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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
 
 
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