F11 encodes coagulation factor XI, a secreted plasma zymogen that forms a disulfide-linked homodimer. Proteolytic activation generates factor XIa, with each subunit containing an apple-domain heavy chain and a catalytic light chain linked by a disulfide bond. Factor XIa activates factor IX by cleaving two internal peptide bonds, sustaining the protease cascade that produces a blood clot. Its A3 apple domain contributes to recognition of factor IX, while the serine-protease domain performs bond hydrolysis. Factor XI also associates peripherally with the external surface of platelets through receptor- and cofactor-dependent interactions. Deficiency of factor XI causes a bleeding disorder, particularly after injury or surgery.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain activated factor XI serine endopeptidase activity. Reason: The EC 3.4.21.27 entry explicitly names internal Arg–Ala and Arg–Val cleavage in factor IX, and the actual human sequence has the mapped trypsin domain and catalytic-histidine signature. PMID:22961984 directly measures sequential internal factor IX cleavage by activated recombinant human FXI, with factor XIIa removal/inhibition controls. This establishes the enzyme activity rather than merely inferring it from coagulation necessity. The zymogen must first be activated; the assay does not establish equivalent processing or activity of both natural products. Propagation Review Root cause: NO FAILURE CORE Sources checked: EC:3.4.21.27 SUPPORTS TRANSFER Current EC chemistry and human target experiments agree. InterPro:IPR001254 SUPPORTS TRANSFER Actual target match covers the C-terminal trypsin domain. InterPro:IPR018114 SUPPORTS TRANSFER Actual target catalytic-histidine signature supports serine-protease chemistry. |
| GO:0004252 serine-type endopeptidase activity | NAS PMID:9593722 Molecular cloning of platelet factor XI, an alternative spli... | ACCEPT | Summary: Activated human factor XI is a serine endopeptidase. Reason: PMID:9593722 characterizes platelet and megakaryocyte transcripts; its discussion of earlier platelet proteolysis is not a new purified splice-product assay. Independent original PMID:15545266 measures substrate hydrolysis by the recombinant human FXIa catalytic domain and resolves substrate-like ecotin contacts. PMID:10823824 also tests human FXI in coagulation assays. These support the established serine endopeptidase activity after activation, without claiming that the circulating zymogen or the separately described 571-residue product was catalytically tested in the transcript study. |
| GO:0004252 serine-type endopeptidase activity | TAS PMID:10823824 The role of high molecular weight kininogen and prothrombin ... | ACCEPT | Summary: Human FXIa has the annotated serine endopeptidase activity. Reason: The immutable TAS source already names serine-type endopeptidase activity. PMID:10823824 tests human recombinant FXI in activated-platelet and phospholipid-supported clotting assays and describes conversion to FXIa. Independent original PMID:15545266 directly measures peptide-substrate hydrolysis by the human FXIa catalytic domain and resolves its serine-protease substrate-binding architecture. Retain this established catalytic activity after activation, without claiming constitutive activity of the zymogen or a demonstrated assay of the shorter natural splice product. |
| GO:0005515 protein binding | IPI PMID:15545266 Crystal structures of the FXIa catalytic domain in complex w... | KEEP AS NON CORE | Summary: Human FXIa catalytic domain binds engineered ecotin inhibitors and substrates. Reason: The original PMID:15545266 Experimental Procedures and Results describe human FXIa catalytic-domain residues 370–607 in the paper’s mature-protein numbering, expressed in Pichia pastoris, and E. coli-produced ecotin M84R/M84D/M84P variants. Purified complexes and crystal structures establish direct association, with inhibitor or substrate behavior depending on the ecotin mutant. These are engineered domain preparations, not an endogenous human regulatory complex. The inspected ontology alternatives would assign protease binding or inhibitor activity to the opposite partner; no suitable more specific inhibitor-binding MF was established. Retain positive binding as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:2844223 Inactivation of human plasma kallikrein and factor XIa by pr... | UNDECIDED | Summary: The reported FXIa–protein C inhibitor association remains positive but incompletely verified. Reason: The verified PMID:2844223 abstract explicitly reports inhibition of human FXIa by protein C inhibitor, heparin-dependent acceleration, and complex detection by electrophoresis and immunoblotting. The