Coagulation Factor XI

Factor XI (plasma thromboplastin antecedent) is a plasma glycoprotein, and a zymogen acting as a serine protease which participates in blood coagulation as a catalyst in the conversion of factor IX to factor IXa in the presence of calcium ions. It is an unusual dimeric protease, with structural features that distinguish it from vitamin K-dependent coagulation proteases. The factor XI is synthesized in the liver as a single polypeptide chain with a molecular weight estimated between 125 ~160 kDa and then is processed into a disulfide-bond linked homodimer. FXI is a homodimer, with each subunit containing four apple domains and a protease domain. The apple domains form a disk structure with binding sites for platelets, high molecular weight kininogen, and the substrate factor IX (FIX). FXI is converted to the active protease FXIa by cleavage of the Arg369-Ile370 bond on each subunit. After the activation reaction, Factor XIa is composed of two heavy and two light chains held together by three disulfide bonds. The heavy chains are derived from the amino termini of the zymogen and responsible for the binding of factor XI to high molecular weight kininogen and for the activation of factor IX, while the light chain contains the catalytic portion of the enzyme and is homologous to the trypsin family of serine proteases. FXI deficiency is a disorder characterized by a mild or no bleeding tendency. Severe FXI deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide.

Coagulation Factor XI Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Coagulation Factor XI

Immunology>>Innate Immunity>>Coagulation>>Coagulation Factor XI

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Coagulation Factor XI Alternative Names

Coagulation Factor XI, FXI, F11, MGC141891 [Homo sapiens]

Coagulation Factor XI, FXI, F11, 1600027G01Rik, AI503996, Cf11 [Mus musculus]

Summaries for Coagulation Factor XI

Entrez Gene summary for Coagulation Factor XI:

This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality.

OMIM - description for Coagulation Factor XI:

Factor XI is a glycoprotein that circulates in plasma as a noncovalent complex with high molecular weight kininogen (HMWK; see 612358). It is converted to an active protease, factor XIa, by factor XIIa (F12; 610619). It participates in blood coagulation as a catalyst in the conversion of factor IX to factor IXa in the presence of calcium ions

Wikipedia summary for Coagulation Factor XI:

Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene

Human Coagulation Factor XI Protein General Information

 

• Protein names: Recommended name: Coagulation factor XI Short name=FXI
• Sequence length: 625 AA.
• Domain: Repeat Signal
• Sequence similarities: Belongs to the peptidase S1 family. Plasma kallikrein subfamily. Contains 4 apple domains. Contains 1 peptidase S1 domain.
• Post-translational modification: Activated by factor XIIa (or XII), which cleaves each polypeptide after Arg-387 into the light chain, which contains the active site, and the heavy chain, which associates with high molecular weight (HMW) kininogen.
• Subcellular location: Secreted.
• Tissue specificity: Isoform 2 is produced by platelets and megakaryocytes but absent from other blood cells.
• Involvement in disease: Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.

General information above from UniProt

Function for Coagulation Factor XI Protein

UniProtKB:

Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.

Genatlas:

• Coagulation Factor XI triggere the middle phase of the intrinsic pathway of blood coagulation by activating factor IX
• Coagulation Factor XI promotes hemostasis and thrombosis through enhancement of thrombin generation and may play a critical role in the formation of occlusive thrombi in arterial injury models (White-Adams 2009)

Phenotype Information for Coagulation Factor XI

• Gene/Locus: F11
• Phenotype: Factor XI deficiency, autosomal dominant Factor XI deficiency, autosomal recessive

Phenotype Information for Coagulation Factor XI from OMIM (Online Mendelian Inheritance in Man)

Drugs for Coagulation Factor XI

Target	Drug Name	Disease	Drug Status
Coagulation Factor XI	Octopamine	Thromboembolic Disorders	Discontinued in Phase IIa
Coagulation Factor XI	SR-123781A	Acute Coronary Syndromes	Discontinued in Phase II
Coagulation Factor XI	SR-123781A	Venous Thromboembolism Phase III completed, and Positive results in a large European	Phase III trial
Coagulation Factor XI	Apixaban	Atrial Fibrillation	Phase III

Drugs for Coagulation Factor XI from TTD (Therapeutic Targets Database)