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| Cathepsin C (dipeptidyl peptidase I) | |||||||||||
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 PDB rendering based on 1k3b. |
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| Available structures | |||||||||||
| 1k3b, 2djf, 2djg | |||||||||||
| Identifiers | |||||||||||
| Symbols | CTSC; CPPI; DPP1; DPPI; HMS; JP; JPD; PALS; PLS | ||||||||||
| External IDs | OMIM: 602365 MGI: 109553 HomoloGene: 1373 GeneCards: CTSC Gene | ||||||||||
| EC number | 3.4.14.1 | ||||||||||
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| RNA expression pattern | |||||||||||
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| More reference expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 1075 | 13032 | |||||||||
| Ensembl | ENSG00000109861 | ENSMUSG00000030560 | |||||||||
| UniProt | P53634 | Q3TIF1 | |||||||||
| RefSeq (mRNA) | NM_001814 | NM_009982 | |||||||||
| RefSeq (protein) | NP_001805 | NP_034112 | |||||||||
| Location (UCSC) | Chr 11: 87.67 - 87.71 Mb |
Chr 7: 88.15 - 88.19 Mb |
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| PubMed search | [1] | [2] | |||||||||
Cathepsin C (dipeptidyl peptidase I) is a lysosomal exo-cysteine protease belonging to the peptidase C1 family. In humans, it is encoded by the CTSC gene.[1][2]
Contents |
Function
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.
Structure
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, 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
Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre disease,[5][6] an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis.
References
- ^ "Entrez Gene: CTSC cathepsin C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1075.
- ^ Paris A, Strukelj B, Pungercar J, Renko M, Dolenc I, Turk V (August 1995). "Molecular cloning and sequence analysis of human preprocathepsin C". FEBS Letters 369 (2-3): 326–30. doi:. PMID 7649281.
- ^ Hola-Jamriska L, Tort JF, Dalton JP, Day SR, Fan J, Aaskov J, Brindley PJ (August 1998). "Cathepsin C from Schistosoma japonicum--cDNA encoding the preproenzyme and its phylogenetic relationships". European Journal of Biochemistry / FEBS 255 (3): 527–34. doi:. PMID 9738890.
- ^ Kominami E, Ishido K, Muno D, Sato N (July 1992). "The primary structure and tissue distribution of cathepsin C". Biological Chemistry Hoppe-Seyler 373 (7): 367–73. PMID 1515062.
- ^ Wani AA, Devkar N, Patole MS, Shouche YS (2006). "Description of two new cathepsin C gene mutations in patients with Papillon-Lefèvre syndrome". J. Periodontol. 77 (2): 233–7. doi:. PMID 16460249.
- ^ Meade JL, de Wynter EA, Brett P, Sharif SM, Woods CG, Markham AF, Cook GP (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): 3665–3668. doi:. PMID 16410452.
Further reading
- McGuire MJ, Lipsky PE, Thiele DL (1992). "Purification and characterization of dipeptidyl peptidase I from human spleen.". Arch. Biochem. Biophys. 295 (2): 280–8. doi:. PMID 1586157.
- Paris A, Strukelj B, Pungercar J, et al. (1995). "Molecular cloning and sequence analysis of human preprocathepsin C.". FEBS Lett. 369 (2-3): 326–30. doi:. PMID 7649281.
- Dolenc I, Turk B, Pungercic G, et al. (1995). "Oligomeric structure and substrate induced inhibition of human cathepsin C.". J. Biol. Chem. 270 (37): 21626–31. doi:. PMID 7665576.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:. PMID 8125298.
- Rao NV, Rao GV, Hoidal JR (1997). "Human dipeptidyl-peptidase I. Gene characterization, localization, and expression.". J. Biol. Chem. 272 (15): 10260–5. doi:. PMID 9092576.
- Fischer J, Blanchet-Bardon C, Prud'homme JF, et al. (1997). "Mapping of Papillon-Lefevre syndrome to the chromosome 11q14 region.". Eur. J. Hum. Genet. 5 (3): 156–60. PMID 9272739.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:. PMID 9373149.
- Cigić B, Krizaj I, Kralj B, et al. (1998). "Stoichiometry and heterogeneity of the pro-region chain in tetrameric human cathepsin C.". Biochim. Biophys. Acta 1382 (1): 143–50. PMID 9507095.
- Toomes C, James J, Wood AJ, et al. (1999). "Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.". Nat. Genet. 23 (4): 421–4. doi:. PMID 10581027.
- Hart TC, Hart PS, Bowden DW, et al. (2000). "Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome.". J. Med. Genet. 36 (12): 881–7. PMID 10593994.
- Hart TC, Hart PS, Michalec MD, et al. (2000). "Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C.". J. Med. Genet. 37 (2): 88–94. doi:. PMID 10662807.
- Hart TC, Hart PS, Michalec MD, et al. (2000). "Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation.". J. Med. Genet. 37 (2): 95–101. doi:. PMID 10662808.
- Suzuki Y, Ishihara D, Sasaki M, et al. (2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries.". Genomics 64 (3): 286–97. doi:. PMID 10756096.
- Cigić B, Dahl SW, Pain RH (2000). "The residual pro-part of cathepsin C fulfills the criteria required for an intramolecular chaperone in folding and stabilizing the human proenzyme.". Biochemistry 39 (40): 12382–90. doi:. PMID 11015218.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–1795. doi:. PMID 11076863.
- Hart PS, Zhang Y, Firatli E, et al. (2001). "Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients.". J. Med. Genet. 37 (12): 927–32. doi:. PMID 11106356.
- Zhang Y, Lundgren T, Renvert S, et al. (2001). "Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefèvre syndrome patients.". J. Med. Genet. 38 (2): 96–101. doi:. PMID 11158173.
- Nakano A, Nomura K, Nakano H, et al. (2001). "Papillon-Lefèvre syndrome: mutations and polymorphisms in the cathepsin C gene.". J. Invest. Dermatol. 116 (2): 339–43. doi:. PMID 11180012.
- Allende LM, García-Pérez MA, Moreno A, et al. (2001). "Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation.". Hum. Mutat. 17 (2): 152–3. doi:. PMID 11180601.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:. PMID 11230166.
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