PROFILPELAJAR.COM

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Cathepsin C exclusion domain
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
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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)
End	88,359,684 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	87,960,096 bp
RNA expression pattern
	Top expressed in
	palpebral conjunctiva; ; epithelium of nasopharynx; ; stromal cell of endometrium; ; gallbladder; ; appendix; ; bronchial epithelial cell; ; lymph node; ; rectum; ; monocyte; ; granulocyte;
	Top expressed in
	left lung lobe; ; right lung lobe; ; hair follicle; ; stroma of bone marrow; ; carotid body; ; yolk sac; ; parotid gland; ; primitive streak; ; ciliary body; ; conjunctival fornix;
	More reference expression data
	More reference expression data
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; endoplasmic reticulum; COPII-coated ER to Golgi transport vesicle; lysosome; extracellular exosome; endoplasmic reticulum-Golgi intermediate compartment membrane; Golgi membrane; extracellular region; extracellular space; nucleoplasm; centrosome; azurophil granule lumen; intracellular membrane-bounded organelle; collagen-containing extracellular matrix; cytoplasm;
Biological process	ageing; positive regulation of proteolysis involved in cellular protein catabolic process; positive regulation of apoptotic signaling pathway; response to organic substance; proteolysis; endoplasmic reticulum to Golgi vesicle-mediated transport; COPII vesicle coating; immune response; proteolysis involved in cellular protein catabolic process; T cell mediated cytotoxicity; apoptotic process; neutrophil degranulation; negative regulation of myelination; positive regulation of microglial cell activation;
	Sources:Amigo / QuickGO
Orthologs
	1075
	13032
	ENSG00000109861
	ENSMUSG00000030560
	P53634
	P97821
	NM_148170; NM_001114173; NM_001814
	NM_009982; NM_001311790
	NP_001107645; NP_001805; NP_680475
	NP_001298719; NP_034112
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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.^[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.

Clinical significance

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.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000109861 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030560 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: CTSC cathepsin C".
^ Paris A, Strukelj B, Pungercar J, Renko M, Dolenc I, Turk V (Aug 1995). "Molecular cloning and sequence analysis of human preprocathepsin C". FEBS Letters. 369 (2–3): 326–30. Bibcode:1995FEBSL.369..326P. doi:10.1016/0014-5793(95)00777-7. PMID 7649281. S2CID 45737414.
^ Hola-Jamriska L, Tort JF, Dalton JP, Day SR, Fan J, Aaskov J, Brindley PJ (Aug 1998). "Cathepsin C from Schistosoma japonicum--cDNA encoding the preproenzyme and its phylogenetic relationships". European Journal of Biochemistry. 255 (3): 527–34. doi:10.1046/j.1432-1327.1998.2550527.x. PMID 9738890.
^ Kominami E, Ishido K, Muno D, Sato N (Jul 1992). "The primary structure and tissue distribution of cathepsin C". Biological Chemistry Hoppe-Seyler. 373 (7): 367–73. doi:10.1515/bchm3.1992.373.2.367. PMID 1515062.
^ Turk D, Janjić V, Stern I, Podobnik M, Lamba D, Dahl SW, Lauritzen C, Pedersen J, Turk V, Turk B (Dec 2001). "Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases". The EMBO Journal. 20 (23): 6570–82. doi:10.1093/emboj/20.23.6570. PMC 125750. PMID 11726493.
^ Wani AA, Devkar N, Patole MS, Shouche YS (Feb 2006). "Description of two new cathepsin C gene mutations in patients with Papillon-Lefèvre syndrome". Journal of Periodontology. 77 (2): 233–7. doi:10.1902/jop.2006.050124. PMID 16460249.
^ Meade JL, de Wynter EA, Brett P, Sharif SM, Woods CG, Markham AF, Cook GP (May 2006). "A family with Papillon-Lefevre syndrome reveals a requirement for cathepsin C in granzyme B activation and NK cell cytolytic activity". Blood. 107 (9): 3665–8. doi:10.1182/blood-2005-03-1140. PMID 16410452.

External links

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)