complete original Methods and target-specific complex results were not recovered from the publisher or institutional record. This prevents a fully verified source-specific binding disposition here; it does not contradict the interaction or imply that the curator selected the wrong gene. Inhibitor activity belongs to SERPINA5, and no supported more specific binding refinement for FXIa was established from the accessible material. Supporting Evidence: |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the extracellular plasma pool. Reason: Native human factor XI was purified from plasma and activated in the operative experiments of PMID:89876. Human recombinant FXI is also recovered from conditioned medium in PMID:22961984. These independently support extracellular location. The recovered PTN002548665 IBD includes target experimental evidence, but the current family-version discrepancy prevents verification of the inherited target path. Retain the sound location without claiming that the phylogeny or every natural product was validated. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN002548665 UNRESOLVED The actual IBD assertion is recovered, but target descent was not verified. Immutable UniProt/InterPro membership says PTHR24252; current PANTHER v19 geneinfo says PTHR24253. The recovered 24252 MSA contains no exact canonical target sequence, and the required trees/mapped-family MSA timed out. This is an access/version limitation, not evidence against the biological function or an invalid self-WITH. |
| GO:0005576 extracellular region | IDA PMID:89876 Hageman-factor-dependent fibrinolysis: generation of fibrino... | ACCEPT | Summary: Native human factor XI is an extracellular plasma protein. Reason: The actually read PMID:89876 Materials and Methods, p. 851, purify factor XI from human plasma before Hageman-fragment activation. The original PMID:16699514 Supplementary Methods independently describe native FXI purification from fresh-frozen plasma. This directly supports extracellular region. Neither preparation resolves all splice products, and extracellular localization does not exclude intracellular biosynthesis or a peripheral platelet-associated pool. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Retain extracellular localization despite a current rule-reconstruction gap. Reason: The exact SL-0243 mapping is extracellular region and the actual IPR000177 target matches support the secreted apple-domain protein context. Independent native human plasma purification in PMID:89876 verifies this location. No current ARBA00027128 condition set matches the captured target features, so the historical combined-source rule cannot be fully reconstructed; this does not negate the positive human location. The rat source and current rule are not used to assign all human products to plasma. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER The associated official SL-0243 definition and GO mapping specify extracellular region; native human evidence independently supports it. InterPro:IPR000177 SUPPORTS TRANSFER Exact target apple-domain matches carry the extracellular mapping. ARBA:ARBA00027128 UNRESOLVED Current conditions were completely evaluated against captured target features without a matching clause; historical applicability remains unresolved. |
| GO:0005576 extracellular region | NAS PMID:9593722 Molecular cloning of platelet factor XI, an alternative spli... | ACCEPT | Summary: The extracellular location is independently supported by human plasma preparations. Reason: PMID:9593722 is primarily a transcript-cloning study and distinguishes liver/plasma and platelet-associated sources. Native human plasma purification in the actually read PMID:89876 Methods and PMID:16699514 Supplementary Methods supplies independent evidence for the extracellular location. Retain this broad, correct location without treating the platelet transcript as a localization or secretion assay for a purified 571-residue protein. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-158145 | ACCEPT | Summary: Retain extracellular factor XI before platelet-receptor association. Reason: Reactome R-HSA-158145 explicitly inputs the extracellular FXI homodimer 158234 containing human P03951 residues 19–625 (entity 158260), and outputs the GPIb–IX–V-associated pool. Thus extracellular region is supported by the target participant, not only the reaction compartment. Native plasma purification in PMID:89876 corroborates this source model. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9936440 | ACCEPT | Summary: Retain the extracellular FXI–kininogen pool. Reason: In R-HSA-9936440, extracellular FXI 158234 containing P03951(19–625) is both a free input and a component of the FXI–kininogen product 9936459. Factor XI is a binding partner here; the model does not assign it kininogen-cleaving chemistry. The native plasma pool is independently supported by PMID:89876. