Summary for peptidase C01.032: cathepsin L

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST 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
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 1089 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 79 112 6 193 211 100 100 105
Pro 46 67 24 4 1 133 136 159
Ala 78 85 27 112 145 109 101 65
Val 57 57 220 18 34 53 61 46
Leu 65 154 314 55 34 57 60 50
Ile 49 66 142 21 33 56 42 31
Met 25 32 8 24 14 6 8 13
Phe 45 55 155 37 18 32 29 14
Tyr 32 24 94 13 10 22 22 17
Trp 14 11 32 10 5 4 3 6
Ser 69 93 12 106 189 95 90 86
Thr 37 65 10 104 79 73 45 75
Cys 15 16 6 17 4 16 13 11
Asn 35 53 3 52 48 28 52 45
Gln 45 37 6 115 32 79 59 51
Asp 38 24 3 29 31 46 59 123
Glu 84 32 4 86 64 60 56 94
Lys 16 15 7 29 26 35 45 25
Arg 16 12 2 27 34 15 24 15
His 29 37 8 35 65 53 68 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 - 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
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