CATD_HUMAN
ID CATD_HUMAN Reviewed; 412 AA.
AC P07339; Q6IB57;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Cathepsin D;
DE EC=3.4.23.5;
DE Contains:
DE RecName: Full=Cathepsin D light chain;
DE Contains:
DE RecName: Full=Cathepsin D heavy chain;
DE Flags: Precursor;
GN Name=CTSD; Synonyms=CPSD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3927292; DOI=10.1073/pnas.82.15.4910;
RA Faust P.L., Kornfeld S., Chirgwin J.M.;
RT "Cloning and sequence analysis of cDNA for human cathepsin D.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:4910-4914(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3588310; DOI=10.1093/nar/15.9.3773;
RA Westley B.R., May F.E.B.;
RT "Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human
RT breast cancer cells.";
RL Nucleic Acids Res. 15:3773-3786(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2069717; DOI=10.1089/dna.1991.10.423;
RA Redecker B., Heckendorf B., Grosch H.W., Mersmann G., Hasilik A.;
RT "Molecular organization of the human cathepsin D gene.";
RL DNA Cell Biol. 10:423-431(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RX PubMed=8262386; DOI=10.1016/0378-1119(93)90107-e;
RA May F.E., Smith D.J., Westley B.R.;
RT "The human cathepsin D-encoding gene is transcribed from an estrogen-
RT regulated and a constitutive start point.";
RL Gene 134:277-282(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RX PubMed=7935485; DOI=10.1210/mend.8.6.7935485;
RA Augereau P., Miralles F., Cavailles V., Gaudelet C., Parker M.,
RA Rochefort H.;
RT "Characterization of the proximal estrogen-responsive element of human
RT cathepsin D gene.";
RL Mol. Endocrinol. 8:693-703(1994).
RN [9]
RP PROTEIN SEQUENCE OF 170-180.
RC TISSUE=Liver;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RL Submitted (JUN-1992) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 154-162 AND 169-180, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=1426530; DOI=10.1016/0020-711x(92)90076-d;
RA Kobayashi T., Honke K., Gasa S., Fujii T., Maguchi S., Miyazaki T.,
RA Makita A.;
RT "Proteolytic processing sites producing the mature form of human cathepsin
RT D.";
RL Int. J. Biochem. 24:1487-1491(1992).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [12]
RP GLYCOSYLATION AT ASN-263.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [14]
RP INVOLVEMENT IN CLN10, AND VARIANT ARG-282.
RX PubMed=16670177; DOI=10.1093/brain/awl107;
RA Siintola E., Partanen S., Stromme P., Haapanen A., Haltia M., Maehlen J.,
RA Lehesjoki A.E., Tyynela J.;
RT "Cathepsin D deficiency underlies congenital human neuronal ceroid-
RT lipofuscinosis.";
RL Brain 129:1438-1445(2006).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-263.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-134 AND ASN-263.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=20551380; DOI=10.1074/mcp.m110.001693;
RA Didangelos A., Yin X., Mandal K., Baumert M., Jahangiri M., Mayr M.;
RT "Proteomics characterization of extracellular space components in the human
RT aorta.";
RL Mol. Cell. Proteomics 9:2048-2062(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP GLYCOSYLATION AT THR-63, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP INTERACTION WITH ADAM30, IDENTIFICATION BY MASS SPECTROMETRY, AND CLEAVAGE.
RX PubMed=27333034; DOI=10.1016/j.ebiom.2016.06.002;
RA Letronne F., Laumet G., Ayral A.M., Chapuis J., Demiautte F., Laga M.,
RA Vandenberghe M.E., Malmanche N., Leroux F., Eysert F., Sottejeau Y.,
RA Chami L., Flaig A., Bauer C., Dourlen P., Lesaffre M., Delay C., Huot L.,
RA Dumont J., Werkmeister E., Lafont F., Mendes T., Hansmannel F., Dermaut B.,
RA Deprez B., Herard A.S., Dhenain M., Souedet N., Pasquier F., Tulasne D.,
RA Berr C., Hauw J.J., Lemoine Y., Amouyel P., Mann D., Deprez R., Checler F.,
RA Hot D., Delzescaux T., Gevaert K., Lambert J.C.;
RT "ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in
RT Alzheimer's Disease.";
RL EBioMedicine 9:278-292(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS).
