cathepsin-C (cathepsinJ, dipeptidyl peptidase-1, DPP-1, DPP1, PPCTSC, CPPI)
Jump to navigation
Jump to search
Function
- thiol protease
- role in activating neutrophil serine proteases
- has dipeptidylpeptidase activity
- sctive as both an exopeptidase & endopeptidase
- activates serine proteases such as elastase, cathepsin G & granzymes A & B
- can also activate neuraminidase & factor XIII
- release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro
Cofactor: binds 1 Cl- per heavy chain
Structure
- tetramer of heterotrimers consisting of exclusion domain, heavy- & light chains
- in approximately 50% of the complexes the exclusion domain is cleaved at position 58 or 61; the 2 parts of the exclusion domain are held together by a disulfide bond
- N-glycosylated
- belongs to the peptidase C1 family
Compartment
Expression
- ubiquitous.
- expressed in lung, kidney & placenta > colon, small intestine, spleen & pancreas
- up-regulated in lymphocytes by IL2
Pathology
- involved in neutrophilic inflammation & tissue damage.
- defects in CTSC are a cause of
Pharmacology
- DPP-1 inhibitor brensocatib may reduce activity of neutrophil proteases that contribute to airway inflammation of bronchiectasis[2]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P53634.html
- ↑ 2.0 2.1 Chalmers JD et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med 2025 Apr 24; 392:1569 PMID: https://pubmed.ncbi.nlm.nih.gov/40267423 https://www.nejm.org/doi/10.1056/NEJMoa2411664
Bell SC, Grimwood K. Brensocatib in bronchiectasis - A new sheriff in town? N Engl J Med 2025 Apr 24; 392:1647. PMID: https://pubmed.ncbi.nlm.nih.gov/40267431 https://www.nejm.org/doi/10.1056/NEJMe2502618 - ↑ CTSCbase; Note: CTSC mutation db http://bioinf.uta.fi/CTSCbase/
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1075
- OMIM: https://mirror.omim.org/entry/170650
- OMIM: https://mirror.omim.org/entry/245000
- OMIM: https://mirror.omim.org/entry/245010
- OMIM: https://mirror.omim.org/entry/602365
- UniProt: http://www.uniprot.org/uniprot/P53634.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=337936