Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person This Reactome event shows interaction between the activated ...
| Class:Id | Summation:9657696 |
|---|---|
| _displayName | This Reactome event shows interaction between the activated ... |
| _timestamp | 2025-02-18 10:25:23 |
| created | [InstanceEdit:9657703] Shamovsky, Veronica, 2019-08-09 |
| literatureReference | [LiteratureReference:9657704] Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin [LiteratureReference:9657699] The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II [LiteratureReference:9657712] Immunopurification and protease inhibitory properties of protease nexin-2/amyloid beta-protein precursor [LiteratureReference:140312] Protease nexin-II (amyloid beta-protein precursor): a platelet alpha-granule protein [LiteratureReference:9660294] Progress curve analysis of the kinetics with which blood coagulation factor XIa is inhibited by protease nexin-2 [LiteratureReference:9660296] Protease nexin II interactions with coagulation factor XIa are contained within the Kunitz protease inhibitor domain of protease nexin II and the factor XIa catalytic domain [LiteratureReference:9660812] Mechanisms and specificity of factor XIa and trypsin inhibition by protease nexin 2 and basic pancreatic trypsin inhibitor [LiteratureReference:9660805] Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2 [LiteratureReference:9660810] The mechanism by which heparin promotes the inhibition of coagulation factor XIa by protease nexin-2 [LiteratureReference:9660807] Zinc (II) selectively enhances the inhibition of coagulation factor XIa by protease nexin-2/amyloid beta-protein precursor [LiteratureReference:9660808] P1 and P2' site mutations convert protease nexin-2 from a factor XIa inhibitor to a plasmin inhibitor [LiteratureReference:9660813] Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid β-protein precursor abolishes its anti-thrombotic properties in vivo [LiteratureReference:9660799] The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis |
| modified | [InstanceEdit:9660816] Shamovsky, Veronica, 2019-09-11 [InstanceEdit:9935180] Shamovsky, Veronica, 2025-01-13 [InstanceEdit:9938608] Shamovsky, Veronica, 2025-02-18 |
| text | This Reactome event shows interaction between the activated factor XI (FXIa) and amyloid‑β precursor protein (AβPP, APP (18‑770), also known as protease nexin 2 (PN2)). Following platelet activation by physiological stimulators, APP (18‑770) is secreted from α‑granules into plasma (Oltersdorf T et al., 1989; Van Nostrand WE et al., 1990a, b; Smith RP & Broze GJ Jr, 1992). APP (18‑770) (PN2) is a Kunitz‑type protease inhibitor (KPI) that acts as a slow, tight-binding inhibitor of activated FXIa, with a Ki of 290‑450 pM (Van Nostrand WE et al., 1990; Scandura JM et al., 1997). The inhibition of FXIa by APP (18‑770) requires specific interactions between the catalytic domain of FXIa and the KPI domain of PN2 (APP (18‑770)) (Badellino KO & Walsh PN, 2000). The isolated KPI domain of PN2 and the catalytic domain of FXIa have been co‑crystallized, with their structure solved to a resolution of 2.6 Å (Navaneetham D et al., 2005). Structural and mutational analyses revealed several critical residues, including the P1 site residue within the KPI domain of PN2, which directly interacts with the catalytic domain of FXIa by forming a salt bridge within the S1 specificity pocket (Navaneetham D et al., 2005, 2010). Mechanistic studies suggest that inhibition proceeds via a slow equilibration process between the free enzyme and the inhibitor, rather than through a loosely associated complex (Navaneetham D et al., 2010). Zn2+ enhances PN2-mediated inhibition of FXIa, whereas high molecular weight kininogen (HMWK) dose-dependently protects FXIa from inhibition by PN2, with an EC50 value of 61 nM (Van Nostrand WE, 1995; Scandura JM et al., 1997). Heparin also enhances FXIa inhibition by PN2, though this enhancement is partially abrogated by HK (Zhang Y et al., 1997). Furthermore, administration of the KPI domain of PN2 prolonged clotting time and inhibited FXIa activity in both human and murine plasma (Wu W et al., 2012; Xu F et al., 2017). In mice, intravenous administration of the KPI domain of PN2 significantly reduced thrombus formation in a murine model of FeCl3‑induced carotid injury, further supporting the antithrombotic function of PN2 (APP(18‑770)) (Wu W et al., 2012; Navaneetham D et al., 2013). |
| (summation) | [Reaction:9657706] factor XIa binds APP(18-770) [Homo sapiens] |
| [Change default viewing format] | |
