ID   CATD_CLUHA              Reviewed;         396 AA.
AC   Q9DEX3;
DT   25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=Cathepsin D;
DE            EC=3.4.23.5;
DE   Flags: Precursor;
GN   Name=ctsd;
OS   Clupea harengus (Atlantic herring).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Clupei; Clupeiformes; Clupeoidei;
OC   Clupeidae; Clupea.
OX   NCBI_TaxID=7950 {ECO:0000312|EMBL:AAG27733.1};
RN   [1] {ECO:0000312|EMBL:AAG27733.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Nielsen L.B., Stougaard P., Andersen P.S., Pedersen L.H.;
RT   "Cloning and sequence determination of herring muscle cathepsin D.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000305}
RP   PROTEIN SEQUENCE OF 62-82.
RC   TISSUE=Skeletal muscle;
RX   PubMed=11207447; DOI=10.1016/s1096-4959(00)00332-8;
RA   Nielsen L.B., Nielsen H.H.;
RT   "Purification and characterization of cathepsin D from herring muscle
RT   (Clupea harengus).";
RL   Comp. Biochem. Physiol. 128B:351-363(2001).
CC   -!- FUNCTION: Acid protease active in intracellular protein breakdown.
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; Evidence={ECO:0000269|PubMed:11207447};
CC   -!- ACTIVITY REGULATION: Inhibited by pepstatin.
CC       {ECO:0000269|PubMed:11207447}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 2.5 with hemoglobin as substrate.;
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.;
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11207447}.
CC   -!- SUBCELLULAR LOCATION: Lysosome.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   EMBL; AF312364; AAG27733.1; -; mRNA.
DR   RefSeq; NP_001296757.1; NM_001309828.1.
DR   AlphaFoldDB; Q9DEX3; -.
DR   SMR; Q9DEX3; -.
DR   MEROPS; A01.009; -.
DR   GeneID; 105898046; -.
DR   CTD; 1509; -.
DR   OrthoDB; 1619495at2759; -.
DR   BRENDA; 3.4.23.5; 1542.
DR   Proteomes; UP000515152; Genome assembly.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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   Aspartyl protease; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hydrolase; Lysosome; Protease; Reference proteome; Signal; Zymogen.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..61
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:11207447"
FT                   /id="PRO_0000025970"
FT   CHAIN           62..396
FT                   /note="Cathepsin D"
FT                   /id="PRO_0000025971"
FT   DOMAIN          76..393
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        94
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        281
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        107..114
FT                   /evidence="ECO:0000250"
FT   DISULFID        272..276
FT                   /evidence="ECO:0000250"
FT   DISULFID        315..352
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   396 AA;  43316 MW;  D0375DC38567A31B CRC64;
     MKFLYLFLFA VFAWTSDAIV RIPLKKFRSI RRTLSDSGLN VEQLLAGTNS LQHNQGFPSS
     NAPTPETLKN YMDAQYYGEI GLGTPVQMFT VVFDTGSSNL WLPSIHCSFT DIACLLHHKY
     NGAKSSTYVK NGTEFAIQYG SGSLSGYLSQ DSCTIGDIVV EKQLFGEAIK QPGVAFIAAK
     FDGILGMAYP RISVDGVPPV FDMMMSQKKV EQNVFSFYLN RNPDTEPGGE LLLGGTDPKY
     YTGDFNYVPV TRQAYWQIHM DGMSIGSQLT LCKDGCEAIV DTGTSLITGP PAEVRALQKA
     IGAIPLIQGE YMIDCKKVPT LPTISFNVGG KTYSLTGEQY VLKESQGGKT ICLSGLMGLE
     IPPPAGPLWI LGDVFIGQYY TVFDRESNRV GFAKST