can be refined to endopeptidase activity: activated FVIIa cleaves internal peptide bonds during coagulation, rather than removing terminal residues. PMID:3037537 supplies TAS background, while independent human WT biochemical characterization in PMID:8940045 supports the active protease. The current GO:0004252 is an is_a descendant of GO:0008236. This activity is not assigned to unactivated precursor FVII. Proposed replacements: serine-type endopeptidase activity |
| GO:0009725 response to hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat hormone-response experiment does not settle this human context. Reason: The Q8K3U6 IEP source PMID:18336749 reports differential rat coagulation-factor responses to TRH, TSH, T3 and T4, including reduced FVII activity after some treatments. Complete original Methods/Results were unavailable. The response term need not mean hormone binding, but its conservation and exact conditions cannot be adjudicated from the abstract alone. |
| GO:0010037 response to carbon dioxide | IEA GO_REF:0000107 | UNDECIDED | Summary: Retain uncertainty about a specific human carbon-dioxide response. Reason: The complete rat original PMID:26855512 used female Wistar rats exposed to CO2 pneumoperitoneum at two pressures and durations. FVII activity increased only at 12 mmHg for one hour, with pressure, procedure and reperfusion accompanying exposure. The response term does not require a CO2 receptor, but this design does not isolate a CO2-specific effect and its transfer to human F7 remains unresolved. This differs from the independently supported vitamin-K-dependent biosynthetic response: uncertainty is about stimulus attribution and conservation, not a requirement for autonomous sensing. |
| GO:0010641 positive regulation of platelet-derived growth factor receptor signaling pathway | IDA PMID:17991872 TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced... | KEEP AS NON CORE | Summary: Retain context-dependent PDGFRΞ² signaling enhancement. Reason: Actual PMID:17991872 Methods identify human FVIIa and human TF/PDGFRΞ² expressed in porcine aortic endothelial cells. Figures 4β5 and the associated Results show rapid PDGFRΞ² phosphorylation, PAR2 dependence and Src-inhibitor sensitivity; human monocyte and fibroblast migration provides a separate cellular arm. FVIIa is an upstream protease-associated signal, not a PDGFR kinase. Retain this experimentally supported signaling consequence as non-core, with the engineered-host and selected-original-access limits explicit. Supporting Evidence: |
| GO:0016485 protein processing | IBA GO_REF:0000033 | MODIFY | Summary: Specify zymogen activation performed by FVIIa. Reason: The exact human PTN002542619 is below the actual protein-processing IBD PTN002800588, seeded by experimental human P08709 evidence; self-WITH is appropriate. Native TF:FVIIa reactions cleave FIX and FX to active proteases, supporting the more specific zymogen-activation term. The refinement concerns substrates processed by FVIIa, not maturation of FVII by another enzyme. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002800588 SUPPORTS TRANSFER Actual positive protein-processing IBD and target descent inspected; independent native-human reactions support the specific processing step. Proposed replacements: zymogen activation Supporting Evidence: GO_REF:0000033 Reactome:R-HSA-9929051 Reactome:R-HSA-9822514 |
| GO:0016485 protein processing | IDA PMID:24998411 MicroRNA-19b functions as potential anti-thrombotic protecto... | MODIFY | Summary: Specify zymogen activation performed by FVIIa. Reason: The relevant processing role is FVIIa-mediated conversion of coagulation zymogen substrates such as FIX and FX to active enzymes, not processing of FVII by another protease. The exact TF-expression study PMID:24998411 remains abstract-only; its individual reagent details are not inferred. The accepted source assertion is corroborated by the explicit human-FIX/TFβFVIIa activation account in PMID:8632006 and human FVII WT biochemical characterization in PMID:8940045/PMID:9414278. Current GO:0031638 is a typed specialization of protein processing and describes the performed step. Proposed replacements: zymogen activation |
| GO:0030194 positive regulation of blood coagulation | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the positive effect of FVIIa on coagulation. Reason: The rat donor PMID:12757778 abstract reports recombinant rat FVII restoring clotting in FVII-deficient human plasma and supporting TF-dependent activity; its complete Methods remain unavailable. Independently, the actual human TF-binding experiment and native TF:FVIIa protease reactions establish the targetβs positive contribution to coagulation. Retain that role without equating the rat construct with a human protein or claiming autonomous activity of the unactivated precursor. |
