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
EC Number: 3.4.14.1

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
Ligand Sp. Action Value Parameter Reference brensocatib Hs Inhibition 8.6 pKd 1 ⤷ pKd 8.6 (Kd 2.5x10-9 M) [1] Description: Surface plasmon resonance direct binding assay compound 3d [PMID: 3941405] Hs Inhibition 5.6 pKi 4 ⤷ pKi 5.6 (Ki 2.7x10-6 M) [4] brensocatib Hs Inhibition 8.4 pIC50 1 ⤷ pIC50 8.4 (IC50 3.98x10-9 M) [1] Description: In vitro enzyme assay IcatCXPZ-01 Hs Inhibition 7.8 pIC50 3 ⤷ pIC50 7.8 (IC50 1.5x10-8 M) [3] brensocatib Rn Inhibition 7.7 pIC50 1 ⤷ pIC50 7.7 (IC50 1.99x10-8 M) [1] Description: In vitro enzyme assay brensocatib Mm Inhibition 7.6 pIC50 1 ⤷ pIC50 7.6 (IC50 2.51x10-8 M) [1] Description: In vitro enzyme assay
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

Immuno Cell Type:  Mast cells

Immuno Cell Type:  T cells Cell Ontology Term:   mature CD8 single-positive thymocyte (CL:0002437)

Immuno Cell Type:  Granulocytes Cell Ontology Term:   mature neutrophil (CL:0000096) neutrophil (CL:0000775)

Immuno Cell Type:  Natural killer cells Cell Ontology Term:   natural killer cell (CL:0000623)

Clinically-Relevant Mutations and Pathophysiology
Disease:  Haim-Munk syndrome OMIM: 245010 Orphanet: ORPHA2342
Disease:  Papillon-Lefevre syndrome Synonyms: Papillon-Lefevre disease [Disease Ontology: DOID:3389] Disease Ontology: DOID:3389 OMIM: 245000 Orphanet: ORPHA678
Disease:  Periodontitis, aggressive, 1 Synonyms: Aggressive periodontitis [Disease Ontology: DOID:1474] Disease Ontology: DOID:1474 OMIM: 170650