RC TISSUE=Spleen;
RX PubMed=8467789; DOI=10.1002/j.1460-2075.1993.tb05774.x;
RA Metcalf P., Fusek M.;
RT "Two crystal structures for cathepsin D: the lysosomal targeting signal and
RT active site.";
RL EMBO J. 12:1293-1302(1993).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=8393577; DOI=10.1073/pnas.90.14.6796;
RA Baldwin E.T., Bhat T.N., Gulnik S., Hosur M.V., Sowder R.C. II,
RA Cachau R.E., Collins J., Silva A.M., Erickson J.W.;
RT "Crystal structures of native and inhibited forms of human cathepsin D:
RT implications for lysosomal targeting and drug design.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6796-6800(1993).
RN [25]
RP VARIANT VAL-58.
RX PubMed=10716266;
RX DOI=10.1002/1531-8249(200003)47:3<399::aid-ana22>3.0.co;2-5;
RA Papassotiropoulos A., Bagli M., Kurz A., Kornhuber J., Forstl H., Maier W.,
RA Pauls J., Lautenschlager N., Heun R.;
RT "A genetic variation of cathepsin D is a major risk factor for Alzheimer's
RT disease.";
RL Ann. Neurol. 47:399-403(2000).
RN [26]
RP VARIANTS CLN10 ILE-229 AND CYS-383.
RX PubMed=16685649; DOI=10.1086/504159;
RA Steinfeld R., Reinhardt K., Schreiber K., Hillebrand M., Kraetzner R.,
RA Bruck W., Saftig P., Gartner J.;
RT "Cathepsin D deficiency is associated with a human neurodegenerative
RT disorder.";
RL Am. J. Hum. Genet. 78:988-998(2006).
RN [27]
RP VARIANT CLN10 ILE-229.
RX PubMed=21990111; DOI=10.1002/humu.21624;
RA Kousi M., Lehesjoki A.E., Mole S.E.;
RT "Update of the mutation spectrum and clinical correlations of over 360
RT mutations in eight genes that underlie the neuronal ceroid
RT lipofuscinoses.";
RL Hum. Mutat. 33:42-63(2012).
CC -!- FUNCTION: Acid protease active in intracellular protein breakdown.
CC Plays a role in APP processing following cleavage and activation by
CC ADAM30 which leads to APP degradation (PubMed:27333034). Involved in
CC the pathogenesis of several diseases such as breast cancer and possibly
CC Alzheimer disease. {ECO:0000269|PubMed:27333034}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specificity similar to, but narrower than, that of pepsin A.
CC Does not cleave the 4-Gln-|-His-5 bond in B chain of insulin.;
CC EC=3.4.23.5;
CC -!- SUBUNIT: Consists of a light chain and a heavy chain (PubMed:8393577,
CC PubMed:1426530). Interacts with ADAM30; this leads to activation of
CC CTSD (PubMed:27333034). Interacts with GRN; stabilizes CTSD; increases
CC its proteolytic activity (By similarity).
CC {ECO:0000250|UniProtKB:P18242, ECO:0000269|PubMed:1426530,
CC ECO:0000269|PubMed:27333034, ECO:0000269|PubMed:8393577}.
