Coagulation factor X

Function

Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner. Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1/F2R-dependent manner. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues. Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues. Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues. Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues. Activates pro-inflammatory and pro-fibrotic responses in dermal fibroblasts and enhances wound healing probably via PAR-2/F2RL1-dependent mechanism. Activates barrier protective signaling responses in endothelial cells in PAR-2/F2RL1-dependent manner; the activity depends on the cleavage of PAR-2/F2RL1 by factor Xa. Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues.

Classification

Family (Pfam)

PF00008 EGF, PF14670 FXa_inhibition, PF00594 Gla, PF00089 Trypsin

InterPro

Coagulation_fac-like_Gla_dom, EGF, EGF-like_Ca-bd_dom, EGF-type_Asp/Asn_hydroxyl_site, EGF_Ca-bd_CS, GLA-like_dom_SF, GLA_domain, Pept_S1A_FX, Peptidase_S1_coag_factors, Peptidase_S1_PA, Peptidase_S1_PA_chymotrypsin, Peptidase_S1A, Trypsin_dom, TRYPSIN_HIS, TRYPSIN_SER

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 186

• 1C5M X-ray 1.95A
• 1EZQ X-ray 2.20A
• 1F0R X-ray 2.10A
• 1F0S X-ray 2.10A
• 1FAX X-ray 3.00A
• 1FJS X-ray 1.92A
• 1FXY X-ray 2.15A
• 1G2L X-ray 1.90A
• 1G2M X-ray 3.02A
• 1HCG X-ray 2.20A
• 1IOE X-ray 2.90A
• 1IQE X-ray 2.90A
• … and 174 more

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005788 endoplasmic reticulum lumen
• GO:0009897 external side of plasma membrane
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005796 Golgi lumen
• GO:0005886 plasma membrane
• GO:0005509 calcium ion binding
• GO:0005543 phospholipid binding
• GO:0004252 serine-type endopeptidase activity
• GO:0007596 blood coagulation
• GO:0030335 positive regulation of cell migration
• GO:0032008 positive regulation of TOR signaling
• GO:0006508 proteolysis

Disease associations

• congenital factor X deficiency MONDO:0009212

Drugs targeting this protein · 8

• LETAXABAN inhibitor
• DAREXABAN inhibitor
• RIVAROXABAN inhibitor
• EDOXABAN TOSYLATE inhibitor
• APIXABAN inhibitor
• OTAMIXABAN inhibitor
• BETRIXABAN inhibitor
• IDRAPARINUX SODIUM inhibitor

Related proteins · sequence + function similarity

• Coagulation factor X 0.98
• Coagulation factor X 0.96
• Coagulation factor X 0.96
• Coagulation factor X 0.94
• Coagulation factor X 0.93
• Venom prothrombin activator porpharin-D 0.92
• Coagulation factor IX 0.91
• Venom prothrombin activator oscutarin-C catalytic subunit 0.91
• Coagulation factor IX 0.91
• Coagulation factor X isoform 2 0.91
• Coagulation factor IX 0.91
• Venom prothrombin activator omicarin-C catalytic subunit 0.91

Co-cited proteins · studied together in the literature

• Ixolaris 4 shared papers
• FXa-directed anticoagulant 2 shared papers
• Coagulation factor X 3 shared papers
• Coagulation factor X 1 shared papers
• Proteinase-activated receptor 1 3 shared papers
• Prothrombin 4 shared papers
• Coagulation factor X 2 shared papers
• Proteinase-activated receptor 2 1 shared papers
• Simukunin 1 shared papers
• Hexon protein 1 shared papers
• Protein Z-dependent protease inhibitor 1 shared papers
• Proteinase-activated receptor 2 1 shared papers

Literature · 55 cited papers

• Molecular basis of vitamin-K-driven gamma-carboxylation at the membrane interface. Nature · 2025
• Structure-derived insights from blood factors binding to the surfaces of different adenoviruses. Nat. Commun. · 2024
• Guianensin, a Simulium guianense salivary protein, has broad anti-hemostatic and anti-inflammatory properties. Front. Immunol. · 2023
• Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus, Displays Anti-FXa-PAR Signaling In Vitro and In Vivo. Immunohorizons · 2022
• Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1. Cells · 2021
• Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement. Int. J. Mol. Sci. · 2021
• NMR structure determination of Ixolaris and factor X(a) interaction reveals a noncanonical mechanism of Kunitz inhibition. Blood · 2019
• TAK-442, a Direct Factor Xa Inhibitor, Inhibits Monocyte Chemoattractant Protein 1 Production in Endothelial Cells via Involvement of Protease-Activated Receptor 1. Front. Pharmacol. · 2018
• Frequency of the p.Gly262Asp mutation in congenital Factor X deficiency. Eur. J. Clin. Invest. · 2015
• Molecular dynamics characterization of five pathogenic Factor X mutants associated with decreased catalytic activity. Biochemistry · 2014
• Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue. Eur. J. Pharmacol. · 2013
• Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells. Biochemistry · 2012
• … and 43 more in the literature graph