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Protein

Cathepsin D

Gene

CTSD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.1 Publication

Catalytic activityi

Specificity similar to, but narrower than, that of pepsin A. Does not cleave the 4-Gln-|-His-5 bond in B chain of insulin.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei97PROSITE-ProRule annotation1 Publication1
Active sitei295PROSITE-ProRule annotation1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aspartyl protease, Hydrolase, Protease

Enzyme and pathway databases

BioCyciMetaCyc:HS04183-MONOMER.
ZFISH:HS04183-MONOMER.
BRENDAi3.4.23.5. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
R-HSA-2132295. MHC class II antigen presentation.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiA01.009.

Names & Taxonomyi

Protein namesi
Recommended name:
Cathepsin D (EC:3.4.23.5)
Cleaved into the following 2 chains:
Gene namesi
Name:CTSD
Synonyms:CPSD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:2529. CTSD.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • membrane raft Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Secreted

Pathology & Biotechi

Involvement in diseasei

Ceroid lipofuscinosis, neuronal, 10 (CLN10)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:610127
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029362229F → I in CLN10. 2 PublicationsCorresponds to variant rs121912789dbSNPEnsembl.1
Natural variantiVAR_029363383W → C in CLN10. 1 PublicationCorresponds to variant rs121912790dbSNPEnsembl.1

Keywords - Diseasei

Alzheimer disease, Disease mutation, Neurodegeneration, Neuronal ceroid lipofuscinosis

Organism-specific databases

DisGeNETi1509.
MalaCardsiCTSD.
MIMi610127. phenotype.
OpenTargetsiENSG00000117984.
Orphaneti228337. CLN10 disease.
PharmGKBiPA27029.

Chemistry databases

ChEMBLiCHEMBL2581.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2345.

Polymorphism and mutation databases

BioMutaiCTSD.
DMDMi115717.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002594921 – 64Activation peptideCombined sourcesAdd BLAST44
ChainiPRO_000002595065 – 412Cathepsin DAdd BLAST348
ChainiPRO_000002595165 – 162Cathepsin D light chain1 PublicationAdd BLAST98
ChainiPRO_0000025952169 – 412Cathepsin D heavy chain1 PublicationAdd BLAST244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63O-linked (GalNAc...)1 Publication1
Disulfide bondi91 ↔ 1601 Publication
Disulfide bondi110 ↔ 1171 Publication
Glycosylationi134N-linked (GlcNAc...)1 Publication1
Glycosylationi263N-linked (GlcNAc...)5 Publications1
Disulfide bondi286 ↔ 2901 Publication
Disulfide bondi329 ↔ 366

Post-translational modificationi

N- and O-glycosylated.5 Publications
Undergoes proteolytic cleavage and activation by ADAM30.1 Publication
As well as the major heavy chain which starts at Leu-169, 2 minor forms starting at Gly-170 and Gly-171 have been identified (PubMed:1426530). An additional form starting at Ala-168 has also been identified (PubMed:27333034).2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP07339.
PaxDbiP07339.
PeptideAtlasiP07339.
PRIDEiP07339.
TopDownProteomicsiP07339.

2D gel databases

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

PTM databases

iPTMnetiP07339.
PhosphoSitePlusiP07339.
SwissPalmiP07339.

Miscellaneous databases

PMAP-CutDBP07339.

Expressioni

Tissue specificityi

Expressed in the aorta extrcellular space (at protein level) (PubMed:20551380). Expressed in liver (at protein level) (PubMed:1426530).2 Publications

Gene expression databases

BgeeiENSG00000117984.
CleanExiHS_CTSD.
ExpressionAtlasiP07339. baseline and differential.
GenevisibleiP07339. HS.

Organism-specific databases

HPAiCAB000109.
HPA003001.

Interactioni

Subunit structurei

Consists of a light chain and a heavy chain (PubMed:8393577, PubMed:1426530). Interacts with ADAM30; this leads to activation of CTSD (PubMed:27333034).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050672EBI-2115097,EBI-77613

Protein-protein interaction databases

BioGridi107889. 44 interactors.
DIPiDIP-43906N.
IntActiP07339. 21 interactors.
MINTiMINT-3005628.
STRINGi9606.ENSP00000236671.

Chemistry databases

BindingDBiP07339.