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9936451 | ACCEPT | Summary: Retain extracellular FXI in the receptor-binding transition. Reason: R-HSA-9936451 inputs extracellular FXI–kininogen 9936459, with the explicit P03951(19–625) component, and outputs a GPIb–IX–V-associated complex. Both the extracellular input and the membrane-associated output are genuinely target-containing. Retain this extracellular assertion separately from the more precise external-membrane-side refinement for the bound pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158145 | MODIFY | Summary: Specify the external platelet-membrane side. Reason: R-HSA-158145 outputs complex 158162 containing GPIb–IX–V and human FXI 158143/158208. The source models receptor-associated P03951(19–625), not an integral membrane protein. PMID:10823824 directly measures radiolabeled FXI binding to washed stimulated human platelets with cofactor and competition controls. GO:0009897 explicitly includes peripherally associated proteins on the extracellular face and is a supported descendant of plasma membrane. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158300 | MODIFY | Summary: Specify the external surface for receptor-bound FXI activation. Reason: R-HSA-158300 inputs receptor-bound FXI and outputs receptor-bound FXIa containing human heavy and light chains 19–387 and 388–625. Factor XIIa performs the activation cleavage; FXI is its substrate in this event. The location is nevertheless real and can be refined to the external membrane face, supported independently by the human platelet-binding experiment in PMID:10823824. This does not propose activation-process participation from substrate necessity. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158333 | MODIFY | Summary: Specify the external surface of the factor IX activation catalyst. Reason: The catalystActivity 158128 in R-HSA-158333 resolves to the GPIb-associated FXIa complex 158130 and its human F11 heavy/light chains. Here FXIa performs internal factor IX cleavage, independently measured in PMID:22961984. The receptor-associated extracellular-facing pool fits GO:0009897 more precisely than the broad membrane term; no membrane-spanning topology is implied. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158419 | MODIFY | Summary: Specify the external surface for thrombin-activated receptor-bound FXI. Reason: R-HSA-158419 contains the same native human receptor-bound FXI input and FXIa-chain output. Thrombin is the activating catalyst, whereas F11 is the processed substrate in this particular event. The traced GPIb-associated target and independent platelet-binding assay justify external side of plasma membrane without attributing thrombin catalysis to F11. The regulatedBy branches were included in the source traversal. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9653838 | MODIFY | Summary: Specify the external surface of the modeled inhibitor-associated FXIa pool. Reason: R-HSA-9653838 inputs GPIb-associated human FXIa complex 158130 and retains it in the SERPING1-bound product 9653851. Its F11 components are native heavy/light chains, not a disease variant. The model and independent human platelet association support the external membrane face. F11 is the inhibited enzyme here; no inhibitor activity or universal location of every FXIa–SERPING1 complex is inferred. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9655851 | MODIFY | Summary: Specify the external face of the modeled SERPINE1-associated FXIa pool. Reason: R-HSA-9655851 retains GPIb-associated FXIa 158130 inside product 9655836. The event narrative also discusses endothelial-cell SERPINE1-dependent uptake, which is a distinct experimental context from the modeled platelet receptor complex. The explicit native F11 participant and independent human platelet binding support external membrane association; they do not make all inhibitor-bound or internalized FXIa membrane-localized. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9657706 | MODIFY | Summary: Specify the external face of the APP-associated FXIa source model. Reason: R-HSA-9657706 inputs receptor-bound FXIa 158130 and contains the same native human heavy/light chains within APP(18–770)-bound product 9657716. This is a target-specific peripheral membrane model, corroborated at the gene level by the human platelet-binding assay. Refine to GO:0009897 without assigning APP processing or inhibitor activity to F11. