Summary for peptidase C01.034: cathepsin S

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature 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
PANTHERhttp://www.pantherdb.org/panther/familyList.do?searchType=basic&fieldName=all&listType=6&fieldValue=PTHR12411:SF525
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 3119 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 250 257 9 394 278 287 337 243
Pro 247 203 21 4 7 292 353 380
Ala 264 286 62 269 400 364 299 197
Val 187 199 798 25 177 169 183 155
Leu 169 268 1100 184 264 120 160 106
Ile 123 193 267 27 143 144 174 132
Met 56 66 195 66 80 21 32 21
Phe 86 125 283 54 98 63 135 66
Tyr 67 76 133 44 77 55 103 53
Trp 39 32 24 22 26 30 51 24
Ser 202 181 24 267 338 289 154 160
Thr 130 146 47 317 158 210 125 151
Cys 48 56 80 51 34 44 24 27
Asn 124 117 14 121 89 116 145 157
Gln 186 114 39 283 170 144 106 129
Asp 169 96 0 87 193 166 269 354
Glu 238 202 6 267 302 239 202 391
Lys 190 211 6 371 132 176 94 171
Arg 121 205 4 225 90 107 80 102
His 86 62 5 41 57 76 87 92
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
Relevant inhibitors relacatib
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