Cathepsin C

Cathepsins are proteases found in many types of cells conserved in all animals, which have a vital role in mammalian cellular turnover such as bone resorption. The lysosomal cysteine protease Cathepsin C (CTSC), also known as dipeptidyl peptidase I (DPPI/DPP1), activates a number of granule-associated serine proteases with pro-inflammatory and immune functions by removal of their inhibitory N-terminal dipeptides. This lysosomal exo-cysteine protease belonging to the peptidase C1 family. Active cathepsin C is found in lysosomes as a 200-kDa multimeric enzyme. Subunits constituting this assembly all arise from the proteolytic cleavage of a single precursor giving rise to three peptides: the propeptide, the alpha- and the beta-chains. It is a central coordinator for activation of many serine proteases in immune/inflammatory cells. Defects in the Cathepsin C have been shown to be a cause of Papillon-Lefevre disease, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. Cathepsin C plays a key role in the activation of several degradative enzymes linked to tissue destruction in inflammatory diseases. Thus, it is a therapeutic target for the treatment of a number of inflammatory and autoimmune diseases.

Cathepsin C Related Areas

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Cathepsin Family>>Cathepsin C/DPP1/CTSC

Cancer>>Angiogenesis>>Cathepsin Family>>Cathepsin C/DPP1/CTSC

Immunology>>Innate Immunity>>Lysosomal Enzyme>>Cathepsin Family>>Cathepsin C/DPP1/CTSC

Cathepsin C Alternative Names

Cathepsin C, CTSC, DPP1, DPPI, CPPI, HMS, JP, JPD, PALS, PLS [Homo sapiens]

Cathepsin C, Ctsc, DPP1, DPPI, AI047818 [Mus musculus]

Summaries for Cathepsin C

Entrez Gene summary for Cathepsin C:

The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in immune/inflammatory cells. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor, and a residual portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. Multiple transcript variants encoding different isoforms have been found for this gene.

OMIM - description for Cathepsin C:

Cathepsin C, or dipeptidyl aminopeptidase I (EC 3.4.14.1), is a lysosomal protease capable of removing dipeptides from the amino terminus of protein substrates. Unlike cathepsins B (116810), H(116820), L (116880), and S (116845), which are small monomeric enzymes, cathepsin C is a large (200 kD) oligomeric protein (Paris et al. (1995)).

Wikipedia summary for Cathepsin C:

Cathepsin C (CTSC) also known as dipeptidyl peptidase I (DPP-I) is a lysosomal exo-cysteine protease belonging to the peptidase C1 family. In humans, it is encoded by the CTSC gene

Human Cathepsin C Protein General Information

 

• Protein names: Recommended name: Dipeptidyl peptidase 1
• Sequence length: 463 AA.
• Domain: Signal
• Sequence similarities: Belongs to the peptidase C1 family.
• Post-translational modification: N-glycosylated. In approximately 50% of the complexes the exclusion domain is cleaved at position 58 or 61. The two parts of the exclusion domain are held together by a disulfide bond.
• Subunit structure: Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains
• Subcellular location: Lysosome.
• Tissue specificity: Ubiquitous. Highly expressed in lung, kidney and placenta. Detected at intermediate levels in colon, small intestine, spleen and pancreas.
• Involvement in disease: Defects in CTSC are a cause of Papillon-Lefevre syndrome (PLS) [MIM:245000]; also known as keratosis palmoplantaris with periodontopathia. PLS is an autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees. Defects in CTSC are a cause of Haim-Munk syndrome (HMS) [MIM:245010]; also known as keratosis palmoplantaris with periodontopathia and onychogryposis or Cochin Jewish disorder. HMS is an autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis. Ref.19 Defects in CTSC are a cause of aggressive periodontititis type 1 (AP1) [MIM:170650]; also known as juvenile periodontitis (JPD) and prepubertal periodontitis (PPP). AP1 is characterized by severe and protracted gingival infections, leading to tooth loss. AP1 inheritance is autosomal dominant.

General information above from UniProt

Function for Cathepsin C Protein

UniProtKB:

Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII.

Genatlas:

• Cathepsin C cysteine protease with dipeptidase activity involved in the pathogenesis of bronchial asthma
• Cathepsin C can act as both an exopeptidase and endopeptidase
• Cathepsin C activates serine proteases such as elastase, cathepsin G and granzymes A and B
• Cathepsin C plays a key role in regulating neutrophil recruitment at sites of inflammation
• Cathepsin C has a necessary role for neutrophil recruitment into the diseased aorta and acting to amplify vascular wall inflammation that leads to abdominal aortic aneurysms
• cysteine protease required for the activation of several pro-inflammatory serine proteases
• propeptide of cathepsin C may stimulate the sorting to the lysosome
• potentially involved with chloride in the regulation of proleolysis in the lysosome
• Cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells

Phenotype Information for Cathepsin C

• Gene/Locus: CTSC, CPPI, PALS, PLS, HMS, JPD
• Phenotype: Haim-Munk syndrome Papillon-Lefevre syndrome Periodontitis, juvenile

Phenotype Information for Cathepsin C from OMIM (Online Mendelian Inheritance in Man)