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P07339 (CATD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cathepsin D

EC=3.4.23.5

Cleaved into the following 2 chains:

  1. Cathepsin D light chain
  2. Cathepsin D heavy chain
Gene names
Name:CTSD
Synonyms:CPSD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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 structure

Consists of a light chain and a heavy chain.

Subcellular location

Lysosome. Melanosome. Secretedextracellular space. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. In aortic samples, detected as an extracellular protein loosely bound to the matrix (Ref.17). Ref.10 Ref.14 Ref.17

Tissue specificity

Expressed in the aorta extrcellular space (at protein level). Ref.17

Post-translational modification

N- and O-glycosylated. Ref.11 Ref.19

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.

Involvement in disease

Ceroid lipofuscinosis, neuronal, 10 (CLN10) [MIM:610127]: A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.23 Ref.24

Sequence similarities

Belongs to the peptidase A1 family.

Ontologies

Keywords
   Cellular componentLysosome
Secreted
   Coding sequence diversityPolymorphism
   DiseaseAlzheimer disease
Disease mutation
Neurodegeneration
Neuronal ceroid lipofuscinosis
   DomainSignal
   Molecular functionAspartyl protease
Hydrolase
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

autophagic vacuole assembly

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

collagen catabolic process

Traceable author statement. Source: Reactome

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentextracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from direct assay Ref.17. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

lysosomal lumen

Traceable author statement. Source: Reactome

lysosome

Inferred from direct assay PubMed 1837142. Source: UniProtKB

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionaspartic-type endopeptidase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

APPP050672EBI-2115097,EBI-77613

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818
Propeptide19 – 6446Activation peptide
PRO_0000025949
Chain65 – 412348Cathepsin D
PRO_0000025950
Chain65 – 16197Cathepsin D light chain Probable
PRO_0000025951
Chain169 – 412244Cathepsin D heavy chain Probable
PRO_0000025952

Sites

Active site971 Ref.21
Active site2951 Ref.21

Amino acid modifications

Glycosylation631O-linked (GalNAc...) Ref.19
Glycosylation1341N-linked (GlcNAc...) Ref.16
Glycosylation2631N-linked (GlcNAc...) Ref.11 Ref.12 Ref.15 Ref.16 Ref.21
Disulfide bond91 ↔ 160 Ref.21
Disulfide bond110 ↔ 117 Ref.21
Disulfide bond286 ↔ 290 Ref.21
Disulfide bond329 ↔ 366

Natural variations

Natural variant581A → V Associated with increased risk for AD; possibly influences secretion and intracellular maturation. Ref.22
Corresponds to variant rs17571 [ dbSNP | Ensembl ].
VAR_011621
Natural variant2291F → I in CLN10. Ref.23 Ref.24
VAR_029362
Natural variant2821G → R. Ref.13
Corresponds to variant rs147278302 [ dbSNP | Ensembl ].
VAR_058490
Natural variant3831W → C in CLN10. Ref.23
VAR_029363

Secondary structure

.......................................................................... 412
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07339 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 903FB8412E0CF0B0

FASTA41244,552
        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 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of cDNA for human cathepsin D."
Faust P.L., Kornfeld S., Chirgwin J.M.
Proc. Natl. Acad. Sci. U.S.A. 82:4910-4914(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cells."
Westley B.R., May F.E.B.
Nucleic Acids Res. 15:3773-3786(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Molecular organization of the human cathepsin D gene."
Redecker B., Heckendorf B., Grosch H.W., Mersmann G., Hasilik A.
DNA Cell Biol. 10:423-431(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
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.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[7]"The human cathepsin D-encoding gene is transcribed from an estrogen-regulated and a constitutive start point."
May F.E., Smith D.J., Westley B.R.
Gene 134:277-282(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[8]"Characterization of the proximal estrogen-responsive element of human cathepsin D gene."
Augereau P., Miralles F., Cavailles V., Gaudelet C., Parker M., Rochefort H.
Mol. Endocrinol. 8:693-703(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[9]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
Cited for: PROTEIN SEQUENCE OF 170-180.
Tissue: Liver.
[10]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
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.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[11]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-263.
[12]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263.
Tissue: Plasma.
[13]"Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis."
Siintola E., Partanen S., Stromme P., Haapanen A., Haltia M., Maehlen J., Lehesjoki A.E., Tyynela J.
Brain 129:1438-1445(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CLN10, VARIANT ARG-282.
[14]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
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.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[15]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263.
Tissue: Platelet.
[16]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-134 AND ASN-263.
Tissue: Liver.
[17]"Proteomics characterization of extracellular space components in the human aorta."
Didangelos A., Yin X., Mandal K., Baumert M., Jahangiri M., Mayr M.
Mol. Cell. Proteomics 9:2048-2062(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins."
Halim A., Ruetschi U., Larson G., Nilsson J.
J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-63, IDENTIFICATION BY MASS SPECTROMETRY.
[20]"Two crystal structures for cathepsin D: the lysosomal targeting signal and active site."
Metcalf P., Fusek M.
EMBO J. 12:1293-1302(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS).
Tissue: Spleen.
[21]"Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design."
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.
Proc. Natl. Acad. Sci. U.S.A. 90:6796-6800(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Tissue: Liver.
[22]"A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease."
Papassotiropoulos A., Bagli M., Kurz A., Kornhuber J., Forstl H., Maier W., Pauls J., Lautenschlager N., Heun R.
Ann. Neurol. 47:399-403(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-58.
[23]"Cathepsin D deficiency is associated with a human neurodegenerative disorder."
Steinfeld R., Reinhardt K., Schreiber K., Hillebrand M., Kraetzner R., Bruck W., Saftig P., Gartner J.
Am. J. Hum. Genet. 78:988-998(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN10 ILE-229 AND CYS-383.
[24]"Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses."
Kousi M., Lehesjoki A.E., Mole S.E.
Hum. Mutat. 33:42-63(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN10 ILE-229.
+Additional computationally mapped references.

