Summary for peptidase C01.032: cathepsin L

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

 

Names
MEROPS Namecathepsin L
Other namesSPase (Cercopithecus aethiops)
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.032
Holotypecathepsin L (Homo sapiens), Uniprot accession P07711 (peptidase unit: 113-333), MERNUM MER0000622
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00060
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.15
EnzymologyBRENDA database
Proteolytic eventsCutDB database (47 cleavages)
Activity statushuman: active (Kirschke, 2004)
mouse: active (Mason et al., 1989)
PhysiologyEndopeptidase activity in lysosomal proteolysis, and probably also contributes to the generation of antigenic peptides for the MHC II system. In addition, it is reported that cathepsin L synthesised without a signal peptide localises to the nucleus, and functions in the regulation of cell cycle progression through proteolytic processing of the CDP/Cux transcription factor (Goulet et al., 2004).
KnockoutThe gene was inactivated by gene targeting in mouse embryonic stem cells (Roth et al., 2000). The deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. Cathepsin L deficiency was shown to be a molecular defect of the previously-known furless mouse. Combined deficiency of cathepsins B and L in mice is lethal during the second to fourth week, and associated with a degree of brain atrophy not previously seen in mice (Felbor et al., 2002). Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis (Wright et al., 2003).
Pathways KEGGAntigen processing and presentation
KEGGLysosome
KEGGPhagosome
KEGGProteoglycans in cancer
KEGGRheumatoid arthritis
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_L1
TREEFAMhttp://www.treefam.org/family/TF313739
PANTHERhttp://www.pantherdb.org/panther/familyList.do?searchType=basic&fieldName=all&listType=6&fieldValue=PTHR12411:SF57
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/lvfi/-Scissile bond-/-/-/- (based on 2938 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 235 249 9 388 357 233 282 232
Pro 191 139 79 5 8 345 345 484
Ala 244 220 71 273 364 263 266 184
Val 191 152 646 48 139 134 172 131
Leu 170 349 829 128 122 124 162 100
Ile 125 166 369 40 139 142 144 115
Met 51 90 56 80 63 28 56 24
Phe 104 105 391 73 51 51 76 41
Tyr 72 57 243 46 28 47 46 34
Trp 34 29 70 24 7 16 20 12
Ser 169 204 16 241 339 235 184 169
Thr 125 156 30 243 178 174 99 159
Cys 46 40 20 39 25 36 30 17
Asn 96 133 5 109 140 106 139 113
Gln 149 123 18 252 94 169 137 118
Asp 117 68 12 90 160 210 196 388
Glu 203 119 6 230 238 308 237 348
Lys 204 272 21 340 191 132 131 115
Arg 131 135 26 215 178 83 97 66
His 66 90 15 72 105 85 103 70
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 - K/R F R H/S S/H - - xKFR+HSxx Abz-EDDnp Puzer et al., 2004
Rattus norvegicus recombinant - - - - S/A/K - - - xxxx+Sxxx Dansyl-Trp Ménard et al., 1993
Homo sapiens recombinant H/broad K/R/n/M/L F/W/Y R/K - - - - HKFR ACC Choe et al., 2006
Homo sapiens recombinant - - - Iaf/Amf - - - - xxxIaf+xxxx Abz-EDDnp Alves et al., 2001
Homo sapiens recombinant - - - - R/A/K - - - xxx+Rxxx Abz-EDDnp Melo et al., 2001
Relevant inhibitors ALLM, ALLN, CLIK148, E64, K11777, relacatib, SJA6017
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSL1 9q21-q22 ENSG00000135047 1514 CTSL 116880
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctsl 13:B3 ENSMUSG00000021477 13039 MGI:88564