CC -!- INTERACTION:
CC P07339; P05067: APP; NbExp=2; IntAct=EBI-2115097, EBI-77613;
CC P07339; Q9P1A6-3: DLGAP2; NbExp=3; IntAct=EBI-2115097, EBI-12019838;
CC P07339; I6L9I8: EPN3; NbExp=3; IntAct=EBI-2115097, EBI-12866582;
CC P07339; Q9H6S3: EPS8L2; NbExp=3; IntAct=EBI-2115097, EBI-3940939;
CC P07339; Q7Z602: GPR141; NbExp=3; IntAct=EBI-2115097, EBI-21649723;
CC P07339; P28799: GRN; NbExp=4; IntAct=EBI-2115097, EBI-747754;
CC P07339; PRO_0000012695 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335602;
CC P07339; PRO_0000012696 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335615;
CC P07339; PRO_0000012697 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335629;
CC P07339; PRO_0000012698 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335642;
CC P07339; PRO_0000012699 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335656;
CC P07339; PRO_0000012700 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335669;
CC P07339; PRO_0000012701 [P28799]: GRN; NbExp=2; IntAct=EBI-2115097, EBI-21335682;
CC P07339; P68431: H3C12; NbExp=3; IntAct=EBI-2115097, EBI-79722;
CC P07339; Q9Y6F6-3: IRAG1; NbExp=3; IntAct=EBI-2115097, EBI-25840037;
CC P07339; Q12756: KIF1A; NbExp=3; IntAct=EBI-2115097, EBI-2679809;
CC P07339; Q5TA79: LCE2A; NbExp=3; IntAct=EBI-2115097, EBI-10246607;
CC P07339; Q86VF5-3: MOGAT3; NbExp=3; IntAct=EBI-2115097, EBI-25840143;
CC P07339; O15130-2: NPFF; NbExp=3; IntAct=EBI-2115097, EBI-25840002;
CC P07339; Q96LB9: PGLYRP3; NbExp=3; IntAct=EBI-2115097, EBI-12339509;
CC P07339; P09565: PP9974; NbExp=3; IntAct=EBI-2115097, EBI-10196507;
CC P07339; Q9C004: SPRY4; NbExp=3; IntAct=EBI-2115097, EBI-354861;
CC P07339; Q8NBJ7: SUMF2; NbExp=3; IntAct=EBI-2115097, EBI-723091;
CC P07339; Q9BQG1: SYT3; NbExp=3; IntAct=EBI-2115097, EBI-17284568;
CC P07339; P28347-2: TEAD1; NbExp=3; IntAct=EBI-2115097, EBI-12151837;
CC P07339; P45880: VDAC2; NbExp=3; IntAct=EBI-2115097, EBI-354022;
CC P07339; Q15007-2: WTAP; NbExp=3; IntAct=EBI-2115097, EBI-25840023;
CC P07339; O00308: WWP2; NbExp=3; IntAct=EBI-2115097, EBI-743923;
CC P07339; Q5W0Z9-4: ZDHHC20; NbExp=3; IntAct=EBI-2115097, EBI-25840130;
CC P07339; Q6ZNH5: ZNF497; NbExp=4; IntAct=EBI-2115097, EBI-10486136;
CC -!- SUBCELLULAR LOCATION: Lysosome. Melanosome. Secreted, extracellular
CC space. Note=Identified by mass spectrometry in melanosome fractions
CC from stage I to stage IV. In aortic samples, detected as an
CC extracellular protein loosely bound to the matrix (PubMed:20551380).
CC {ECO:0000269|PubMed:20551380}.
CC -!- TISSUE SPECIFICITY: Expressed in the aorta extracellular space (at
CC protein level) (PubMed:20551380). Expressed in liver (at protein level)
CC (PubMed:1426530). {ECO:0000269|PubMed:1426530,
CC ECO:0000269|PubMed:20551380}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:12754519,
CC ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23234360}.
CC -!- PTM: Undergoes proteolytic cleavage and activation by ADAM30.
CC {ECO:0000269|PubMed:27333034}.
CC -!- PTM: As well as the major heavy chain which starts at Leu-169, 2 minor
CC forms starting at Gly-170 and Gly-171 have been identified
CC (PubMed:1426530). An additional form starting at Ala-168 has also been
CC identified (PubMed:27333034). {ECO:0000269|PubMed:1426530,
CC ECO:0000269|PubMed:27333034}.