Web resources

NCL CTSD

Neural Ceroid Lipofuscinoses mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M11233 mRNA. Translation: AAB59529.1.
X05344 mRNA. Translation: CAA28955.1.
M63138 expand/collapse EMBL AC list , M63134, M63135, M63136, M63137 Genomic DNA. Translation: AAA51922.1.
CR456947 mRNA. Translation: CAG33228.1.
BT006910 mRNA. Translation: AAP35556.1.
BT020155 mRNA. Translation: AAV38957.1.
BC016320 mRNA. Translation: AAH16320.1.
L12980 Genomic DNA. Translation: AAA16314.1.
S74689 Genomic DNA. Translation: AAD14156.1.
S52557 Genomic DNA. Translation: AAD13868.1.
PIRKHHUD. A25771.
RefSeqNP_001900.1. NM_001909.4.
UniGeneHs.654447.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LYAX-ray2.50A/C65-161[»]
B/D170-410[»]
1LYBX-ray2.50A/C65-161[»]
B/D170-410[»]
1LYWX-ray2.50A/C/E/G65-161[»]
B/D/F/H170-410[»]
ProteinModelPortalP07339.
SMRP07339. Positions 21-410.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107889. 17 interactions.
IntActP07339. 18 interactions.
MINTMINT-3005628.
STRING9606.ENSP00000236671.

Chemistry

BindingDBP07339.
ChEMBLCHEMBL2581.
DrugBankDB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.
GuidetoPHARMACOLOGY2345.

Protein family/group databases

MEROPSA01.009.

PTM databases

PhosphoSiteP07339.

Polymorphism databases

DMDM115717.

2D gel databases

DOSAC-COBS-2DPAGEP07339.
REPRODUCTION-2DPAGEIPI00011229.
SWISS-2DPAGEP07339.
UCD-2DPAGEP07339.

Proteomic databases

PaxDbP07339.
PeptideAtlasP07339.
PRIDEP07339.

Protocols and materials databases

DNASU1509.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000236671; ENSP00000236671; ENSG00000117984.
GeneID1509.
KEGGhsa:1509.
UCSCuc001luc.2. human.

Organism-specific databases

CTD1509.
GeneCardsGC11M001773.
H-InvDBHIX0009359.
HGNCHGNC:2529. CTSD.
HPACAB000109.
HPA003001.
MIM116840. gene.
610127. phenotype.
neXtProtNX_P07339.
Orphanet228337. CLN10 disease.
PharmGKBPA27029.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG248684.
HOGENOMHOG000197681.
HOVERGENHBG000482.
InParanoidP07339.
KOK01379.
OMAGEYMISC.
PhylomeDBP07339.
TreeFamTF314990.

Enzyme and pathway databases

BioCycMetaCyc:HS04183-MONOMER.
ReactomeREACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP07339.
BgeeP07339.
CleanExHS_CTSD.
GenevestigatorP07339.

Family and domain databases

Gene3D2.40.70.10. 2 hits.
InterProIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERPTHR13683. PTHR13683. 1 hit.
PfamPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSPR00792. PEPSIN.
SUPFAMSSF50630. SSF50630. 1 hit.
PROSITEPS00141. ASP_PROTEASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP07339.
GeneWikiCathepsin_D.
GenomeRNAi1509.
NextBio6247.
PMAP-CutDBP07339.
PROP07339.
SOURCESearch...

Entry information

Entry nameCATD_HUMAN
AccessionPrimary (citable) accession number: P07339
Secondary accession number(s): Q6IB57
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: April 16, 2014
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM