Protein Z
Encyclopedia
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. It is a glycoprotein
.
s of the coagulation cascade: factors VII
, IX
, X
and protein C
. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid
surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor
(ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI
, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to thrombosis
. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis
.
large and 396 amino acid
s long. The PROZ gene
has been linked to the thirteenth chromosome
(13q34).
It has four domains: a gla
-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine
residue that would make it catalytically active as a serine protease
.
blood by Prowse and Esnouf in 1977, and Broze & Miletich determined it in human plasma in 1984.
, the secondary structure of Protein Z was determined. The Ramachandran plot utilizes mathematical equations to determine the possible angles of the amino acids within the primary sequence of Protein Z. The possible angles results in a plot of possible secondary structures. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all aphla domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the PROZ 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...
.
Protein Z is a member 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...
, the group of blood proteins that leads to the formation of blood clots. It is vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
-dependent, and its functionality is therefore impaired in warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
therapy. It is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
.
Physiology
Although it is not enzymatically active, it is structurally related to several serine proteaseSerine 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...
s of the coagulation cascade: factors VII
Factor VII
Factor VII is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients...
, 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...
, 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:...
and protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor
Protein Z-related protease inhibitor
Protein Z-dependent protease inhibitor is a protein circulating in the blood which inhibits factors Xa and XIa of the coagulation cascade. It is a member of the class of the serine protease inhibitors...
(ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI
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....
, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to 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...
. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for 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...
.
Genetics
It is 62 kDaKDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
large and 396 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s long. The PROZ 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...
has been linked to the thirteenth chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
(13q34).
It has four domains: a gla
Carboxyglutamate
Carboxyglutamic acid , is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium...
-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residue that would make it catalytically active as 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...
.
History
Protein Z was first isolated in cattleCattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
blood by Prowse and Esnouf in 1977, and Broze & Miletich determined it in human plasma in 1984.
Structure
Structural analysis of protein Z will allow better understanding of its function. From a Ramachandran plotRamachandran plot
-Introduction and early history:A Ramachandran plot , originally developed in 1963 by G. N. Ramachandran C. Ramakrishnan and V...
, the secondary structure of Protein Z was determined. The Ramachandran plot utilizes mathematical equations to determine the possible angles of the amino acids within the primary sequence of Protein Z. The possible angles results in a plot of possible secondary structures. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all aphla domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.