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 27-MAR-2024, entry version 248. 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>3.3.co;2-x; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 149. DR DIP; DIP-43906N; -. DR IntAct; P07339; 66. 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 GlyCosmos; P07339; 3 sites, 44 glycans. DR GlyGen; P07339; 8 sites, 44 N-linked glycans (2 sites), 3 O-linked glycans (4 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 CPTAC; CPTAC-486; -. DR CPTAC; CPTAC-487; -. DR CPTAC; CPTAC-658; -. DR EPD; P07339; -. DR jPOST; P07339; -. DR MassIVE; P07339; -. DR PaxDb; 9606-ENSP00000236671; -. DR PeptideAtlas; P07339; -. DR ProteomicsDB; 51994; -. DR Pumba; P07339; -. DR TopDownProteomics; P07339; -. DR Antibodypedia; 880; 1270 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 AGR; HGNC:2529; -. 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; 79262; Adult neuronal ceroid lipofuscinosis. DR Orphanet; 168486; Congenital neuronal ceroid lipofuscinosis. DR Orphanet; 79263; Infantile neuronal ceroid lipofuscinosis. DR Orphanet; 79264; Juvenile neuronal ceroid lipofuscinosis. DR Orphanet; 168491; Late infantile neuronal ceroid lipofuscinosis. 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; KYDHDAS; -. DR OrthoDB; 1120702at2759; -. DR PhylomeDB; P07339; -. DR TreeFam; TF314990; -. DR BioCyc; MetaCyc:HS04183-MONOMER; -. 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-77387; Insulin receptor recycling. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR SignaLink; P07339; -. DR SIGNOR; P07339; -. DR BioGRID-ORCS; 1509; 9 hits in 1161 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 199 other cell types or tissues. DR ExpressionAtlas; P07339; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0031904; C:endosome lumen; IEA:Ensembl. 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:1901143; P:insulin catabolic process; IEA:Ensembl. DR GO; GO:0038020; P:insulin receptor recycling; 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; Acid Proteases; 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; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1. DR PANTHER; PTHR47966:SF42; CATHEPSIN D; 1. DR Pfam; PF07966; A1_Propeptide; 1. DR Pfam; PF00026; Asp; 1. DR PRINTS; PR00792; PEPSIN. DR SUPFAM; SSF50630; Acid proteases; 1. DR PROSITE; PS00141; ASP_PROTEASE; 2. DR PROSITE; PS51767; PEPTIDASE_A1; 1. DR SWISS-2DPAGE; P07339; -. DR UCD-2DPAGE; P07339; -. DR Genevisible; P07339; HS. 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 //