CC -!- POLYMORPHISM: The Val-58 allele is significantly overrepresented in
CC demented patients (11.8%) compared with non-demented controls (4.9%).
CC Carriers of the Val-58 allele have a 3.1-fold increased risk for
CC developing AD than non-carriers.
CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 10 (CLN10) [MIM:610127]: A
CC form of neuronal ceroid lipofuscinosis with onset at birth or early
CC childhood. Neuronal ceroid lipofuscinoses are progressive
CC neurodegenerative, lysosomal storage diseases characterized by
CC intracellular accumulation of autofluorescent liposomal material, and
CC clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
CC {ECO:0000269|PubMed:16670177, ECO:0000269|PubMed:16685649,
CC ECO:0000269|PubMed:21990111}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NCL CTSD; Note=Neural Ceroid Lipofuscinoses mutation
CC db;
CC URL="https://www.ucl.ac.uk/ncl/catD.shtml";
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DR EMBL; M11233; AAB59529.1; -; mRNA.
DR EMBL; X05344; CAA28955.1; -; mRNA.
DR EMBL; M63138; AAA51922.1; -; Genomic_DNA.
DR EMBL; M63134; AAA51922.1; JOINED; Genomic_DNA.
DR EMBL; M63135; AAA51922.1; JOINED; Genomic_DNA.
DR EMBL; M63136; AAA51922.1; JOINED; Genomic_DNA.
DR EMBL; M63137; AAA51922.1; JOINED; Genomic_DNA.
DR EMBL; CR456947; CAG33228.1; -; mRNA.
DR EMBL; BT006910; AAP35556.1; -; mRNA.
DR EMBL; BT020155; AAV38957.1; -; mRNA.
DR EMBL; BC016320; AAH16320.1; -; mRNA.
DR EMBL; L12980; AAA16314.1; -; Genomic_DNA.
DR EMBL; S74689; AAD14156.1; -; Genomic_DNA.
DR EMBL; S52557; AAD13868.1; -; Genomic_DNA.
DR CCDS; CCDS7725.1; -.
DR PIR; A25771; KHHUD.
DR RefSeq; NP_001900.1; NM_001909.4.
DR PDB; 1LYA; X-ray; 2.50 A; A/C=65-161, B/D=170-410.
DR PDB; 1LYB; X-ray; 2.50 A; A/C=65-161, B/D=170-410.
DR PDB; 1LYW; X-ray; 2.50 A; A/C/E/G=65-161, B/D/F/H=170-410.
DR PDB; 4OBZ; X-ray; 2.90 A; A/C=60-162, B/D=170-412.
DR PDB; 4OC6; X-ray; 2.64 A; A=60-162, B=170-412.
DR PDB; 4OD9; X-ray; 1.90 A; A/C=60-162, B/D=170-412.
DR PDBsum; 1LYA; -.
DR PDBsum; 1LYB; -.
DR PDBsum; 1LYW; -.
DR PDBsum; 4OBZ; -.
DR PDBsum; 4OC6; -.
DR PDBsum; 4OD9; -.
DR AlphaFoldDB; P07339; -.
DR SMR; P07339; -.
DR BioGRID; 107889; 116.
DR DIP; DIP-43906N; -.
DR IntAct; P07339; 60.
DR MINT; P07339; -.
DR STRING; 9606.ENSP00000236671; -.
DR BindingDB; P07339; -.
DR ChEMBL; CHEMBL2581; -.
DR DrugBank; DB03028; 1h-Benoximidazole-2-Carboxylic Acid.
DR DrugBank; DB03096; 2-Morpholinoethylamine.
DR DrugBank; DB07542; 5-Amino-6-cyclohexyl-4-hydroxy-2-isobutyl-hexanoic acid.
