DB code: D00484

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1
E.C. 3.4.23.5
CSA 1lya
M-CSA 1lya
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00436 D00438 D00439 D00440 D00441 D00442 D00443 D00437 D00444 D00423 D00445 M00206 M00166 D00231 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P07339 Cathepsin D
EC 3.4.23.5
Cathepsin D light chain
Cathepsin D heavy chain
NP_001900.1 (Protein)
NM_001909.4 (DNA/RNA sequence)
A01.009 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
cathepsin D

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P07339 CATD_HUMAN Specificity similar to, but narrower than, that of pepsin A. Does not cleave the 4-Gln-|-His-5 bond in B chain of insulin. Consists of a light chain and a heavy chain. Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00001 C00017 C00012 I00136
E.C.
Compound Protein Peptide H2O Protein Peptide Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1lyaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lyaC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lybA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-STA-ALA-STA (chain I)
1lybC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-STA-ALA-STA (chain J)
1lywA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lyaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lyaD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lybB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lybD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lywH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P07339

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1lyaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lyaC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lybA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lybC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lywA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lywC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lywE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lywG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 33
1lyaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lyaD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lybB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lybD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lywB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lywD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lywF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231
1lywH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 231

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[8]
[9]

References
[1]
Resource
Comments
Medline ID
PubMed ID 3202970
Journal Biol Chem Hoppe Seyler
Year 1988
Volume 369 Suppl
Pages 323-7
Authors Bonelli G, Kay J, Tessitore L, Jupp RA, Isidoro C, Norey CG, Autelli R, Richards AD, Baccino FM
Title Purification and properties of cathepsin D from rat Yoshida ascites hepatoma AH-130.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2512908
Journal Biochem J
Year 1989
Volume 263
Pages 601-4
Authors Conner GE
Title Isolation of procathepsin D from mature cathepsin D by pepstatin affinity chromatography. Autocatalytic proteolysis of the zymogen form of the enzyme.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2002505
Journal J Mol Biol
Year 1991
Volume 218
Pages 21-2
Authors Baudys M, Ghosh M, Harlos K, Mares M, Fusek M, Kostka V, Blake CC
Title Crystallization and preliminary crystallographic study of cathepsin D inhibitor from potatoes.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1331083
Journal J Biol Chem
Year 1992
Volume 267
Pages 23357-63
Authors Cantor AB, Kornfeld S
Title Phosphorylation of Asn-linked oligosaccharides located at novel sites on the lysosomal enzyme cathepsin D.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1433300
Journal J Mol Biol
Year 1992
Volume 227
Pages 1265-8
Authors Bieber F, Brachvogel V, Arni R, Fusek M, Metcalf P
Title Crystallization and initial crystallographic results for pepstatin A inhibited bovine cathepsin D.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1640466
Journal J Mol Biol
Year 1992
Volume 226
Pages 555-7
Authors Fusek M, Baudys M, Metcalf P
Title Purification and crystallization of human cathepsin D.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1522590
Journal J Mol Biol
Year 1992
Volume 227
Pages 265-70
Authors Gulnik S, Baldwin ET, Tarasova N, Erickson J
Title Human liver cathepsin D. Purification, crystallization and preliminary X-ray diffraction analysis of a lysosomal enzyme.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS)
Medline ID 93223670
PubMed ID 8467789
Journal EMBO J
Year 1993
Volume 12
Pages 1293-302
Authors Metcalf P, Fusek M
Title Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.
Related PDB
Related UniProtKB P07339
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID 93342076
PubMed ID 8393577
Journal Proc Natl Acad Sci U S A
Year 1993
Volume 90
Pages 6796-800
Authors Baldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW
Title Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.
Related PDB 1lya 1lyb
Related UniProtKB P07339
[10]
Resource
Comments
Medline ID
PubMed ID 8540315
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 155-66
Authors Aguilar CF, Dhanaraj V, Guruprasad K, Dealwis C, Badasso M, Cooper JB, Wood SP, Blundell TL
Title Comparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8540317
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 181-92
Authors Erickson JW, Baldwin ET, Bhat TN, Gulnik S
Title Structure of human cathepsin D: comparison of inhibitor binding and subdomain displacement with other aspartic proteases.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8540327
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 273-8
Authors Koelsch G, Metcalf P, Vetvicka V, Fusek M
Title Human procathepsin D: three-dimensional model and isolation.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8540319
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 193-200
Authors Metcalf P, Fusek M
Title Cathepsin D crystal structures and lysosomal sorting.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7657721
Journal J Cell Sci
Year 1995
Volume 108
Pages 2007-15
Authors Schorey JS, Fortenberry SC, Chirgwin JM
Title Lysine residues in the C-terminal lobe and lysosomal targeting of procathepsin D.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8663051
Journal J Biol Chem
Year 1996
Volume 271
Pages 15590-6
Authors Beyer BM, Dunn BM
Title Self-activation of recombinant human lysosomal procathepsin D at a newly engineered cleavage junction, "short" pseudocathepsin D.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9195867
Journal Chem Biol
Year 1997
Volume 4
Pages 297-307
Authors Kick EK, Roe DC, Skillman AG, Liu G, Ewing TJ, Sun Y, Kuntz ID, Ellman JA
Title Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9232647
Journal Protein Sci
Year 1997
Volume 6
Pages 1458-66
Authors Majer P, Collins JR, Gulnik SV, Erickson JW
Title Structure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9561243
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 363-73
Authors Silva AM, Lee AY, Erickson JW, Goldberg DE
Title Structural analysis of plasmepsin II. A comparison with human aspartic proteases.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9694859
Journal J Biol Chem
Year 1998
Volume 273
Pages 21067-76
Authors Cuozzo JW, Tao K, Cygler M, Mort JS, Sahagian GG
Title Lysine-based structure responsible for selective mannose phosphorylation of cathepsin D and cathepsin L defines a common structural motif for lysosomal enzyme targeting.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9783744
Journal Nat Struct Biol
Year 1998
Volume 5
Pages 866-71
Authors Lee AY, Gulnik SV, Erickson JW
Title Conformational switching in an aspartic proteinase.
Related PDB 1lyw
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9514263
Journal Protein Sci
Year 1998
Volume 7
Pages 88-95
Authors Beyer BM, Dunn BM
Title Prime region subsite specificity characterization of human cathepsin D: the dominant role of position 128.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9890884
Journal Biochemistry
Year 1999
Volume 38
Pages 73-80
Authors Lukong KE, Elsliger MA, Mort JS, Potier M, Pshezhetsky AV
Title Identification of UDP-N-acetylglucosamine-phosphotransferase-binding sites on the lysosomal proteases, cathepsins A, B, and D.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11731271
Journal Matrix Biol
Year 2001
Volume 20
Pages 543-53
Authors Handley CJ, Mok MT, Ilic MZ, Adcocks C, Buttle DJ, Robinson HC
Title Cathepsin D cleaves aggrecan at unique sites within the interglobular domain and chondroitin sulfate attachment regions that are also cleaved when cartilage is maintained at acid pH.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11687971
Journal Oncogene
Year 2001
Volume 20
Pages 6920-9
Authors Glondu M, Coopman P, Laurent-Matha V, Garcia M, Rochefort H, Liaudet-Coopman E
Title A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11906282
Journal J Med Chem
Year 2002
Volume 45
Pages 1412-9
Authors Huo S, Wang J, Cieplak P, Kollman PA, Kuntz ID
Title Molecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insight into structure-based ligand design.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12350228
Journal Biochem J
Year 2003
Volume 369
Pages 55-62
Authors Partanen S, Storch S, Loffler HG, Hasilik A, Tyynela J, Braulke T
Title A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 14695825
Journal J Med Chem
Year 2004
Volume 47
Pages 110-22
Authors Ersmark K, Feierberg I, Bjelic S, Hamelink E, Hackett F, Blackman MJ, Hulten J, Samuelsson B, Aqvist J, Hallberg A
Title Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-A1. This enzyme is composed of two chains, light chain and heavy chain.
As it has a catalytic dyad, composed of two aspartic acid residues, it must have a similar mechanism to that of pepsin (D00436 in EzCatDB)

Created Updated
2004-03-03 2012-06-28