SERPINA10

Last update 08 May 2025

Basic Info

Synonyms

Protein Z-dependent protease inhibitor, PZ-dependent protease inhibitor, PZI

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Introduction

Inhibits activity of the coagulation protease factor Xa in the presence of PROZ, calcium and phospholipids. Also inhibits factor XIa in the absence of cofactors.

100 Clinical Results associated with SERPINA10

100 Translational Medicine associated with SERPINA10

0 Patents (Medical) associated with SERPINA10

123

Literatures (Medical) associated with SERPINA10

01 Jun 2025·Clinica Chimica Acta

Data independent acquisition proteomics and machine learning reveals that proteins associated with immunity are potential molecular markers for early diagnosis of autism

Article

Author: Yan, Kang ; Cheng, Yuxia ; Gong, Xiaohui ; Wang, Tuanmei ; Hu, Erlin ; Zhaohui, Sun ; Ming, Zhu ; Zhou, Wenjuan ; Gan, Tuoyu ; Peng, Xiangwen ; Kuang, Xiaoni ; Ye, Chunhua ; Wang, Sifeng

BACKGROUNDEarly diagnosis of autism is critical to its treatment, but so far, there is no clear molecular marker for early diagnosis in children.METHODSWe used data independent acquisition (DIA) mass spectrometry to compare protein expression in serum from 99 Chinese children with autism spectrum disorders with 70 healthy children.RESULTSWe identified 347 downregulated and 394 upregulated proteins. Based on bioinformatics analysis, differential proteins were enriched in the immune system, immune disease, cell motility, and focal adhesion. Machine learning revealed a model with eight proteins (IGH c1898_heavy_IGHV3-33_IGHD3-9_IGHJ4, LYZ, IGL c1860_light_IGLV8-61_IGLJ2, SERPINA10, IG c1421_light_IGKV1-27_IGKJ4, rheumatoid factor RF-ET1, IGL c600_light_IGKV4-1_IGKJ4, and SELL) that were mostly associated with immunity, and accurate for diagnosis of autism. The protein family was verified by a logic-regression leave-one cross-validation method with bidirectional feature screening. The accuracy of this model was 0.9527, and the kappa coefficient was 0.9025.CONCLUSIONSOur study showed that immunity is closely related to the onset of autism and can be used for early screening of patients. A model with eight proteins (IGH c1898_heavy_IGHV3-33_IGHD3-9_IGHJ4, LYZ, IGL c1860_light_IGLV8-61_IGLJ2, SERPINA10, IG c1421_light_IGKV1-27_IGKJ4, rheumatoid factor RF-ET1, IGL c600_light_IGKV4-1_IGKJ4, and SELL), which are mostly associated with immunity, is accurate for diagnosis of autism.

01 May 2025·Arteriosclerosis, Thrombosis, and Vascular Biology

Tapping Into the Natural PZ-Independent Anticoagulant Function of ZPI to Inhibit Thrombosis With Minimal Effect on Hemostasis

Article

Author: Wang, Can ; Swanson, Richard ; Du, Xiaoping ; Huang, Xin

BACKGROUND:The protein ZPI (Z-dependent protease inhibitor) binds to PZ (protein Z), which enables ZPI to inhibit membrane-bound FXa (activated factor X). ZPI also inhibits FXIa (activated factor XI) independently of PZ.METHODS:To study the PZ-independent ZPI function, we tested the in vitro and in vivo effect of disrupting the ZPI-PZ interaction by mutating ZPI Asp 293 to Ala (D293A).RESULTS: D293A mutation reduced PZ-dependent FXa inhibition without affecting FXIa inhibition. D293A also diminished FXIIa (activated FXII)-induced thrombin generation but reduced TF (tissue factor)-induced thrombin generation only at low TF concentrations. This suggests that D293A selectively inhibits the intrinsic pathway and the thrombin-FXI (factor XI) feedback loop that enhances low-dose TF-initiated coagulation. Wild-type and D293A ZPI both showed selectivity in inhibiting activated partial thromboplastin time but not prothrombin time. Increasing PZ in plasma enhances activated partial thromboplastin time inhibition and enables prothrombin time inhibition by wild-type but not D293A ZPI, further indicating that D293A ZPI selectively inhibits the intrinsic pathway independently of PZ. In mouse models, D293A inhibited FeCl 3 -induced occlusive carotid artery thrombosis and venous thrombosis in the inferior vena cava. Thus, PZ-independent ZPI function plays a major role in ZPI inhibition of occlusive thrombosis, and D293A ZPI is an effective antithrombotic. Importantly, administering D293A ZPI did not affect tail bleeding time and showed improved hemostasis in a saphenous vein hemostasis model as compared with wild-type ZPI. CONCLUSIONS:The PZ-binding defective variant of ZPI, D293A, selectively inhibits the intrinsic coagulation pathway and is a new anticoagulant with reduced bleeding risk.

01 Mar 2025·Thrombosis and Haemostasis

An Inhibitory Single-Domain Antibody against Protein Z-Dependent Protease Inhibitor Promotes Thrombin Generation in Severe Hemophilia A and FXI Deficiency

Article

Author: Lenting, Peter ; Nguyen, Tung-Son ; Bianchini, Elsa P. ; Saller, François ; Repérant, Christelle ; Daramé, Sadyo ; Auditeau, Claire ; Blandinières, Adeline ; Borgel, Delphine ; Devaux, Floriane ; Peyron, Ivan ; Denis, Cécile V.

Background Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that targets factor Xa (FXa) in the presence of protein Z (PZ), and factor XIa (FXIa). In factor-VIII-deficient mice, PZ or ZPI gene knock-out mitigates the bleeding phenotype, and pharmacological inhibition of PZ enhances thrombin generation in plasma from patients with hemophilia. Aims To develop a single-domain antibody (sdAb) directed against ZPI to inhibit its anticoagulant activity. Methods We screened for anti-ZPI sdAbs in a llama-derived phage display immune library of sdAbs. The sdAbs that bound ZPI were produced and purified for characterization. The binding of sdAbs to ZPI or other serpins was evaluated using ELISAs, and ZPI inhibition was measured in an anti-FXa or anti-FXIa chromogenic assay. The sdAbs's procoagulant activity was assessed in a thrombin generation assay in normal plasma, factor VIII- and FXI-deficient plasma. Results Of the four sdAbs found to bind to ZPI, one (referred to as ZPI-sdAb2) dose-dependently inhibited ZPI's anti-FXa and anti-FXIa activities with a mean half-maximal inhibitory concentration of 1.8 and 1.3 µM, respectively. ZPI-sdAb2 did not cross-react with other plasma serpins, such as antithrombin and α1-antitrypsin. ZPI-sdAb2 induced a significant increase in thrombin generation in plasma samples from healthy donors, patients with severe hemophilia A, and patients with FXI deficiency. Conclusion ZPI-sdAb2 is the first specific, direct ZPI inhibitor found to exhibit procoagulant activity in plasma. This sdAb might have potential as a treatment for hemophilia or other bleeding disorders.

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SERPINA10

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