DR DrugBank; DB08740; CYCLOHEXYLMETHYL-2,3-DIHYDROXY-5-METHYL-HEXYLAMIDE.
DR DrugBank; DB02216; S-Methylcysteine.
DR DrugCentral; P07339; -.
DR GuidetoPHARMACOLOGY; 2345; -.
DR MEROPS; A01.009; -.
DR GlyConnect; 1079; 44 N-Linked glycans (2 sites).
DR GlyGen; P07339; 6 sites, 44 N-linked glycans (2 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; P07339; -.
DR MetOSite; P07339; -.
DR PhosphoSitePlus; P07339; -.
DR SwissPalm; P07339; -.
DR BioMuta; CTSD; -.
DR DMDM; 115717; -.
DR DOSAC-COBS-2DPAGE; P07339; -.
DR REPRODUCTION-2DPAGE; IPI00011229; -.
DR SWISS-2DPAGE; P07339; -.
DR UCD-2DPAGE; P07339; -.
DR CPTAC; CPTAC-486; -.
DR CPTAC; CPTAC-487; -.
DR CPTAC; CPTAC-658; -.
DR EPD; P07339; -.
DR jPOST; P07339; -.
DR MassIVE; P07339; -.
DR PaxDb; P07339; -.
DR PeptideAtlas; P07339; -.
DR PRIDE; P07339; -.
DR ProteomicsDB; 51994; -.
DR TopDownProteomics; P07339; -.
DR Antibodypedia; 880; 1185 antibodies from 47 providers.
DR DNASU; 1509; -.
DR Ensembl; ENST00000236671.7; ENSP00000236671.2; ENSG00000117984.15.
DR GeneID; 1509; -.
DR KEGG; hsa:1509; -.
DR MANE-Select; ENST00000236671.7; ENSP00000236671.2; NM_001909.5; NP_001900.1.
DR CTD; 1509; -.
DR DisGeNET; 1509; -.
DR GeneCards; CTSD; -.
DR HGNC; HGNC:2529; CTSD.
DR HPA; ENSG00000117984; Low tissue specificity.
DR MalaCards; CTSD; -.
DR MIM; 116840; gene.
DR MIM; 610127; phenotype.
DR neXtProt; NX_P07339; -.
DR OpenTargets; ENSG00000117984; -.
DR Orphanet; 228337; CLN10 disease.
DR PharmGKB; PA27029; -.
DR VEuPathDB; HostDB:ENSG00000117984; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000155733; -.
DR HOGENOM; CLU_013253_3_3_1; -.
DR InParanoid; P07339; -.
DR OMA; DKSHYTG; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; P07339; -.
DR TreeFam; TF314990; -.
DR BioCyc; MetaCyc:HS04183-MON; -.
DR BRENDA; 3.4.23.5; 2681.
DR PathwayCommons; P07339; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; P07339; -.
DR SIGNOR; P07339; -.
DR BioGRID-ORCS; 1509; 7 hits in 1081 CRISPR screens.
DR ChiTaRS; CTSD; human.
DR EvolutionaryTrace; P07339; -.
DR GeneWiki; Cathepsin_D; -.
DR GenomeRNAi; 1509; -.
DR Pharos; P07339; Tchem.
DR PRO; PR:P07339; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P07339; protein.
DR Bgee; ENSG00000117984; Expressed in right adrenal gland cortex and 197 other tissues.
DR ExpressionAtlas; P07339; baseline and differential.
DR Genevisible; P07339; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0010008; C:endosome membrane; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; IDA:ARUK-UCL.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0070001; F:aspartic-type peptidase activity; ISS:ARUK-UCL.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0008233; F:peptidase activity; IDA:ARUK-UCL.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0000045; P:autophagosome assembly; IEA:Ensembl.
DR GO; GO:0042159; P:lipoprotein catabolic process; IDA:ARUK-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ARUK-UCL.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:ARUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ARUK-UCL.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IDA:ARUK-UCL.