| GO:0030335 positive regulation of cell migration | TAS PMID:18612547 Formation of tissue factor-factor VIIa-factor Xa complex ind... | UNDECIDED | Summary: Keep the FVII-specific migration contribution unresolved in this ternary-complex study. Reason: The PMID:18612547 abstract reports TFβFVIIaβFXa-dependent mTOR activation and migration in human breast cancer cells, but complete operative Methods and Results remain inaccessible. It does not resolve which active protease drives the effect, the FVII reagent/processing state, or controls distinguishing FVIIa from downstream FXa. Positive chemotaxis in the distinct PMID:17991872 setting is retained separately; it does not verify this ternary-complex cancer-cell assertion. UNDECIDED records access and attribution limits, not a negative migration result. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | KEEP AS NON CORE | Summary: Retain the contextual ECM-fraction observation without assigning a structural matrix function. Reason: The actual PMID:25037231 supplementary workbook lists F7/P08709 in both the complete dataset and Matrisome sheets (row 281), with positive peptides in normal-liver pools and one liver-metastasis patient. The reported protein group includes P08709, P08709-2 and B4DPM2, so it is not isoform-resolved. Methods describe sequential extraction and LCβMS/MS of an insoluble ECM-enriched fraction, with fractionation controls. Retain this positive experimental location context; potential co-isolation is not proof of contamination, and no constitutive structural ECM role or universal tissue localization is inferred. Supporting Evidence: |
| GO:0031100 animal organ regeneration | IEA GO_REF:0000107 | UNDECIDED | Summary: Regeneration participation cannot be resolved from the donor source available here. Reason: The available original abstract for rat PMID:14724430 reports FVII levels falling and recovering after 90% hepatectomy and uses this short-lived plasma factor as an indicator of hepatic protein production. GO:0031100 concerns regrowth of a lost or destroyed organ; the inspected text does not identify a regenerative step performed by FVII. Complete Methods/Results remain inaccessible after bounded publisher/repository searches, so the remaining experiments cannot be adjudicated. Retain UNDECIDED rather than converting incomplete evidence into a negative finding or marking the experimental donor wrong. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | UNDECIDED | Summary: The human nutrient-response inference remains unresolved. Reason: Rat IDA PMID:11880553 reports increased FVIIa activity after fat gavage while FVII coagulant activity, antigen and thrombin-antithrombin measures were unchanged. Its complete Methods/Results remain unavailable. Independent PMID:15604416 shows feeding-dependent modulation of mouse FVII activity rhythms, but human sampling combines time of day and a meal and does not isolate a nutrient effect. Response terms can include altered activity without direct nutrient binding; the precise human transfer and original assay context remain unresolved. |
| GO:0031982 vesicle | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat vesicle-localization inference remains unresolved. Reason: The current donor GOA points to IDA PMID:4307182. No abstract or complete original body was recovered. Bibliographic liver/microsome indexing is not a target protein assay or a defined vesicle topology. The human assertion is therefore left undecided rather than removed or refined on title alone. |
| GO:0032008 positive regulation of TOR signaling | IDA PMID:18612547 Formation of tissue factor-factor VIIa-factor Xa complex ind... | UNDECIDED | Summary: Keep FVII-specific positive TOR regulation unresolved. Reason: PMID:18612547 reports a positive TFβFVIIaβFXa/mTOR association in its abstract, but the full original assay and perturbation scope remains unavailable. FVIIa and FXa are distinct proteases; without the operative controls this cannot be assigned to FVIIa-specific causal regulation or a particular native product. Preserve the source assertion as UNDECIDED rather than rejecting it from the abstract or treating membership in the ternary complex as a completed mechanistic demonstration. Supporting Evidence: |
| GO:0032008 positive regulation of TOR signaling | IEA GO_REF:0000117 | UNDECIDED | Summary: The TOR-signaling assertion remains source-limited. Reason: Current ARBA00092062 condition set 4 matches the actual target FunFam/taxon conditions. The relevant human cancer-cell PMID:18612547 abstract positively reports TFβFVIIaβXa-induced mTOR/p70S6K phosphorylation and rapamycin-sensitive migration, with PAR1/2 involvement described as probable. Full original Methods/Results remain unavailable, preventing discrimination of the individual active FVIIa/Xa requirements and precise pathway role. The matching rule does not resolve that experimental attribution. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat estradiol response remains unverified for the human target. Reason: Rat IEP PMID:20838740 reports increased hepatic F7 expression after prolonged estradiol treatment in ovariectomized rats. The complete original Methods/Results were not recovered. This is positive response evidence, not evidence that FVII binds estradiol; its target-human conservation and exact protein/activity scope remain unresolved. |
