Cathepsin C

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Cathepsin C
Protein CTSC PDB 1k3b.png
PDB rendering based on 1k3b.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM602365 MGI109553 HomoloGene1373 ChEMBL: 2252 GeneCards: CTSC Gene
EC number
RNA expression pattern
PBB GE CTSC 201487 at tn.png
More reference expression data
Species Human Mouse
Entrez 1075 13032
Ensembl ENSG00000109861 ENSMUSG00000030560
UniProt P53634 P97821
RefSeq (mRNA) NM_001114173 NM_009982
RefSeq (protein) NP_001107645 NP_034112
Location (UCSC) Chr 11:
88.29 – 88.34 Mb
Chr 7:
88.28 – 88.31 Mb
PubMed search [1] [2]
Cathepsin C exclusion domain
PDB 2djg EBI.jpg
re-determination of the native structure of human dipeptidyl peptidase i (cathepsin c)
Symbol CathepsinC_exc
Pfam PF08773
InterPro IPR014882
SCOP 1k3b

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.[1][2]


Cathepsin C appears to be a central coordinator for activation of many serine proteases in immune/inflammatory cells.

Cathepsin C catalyses excision of dipeptides from the N-terminus of protein and peptide substrates, except if (i) the amino group of the N-terminus is blocked, (ii) the site of cleavage is on either side of a proline residue, (iii) the N-terminal residue is lysine or arginine, or (iv) the structure of the peptide or protein prevents further digestion from the N-terminus.


The cDNAs encoding rat, human, murine, bovine, dog and two Schistosome cathepsin Cs have been cloned and sequenced and show that the enzyme is highly conserved.[3] The human and rat cathepsin C cDNAs encode precursors (prepro-cathepsin C) comprising signal peptides of 24 residues, pro-regions of 205 (rat cathepsin C) or 206 (human cathepsin C) residues and catalytic domains of 233 residues which contain the catalytic residues and are 30-40% identical to the mature amino acid sequences of papain and a number of other cathepsins including cathepsins, B, H, K, L, and S.[4]

The translated prepro-cathepsin C is processed into the mature form by at least four cleavages of the polypeptide chain. The signal peptide is removed during translocation or secretion of the pro-enzyme (pro-cathepsin C) and a large N-terminal proregion fragment (also known as the exclusion domain),[5] which is retained in the mature enzyme, is separated from the catalytic domain by excision of a minor C-terminal part of the pro-region, called the activation peptide. A heavy chain of about 164 residues and a light chain of about 69 residues are generated by cleavage of the catalytic domain.

Unlike the other members of the papain family, mature cathepsin C consists of four subunits, each composed of the N-terminal proregion fragment, the heavy chain and the light chain. Both the pro-region fragment and the heavy chain are glycosylated.

Clinical significance[edit]

Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre disease,[6][7] an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis.

Cathepsin C functions as a key enzyme in the activation of granule serine peptidases in inflammatory cells, such as elastase and cathepsin G in neutrophils cells and chymase and tryptase in mast cells. In many inflammatory diseases, such as Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease (COPD), Inflammatory Bowel Disease, Asthma, Sepsis and Cystic Fibrosis, a significant part of the pathogenesis is caused by increased activity of some of these inflammatory proteases. Once activated by cathepsin C, the proteases are capable of degrading various extracellular matrix components, which can lead to tissue damage and chronic inflammation.


  1. ^ "Entrez Gene: CTSC cathepsin C". 
  2. ^ Paris A, Strukelj B, Pungercar J, Renko M, Dolenc I, Turk V (Aug 1995). "Molecular cloning and sequence analysis of human preprocathepsin C". FEBS Letters 369 (2-3): 326–30. doi:10.1016/0014-5793(95)00777-7. PMID 7649281. 
  3. ^ Hola-Jamriska L, Tort JF, Dalton JP, Day SR, Fan J, Aaskov J, Brindley PJ (Aug 1998). "Cathepsin C from Schistosoma japonicum--cDNA encoding the preproenzyme and its phylogenetic relationships". European Journal of Biochemistry / FEBS 255 (3): 527–34. doi:10.1046/j.1432-1327.1998.2550527.x. PMID 9738890. 
  4. ^ Kominami E, Ishido K, Muno D, Sato N (Jul 1992). "The primary structure and tissue distribution of cathepsin C". Biological Chemistry Hoppe-Seyler 373 (7): 367–73. doi:10.1515/bchm3.1992.373.2.367. PMID 1515062. 
  5. ^ Turk D, Janjić V, Stern I, Podobnik M, Lamba D, Dahl SW, Lauritzen C, Pedersen J, Turk V, Turk B (Dec 2001). "Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases". The EMBO Journal 20 (23): 6570–82. doi:10.1093/emboj/20.23.6570. PMC 125750. PMID 11726493. 
  6. ^ Wani AA, Devkar N, Patole MS, Shouche YS (Feb 2006). "Description of two new cathepsin C gene mutations in patients with Papillon-Lefèvre syndrome". Journal of Periodontology 77 (2): 233–7. doi:10.1902/jop.2006.050124. PMID 16460249. 
  7. ^ Meade JL, de Wynter EA, Brett P, Sharif SM, Woods CG, Markham AF, Cook GP (May 2006). "A family with Papillon-Lefevre syndrome reveals a requirement for cathepsin C in granzyme B activation and NK cell cytolytic activity". Blood 107 (9): 3665–8. doi:10.1182/blood-2005-03-1140. PMID 16410452. 

Further reading[edit]

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