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9673223 | MODIFY | Summary: Retain native FXIa external-surface localization in the disease reaction. Reason: The disease event R-HSA-9673223 concerns a factor IX variant substrate. Its catalystActivity 158128 is the same native human GPIb-associated FXIa complex 158130, with no disease modification on the F11 chains. This is not a mutant-F11 location projected onto the normal gene. Refine the supported receptor-associated F11 pool to the external membrane side. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9936430 | MODIFY | Summary: Specify the external face of the kininogen-containing activation complex. Reason: R-HSA-9936430 resolves from FXI–kininogen–GPIb input 9936436 to FXIa–kininogen–GPIb output 9936479; the target chains are native human F11. Factor XIIa performs activation. Human platelet binding in PMID:10823824 supports the extracellular-facing association and distinguishes this receptor-bound pool from an integral membrane product. Proposed replacements: external side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9936451 | MODIFY | Summary: Specify the external face of receptor-bound FXI–kininogen. Reason: The R-HSA-9936451 product 9936436 contains FXI 158143/158208 bound with kininogen and GPIb–IX–V. Both this exact participant chain and the cofactor-dependent human platelet assay support the external plasma-membrane surface. This gene-level refinement is not evidence that the 571-residue splice product was the tested protein. Proposed replacements: external side of plasma membrane |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Refine proteolysis to the demonstrated activation of a zymogen. Reason: Activated human FXI directly cleaves inactive factor IX to its active form in PMID:22961984. Current GO:0031638 defines precisely this proteolytic activation and is a descendant of protein processing and proteolysis. F11 performs the cleavage here; it is not merely the substrate of its own F12/F2-dependent activation. The InterPro mappings remain valid but broader than the measured target role. GO:0031639 plasminogen activation is an is_a descendant of GO:0031638, but it describes a different substrate-specific reaction. The independent FIX-cleavage experiment supports retaining zymogen activation for the central coagulation role; plasminogen activation remains a specialized non-core context. This is refinement of an existing proteolysis assertion, not a NEW term added for graph coverage. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR000177 SUPPORTS TRANSFER The broad proteolysis mapping is valid; target experiments identify the particular performed step. InterPro:IPR001254 SUPPORTS TRANSFER Target trypsin-domain match agrees with the observed zymogen activation. InterPro:IPR018114 SUPPORTS TRANSFER Target catalytic-histidine signature agrees with direct internal cleavage. Proposed replacements: zymogen activation |
| GO:0007596 blood coagulation | IDA PMID:9169594 Modification of the N-terminus of human factor IX by defecti... | MODIFY | Summary: Refine coagulation participation to the intrinsic pathway. Reason: The publisher-indexed original PMID:9169594 Results, p. 633, compares FXIa-mediated activation of normal human FIX and FIX Boxtel. Complete Methods and FXIa reagent provenance remain unread there; FIX phospholipid-binding results are not assigned to F11. Independently, PMID:22961984 Experimental Procedures and Figure 2 directly measure recombinant human FXIa cleavage of human FIX, and PMID:10823824 uses kaolin-activated partial thromboplastin-time assays in FXI-deficient plasma. The current GO:0007597 definition explicitly includes the FXIa-to-FIXa step, supporting intrinsic-pathway participation rather than only broad coagulation. The typed path to blood coagulation consists of part_of relations. This refinement does not make F11 merely a substrate of upstream activation or imply that all FXI activation must start with FXII. Proposed replacements: blood coagulation, intrinsic pathway |
| GO:0007596 blood coagulation | NAS PMID:9593722 Molecular cloning of platelet factor XI, an alternative spli... | MODIFY | Summary: Refine coagulation participation to the intrinsic pathway. Reason: PMID:9593722 establishes a platelet/megakaryocyte splice transcript and discusses prior coagulation work; it does not demonstrate equivalent catalytic activity of the shorter product. Independent human recombinant FXI clotting assays in PMID:10823824 and direct FXIa-mediated FIX cleavage in PMID:22961984 support the step explicitly included in GO:0007597. Refine the broad NAS process to blood coagulation, intrinsic pathway, without transferring those assays to the cloned shorter transcript. Current ontology links this pathway to blood coagulation through part_of relations; alternative upstream activation of FXI is not excluded. Proposed replacements: blood coagulation, intrinsic pathway |
