Cathepsin

Function

Cathepsin (CTS) is a protease which becomes activated at low pH. It is found in lysosomes. Members of the CTS group are denoted as CTSA, CTSB etc and cleave proteins at different peptide bonds. The CTSs are expressed as an inactive precursor pro-CTS (PCTS) which becomes active when a long residue prosegment is cleaved off producing the mature CTS (MCTS).^[1] For details on pro-CTS see Molecular Playground/Human PPCA.

• CTS B, F, H, L, L1, L2 or V are cysteine proteases.
  
• CTS D, E are aspartyl proteases which degrade insulin.
  
• CTS G is a serine protease with activity similar to chymotrypsin C.
  
• CTS K is a cysteine protease involved in bone resorption. For details see Cathepsin k.
  
• CTS S is a cysteine protease involved in degradation of antigenic proteins.
  
• CTS X is a cysteine protease cleaving proteins at their C-terminus.
  

Disease

CTS B overexpression is associated with metastatic phenotypes in cancer. CTS C mutations are responsible for the Papillon-Lefevre syndrome. CTS K is involved in osteoporosis. CTS H overexpression is associated with prostate cancer. CTS L1 is implicated in myofibril necrosis.

Relevance

CTS B breaks down proteins which are involved in amyloid plaques. CTS D is used as a breast cancer marker. CTS L is a potential drug target in cancer treatment. CTS L2 is expressed by cells of breast and colorectal carcinomas.

Structural highlights

CTS B is a cysteine protease. The active site contains a C26 residue from the N-terminal domain and H199 residue from the C-terminal domain (in cyan).^[2]

3D Structures of Cathepsin

Cathepsin 3D structures