Cathepsin C

CTSC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4OEM, 1K3B, 2DJF, 2DJG, 3PDF, 4CDC, 4CDD, 4CDE, 4CDF, 4OEL
Identifiers
Aliases	CTSC, CPPI, DPP-I, DPP1, DPPI, HMS, JP, JPD, PALS, PDON1, PLS, cathepsin C
External IDs	OMIM: 602365 MGI: 109553 HomoloGene: 1373 GeneCards: CTSC
Gene ontology Molecular function • peptidase activator activity involved in apoptotic process • phosphatase binding • cysteine-type peptidase activity • chaperone binding • protein self-association • peptidase activity • protein binding • identical protein binding • chloride ion binding • cysteine-type endopeptidase activity • serine-type endopeptidase activity • hydrolase activity Cellular component • Golgi apparatus • endoplasmic reticulum lumen • membrane • extracellular space • endoplasmic reticulum • ER to Golgi transport vesicle • lysosome • extracellular exosome • endoplasmic reticulum-Golgi intermediate compartment membrane • Golgi membrane Biological process • aging • positive regulation of proteolysis involved in cellular protein catabolic process • positive regulation of apoptotic signaling pathway • response to organic substance • proteolysis • ER to Golgi vesicle-mediated transport • COPII vesicle coating • immune response • proteolysis involved in cellular protein catabolic process • T cell mediated cytotoxicity • apoptotic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1075	13032
Ensembl	ENSG00000109861	ENSMUSG00000030560
UniProt	P53634	P97821
RefSeq (mRNA)	NM_148170 NM_001114173 NM_001814	NM_009982 NM_001311790
RefSeq (protein)	NP_001107645.1 NP_001805.3 NP_680475.1	NP_034112.3
Location (UCSC)	Chr 11: 88.29 – 88.34 Mb	Chr 7: 88.28 – 88.31 Mb
PubMed search	[1]	[2]
Wikidata

Cathepsin C exclusion domain
re-determination of the native structure of human dipeptidyl peptidase i (cathepsin c)
Identifiers
Symbol	CathepsinC_exc
Pfam	PF08773
InterPro	IPR014882
SCOP	1k3b
SUPERFAMILY	1k3b
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Cathepsin C (CTSC) also known as dipeptidyl peptidase I (DPP-I) is a lysosomal exo-cysteine protease belonging to the peptidase C1 family. In humans, it is encoded by the CTSC gene.^[3][4]

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.^[5] 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.^[6]

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 (also known as the exclusion domain),^[7] 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,^[8][9] an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis.

Cathepsin C functions as a key enzyme in the activation of granule serine peptidases in inflammatory cells, such as elastase and cathepsin G in neutrophils cells and chymase and tryptase in mast cells. In many inflammatory diseases, such as Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease (COPD), Inflammatory Bowel Disease, Asthma, Sepsis and Cystic Fibrosis, a significant part of the pathogenesis is caused by increased activity of some of these inflammatory proteases. Once activated by cathepsin C, the proteases are capable of degrading various extracellular matrix components, which can lead to tissue damage and chronic inflammation.

References

Further reading

External links

• The MEROPS online database for peptidases and their inhibitors: C01.070
• Cathepsin C at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1k3b: Crystal Structure of Human Dipeptidyl Peptidase I (Cathepsin C): Exclusion Domain Added to an Endopeptidase Framework Creates the Machine for Activation of Granular Serine Proteases  2djf: Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2  2djg: Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)