Summary for peptidase C01.060: cathepsin B

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

 

Names
MEROPS Namecathepsin B
Other namescathepsin B1, cathepsin II (obs.), CTSB g.p. (Homo sapiens), longipain, vitellogenic cathepsin B (Aedes aegypti)
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.060
Holotypecathepsin B (Homo sapiens), Uniprot accession P07858 (peptidase unit: 80-331), MERNUM MER0000686
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00067
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.1
EnzymologyBRENDA database
Proteolytic eventsCutDB database (35 cleavages)
Activity statushuman: active (Mort, 2004)
mouse: active (Mort et al., 1988)
PhysiologyContributes to antigen processing for MHC II in mouse, but is not indespensable (Deussing et al., 1998). Suggested to mediate post-translational processing and activation of prorenin (Jutras & Reudelhuber, 1999).
KnockoutAntisense-transfected osteosarcoma cells with depressed expression of cathepsin B showed lower invasive activity in Transwell chambers, consistent with the proposal that cathepsin B is involved in the proteolytic processes in invasive osteosarcomas (Kruger et al., 1999). 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).
Pharmaceutical relevancePotential drug target for cancer (e.g. Bervar et al., 2003), but may be required for induction of caspase-independent cell death (Broker et al., 2004). Proposed to be responsible for premature activation of trypsinogen in acute pancreatitis (Figarella et al., 1988; Szilagyi et al., 2001). It has been reported that down-regulation of expression of both cathepsin B and u-plasminogen activator has anti-tumour activity in experimental systems (Gondi et al., 2004).
Pathways KEGGAntigen processing and presentation
KEGGLysosome
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_B
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/gScissile bond-/-/g/- (based on 632 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 71 61 13 177 96 69 246 95
Pro 39 61 18 3 7 17 32 40
Ala 52 56 107 87 63 84 54 59
Val 36 38 88 5 51 79 29 37
Leu 37 97 60 42 82 55 20 28
Ile 34 33 40 1 33 46 10 38
Met 22 14 15 24 12 6 0 6
Phe 19 40 60 13 67 18 18 27
Tyr 8 24 28 7 22 9 8 14
Trp 4 8 8 2 6 8 5 5
Ser 32 32 55 34 58 57 33 46
Thr 23 21 27 44 28 49 17 30
Cys 9 6 6 16 5 2 5 6
Asn 23 15 9 18 20 22 14 12
Gln 32 20 14 53 8 22 12 24
Asp 18 4 12 15 7 9 13 32
Glu 29 20 8 28 5 12 16 21
Lys 15 10 6 8 3 8 6 13
Arg 10 12 23 41 7 3 5 5
His 16 12 18 14 14 9 18 18
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 - - F/Y R/K F F - - xxFR+FFxx Dnp-Trp Cezari et al., 2002
Homo sapiens recombinant - - - - F/L - - - xxx+Fxxx Abz-EDDnp Melo et al., 2001
Homo sapiens recombinant R/H/broad n/L V/M/n R/K - - - - RnVR ACC Choe et al., 2006
Homo sapiens recombinant - - V/F/Y R/L/S/A A - - - xxVR+Axxx Abz-Dnp Cotrin et al., 2004
Homo sapiens recombinant - - - R - - - - xxxR+xxxx Abz-EDDnp Del Nery et al., 2000
Homo sapiens recombinant Q/G S V/A G/Q F A/V - - QSVG+FAxx Tyr(NO2)-Abz Peterson et al., 1998
Rattus norvegicus recombinant - - - - L/F - - - xxxx+Lxxx Dansyl-Trp Ménard et al., 1993
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSB 8p22 ENSG00000164733 1508 CTSB 116810
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctsb 14:C3 ENSMUSG00000021939 13030 MGI:88561