Cathepsin B

3PBH, 1CSB, 1GMY, 1HUC, 1PBH, 2IPP, 2PBH, 3AI8, 3CBJ, 3CBK, 3K9M150813030ENSG00000164733ENSMUSG00000021939P07858P10605NM_001317237NM_007798NP_680093NP_031824Cathepsin B is in humans encoded by the CTSB gene. Cathepsin B belongs to a family of lysosomal cysteine proteases and plays an important role in intracellular proteolysis. Upregulation of cathepsin B is found in premalignant lesions and various pathological conditions, as well as cancers.1csb: CRYSTAL STRUCTURE OF CATHEPSIN B INHIBITED WITH CA030 AT 2.1 ANGSTROMS RESOLUTION: A BASIS FOR THE DESIGN OF SPECIFIC EPOXYSUCCINYL INHIBITORS1gmy: CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR1huc: THE REFINED 2.15 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF HUMAN LIVER CATHEPSIN B: THE STRUCTURAL BASIS FOR ITS SPECIFICITY1pbh: CRYSTAL STRUCTURE OF HUMAN RECOMBINANT PROCATHEPSIN B AT 3.2 ANGSTROM RESOLUTION1sp4: Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft2ipp: Crystal Structure of the tetragonal form of human liver cathepsin B2pbh: CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN B AT 3.3 ANGSTROM RESOLUTION3pbh: REFINED CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN B AT 2.5 ANGSTROM RESOLUTION Cathepsin B is in humans encoded by the CTSB gene. Cathepsin B belongs to a family of lysosomal cysteine proteases and plays an important role in intracellular proteolysis. Upregulation of cathepsin B is found in premalignant lesions and various pathological conditions, as well as cancers. CTSB gene is located at chromosome 8p22, consisting of 13 exons.The promoter of CTSB gene contains a GC-rich region including many SP1 sites, which is similar to housekeeping gene. At least five transcript variants encoding the same protein have been found for this gene. Cathepsin B is synthesized on the rough endoplasmic reticulum as a preproenzyme of 339 amino acid with a signal peptide of 17 amino acids. Procathepsin B of 43/46 kDa is then transported to the Golgi apparatus and cathepsin B is formed. Mature cathepsin B is composed of a heavy chain of 25-26 kDa and a light chain of 5kDa, which are linked by a dimer of disulfide. Cathepsin B may enhance the activity of other protease, including matrix metalloproteinase, urokinase (serine protease urokinase plasminogen activator), and cathepsin D, and thus it has an essential position for in the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression. It is also involved in autophagy and catabolism, which is advantageous in tumor malignancy and is possibly involved in specific immune resistance. Cathepsin B has been proposed as a potentially effective biomarker for a variety of cancers. Overexpression of cathepsin B is correlated with invasive and metastatic cancers.Cathepsin B is produced in muscle tissue during metabolism. It is capable of crossing the blood-brain barrier and is associated with neurogenesis, specifically in the mouse dentate gyrus.A wide array of diseases result in elevated levels of cathepsin B, which causes numerous pathological processes including cell death, inflammation, and production of toxic peptides. Focusing on neurological diseases, cathepsin B gene knockout studies in an epileptic rodent model have shown cathepsin B causes a significant amount of the apoptotic cell death that occurs as a result of inducing epilepsy. Cathepsin B inhibitor treatment of rats in which a seizure was induced resulted in improved neurological scores, learning ability and much reduced neuronal cell death and pro-apoptotic cell death peptides. Similarly, cathepsin B gene knockout and cathepsin B inhibitor treatment studies in traumatic brain injury mouse models have shown cathepsin B to be key to causing the resulting neuromuscular dysfunction, memory loss, neuronal cell death and increased production of pro-necrotic and pro-apoptotic cell death peptides. In ischemic non-human primate and rodent models, cathepsin B inhibitor treatment prevented a significant loss of brain neurons, especially in the hippocampus. In a streptococcus pneumoniae meningitis rodent model, cathepsin B inhibitor treatment greatly improved the clinical course of the infection and reduced brain inflammation and inflammatory Interleukin-1β (IL1-β) and tumor necrosis factor-α (TNF-α). In a transgenic Alzheimer's disease (AD) animal model expressing human amyloid precursor protein (APP) containing the wild-type beta-secretase site sequence found in most AD patients or in guinea pigs, which are a natural model of human wild-type APP processing, genetically deleting the cathepsin B gene or chemically inhibiting cathepsin B brain activity resulted in a significant improvement in the memory deficits that develop in such mice and reduces levels of neurotoxic full-length Abeta(1-40/42) and the particularly pernicious pyroglutamate Abeta(3-40/42), which are thought to cause the disease. In a non-transgenic senescence-accelerated mouse strain, which also has APP containing the wild-type beta-secretase site sequence, treatment with bilobalide, which is an extract of Ginko biloba leaves, also lowered brain Abeta by inhibiting cathepsin B. Moreover, siRNA silencing or chemically inhibiting cathepsin B in primary rodent hippocampal cells or bovine chromaffin cells, which have human wild-type beta-secretase activity, reduces secretion of Abeta by the regulated secretory pathway.Mutations in the CTSB gene have been linked to tropical pancreatitis, a form of chronic pancreatitis. Cathepsin B has been shown to interact with: Cathepsin B is inhibited by: