Effects of the storage conditions on the stability of natural and synthetic cannabis in biological matrices for forensic toxicology analysis: An update from the literature

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; OMA:CTSC - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q14.2 Start 88,265,069 bp[1] End 88,359,684 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 D3 Start 87,927,293 bp[2] End 87,960,096 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Top expressed in More reference expression data BioGPS More reference expression data
Gene ontology Molecular function Cellular component Biological process Sources:Amigo / QuickGO
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 NP_001805 NP_680475 NP_001298719 NP_034112 Location (UCSC) Chr 11: 88.27 – 88.36 Mb Chr 7: 87.93 – 87.96 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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
SCOP2	1k3b / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   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 protein family, a subgroup of the cysteine cathepsins. In humans, it is encoded by the CTSC gene.^[5][6]

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.

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.^[7] 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.^[8]

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),^[9] 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.

Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre disease,^[10][11] 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 portion 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.

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