cathepsin C | C1: Papain | IUPHAR Guide to IMMUNOPHARMACOLOGY

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cathepsin C

  Target has curated data in GtoImmuPdb

Target id: 2344

Nomenclature: cathepsin C

Family: C1: Papain

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

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-E1.1 Ctsc cathepsin C
Rat - 462 1q32 Ctsc cathepsin C
Previous and Unofficial Names
CATC | cathepsin J | dipeptidyl peptidase 1 | dipeptidyl transferase | DPP1 | PALS | PLS
Database Links
Specialist databases
MEROPS C01.070 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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 Affinity Parameter Reference
AZD7986 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 2
pKi 5.6 (Ki 2.7x10-6 M) [2]
AZD7986 Hs Inhibition 8.4 pIC50 1
pIC50 8.4 (IC50 3.98x10-9 M) [1]
Description: In vitro enzyme assay
AZD7986 Rn Inhibition 7.7 pIC50 1
pIC50 7.7 (IC50 1.99x10-8 M) [1]
Description: In vitro enzyme assay
AZD7986 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 is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin 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. AZD7986).
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)
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001913 T cell mediated cytotoxicity IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001913 T cell mediated cytotoxicity IEA
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

References

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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. 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]

How to cite this page

C1: Papain: cathepsin C. Last modified on 02/12/2016. Accessed on 21/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2344.