DR CDD; cd05490; Cathepsin_D2; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR012848; Aspartic_peptidase_N.
DR InterPro; IPR033144; Cathepsin_D.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF07966; A1_Propeptide; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alzheimer disease; Aspartyl protease;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Hydrolase; Lysosome; Neurodegeneration; Neuronal ceroid lipofuscinosis;
KW Protease; Reference proteome; Secreted; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..64
FT /note="Activation peptide"
FT /id="PRO_0000025949"
FT CHAIN 65..412
FT /note="Cathepsin D"
FT /id="PRO_0000025950"
FT CHAIN 65..162
FT /note="Cathepsin D light chain"
FT /evidence="ECO:0000305|PubMed:1426530"
FT /id="PRO_0000025951"
FT CHAIN 169..412
FT /note="Cathepsin D heavy chain"
FT /evidence="ECO:0000305|PubMed:1426530"
FT /id="PRO_0000025952"
FT DOMAIN 79..407
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:8393577"
FT ACT_SITE 295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:8393577"
FT CARBOHYD 63
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:8393577"
FT DISULFID 91..160
FT /evidence="ECO:0000269|PubMed:8393577"
FT DISULFID 110..117
FT /evidence="ECO:0000269|PubMed:8393577"
FT DISULFID 286..290
FT /evidence="ECO:0000269|PubMed:8393577"
FT DISULFID 329..366
FT VARIANT 58
FT /note="A -> V (associated with increased risk for AD;
FT possibly influences secretion and intracellular maturation;
FT dbSNP:rs17571)"
FT /evidence="ECO:0000269|PubMed:10716266"
FT /id="VAR_011621"
FT VARIANT 229
FT /note="F -> I (in CLN10; dbSNP:rs121912789)"
FT /evidence="ECO:0000269|PubMed:16685649,
FT ECO:0000269|PubMed:21990111"
FT /id="VAR_029362"
FT VARIANT 282
FT /note="G -> R (in dbSNP:rs147278302)"
FT /evidence="ECO:0000269|PubMed:16670177"
FT /id="VAR_058490"
FT VARIANT 383
FT /note="W -> C (in CLN10; dbSNP:rs121912790)"
FT /evidence="ECO:0000269|PubMed:16685649"
FT /id="VAR_029363"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 146..159
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 172..184
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 214..220
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:1LYW"
FT STRAND 239..249
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 255..263
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 267..270
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:1LYW"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 305..314
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:1LYA"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 329..334
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 338..342
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 355..360
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 363..372
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:4OD9"
FT HELIX 387..392
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 393..398
FT /evidence="ECO:0007829|PDB:4OD9"
FT TURN 399..402
FT /evidence="ECO:0007829|PDB:4OD9"
FT STRAND 403..409
FT /evidence="ECO:0007829|PDB:4OD9"
SQ SEQUENCE 412 AA; 44552 MW; 903FB8412E0CF0B0 CRC64;
MQPSSLLPLA LCLLAAPASA LVRIPLHKFT SIRRTMSEVG GSVEDLIAKG PVSKYSQAVP
AVTEGPIPEV LKNYMDAQYY GEIGIGTPPQ CFTVVFDTGS SNLWVPSIHC KLLDIACWIH
HKYNSDKSST YVKNGTSFDI HYGSGSLSGY LSQDTVSVPC QSASSASALG GVKVERQVFG
EATKQPGITF IAAKFDGILG MAYPRISVNN VLPVFDNLMQ QKLVDQNIFS FYLSRDPDAQ
PGGELMLGGT DSKYYKGSLS YLNVTRKAYW QVHLDQVEVA SGLTLCKEGC EAIVDTGTSL
MVGPVDEVRE LQKAIGAVPL IQGEYMIPCE KVSTLPAITL KLGGKGYKLS PEDYTLKVSQ
AGKTLCLSGF MGMDIPPPSG PLWILGDVFI GRYYTVFDRD NNRVGFAEAA RL