Heparanase, also known as HPSE, is an enzyme Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Since enzymes are selective for their that acts both at the cell-surface and within the extracellular matrix In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals to degrade polymeric heparan sulfate Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including molecules into shorter chain length oligosaccharides An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars (monosaccharides). The name is derived from the Greek word oligos, meaning "a few", and from the Latin/Greek word sacchar which means "sugar". Oligosaccharides can have many functions; for example, they are.[1][2]

Contents

Synthesis and structure

The protein is originally synthesised in an inactive 65 kDa proheparanase form in the golgi apparatus The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi and was named after him and transferred to late endosomes In biology, an endosome is a membrane bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma/lysosomes Lysosomes are spherical organelles that contain enzymes . They break up food so it is easier to digest. They are found in animal cells, while in yeast and plants the same roles are performed by lytic vacuoles. Lysosomes digest excess or worn-out organelles, food particles, and engulfed viruses or bacteria. The membrane around a lysosome allows the for transport to the cell-surface. In the lysosome it is proteolytically processed Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion into its active form. Proteolytic processing results in the production of three products,

The 8 kDa and 50 kDa fragments form a heterodimer and it is this heterodimer that constitutes the active heparanase molecule.[3] The linker protein is so called because prior to its excision it physically links the 8 kDa and 50 kDa proheparanase fragments. Complete excision of the linker peptide appears to be a prerequisite to the complete activation of the heparanase enzyme.

Endoglycosidic_action">

Endoglycosidic action An Endoglycosidase is an enzyme that releases oligosaccharides from glycoproteins or glycolipids. Or it merely cleaves polysaccharide chains between residues that are not the terminal residue, although releasing oligosaccharides from conjugated protein and lipid molecules is more common

Heparanase cleaves polymeric heparan sulfate Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including molecules at sites which are internal within the polymeric chain.[4] In ocular surface physiology this activity functions as an off/on switch for the prosecretory mitogen lacritin Lacritin is a 12.3 kDa glycoprotein encoded in humans by the LACRT gene. Lacritin is a secreted protein found in tears and saliva. Lacritin also promotes tear secretion and proliferation of some epithelial cells. Lacritin is thus a prosecretory mitogen. Lacritin binds the cell surface heparan sulfate proteoglycan syndecan-1 Syndecan 1 is a protein which in humans is encoded by the SDC1 gene only in the presence of active heparanase. Heparanase partially or completely cleaves heparan sulfate Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including to expose a binding site in the N-terminal 50 amino acids of syndecan-1 Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.[5]

metastasis_and_angiogenesis">

Role in metastasis Metastasis , or metastatic disease (sometimes abbreviated mets), is the spread of a disease from one organ or part to another non-adjacent organ or part. It had been previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research and angiogenesis Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones

The successful penetration of the endothelial cell layer The endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. These cells reduce that lines the interior surface of blood vessels The blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from is an important process in the formation of blood borne tumour metastases Metastasis , or metastatic disease (sometimes abbreviated mets), is the spread of a disease from one organ or part to another non-adjacent organ or part. It had been previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research. Heparan sulfate Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including proteoglycans Proteoglycans are glycoproteins that are heavily glycosylated. They have a core protein with one or more covalently attached glycosaminoglycan chain(s). The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions, due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in the are major constituents of this layer and it has been shown that increased metastatic potential corresponds with increased heparanase activity for a number of cell lines.[6][7] Due to the contribution of heparinase activity to metastasis and also to angiogenesis, the inhibition of heparinase activity it is considered to be a potential target for anti-cancer therapies.

References

  1. ^ Vlodavsky I, Friedmann Y, Elkin M, Aingorn H, Atzmon R, Ishai-Michaeli R, Bitan M, Pappo O, Peretz T, Michal I, Spector L, Pecker I (July 1999). "Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis". Nature medicine 5 (7): 793–802. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1038/10518. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 10395325.
  2. ^ Hulett MD, Freeman C, Hamdorf BJ, Baker RT, Harris MJ, Parish CR (July 1999). "Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis". Nature medicine 5 (7): 803–9. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1038/10525. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 10395326.
  3. ^ Vlodavsky I, Ilan N, Naggi A, Casu B (2007). "Heparanase: structure, biological functions, and inhibition by heparin-derived mimetics of heparan sulfate". Curr. Pharm. Des. 13 (20): 2057–2073. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.2174/138161207781039742. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 17627539.
  4. ^ Pikas DS, Li JP, Vlodavsky I, Lindahl U (1998). "Substrate specificity of heparanases from human hepatoma and platelets.". J. Biol. Chem. 273 (30): 18770–7. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1074/jbc.273.30.18770. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 9668050.
  5. ^ Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW (September 2006). "Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin". The Journal of cell biology 174 (7): 1097–106. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1083/jcb.200511134. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 16982797.
  6. ^ Nakajima M, Irimura T, Nicolson GL. (1988). "Heparanases and tumor metastasis". J. Cell. Biochem. 36 (2): 157–167. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1002/jcb.240360207. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 3281960.
  7. ^ Vlodavsky I, Goldshmidt O, Zcharia E, et al. (2003). "Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development.". Semin. Cancer Biol. 12 (2): 121–9. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1006/scbi.2001.0420. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 12027584.

Further reading

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Categories: Human proteins | Peripheral membrane proteins

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