| GO:0032571 response to vitamin K | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the vitamin-K-dependent biosynthetic response as non-core. Reason: The complete rat original PMID:3379837 directly measures reduced FVII coagulant activity during dietary vitamin-K deficiency, with sex- and time-dependent effects. Independently, human Reactome R-HSA-159761 models vitamin-K-dependent GGCX modification of the actual FVII precursor. Together these support a contextual biosynthetic response and its human relevance. GGCX performs carboxylation; F7 is its substrate, not a vitamin-K receptor or carboxylase. This mechanistic connection distinguishes this non-core response from the unresolved CO2/pressure experiment. |
| GO:0033595 response to genistein | IEA GO_REF:0000107 | UNDECIDED | Summary: The genistein-response transfer remains unresolved. Reason: Rat IEP PMID:20838740 reports increased F7 expression after dietary genistein in ovariectomized rats. Complete original Methods/Results were unavailable, so the human response and assay-specific extent cannot be adjudicated. Preserve the positive donor report without inferring genistein binding or autonomous hormone signaling by FVII. |
| GO:0043627 response to estrogen | IEA GO_REF:0000107 | UNDECIDED | Summary: The estrogen-response transfer remains unresolved. Reason: Rat IEP PMID:2821645 reports reduced FVII activity after high-dose estrogen and discusses liver dysfunction, explicitly cautioning about extrapolation of the rat model. The full original was not recovered. This is not a demonstrated absence of response, but neither the exposure-specific mechanism nor the human ortholog assertion can be settled from the abstract. |
| GO:0050878 regulation of body fluid levels | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the broad body-fluid homeostasis consequence as non-core. Reason: Current ARBA00029145 condition set 3 matches the actual F7 FunFam memberships and Euarchontoglires taxon. FVIIaβs coagulation contribution helps limit blood loss, consistent with this broad regulation term. Retain it as a higher-level consequence rather than adding an independent fluid-transport, pump or endocrine activity. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-9822514 |
| GO:0050927 positive regulation of positive chemotaxis | IDA PMID:17991872 TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced... | KEEP AS NON CORE | Summary: Retain enhancement of positive chemotaxis as a contextual signaling consequence. Reason: The inspected PMID:17991872 Methods/Results show human FVIIa increasing PDGF-BB-directed migration in the tested human monocytes/fibroblasts and engineered PAE system. PAR2/Src/PLC perturbations support a signaling route that enhances an existing attractant response. This is distinct from FVIIa serving as the gradient cue or directly phosphorylating PDGFRΞ². Retain the positive chemotaxis regulation as non-core and do not generalize it to every cell type, precursor product or proteolytic state. Supporting Evidence: |
| GO:0060416 response to growth hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: The growth-hormone-response transfer remains unresolved. Reason: Rat IEP PMID:7493602 reports reduced FVII after growth-hormone treatment and the opposite response under somatostatin. Complete original Methods/Results were unavailable. The positive donor result does not establish a direct receptor mechanism or its conservation in human F7, and is not dismissed merely because it is contextual. |
| GO:0070723 response to cholesterol | IEA GO_REF:0000107 | UNDECIDED | Summary: The cholesterol-response transfer remains unresolved. Reason: Rat IDA PMID:15670042 reports increased FVII coagulant activity during prolonged cholesterol-rich feeding, alongside a broader thrombosis experiment. The full original was unavailable. GO:0070723 permits a change in activity as a response and does not require FVII to mediate the entire treatment outcome. The positive donor observation is retained, but the complete assay context and its transfer to human F7 remain unresolved. |
| GO:0097066 response to thyroid hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: The thyroid-hormone-response transfer remains unresolved. Reason: Rat IEP PMID:21382270 reports FVII antigen changes after thyroid-axis hormone treatment. Only the original abstract/metadata were available; the complete Methods and Results were not recovered. Antigen response is kept distinct from direct hormone binding, synthesis-rate measurement and established human target conservation. |
