Factor XI
Encyclopedia
Factor XI or plasma thromboplastin antecedent is the zymogen
form of factor XIa, one of the enzyme
s of the coagulation cascade
. Like many other coagulation factors, it is a serine protease
. In humans, Factor XI is encoded by the F11 gene
.
and circulates as a homo-dimer
in its inactive form. The plasma half-life of FXI is approximately 52 hours. The zymogen factor is activated into factor XIa by factor XII
a (FXIIa), thrombin
, and it is also autocatalytic, and FXI is a member of the "contact pathway" due to activation by FXIIa (with includes HMWK, prekallikrein
, factor XII
, factor XI and factor IX
).
Factor XIa activates factor IX by selectively cleaving arg
-ala
and arg
-val
peptide bond
s. Factor IXa, in turn, activates factor X
.
Inhibitors of factor XIa include protein Z-dependent protease inhibitor (ZPI, a member of the serine protease inhibitor/serpin class of proteins), which is independent of protein Z
(its action on factor X, however, is protein Z-dependent, hence its name).
The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.
; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population, of both sexes. The condition has been described in other populations at around 1% of cases. It is an autosomal recessive disorder. There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.
Low levels of factor XI also occur in many other disease states, including Noonan syndrome
.
High levels of factor XI have been implicated in thrombosis
, although it is uncertain what determines these levels and how serious the procoagulant state is.
Zymogen
A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
form of factor XIa, one of the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s of the coagulation cascade
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
. Like many other coagulation factors, it is a serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
. In humans, Factor XI is encoded by the F11 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Physiology
Factor XI (FXI) is produced by the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and circulates as a homo-dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
in its inactive form. The plasma half-life of FXI is approximately 52 hours. The zymogen factor is activated into factor XIa by factor XII
Factor XII
Coagulation factor XII also known as Hageman factor is a plasma protein. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.- Function :...
a (FXIIa), thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
, and it is also autocatalytic, and FXI is a member of the "contact pathway" due to activation by FXIIa (with includes HMWK, prekallikrein
Prekallikrein
Prekallikrein , also known as Fletcher factor, is a 85,000 Mr serine protease that complexes with High-molecular-weight kininogen. PK is the precursor of plasma kallikrein, which is a serine protease that activates kinins. PK is cleaved to produce kallikrein by activated Factor XII . -...
, factor XII
Factor XII
Coagulation factor XII also known as Hageman factor is a plasma protein. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.- Function :...
, factor XI and factor IX
Factor IX
Factor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to...
).
Factor XIa activates factor IX by selectively cleaving arg
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
-ala
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
and arg
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
-val
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
s. Factor IXa, in turn, activates factor X
Factor X
Factor X, also known by the eponym Stuart-Prower factor or as prothrombinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase .-Physiology:...
.
Inhibitors of factor XIa include protein Z-dependent protease inhibitor (ZPI, a member of the serine protease inhibitor/serpin class of proteins), which is independent of protein Z
Protein Z
Protein Z also known as PROZ is a protein which in humans is encoded by the PROZ gene.Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy...
(its action on factor X, however, is protein Z-dependent, hence its name).
Protein structure and molecular biology
Although synthesized as a single polypeptide chain, FXI circulates as a homodimer. Every chain has a relative molecular mass of approximately 80000. Typical plasma concentrations of FXI are 5 μg/mL, corresponding to a plasma concentration (of FXI dimers) of approximately 30 nM.The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.
Role in disease
Deficiency of factor XI causes the rare Haemophilia CHaemophilia C
Haemophilia C is a mild form of haemophilia affecting both sexes. However, it predominantly occurs in Jews of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B...
; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population, of both sexes. The condition has been described in other populations at around 1% of cases. It is an autosomal recessive disorder. There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.
Low levels of factor XI also occur in many other disease states, including Noonan syndrome
Noonan syndrome
Noonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
.
High levels of factor XI have been implicated in thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, although it is uncertain what determines these levels and how serious the procoagulant state is.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: S01.213