| GO:0007596 blood coagulation | TAS PMID:10823824 The role of high molecular weight kininogen and prothrombin ... | MODIFY | Summary: Refine coagulation participation to the intrinsic pathway. Reason: PMID:10823824 Experimental Procedures use human recombinant FXI, washed human platelets and kaolin-activated partial thromboplastin-time assays in FXI-deficient plasma. Results and Table III distinguish platelet-supported from phospholipid-supported activity of A3 substitutions. These positive wild-type clotting assays, together with direct human FXIa-mediated FIX activation in PMID:22961984, support GO:0007597, whose definition explicitly includes that executed step. Refine the broad coagulation term to the intrinsic pathway. This does not assign autonomous proteolysis to inactive FXI, demonstrate activity of the exon-V-deleted natural product, or exclude thrombin-dependent upstream activation. Proposed replacements: blood coagulation, intrinsic pathway |
| GO:0008236 serine-type peptidase activity | IBA GO_REF:0000033 | MODIFY | Summary: Refine broad serine peptidase activity to endopeptidase activity. Reason: PTN002543071 has the actual broad peptidase IBD assertion, but current target ancestry cannot be reconstructed across the family-version discrepancy. Independently, the human FXIa factor IX-cleavage experiment in PMID:22961984 and EC 3.4.21.27 establish internal peptide-bond hydrolysis. GO:0004252 is the more precise descendant. This specificity correction does not reject the ancestral catalytic function or infer weakness from the number of donors. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002543071 UNRESOLVED The actual IBD assertion is recovered, but target descent was not verified. Immutable UniProt/InterPro membership says PTHR24252; current PANTHER v19 geneinfo says PTHR24253. The recovered 24252 MSA contains no exact canonical target sequence, and the required trees/mapped-family MSA timed out. This is an access/version limitation, not evidence against the biological function or an invalid self-WITH. Proposed replacements: serine-type endopeptidase activity |
| GO:0016020 membrane | NAS PMID:9593722 Molecular cloning of platelet factor XI, an alternative spli... | MODIFY | Summary: Peripheral association with the external platelet membrane is more precise than membrane. Reason: PMID:9593722 discusses platelet-associated FXI but principally assays RNA. Independent PMID:10823824 directly measures saturable binding of radiolabeled human FXI to activated washed human platelets, with cofactor, competition and nonspecific-binding controls; its A3 variants connect surface binding to clotting. Current GO:0009897 explicitly includes proteins peripherally associated with the extracellular membrane leaflet. This supports the finer external-face location, not an integral transmembrane topology or a demonstrated property of the 571-residue splice product. Proposed replacements: external side of plasma membrane |
| GO:0031639 plasminogen activation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain experimentally supported plasminogen activation as contextual. Reason: PMID:89876 reports plasminogen-dependent fibrinolytic activity after activation of purified native human FXI, with antibody adsorption, kallikrein-contamination and activating-factor controls. This is positive target evidence for the transferred function. The fibrin-plate comparison used concentrations about 30 times plasma levels and does not establish a dominant physiological fibrinolytic role. Retain the contextual activity; current PAINT ancestry remains unverified despite the recovered IBD, and the target in its own WITH is legitimate experimental grounding. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002548665 UNRESOLVED The actual IBD assertion is recovered, but target descent was not verified. Immutable UniProt/InterPro membership says PTHR24252; current PANTHER v19 geneinfo says PTHR24253. The recovered 24252 MSA contains no exact canonical target sequence, and the required trees/mapped-family MSA timed out. This is an access/version limitation, not evidence against the biological function or an invalid self-WITH. |
