Summary for peptidase C01.034: cathepsin S

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namecathepsin S
Other namesCTSS g.p. (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.034
Holotypecathepsin S (Homo sapiens), Uniprot accession P25774 (peptidase unit: 114-331), MERNUM MER0000633
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00062
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.27
EnzymologyBRENDA database
Proteolytic eventsCutDB database (22 cleavages)
Activity statushuman: active (Kirschke, 2004)
mouse: active (Mason et al., 2001)
PhysiologyLikely roles are in lysosomal proteolysis, extracellular proteolysis including elastin degradation, and the MHC class II immune response. Cathespin S has been proposed to be involved in angiogenesis (Shi et al., 2003) and atherogenesis (Sukhova et al., 2003).
KnockoutAntisense-mediated down-regulation of expression of cathepsin S has implicated the enzyme in degradation of rod outer segments by retinal pigment epithelial cells. The effect might have been direct, or through an alteration in cathepsin D activity (Rakoczy et al., 1998).
Pharmaceutical relevanceHas strong elastinolytic activity, even at neutral pH, and may play a role in tissue damage associated with inflammation (Kirschke et al., 1989; Shi et al., 1992). Facilitates antigen presentation in the MHC class II system by degradation of the invariant chain (Driessen et al., 1999), and may therefore by a target for attenuation of immune response.
Pathways KEGGAntigen processing and presentation
KEGGLysosome
KEGGPhagosome
KEGGTuberculosis
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_S
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/lv/-Scissile bond-/-/-/- (based on 756 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 48 63 5 128 118 86 80 91
Pro 42 51 5 1 0 63 106 79
Ala 63 70 22 87 107 98 82 53
Val 48 47 172 6 24 41 27 30
Leu 40 71 244 44 24 31 23 22
Ile 25 58 76 9 19 34 21 27
Met 20 20 55 15 10 8 2 6
Phe 30 42 69 10 14 16 22 12
Tyr 14 14 28 5 13 6 16 10
Trp 10 7 11 6 4 4 8 4
Ser 51 57 11 85 128 72 51 51
Thr 22 41 17 76 40 59 39 46
Cys 9 20 14 14 15 19 6 14
Asn 30 34 4 41 28 30 39 30
Gln 38 33 14 82 67 51 37 47
Asp 37 19 0 28 33 27 71 77
Glu 59 53 2 81 68 38 42 80
Lys 7 9 1 8 6 26 15 23
Arg 6 7 1 13 6 12 8 8
His 20 17 3 17 26 29 55 40
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant H/broad R/P/I F/M/L K/Q/T/R - - - - HRFK ACC Choe et al., 2006
Homo sapiens recombinant - R W R L E K - xRWR+LEKx Dnp-Abz Alves et al., 2007
Homo sapiens recombinant - - - - A/L/S - - - xxxx+Axxx Dansyl-Trp Ménard et al., 1993
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSS 1q21 ENSG00000163131 1520 CTSS 116845
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctss 3:F2 ENSMUSG00000038642 13040 MGI:107341