Summary for peptidase A01.009: cathepsin D

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

 

Names
MEROPS Namecathepsin D
Other namesBmCatD g.p. (Bombyx mori), CatD, cathepsin D1 (Ictalurus punctatus), cathepsin D2 (Ictalurus punctatus), CLN10 (Homo sapiens), CTSD g.p. (Homo sapiens), lysosomal aspartic protease (Aedes aegypti), longepsin (Haemaphysalis longicornis), todarepsin (Todarodes pacificus)
Domain architecture
MEROPS Classification
Classification Clan AA >> Subclan (none) >> Family A1 >> Subfamily A >> A01.009
Holotypecathepsin D (Homo sapiens), Uniprot accession P07339 (peptidase unit: 66-410), MERNUM MER0000911
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeAspartic
PeplistIncluded in the Peplist with identifier PL00007
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.23 (Aspartic endopeptidases) >> Peptidase 3.4.23.5
EnzymologyBRENDA database
ActivityCathepsin D is an endopeptidase most active at acidic pH.
Proteolytic eventsCutDB database (95 cleavages)
Activity statushuman: active (Conner et al., 2004)
mouse: active (Partanen et al., 2003)
SpecificityCathepsin D has a preference for hydrophobic residues around the scissile bond (Athauda & Takahashi, 2002).
PhysiologyCathepsin D contributes to lysosomal proteolysis, and to processing of at least some antigens for the MHC class II system.
KnockoutIn mouse, young with cathepsin D deficiency develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia at about day 26 (Saftig et al., 1995). The mice also show seizures and blindness in the late stages associated with deposits of ceroid lipofuscin in the CNS neurons (Koike et al., 2000). It is reported that a mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration (Tyynela et al., 2000). Cathepsin D knockout in Drosophila provides a model for neuronal ceroid lipofuscinoses (Myllykangas et al., 2005). Human congenital neuronal ceroid-lipofuscinosis has been attributed to a mutation in the cathepsin D gene (Siintola et al.2006).
Pharmaceutical relevanceReported to be useful in diagnosis and prognosis of breast and other cancers (Rochefort & Liaudet-Coopman, 1999). Also reported to enhance anchorage-independent cell proliferation and subsequently to facilitate tumorigenesis and metastasis of breast cancer cells, so may be a target for cancer therapy (Glondu et al., 2002). There is some genetic association between cathepsin D polymorphism and Alzheimer"s disease (Davidson et al., 2006). A potential role for cathepsin D in p53-dependent tumour suppression and chemosensitivity has been proposed (Wu et al., 1998).
Pathways KEGGLysosome
KEGGTuberculosis
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_D
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/LfScissile bond-/-/-/- (based on 897 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 42 48 27 22 8 56 64 89
Pro 52 30 2 2 3 2 11 55
Ala 67 35 82 46 83 111 80 86
Val 80 94 137 3 98 131 81 49
Leu 136 99 58 416 110 80 112 63
Ile 44 76 70 1 119 50 49 37
Met 21 26 23 35 44 13 25 31
Phe 67 28 19 175 106 16 21 20
Tyr 33 25 26 37 49 12 6 23
Trp 7 7 4 29 7 0 3 1
Ser 35 50 52 12 41 62 55 65
Thr 41 64 67 12 34 69 55 55
Cys 14 7 24 8 14 14 11 7
Asn 29 31 51 5 26 19 43 37
Gln 25 42 25 6 11 50 38 52
Asp 49 60 63 35 37 39 57 50
Glu 67 104 94 44 71 81 101 78
Lys 32 34 31 6 31 68 75 81
Arg 35 27 32 3 2 20 6 2
His 12 5 8 0 0 2 3 7
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSD 11p15.5 ENSG00000117984 1509 CTSD 116840
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctsd 7:F5 ENSMUSG00000007891 13033 MGI:88562