Reviewed, UniProtKB/Swiss-Prot P07339 (CATD_HUMAN)

Names and origin

Protein names

Recommended name:
    Cathepsin D
    EC=3.4.23.5
Cleaved into the following 2 chains:
    1- Recommended name:
            Cathepsin D light chain
    2- Recommended name:
            Cathepsin D heavy chain

Gene names

Name:	CTSD
Synonyms:	CPSD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.10 Ref.13
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	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. Ref.20
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Alzheimer disease Disease mutation Neuronal ceroid lipofuscinosis
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB lysosome Non-traceable author statement. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aspartic-type endopeptidase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Propeptide

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

Sites

Active site

97

1

Ref.18

Active site

295

1

Ref.18

Amino acid modifications

Glycosylation

134

1

N-linked (GlcNAc...)

Glycosylation

263

1

N-linked (GlcNAc...) Ref.11 Ref.12 Ref.14 Ref.18

Disulfide bond

91 ↔ 160

Ref.18

Disulfide bond

110 ↔ 117

Ref.18

Disulfide bond

286 ↔ 290

Ref.18

Disulfide bond

329 ↔ 366

Natural variations

Natural variant

58

1

A → V Associated with increased risk in AD; possibly influences secretion and intracellular maturation. dbSNP rs17571. Ref.19

VAR_011621

Natural variant

229

1

F → I in CLN10. Ref.20

VAR_029362

Natural variant

383

1

W → C in CLN10. Ref.20

VAR_029363

Secondary structure

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412

Helix Strand Turn

Details...

Beta strand

67 – 74

8

Turn

75 – 77

3

Beta strand

78 – 85

8

Turn

86 – 89

4

Beta strand

90 – 97

8

Beta strand

103 – 107

5

Helix

115 – 118

4

Helix

125 – 127

3

Beta strand

132 – 141

10

Beta strand

146 – 159

14

Beta strand

172 – 184

13

Turn

189 – 191

3

Beta strand

194 – 200

7

Helix

204 – 206

3

Helix

208 – 210

3

Helix

214 – 220

7

Beta strand

224 – 233

10

Beta strand

243 – 247

5

Helix

252 – 254

3

Beta strand

255 – 263

9

Turn

267 – 270

4

Beta strand

271 – 279

9

Beta strand

284 – 286

3

Beta strand

290 – 294

5

Beta strand

299 – 303

5

Helix

305 – 315

11

Beta strand

318 – 321

4

Beta strand

324 – 328

5

Helix

329 – 334

6

Beta strand

338 – 342

5

Beta strand

345 – 349

5

Turn

351 – 353

3

Beta strand

354 – 358

5

Turn

359 – 362

4

Beta strand

363 – 372

10

Turn

377 – 379

3

Beta strand

383 – 385

3

Helix

387 – 390

4

Beta strand

393 – 398

6

Turn

399 – 402

4

Beta strand

403 – 409

7

Sequences

	Sequence		Length	Mass (Da)
	P07339-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 903FB8412E0CF0B0	FASTA	412	44,552
	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

References

	« Hide 'large scale' referencesShow '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: 3927292] [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: 3588310] [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: 2069717] [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: 15489334] [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: 8262386] [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: 7935485] [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: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 12754519] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"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: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"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: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263, MASS SPECTROMETRY. Tissue: Platelet.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-134 AND ASN-263, MASS SPECTROMETRY. Tissue: Liver.
[17]	"Two crystal structures for cathepsin D: the lysosomal targeting signal and active site." Metcalf P., Fusek M. EMBO J. 12:1293-1302(1993) [PubMed: 8467789] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS). Tissue: Spleen.
[18]	"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: 8393577] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). Tissue: Liver.
[19]	"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: 10716266] [Abstract] Cited for: VARIANT VAL-58.
[20]	"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: 16685649] [Abstract] Cited for: VARIANTS CLN10 ILE-229 AND CYS-383.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M11233 mRNA. Translation: AAB59529.1.
X05344 mRNA. Translation: CAA28955.1.
M63138 , 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 Unassigned DNA. Translation: AAA16314.1.
S74689 Genomic DNA. Translation: AAD14156.1.
S52557 Genomic DNA. Translation: AAD13868.1.

IPI

IPI00011229.

PIR

KHHUD. A25771.

RefSeq

NP_001900.1.

UniGene

Hs.121575
Hs.654447

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LYA	X-ray	2.50	A/C	65-161	[»]
			B/D	170-410	[»]
1LYB	X-ray	2.50	A/C	65-161	[»]
			B/D	170-410	[»]
1LYW	X-ray	2.50	A/C/E/G	65-161	[»]
			B/D/F/H	170-410	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P07339. 1 interaction.

Protein family/group databases

MEROPS

A01.009.

2-D gel databases

SWISS-2DPAGE

P07339.

DOSAC-COBS-2DPAGE

P07339.

REPRODUCTION-2DPAGE

IPI00011229.

Siena-2DPAGE

P07339.

Proteomic databases

PeptideAtlas

P07339.

PRIDE

P07339.

Genome annotation databases

Ensembl

ENSG00000117984. Homo sapiens. [Contig view]

GeneID

1509.

KEGG

hsa:1509.

Organism-specific databases

GeneCards

GC11M001730.

H-InvDB

HIX0009358.
HIX0009359.

HGNC

HGNC:2529. CTSD.

HPA

CAB000109.
HPA003001.

MIM

116840. gene.
610127. phenotype.

Orphanet

216. Ceroid lipofuscinosis, neuronal.
168486. Congenital neuronal ceroid lipofuscinosis.

PharmGKB

PA27029.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07339.

HOVERGEN

P07339.

OMA

P07339. QDTVSVP.

Enzyme and pathway databases

BRENDA

3.4.23.5. 247.

Pathway_Interaction_DB

ceramidepathway. Ceramide signaling pathway.

Gene expression databases

ArrayExpress

P07339.

Bgee

P07339.

CleanEx

HS_CTSD.

GermOnline

ENSG00000117984. Homo sapiens.

Family and domain databases

InterPro

IPR001461. Peptidase_A1.
IPR001969. Peptidase_aspartic_AS.
IPR009007. Peptidase_aspartic_catalytic.
IPR012848. Propep_A1.
[Graphical view]

Gene3D

G3DSA:2.40.70.10. Pept_Aspartc_cat. 2 hits.

PANTHER

PTHR13683. Peptidase_A1. 1 hit.

Pfam

PF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]

PRINTS

PR00792. PEPSIN.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

NextBio

6247.

PMAP-CutDB

P07339.

SOURCE

Search...

Entry information

Entry name

CATD_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)