| GO:0097068 response to thyroxine | IEA GO_REF:0000107 | UNDECIDED | Summary: The thyroxine-response transfer remains unresolved. Reason: The current rat Q8K3U6 IEP row cites PMID:21382270, whose abstract reports lower FVII antigen after thyroxine treatment. Full Methods/Results were unavailable. The observed donor response is preserved while its human conservation and exact mechanistic interpretation remain undecided. |
| GO:1904400 response to Thyroid stimulating hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: The TSH-response transfer remains unresolved. Reason: Rat IEP PMID:21382270 reports a reduction in FVII antigen after TSH administration. Complete original Methods/Results were unavailable, and this antigen result is not silently equated with the different functional-activity endpoints in PMID:18336749. The human response remains unresolved. |
| GO:1904612 response to 2,3,7,8-tetrachlorodibenzodioxine | IEA GO_REF:0000107 | UNDECIDED | Summary: The dioxin-response transfer remains unresolved. Reason: Rat IEP PMID:10901669 reports sex-dependent reductions of FVII and other coagulation factors after dioxin or related compounds, discussing vitamin-K cycling and other physiological effects. Complete original Methods/Results were unavailable. The positive donor response does not by itself establish a human F7-specific sensor or causal mechanism, but is not evidence of an incorrect experimental annotation. |
| GO:1905217 response to astaxanthin | IEA GO_REF:0000107 | UNDECIDED | Summary: The astaxanthin-response transfer remains unresolved. Reason: Rat IDA PMID:22309505 reports lower FVII activity after astaxanthin supplementation in a diabetic-rat model together with changes in several other coagulation measures. Complete Methods/Results were unavailable. The human ortholog response is undecided, without interpreting this as astaxanthin binding or disproving the positive donor result. |
| GO:1905225 response to thyrotropin-releasing hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: The TRH-response transfer remains unresolved. Reason: Rat IEP PMID:21382270 reports reduced FVII antigen after TRH exposure. Full original Methods/Results were not recovered, so the specific human response cannot be resolved. The protein-antigen endpoint is retained separately from direct hormone recognition and from activity measurements in other thyroid-axis experiments. |
| GO:1905286 serine-type peptidase complex | IPI PMID:24998411 MicroRNA-19b functions as potential anti-thrombotic protecto... | ACCEPT | Summary: Retain membership in the TF:FVIIa serine-peptidase assembly. Reason: The exact PMID:24998411 main article is unavailable, so its specific co-complex assay is not reconstructed from the abstract. Independent human TF-binding experiments in PMID:3455766 and PMID:8940045, together with the primary human FVIIaβTF structure associated with PMID:8598903, support the imported complex-membership claim. Activated FVIIa supplies the protease active site and TF is its receptor/cofactor; inhibited structural preparations establish assembly rather than executed catalysis. The light/heavy chains represent processing, not additional natural isoforms. |
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Download this section (compressed HTML)Q: How do the two annotated F7 precursor products, A (466 residues) and B (444 residues), differ in secretion, maturation and production of active tissue-factor-bound enzyme under physiological expression conditions?
Q: Under which cell-surface conditions can signaling be assigned specifically to FVIIa, separately from signaling by the FXa generated in the same tissue-factor-associated assembly?
Experiment: Express sequence-verified human A and B precursors separately in the same secretion-competent cell system. Measure transcript abundance, secreted protein, N-terminal processing and gamma-carboxylation before comparing activation cleavage, tissue factor binding and FIX/FX cleavage at matched active-site concentrations. Identify the mature chains directly by mass spectrometry rather than transferring precursor-A processing coordinates to precursor B.
Experiment: Compare purified human FVIIa with and without FX on cells bearing defined amounts of tissue factor and the relevant protease-activated receptor. Combine selective FVIIa and FXa inhibition with catalytic-site controls, direct receptor-cleavage measurements and downstream signaling readouts. Quantify generated FXa and keep coagulation endpoints separate from signaling so that an effect of the assembled system is not automatically assigned to FVIIa alone.
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