| GO:0031639 plasminogen activation | IDA PMID:89876 Hageman-factor-dependent fibrinolysis: generation of fibrino... | KEEP AS NON CORE | Summary: Activated human FXI has measured in vitro plasminogen-activating capacity. Reason: The selected original PMID:89876 pages 851, 853, 855, 857 and 859 describe purified human plasma FXI, Hageman-fragment activation and plasminogen-dependent fibrin-plate assays. Anti-FXI versus anti-prekallikrein immunoadsorption and chromogenic comparisons argue against contaminating kallikrein explaining the activity; the authors also discuss conflicting earlier results. Preserve this positive specialized capacity as non-core. Prolonged activation and concentrated preparations, including the Figure 7 comparison at 30-fold plasma concentration, do not establish a dominant physiological fibrinolytic role or activity of every splice product. Supporting Evidence: |
| GO:0031639 plasminogen activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the rule-predicted plasminogen activity as contextual. Reason: The current ARBA00087422 condition requiring FunFam 3.50.4.10:FF:000001 and Primates is satisfied by the official target record. Independently, PMID:89876 supports plasminogen-dependent activity of purified activated human FXI under the stated high-concentration assay conditions. Keep the biological assertion, but not as a principal physiological function; a valid rule match does not strengthen that experimental scope. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00087422 SUPPORTS TRANSFER An exact target FunFam/taxon clause matches, and the positive target assay supports a contextual function. |
| GO:0042802 identical protein binding | IPI P03951-1 PMID:16699514 Crystal structure of the factor XI zymogen reveals a pathway... | MODIFY | Summary: The supported self-association is homodimer formation. Reason: The official Supplementary Methods for PMID:16699514 identify homogeneous native human plasma FXI used for the zymogen crystal structure; the accessible main abstract reports its disulfide-linked dimer. The independently read full original PMID:17884987 resolves the recombinant A4-domain dimer interface and examines whole FXI/FXIa preparations by solution scattering. GO:0042803 captures the established association of identical subunits more precisely than generic identical protein binding. Preserve the source’s P03951-1 designation; the evidence is not transferred to the 571-residue splice product, and the complete 2006 main Results were not inspected. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI P03951-1 PMID:17884987 Solution structure of the A4 domain of factor XI sheds light... | MODIFY | Summary: The A4-mediated self-interaction supports protein homodimerization. Reason: PMID:17884987 Results and Methods analyze the recombinant A4 domain, paper-numbered residues 272–361, and commercial human FXI/FXIa preparations. NMR identifies the disulfide-linked A4 dimer and its noncovalent interface; whole-protein solution-scattering comparisons support a dimeric assembly. This is more specific than generic identical protein binding. The proposed compact activated conformation is a structural model rather than proof of every activation step. Retain the imported P03951-1 scope without equating the isolated domain or mature preparations with the shorter natural splice product. Proposed replacements: protein homodimerization activity Supporting Evidence: |
| GO:0051919 positive regulation of fibrinolysis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the positive fibrinolytic effect in the original assay context. Reason: Activated native human FXI increased plasminogen-dependent fibrin digestion in PMID:89876, with controls addressing kallikrein contamination and the activating Hageman-factor fragment. The term describes an increase in fibrinolysis and fits that positive assay. It does not establish that FXI is a principal fibrinolytic regulator in vivo. Retain as non-core while recording the unverified current PAINT target path separately from this direct target evidence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002548665 UNRESOLVED The actual IBD assertion is recovered, but target descent was not verified. Immutable UniProt/InterPro membership says PTHR24252; current PANTHER v19 geneinfo says PTHR24253. The recovered 24252 MSA contains no exact canonical target sequence, and the required trees/mapped-family MSA timed out. This is an access/version limitation, not evidence against the biological function or an invalid self-WITH. |
| GO:0051919 positive regulation of fibrinolysis | IDA PMID:89876 Hageman-factor-dependent fibrinolysis: generation of fibrino... | KEEP AS NON CORE | Summary: The purified-enzyme experiment supports a bounded profibrinolytic effect. Reason: PMID:89876 measures plasminogen-dependent fibrin lysis after activation of purified human FXI. The selected original Methods and Results include no-Hageman-fragment controls, deficient-plasma comparisons and immunological/enzymatic checks against kallikrein contamination. FXIa therefore performs an upstream activating step rather than merely being a consumed substrate. Retain positive regulation of fibrinolysis as a specialized non-core experimental context; the prolonged, concentrated in vitro preparations and acknowledged disagreement with earlier studies do not establish physiological dominance. Supporting Evidence: |
