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Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 463 | 11q14.2 | CTSC | cathepsin C | |
Mouse | - | 462 | 7 D3 | Ctsc | cathepsin C | |
Rat | - | 462 | 1q32 | Ctsc | cathepsin C |
Previous and Unofficial Names |
CATC | cathepsin J | dipeptidyl peptidase 1 | dipeptidyl transferase | DPP1 | PLS | PALS |
Database Links | |
Specialist databases | |
MEROPS | C01.070 (Hs) |
Other databases | |
Alphafold | P53634 (Hs), P97821 (Mm), P80067 (Rn) |
BRENDA | 3.4.14.1 |
CATH/Gene3D | 2.40.128.80 |
ChEMBL Target | CHEMBL2252 (Hs), CHEMBL3454 (Mm), CHEMBL3308944 (Rn) |
Ensembl Gene | ENSG00000109861 (Hs), ENSMUSG00000030560 (Mm), ENSRNOG00000016496 (Rn) |
Entrez Gene | 1075 (Hs), 13032 (Mm), 25423 (Rn) |
Human Protein Atlas | ENSG00000109861 (Hs) |
KEGG Enzyme | 3.4.14.1 |
KEGG Gene | hsa:1075 (Hs), mmu:13032 (Mm), rno:25423 (Rn) |
OMIM | 602365 (Hs) |
Orphanet | ORPHA120892 (Hs) |
Pharos | P53634 (Hs) |
RefSeq Nucleotide | NM_001114173 (Hs), NM_001814 (Hs), NM_148170 (Hs), NM_009982 (Mm), NM_017097 (Rn) |
RefSeq Protein | NP_680475 (Hs), NP_001107645 (Hs), NP_001805 (Hs), NP_034112 (Mm), NP_058793 (Rn) |
UniProtKB | P53634 (Hs), P97821 (Mm), P80067 (Rn) |
Wikipedia | CTSC (Hs) |
Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific inhibitor tables |
Immunopharmacology Comments |
Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [2]. |
Cell Type Associations | ||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||
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1. Doyle K, Lönn H, Käck H, Van de Poël A, Swallow S, Gardiner P, Connolly S, Root J, Wikell C, Dahl G et al.. (2016) Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986). J Med Chem, 59 (20): 9457-9472. [PMID:27690432]
2. Korkmaz B, Lesner A, Marchand-Adam S, Moss C, Jenne DE. (2020) Lung Protection by Cathepsin C Inhibition: A New Hope for COVID-19 and ARDS?. J Med Chem, 63 (22): 13258-13265. [PMID:32692176]
3. Korkmaz B, Lesner A, Wysocka M, Gieldon A, Håkansson M, Gauthier F, Logan DT, Jenne DE, Lauritzen C, Pedersen J. (2019) Structure-based design and in vivo anti-arthritic activity evaluation of a potent dipeptidyl cyclopropyl nitrile inhibitor of cathepsin C. Biochem Pharmacol, 164: 349-367. [PMID:30978322]
4. Thompson SA, Andrews PR, Hanzlik RP. (1986) Carboxyl-modified amino acids and peptides as protease inhibitors. J Med Chem, 29 (1): 104-11. [PMID:3941405]
C1: Papain: cathepsin C. Last modified on 12/08/2020. Accessed on 07/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2344.