Cathepsin B

Cathepsin B is a papain-family cysteine protease that is normally located in lysosomes, where it is involved in the turnover of proteins and plays various roles in maintaining the normal metabolism of cells. This protease has been implicated in pathological conditions, e.g., tumor progression and arthritis. In disease conditions, increases in the expression of cathepsin B occur at both the gene and protein levels. Cathepsin B is synthesized as a preproenzyme and the primary pathways for its normal trafficking to the lysosome utilize mannose 6-phosphate receptors (MPRs). Mature cathepsin B has the ability to degrade several extracellular matrix components at both neutral and acidic pH and has been implicated in the progression of several human and rodent tumors progression and arthritis. Cathepsin B expression is increased in many human cancers at the mRNA, protein and activity levels. It is also frequently overexpressed in premalignant lesions, an observation that associates this protease with local invasive stages of cancer. Increased expression of cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Active cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Thus CTSB is suggested as a tumor marker. Additionally, Cathepsin B can degrade extracellular matrix proteins, such as collagen IV and laminin, and can activate the precursor form of urokinase plasminogen activator (uPA), perhaps thereby initiating an extracellular proteolytic cascade.

Cathepsin B Related Areas

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Cathepsin Family>>Cathepsin B/CTSB

Cancer>>Angiogenesis>>Cathepsin Family>>Cathepsin B/CTSB

Immunology>>Innate Immunity>>Lysosomal Enzyme>>Cathepsin Family>>Cathepsin B/CTSB

Cathepsin B Alternative Names

Cathepsin B, CTSB, APPS, CPSB, cathepsin B1 [Homo sapiens]

Cathepsin B, Ctsb, CB, cathepsin B1 [Mus musculus]

Summaries for Cathepsin B

Entrez Gene summary for Cathepsin B:

The protein encoded by this gene is a lysosomal cysteine proteinase composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. It is also known as amyloid precursor protein secretase and is involved in the proteolytic processing of amyloid precursor protein (APP). Incomplete proteolytic processing of APP has been suggested to be a causative factor in Alzheimer disease, the most common cause of dementia. Overexpression of the encoded protein, which is a member of the peptidase C1 family, has been associated with esophageal adenocarcinoma and other tumors. At least five transcript variants encoding the same protein have been found for this gene.

OMIM - description for Cathepsin B:

Chan et al. (1986) cloned preprocathepsin B from hepatoma and kidney cDNA libraries. The deduced 339-amino acid preprocathepsin B contains a 17-residue N-terminal prepeptide followed by a 62-residue propeptide, 254 residues that are in the mature (single-chain) cathepsin B, and a 6-residue C-terminal extension. Human, mouse, and rat procathepsin B share at least 68% sequence identity. Moin et al. (1992) purified 3 forms of cathepsin B from normal human liver and several human tumor tissues. SDS-PAGE detected 2 forms of 25 and 26 kD that appeared as a doublet and a third form of about 30 kD. The doublet was associated with the highest cathepsin B activity. N-terminal sequencing revealed that the 25- and 26-kD forms represent the heavy chain of the mature double-chain form of cathepsin B. Endoglycosidase treatment converted the 26-kD form into the 25-kD form, suggesting that cathepsin B exists as both glycosylated and unglycosylated forms. N-terminal sequencing indicated that the 30-kD protein was the single-chain form. Using several biochemical and immunologic criteria, Moin et al. (1992) determined that the tumor and normal liver forms of cathepsin B were similar in all characteristics examined.

Wikipedia summary for Cathepsin B:

Cathepsin B is an enzymatic protein belonging to the peptidase (or protease) families. In humans, it is coded by the CTSB gene

Human Cathepsin B Protein General Information

 

• Protein names: Recommended name: Cathepsin B
• Sequence length: 339 AA.
• Domain: Signal
• Sequence similarities: Belongs to the peptidase C1 family.
• Catalytic activity: Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.
• Subunit structure: Dimer of a heavy chain and a light chain cross-linked by a disulfide bond. Interacts with SRPX2.
• Subcellular location: Lysosome. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

General information above from UniProt

Function for Cathepsin B Protein

UniProtKB:

Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.

Genatlas:

• lysosomal cysteine and aspartyl proteinase, involved in matrix degradation during endochondral ossification
• APP secretase, may be prorenin-processing enzyme
• Cathepsin B is involved in skeletal myoblast differentiation and fusion
• Cathepsin B contribute to cartilage destruction in osteoarthritis and pathological proteolysis in rheumatoid arthritis and cancer
• Cathepsin B plays a role in the physiological functions of placental and decidual macrophages in mediating villous angiogenesis and decidual apoptosis
• essential during initial stages of wound healing, while its contribution to the subsequent processes of proliferation and differentiation of keratinocytes was of less significance
• Cathepsin B might directly cleave ECM constituents or it may initiate proteolytic cascades that involve other proteases with the ability to degrade ECM components
• Cathepsin B pivotal role in cell death induced by SPARC in primitive neuroectodermal tumors cells (PNET)
• Cathepsin B induces apoptosis through BID cleavage in SPARC overexpressed PNET cells