Summary for peptidase C01.013: cathepsin X

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

 

Names
MEROPS Namecathepsin X
Other namescarboxypeptidase LB, cathepsin IV, cathepsin B2, cathepsin P [obs.], cathepsin Y, cathepsin Z [obs.], cathepsin Z1 (Toxocara), CTSZ g.p. (Homo sapiens), cysteine-type carboxypeptidase, lysosomal carboxypeptidase B
Name and HistoryCathepsin X is predominantly a cysteine-type carboxypeptidase with limited endopeptidase or dipeptidyl-peptidase activity, mainly against synthetic substrates (Nagler et al., 1999, Klemencic et al., 2000).
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.013
Holotypecathepsin X (Homo sapiens), Uniprot accession Q9UBR2 (peptidase unit: 57-302), MERNUM MER0004508
History Identifier created: MEROPS 3.03 (10 September 1998)
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00055
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.18 (Cysteine-type carboxypeptidases) >> Peptidase 3.4.18.1
EnzymologyBRENDA database
Proteolytic eventsCutDB database (4 cleavages)
Activity statushuman: active (Menard & Sulea, 2004)
mouse: active (by similarity)
SpecificityThe substrate specificity has been examined by peptide scanning and shows that proline is not tolerated in the P1 or P1' positions and poorly accepted in P2, and Tyr, Met and Cys are marginally prefered in P2, P1 and P1' (Devanathan et al., 2005, Puzer et al., 2005). From the crystal structure of the mature enzyme, a short, five-residue 'mini-loop' which includes the motif His-Xaa-Xaa-Xaa-Tyr restricts access to the S2' binding pocket, and it is the histidine that confers carboxypeptidase activity (Guncar et al., 2000). Rotation of the histidine ring permits dipeptidyl-peptidase substrates to bind.
Biological aspectsCathepsin X is synthesized as an inactive zymogen, but the propeptide lacks the ERFNIN motif characteristic of lysosomal cysteine peptidases. A disulfide bridge can be formed between the proregion and the enzyme which leads to inactivation of the zymogen by the formation of a reversible covalent bond with the active site residue (Sivaraman et al., 2000). The presence of an exposed RGD motif allows binding to beta3-integrin (Obermajer et al., 2006) and the enzyme may have a role in cell signalling.
Pharmaceutical relevanceCathepsin X deficiency leads to accelerated cell senescence (Kraus et al., 2011). Cathepsin X also regulates the immune response to Helicobacter pylori infection (Krueger et al., 2005, Obermajer et al., 2009).
Pathways KEGGLysosome
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_Z
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/-Scissile bond-/-/-/- (based on 46 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 0 0 8 2 0 0 0
Pro 2 4 4 0 1 0 0 0
Ala 0 2 3 4 4 0 0 0
Val 1 1 1 1 1 0 0 0
Leu 4 4 7 6 6 0 0 0
Ile 2 1 1 1 1 0 0 0
Met 1 1 1 1 2 0 0 0
Phe 0 1 4 2 3 0 0 0
Tyr 1 1 1 1 2 0 0 0
Trp 2 2 2 2 1 0 0 0
Ser 0 0 2 2 3 0 0 0
Thr 0 0 0 0 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 3 3 0 2 2 0 0 0
Gln 1 1 1 1 1 0 0 0
Asp 1 1 0 0 1 0 0 0
Glu 3 3 2 6 4 0 0 0
Lys 5 5 5 4 5 0 0 0
Arg 2 0 1 4 3 0 0 0
His 0 0 0 0 0 0 0 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSZ 20q13 ENSG00000101160 1522 CTSZ 603169
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctsz 2:H4 ENSMUSG00000016256 64138 MGI:1891190