Human Gene CTSC (ENST00000227266.10) from GENCODE V44
Description: Homo sapiens cathepsin C (CTSC), transcript variant 1, mRNA. (from RefSeq NM_001814) RefSeq Summary (NM_001814): This gene encodes a member of the peptidase C1 family and lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. [provided by RefSeq, Nov 2015]. Gencode Transcript: ENST00000227266.10 Gencode Gene: ENSG00000109861.17 Transcript (Including UTRs) Position: hg38 chr11:88,293,592-88,337,736 Size: 44,145 Total Exon Count: 7 Strand: - Coding Region Position: hg38 chr11:88,294,006-88,337,672 Size: 43,667 Coding Exon Count: 7
ID:CATC_HUMAN DESCRIPTION: RecName: Full=Dipeptidyl peptidase 1; EC=3.4.14.1; AltName: Full=Cathepsin C; AltName: Full=Cathepsin J; AltName: Full=Dipeptidyl peptidase I; Short=DPP-I; Short=DPPI; AltName: Full=Dipeptidyl transferase; Contains: RecName: Full=Dipeptidyl peptidase 1 exclusion domain chain; AltName: Full=Dipeptidyl peptidase I exclusion domain chain; Contains: RecName: Full=Dipeptidyl peptidase 1 heavy chain; AltName: Full=Dipeptidyl peptidase I heavy chain; Contains: RecName: Full=Dipeptidyl peptidase 1 light chain; AltName: Full=Dipeptidyl peptidase I light chain; Flags: Precursor; FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. CATALYTIC ACTIVITY: Release of an N-terminal dipeptide, Xaa-Yaa-|- Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro. COFACTOR: Binds 1 chloride ion per heavy chain. ENZYME REGULATION: Strongly inhibited by the cysteine peptidase inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N-ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal ion chelators. BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: High activity at pH 4.5-6.8; SUBUNIT: Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains. SUBCELLULAR LOCATION: Lysosome. TISSUE SPECIFICITY: Ubiquitous. Highly expressed in lung, kidney and placenta. Detected at intermediate levels in colon, small intestine, spleen and pancreas. INDUCTION: Up-regulated in lymphocytes by IL2/interleukin-2. PTM: N-glycosylated. While glycosylation at Asn-53, Asn-119 and Asn-276 is mediated by STT3A-containing complexes, glycosylation at Asn-29 is mediated STT3B-containing complexes. PTM: In approximately 50% of the complexes the exclusion domain is cleaved at position 58 or 61. The two parts of the exclusion domain are held together by a disulfide bond. DISEASE: Defects in CTSC are a cause of Papillon-Lefevre syndrome (PLS) [MIM:245000]; also known as keratosis palmoplantaris with periodontopathia. PLS is an autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees. DISEASE: Defects in CTSC are a cause of Haim-Munk syndrome (HMS) [MIM:245010]; also known as keratosis palmoplantaris with periodontopathia and onychogryposis or Cochin Jewish disorder. HMS is an autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis. DISEASE: Defects in CTSC are a cause of aggressive periodontititis type 1 (AP1) [MIM:170650]; also known as juvenile periodontitis (JPD) and prepubertal periodontitis (PPP). AP1 is characterized by severe and protracted gingival infections, leading to tooth loss. AP1 inheritance is autosomal dominant. SIMILARITY: Belongs to the peptidase C1 family. SEQUENCE CAUTION: Sequence=CAD97897.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=CTSCbase; Note=CTSC mutation db; URL="http://bioinf.uta.fi/CTSCbase/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P53634
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001913 T cell mediated cytotoxicity GO:0006508 proteolysis GO:0006888 ER to Golgi vesicle-mediated transport GO:0006915 apoptotic process GO:0006955 immune response GO:0007568 aging GO:0010033 response to organic substance GO:0043312 neutrophil degranulation GO:0048208 COPII vesicle coating GO:0051603 proteolysis involved in cellular protein catabolic process GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process GO:2001235 positive regulation of apoptotic signaling pathway