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi67 – 74Combined sources8
Turni75 – 77Combined sources3
Beta strandi78 – 85Combined sources8
Turni86 – 89Combined sources4
Beta strandi90 – 97Combined sources8
Beta strandi103 – 107Combined sources5
Helixi115 – 118Combined sources4
Helixi125 – 127Combined sources3
Beta strandi132 – 141Combined sources10
Beta strandi146 – 159Combined sources14
Beta strandi172 – 184Combined sources13
Helixi189 – 192Combined sources4
Beta strandi194 – 200Combined sources7
Helixi204 – 206Combined sources3
Helixi208 – 210Combined sources3
Helixi214 – 220Combined sources7
Beta strandi224 – 226Combined sources3
Beta strandi228 – 233Combined sources6
Beta strandi236 – 238Combined sources3
Beta strandi239 – 249Combined sources11
Helixi252 – 254Combined sources3
Beta strandi255 – 263Combined sources9
Turni267 – 270Combined sources4
Beta strandi271 – 274Combined sources4
Beta strandi276 – 279Combined sources4
Turni280 – 282Combined sources3
Beta strandi284 – 286Combined sources3
Beta strandi290 – 294Combined sources5
Beta strandi299 – 303Combined sources5
Helixi305 – 314Combined sources10
Beta strandi318 – 321Combined sources4
Beta strandi325 – 327Combined sources3
Helixi329 – 334Combined sources6
Beta strandi338 – 342Combined sources5
Beta strandi345 – 349Combined sources5
Helixi351 – 354Combined sources4
Beta strandi355 – 360Combined sources6
Beta strandi363 – 372Combined sources10
Turni377 – 379Combined sources3
Beta strandi383 – 385Combined sources3
Helixi387 – 392Combined sources6
Beta strandi393 – 398Combined sources6
Turni399 – 402Combined sources4
Beta strandi403 – 409Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4OBZX-ray2.90A/C60-162[»]
B/D170-412[»]
4OC6X-ray2.64A60-162[»]
B170-412[»]
4OD9X-ray1.90A/C60-162[»]
B/D170-412[»]
ProteinModelPortaliP07339.
SMRiP07339.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07339.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini79 – 407Peptidase A1PROSITE-ProRule annotationAdd BLAST329

Sequence similaritiesi

Belongs to the peptidase A1 family.Curated
Contains 1 peptidase A1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000197681.
HOVERGENiHBG000482.
InParanoidiP07339.
KOiK01379.
OMAiKVERQVF.
OrthoDBiEOG091G0JP7.
PhylomeDBiP07339.
TreeFamiTF314990.

Family and domain databases

CDDicd05490. Cathepsin_D2. 1 hit.
Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR033736. Cathepsin_chordata.
IPR033144. Cathepsin_D.
IPR033121. PEPTIDASE_A1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PTHR13683:SF230. PTHR13683:SF230. 1 hit.
PfamiPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 2 hits.
PS51767. PEPTIDASE_A1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07339-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPSSLLPLA LCLLAAPASA LVRIPLHKFT SIRRTMSEVG GSVEDLIAKG
60 70 80 90 100
PVSKYSQAVP AVTEGPIPEV LKNYMDAQYY GEIGIGTPPQ CFTVVFDTGS
110 120 130 140 150
SNLWVPSIHC KLLDIACWIH HKYNSDKSST YVKNGTSFDI HYGSGSLSGY
160 170 180 190 200
LSQDTVSVPC QSASSASALG GVKVERQVFG EATKQPGITF IAAKFDGILG
210 220 230 240 250
MAYPRISVNN VLPVFDNLMQ QKLVDQNIFS FYLSRDPDAQ PGGELMLGGT
260 270 280 290 300
DSKYYKGSLS YLNVTRKAYW QVHLDQVEVA SGLTLCKEGC EAIVDTGTSL
310 320 330 340 350
MVGPVDEVRE LQKAIGAVPL IQGEYMIPCE KVSTLPAITL KLGGKGYKLS
360 370 380 390 400
PEDYTLKVSQ AGKTLCLSGF MGMDIPPPSG PLWILGDVFI GRYYTVFDRD
410
NNRVGFAEAA RL
Length:412
Mass (Da):44,552
Last modified:April 1, 1988 - v1
Checksum:i903FB8412E0CF0B0
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01162158A → V Associated with increased risk for AD; possibly influences secretion and intracellular maturation. 1 PublicationCorresponds to variant rs17571dbSNPEnsembl.1
Natural variantiVAR_029362229F → I in CLN10. 2 PublicationsCorresponds to variant rs121912789dbSNPEnsembl.1
Natural variantiVAR_058490282G → R.1 PublicationCorresponds to variant rs147278302dbSNPEnsembl.1
Natural variantiVAR_029363383W → C in CLN10. 1 PublicationCorresponds to variant rs121912790dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA. Translation: AAA16314.1.
S74689 Genomic DNA. Translation: AAD14156.1.
S52557 Genomic DNA. Translation: AAD13868.1.
CCDSiCCDS7725.1.
PIRiA25771. KHHUD.
RefSeqiNP_001900.1. NM_001909.4.
UniGeneiHs.654447.

