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UniProtKB/Swiss-Prot entry P07339


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CATD_HUMAN
Primary accession number P07339
Secondary accession number Q6IB57
Integrated into Swiss-Prot on April 1, 1988
Sequence was last modified on April 1, 1988 (Sequence version 1)
Annotations were last modified on    November 4, 2008 (Entry version 109)
Name and origin of the protein
Protein name Cathepsin D [Precursor]
Synonym EC 3.4.23.5
Contains Cathepsin D light chain
Cathepsin D heavy chain
Gene name
Name: CTSD
Synonyms: CPSD
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3927292 [NCBI, ExPASy, EBI, Israel, Japan]
Faust P.L., Kornfeld S., Chirgwin J.M.;
"Cloning and sequence analysis of cDNA for human cathepsin D.";
Proc. Natl. Acad. Sci. U.S.A. 82:4910-4914(1985).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1093/nar/15.9.3773; PubMed=3588310 [NCBI, ExPASy, EBI, Israel, Japan]
Westley B.R., May F.E.B.;
"Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cells.";
Nucleic Acids Res. 15:3773-3786(1987).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2069717 [NCBI, ExPASy, EBI, Israel, Japan]
Redecker B., Heckendorf B., Grosch H.W., Mersmann G., Hasilik A.;
"Molecular organization of the human cathepsin D gene.";
DNA Cell Biol. 10:423-431(1991).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Kidney;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
DOI=10.1016/0378-1119(93)90107-E; PubMed=8262386 [NCBI, ExPASy, EBI, Israel, Japan]
May F.E., Smith D.J., Westley B.R.;
"The human cathepsin D-encoding gene is transcribed from an estrogen-regulated and a constitutive start point.";
Gene 134:277-282(1993).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
DOI=10.1210/me.8.6.693; PubMed=7935485 [NCBI, ExPASy, EBI, Israel, Japan]
Augereau P., Miralles F., Cavailles V., Gaudelet C., Parker M., Rochefort H.;
"Characterization of the proximal estrogen-responsive element of human cathepsin D gene.";
Mol. Endocrinol. 8:693-703(1994).
[9]
PROTEIN SEQUENCE OF 170-180.
TISSUE=Liver;
Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J.;
Submitted (JUN-1992) to UniProtKB.
[10]
SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
DOI=10.1021/pr025562r; PubMed=12643545 [NCBI, ExPASy, EBI, Israel, Japan]
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.;
"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.";
J. Proteome Res. 2:69-79(2003).
[11]
GLYCOSYLATION AT ASN-263.
DOI=10.1038/nbt827; PubMed=12754519 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang H., Li X.-J., Martin D.B., Aebersold R.;
"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.";
Nat. Biotechnol. 21:660-666(2003).
[12]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan]
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
[13]
SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
DOI=10.1021/pr060363j; PubMed=17081065 [NCBI, ExPASy, EBI, Israel, Japan]
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.";
J. Proteome Res. 5:3135-3144(2006).
[14]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1074/mcp.M500324-MCP200; PubMed=16263699 [NCBI, ExPASy, EBI, Israel, Japan]
Lewandrowski U., Moebius J., Walter U., Sickmann A.;
"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach.";
Mol. Cell. Proteomics 5:226-233(2006).
[15]
X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS).
TISSUE=Spleen;
PubMed=8467789 [NCBI, ExPASy, EBI, Israel, Japan]
Metcalf P., Fusek M.;
"Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.";
EMBO J. 12:1293-1302(1993).
[16]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
TISSUE=Liver;
PubMed=8393577 [NCBI, ExPASy, EBI, Israel, Japan]
Baldwin E.T., Bhat T.N., Gulnik S., Hosur M.V., Sowder R.C. II, Cachau R.E., Collins J., Silva A.M., Erickson J.W.;
"Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.";
Proc. Natl. Acad. Sci. U.S.A. 90:6796-6800(1993).
[17]
VARIANT VAL-58.
DOI=10.1002/1531-8249(200003)47:3<399::AID-ANA22>3.3.CO;2-X; PubMed=10716266 [NCBI, ExPASy, EBI, Israel, Japan]