| GO:0051919 positive regulation of fibrinolysis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain the rule-supported fibrinolytic effect as non-core. Reason: ARBA00089948 has an exact match to the target FunFam 3.50.4.10:FF:000001 and Primates lineage. PMID:89876 independently shows an increase in plasminogen-dependent fibrin digestion after FXI activation. The high-concentration purified-protein experiment supports this secondary activity without establishing its dominance in physiological clot turnover. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00089948 SUPPORTS TRANSFER The captured target satisfies the full current clause; physiological scope remains bounded by the original assay. |
| GO:0070009 serine-type aminopeptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Replace unsupported amino-terminal specificity with the demonstrated endopeptidase function. Reason: The Ensembl donor trace reaches rat F11 A0A0G2K4I9 and two RGD IDA records. PMID:15331420 actually measures rat plasma FXI functional activity during an arthritis experiment; its Methods refer the FXI assay to a prior microplate method, and its Results report changes in plasma activity. The other donor paper, PMID:10899350, remains abstract/selected-passage accessible only. Neither inspected scope establishes removal of single N-terminal amino acids, which current GO:0070009 specifically requires. Human FXIa instead directly cleaves internal factor IX bonds in PMID:22961984. Modify to that independently established target activity without claiming the unread donor experiment is false or that the rat orthology is wrong. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:A0A0G2K4I9 UNRESOLVED Exact rat F11 donor and its two IDA sources were recovered. Rat functional-activity measurements do not resolve the claimed amino-terminal substrate specificity in the inspected evidence. ensembl:ENSRNOP00000073061 UNRESOLVED The literal source protein identifier is preserved; no loss or paralog claim is inferred from incomplete assay access. Proposed replacements: serine-type endopeptidase activity |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: F11 was detected in a human urinary extracellular-vesicle preparation. Reason: The original PMID:19056867 Methods use pooled urine from eight healthy people, differential ultracentrifugation and LC-MS/MS. Its linked NHLBI table contains the exact F11/NP_000119 record with one peptide. The study’s ambiguity procedure permits peptides shared by splice products of the same gene, so this does not resolve the 625- versus 571-residue product or active FXIa. Retain the source’s urinary-exosome detection as non-core, without inferring a universal exosome location, a vesicle-biogenesis role, or luminal versus surface topology. The urinary anatomical extension remains confined to the captured raw source. Supporting Evidence: |
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Download this section (compressed HTML)Q: Does the 571-residue platelet-associated splice product form a secreted, correctly processed dimer, and how do its platelet association, activation and factor IX-cleaving activity compare with the 625-residue precursor?
Q: Under which physiological conditions, if any, does factor XIa's measured plasminogen-activating capacity contribute appreciably to fibrinolysis relative to its factor IX-dependent coagulation role?
Experiment: Express sequence-verified 625- and 571-residue F11 products in the same system and measure secretion, chain processing and oligomeric state. Compare matched zymogen and activated preparations for binding to washed human platelets with controlled kininogen or prothrombin, and quantify factor IX cleavage after normalizing to active-site concentration. Include catalytic-site controls and distinguish protein detection from transcript abundance.
Experiment: Compare factor IX activation, plasmin generation and fibrin-clot lysis across physiological concentrations of purified FXIa in defined plasma systems. Include FXI-depleted plasma and add-back, active-site inhibition, plasminogen depletion, and controls for kallikrein and activating-enzyme carryover. Quantify both coagulation and lysis over matched time courses to determine whether the specialized in-vitro capacity contributes under conditions that support clotting.
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