Genome annotation databases

EnsembliENST00000236671; ENSP00000236671; ENSG00000117984.
GeneIDi1509.
KEGGihsa:1509.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NCL CTSD

Neural Ceroid Lipofuscinoses mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA. Translation: AAA16314.1.
S74689 Genomic DNA. Translation: AAD14156.1.
S52557 Genomic DNA. Translation: AAD13868.1.
CCDSiCCDS7725.1.
PIRiA25771. KHHUD.
RefSeqiNP_001900.1. NM_001909.4.
UniGeneiHs.654447.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4OBZX-ray2.90A/C60-162[»]
B/D170-412[»]
4OC6X-ray2.64A60-162[»]
B170-412[»]
4OD9X-ray1.90A/C60-162[»]
B/D170-412[»]
ProteinModelPortaliP07339.
SMRiP07339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107889. 44 interactors.
DIPiDIP-43906N.
IntActiP07339. 21 interactors.
MINTiMINT-3005628.
STRINGi9606.ENSP00000236671.

Chemistry databases

BindingDBiP07339.
ChEMBLiCHEMBL2581.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2345.

Protein family/group databases

MEROPSiA01.009.

PTM databases

iPTMnetiP07339.
PhosphoSitePlusiP07339.
SwissPalmiP07339.

Polymorphism and mutation databases

BioMutaiCTSD.
DMDMi115717.

2D gel databases

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

Proteomic databases

EPDiP07339.
PaxDbiP07339.
PeptideAtlasiP07339.
PRIDEiP07339.
TopDownProteomicsiP07339.

Protocols and materials databases

DNASUi1509.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236671; ENSP00000236671; ENSG00000117984.
GeneIDi1509.
KEGGihsa:1509.

Organism-specific databases

CTDi1509.
DisGeNETi1509.
GeneCardsiCTSD.
GeneReviewsiCTSD.
H-InvDBHIX0009359.
HGNCiHGNC:2529. CTSD.
HPAiCAB000109.
HPA003001.
MalaCardsiCTSD.
MIMi116840. gene.
610127. phenotype.
neXtProtiNX_P07339.
OpenTargetsiENSG00000117984.
Orphaneti228337. CLN10 disease.
PharmGKBiPA27029.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000197681.
HOVERGENiHBG000482.
InParanoidiP07339.
KOiK01379.
OMAiKVERQVF.
OrthoDBiEOG091G0JP7.
PhylomeDBiP07339.
TreeFamiTF314990.

Enzyme and pathway databases

BioCyciMetaCyc:HS04183-MONOMER.
ZFISH:HS04183-MONOMER.
BRENDAi3.4.23.5. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
R-HSA-2132295. MHC class II antigen presentation.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiP07339.
GeneWikiiCathepsin_D.
GenomeRNAii1509.
PMAP-CutDBP07339.
PROiP07339.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117984.
CleanExiHS_CTSD.
ExpressionAtlasiP07339. baseline and differential.
GenevisibleiP07339. HS.

Family and domain databases

CDDicd05490. Cathepsin_D2. 1 hit.
Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR033736. Cathepsin_chordata.
IPR033144. Cathepsin_D.
IPR033121. PEPTIDASE_A1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PTHR13683:SF230. PTHR13683:SF230. 1 hit.
PfamiPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 2 hits.
PS51767. PEPTIDASE_A1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCATD_HUMAN
AccessioniPrimary (citable) accession number: P07339
Secondary accession number(s): Q6IB57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: November 30, 2016
This is version 199 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.