Papassotiropoulos A., Bagli M., Kurz A., Kornhuber J., Forstl H., Maier W., Pauls J., Lautenschlager N., Heun R.;
"A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.";
Ann. Neurol. 47:399-403(2000).
[18]
VARIANTS CLN10 ILE-229 AND CYS-383.
DOI=10.1086/504159; PubMed=16685649 [NCBI, ExPASy, EBI, Israel, Japan]
Steinfeld R., Reinhardt K., Schreiber K., Hillebrand M., Kraetzner R., Bruck W., Saftig P., Gartner J.;
"Cathepsin D deficiency is associated with a human neurodegenerative disorder.";
Am. J. Hum. Genet. 78:988-998(2006).
Comments
  • FUNCTION: Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
  • CATALYTIC ACTIVITY: Specificity similar to, but narrower than, that of pepsin A. Does not cleave the 4-Gln-|-His-5 bond in B chain of insulin.
  • SUBUNIT: Consists of a light chain and a heavy chain.
  • SUBCELLULAR LOCATION: Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
  • POLYMORPHISM: The Val-58 allele is significantly overrepresented in demented patients (11.8%) compared with non-demented controls (4.9%). Carriers of the Val-58 allele have a 3.1-fold increased risk for developing AD than non-carriers.
  • DISEASE: Defects in CTSD are the cause of neuronal ceroid lipofuscinosis 10 (CLN10) [MIM:610127]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. The neuronal ceroid lipofuscinosis are a group of progressive neurodegenerative diseases in children and in adults, characterized by visual and mental decline, motor disturbance, epilepsy and behavioral changes.
  • SIMILARITY: Belongs to the peptidase A1 family [view classification].
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M11233; AAB59529.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X05344; CAA28955.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M63138; AAA51922.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M63134; AAA51922.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M63135; AAA51922.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M63136; AAA51922.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M63137; AAA51922.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CR456947; CAG33228.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT006910; AAP35556.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT020155; AAV38957.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC016320; AAH16320.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L12980; AAA16314.1; -; Unassigned_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S74689; AAD14156.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S52557; AAD13868.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A25771; KHHUD.
RefSeq NP_001900.1; -.
UniGene Hs.121575
3D structure databases
PDB
1LYA; X-ray; 2.50 A; A/C=65-161, B/D=170-410.[ExPASy / RCSB / EBI]
1LYB; X-ray; 2.50 A; A/C=65-161, B/D=170-410.[ExPASy / RCSB / EBI]
1LYW; X-ray; 2.50 A; A/C/E/G=65-161, B/D/F/H=170-410.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1LYA; -.
1LYB; -.
1LYW; -.
ModBase P07339.
Protein family/group databases
MEROPS A01.009; -.
2D gel databases
SWISS-2DPAGE P07339; -.
DOSAC-COBS-2DPAGE P07339; -.
REPRODUCTION-2DPAGE IPI00011229; -.
Siena-2DPAGE P07339; -.
Organism-specific databases
H-InvDB HIX0009358; -.
HIX0009359; -.
HGNC HGNC:2529; CTSD.
GenAtlas CTSD.
HPA CAB000109; -.
HPA003001; -.
MIM 116840; gene. [NCBI / EBI]
610127; phenotype. [NCBI / EBI]
Orphanet 216; Ceroid lipofuscinosis, neuronal.
PharmGKB PA27029; -.
GeneCards P07339.
Gene expression databases
ArrayExpress P07339; -.
CleanEx HS_CTSD; -.
GermOnline ENSG00000117984; Homo sapiens.
Ontologies
GO
GO:0005576; Cellular component: extracellular region (non-traceable author statement from UniProtKB).
GO:0005764; Cellular component: lysosome (non-traceable author statement from UniProtKB).
GO:0004190; Molecular function: aspartic-type endopeptidase activity (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR001969; Pept_Asp_AS.
IPR009007; Pept_Aspartc_cat.
IPR001461; Peptidase_A1.
IPR012848; Propep_A1.
Graphical view of domain structure.
Gene3D G3DSA:2.40.70.10; Pept_Aspartc_cat; 2.
PANTHER PTHR13683; Peptidase_A1; 1.
Pfam PF07966; A1_Propeptide; 1.
PF00026; Asp; 1.
Pfam graphical view of domain structure.
PRINTS PR00792; PEPSIN.
PROSITE PS00141; ASP_PROTEASE; 2.
BLOCKS P07339.
ProtoNet P07339.
Proteomic databases
PeptideAtlas P07339; -.
Genome annotation databases
Ensembl ENSG00000117984; Homo sapiens. [Contig view]
GeneID 1509; -.
KEGG hsa:1509; -.
Phylogenomic databases
HOGENOM P07339; -.
HOVERGEN P07339; -.
Other
DrugBank DB00047; Insulin Glargine recombinant.
DB00046; Insulin Lyspro recombinant.
DB00030; Insulin recombinant.
DB00071; Insulin, porcine.
LinkHub P07339; -.
NextBio 6247; -.
SOURCE CTSD; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alzheimer disease; Aspartyl protease; Direct protein sequencing; Disease mutation; Glycoprotein; Hydrolase; Lysosome; Neuronal ceroid lipofuscinosis; Polymorphism; Protease; Signal; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    18  18      
PROPEP   19    64  46     Activation peptide. PRO_0000025949
CHAIN   65   412  348     Cathepsin D. PRO_0000025950
CHAIN   65   161  97     Cathepsin D light chain (Probable). PRO_0000025951
CHAIN   169   412  244     Cathepsin D heavy chain (Probable). PRO_0000025952
ACT_SITE   97    97         
ACT_SITE   295   295         
CARBOHYD   134   134        N-linked (GlcNAc...). 
CARBOHYD   263   263        N-linked (GlcNAc...). 
DISULFID   91   160         
DISULFID   110   117         
DISULFID   286   290         
DISULFID   329   366         
VARIANT   58    58  1     A -> V (associated with increased risk in AD; possibly influences secretion and intracellular maturation; dbSNP:rs17571 [NCBI]). VAR_011621 
VARIANT   229   229  1     F -> I (in CLN10). VAR_029362 
VARIANT   383   383  1     W -> C (in CLN10). VAR_029363 
STRAND   67    74  8      
TURN   75    77  3      
STRAND   78    85  8      
TURN   86    89  4      
STRAND   90    97  8      
STRAND   103   107  5      
HELIX   115   118  4      
HELIX   125   127  3      
STRAND   132   141  10      
STRAND   146   159  14      
STRAND   172   184  13      
TURN   189   191  3      
STRAND   194   200  7      
HELIX   204   206  3      
HELIX   208   210  3      
HELIX   214   220  7      
STRAND   224   233  10      
STRAND   243   247  5      
HELIX   252   254  3      
STRAND   255   263  9      
TURN   267   270  4      
STRAND   271   279  9      
STRAND   284   286  3      
STRAND   290   294  5      
STRAND   299   303  5      
HELIX   305   315  11      
STRAND   318   321  4      
STRAND   324   328  5      
HELIX   329   334  6      
STRAND   338   342  5      
STRAND   345   349  5      
TURN   351   353  3      
STRAND   354   358  5      
TURN   359   362  4      
STRAND   363   372  10      
TURN   377   379  3      
STRAND   383   385  3      
HELIX   387   390  4      
STRAND   393   398  6      
TURN   399   402  4      
STRAND   403   409  7      
Sequence information
Length: 412 AA [This is the length of the unprocessed precursor] Molecular weight: 44552 Da [This is the MW of the unprocessed precursor] CRC64: 903FB8412E0CF0B0 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MQPSSLLPLA LCLLAAPASA LVRIPLHKFT SIRRTMSEVG GSVEDLIAKG PVSKYSQAVP 

        70         80         90        100        110        120 
AVTEGPIPEV LKNYMDAQYY GEIGIGTPPQ CFTVVFDTGS SNLWVPSIHC KLLDIACWIH 

       130        140        150        160        170        180 
HKYNSDKSST YVKNGTSFDI HYGSGSLSGY LSQDTVSVPC QSASSASALG GVKVERQVFG 

       190        200        210        220        230        240 
EATKQPGITF IAAKFDGILG MAYPRISVNN VLPVFDNLMQ QKLVDQNIFS FYLSRDPDAQ 

       250        260        270        280        290        300 
PGGELMLGGT DSKYYKGSLS YLNVTRKAYW QVHLDQVEVA SGLTLCKEGC EAIVDTGTSL 

       310        320        330        340        350        360 
MVGPVDEVRE LQKAIGAVPL IQGEYMIPCE KVSTLPAITL KLGGKGYKLS PEDYTLKVSQ 

       370        380        390        400        410 
AGKTLCLSGF MGMDIPPPSG PLWILGDVFI GRYYTVFDRD NNRVGFAEAA RL 

P07339 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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