ID   CATD_CHIHA              Reviewed;         396 AA.
AC   O93428;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2007, sequence version 2.
DT   25-MAY-2022, entry version 90.
DE   RecName: Full=Cathepsin D;
DE            EC=3.4.23.5;
DE   Flags: Precursor;
GN   Name=ctsd;
OS   Chionodraco hamatus (Antarctic teleost icefish) (Chaenichthys rhinoceratus
OS   hamatus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC   Eupercaria; Perciformes; Notothenioidei; Channichthyidae; Chionodraco.
OX   NCBI_TaxID=36188;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:CAA07719.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 62-90, ACTIVITY REGULATION,
RP   AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Liver {ECO:0000312|EMBL:CAA07719.1};
RX   PubMed=10209280; DOI=10.1016/s0167-4838(99)00039-4;
RA   Capasso C., Lees W.E., Capasso A., Scudiero R., Carginale V., Kille P.,
RA   Kay J., Parisi E.;
RT   "Cathepsin D from the liver of the Antarctic icefish Chionodraco hamatus
RT   exhibits unusual activity and stability at high temperatures.";
RL   Biochim. Biophys. Acta 1431:64-73(1999).
CC   -!- FUNCTION: Acid protease active in intracellular protein breakdown.
CC       {ECO:0000305}.
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:0000305};
CC   -!- ACTIVITY REGULATION: Inhibited by pepstatin.
CC       {ECO:0000269|PubMed:10209280}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 3.0. {ECO:0000269|PubMed:10209280};
CC       Temperature dependence:
CC         Highly thermostable. Enzyme activity is maintained up to 45 degrees
CC         Celsius. Active at 50 degrees Celsius but with reduced catalytic
CC         activity. {ECO:0000269|PubMed:10209280};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9DEX3}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q9DEX3}.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA07719.1; Type=Frameshift; Evidence={ECO:0000305};
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; AJ007878; CAA07719.1; ALT_FRAME; mRNA.
DR   AlphaFoldDB; O93428; -.
DR   SMR; O93428; -.
DR   MEROPS; A01.009; -.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
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; Signal; Zymogen.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..61
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000255, ECO:0000269|PubMed:10209280"
FT                   /id="PRO_0000285984"
FT   CHAIN           62..396
FT                   /note="Cathepsin D"
FT                   /evidence="ECO:0000269|PubMed:10209280"
FT                   /id="PRO_5000064481"
FT   DOMAIN          76..393
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        94
FT                   /evidence="ECO:0000250|UniProtKB:P07339,
FT                   ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        281
FT                   /evidence="ECO:0000250|UniProtKB:P07339,
FT                   ECO:0000255|PROSITE-ProRule:PRU10094"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        249
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        107..114
FT                   /evidence="ECO:0000250|UniProtKB:P07339"
FT   DISULFID        272..276
FT                   /evidence="ECO:0000250|UniProtKB:P07339"
FT   DISULFID        315..352
FT                   /evidence="ECO:0000250|UniProtKB:P07339"
SQ   SEQUENCE   396 AA;  42958 MW;  B660E5E7FBD023FF CRC64;
     MKMLLLCVFS ALALTNDALV RIPLKKFRSI RRQLTDSGKR AEELLADHHS LKYNLSFPAS
     NAPTPETLKN YLDAQYYGEI GLGTPPQPFT VVFDTGSSNL WVPSIHCSLL DIACLLHHKY
     NSGKSSTYVK NGTAFAIQYG SGSLSGYLSQ DTCTIGDLAI DSQLFGEAIK QPGVAFIAAK
     FDGILGMAYP RISVDGVAPV FDNIMSQKKV EQNVFSFYLN RNPDTEPGGE LLLGGTDPKY
     YTGDFNYVNV TRQAYWQIRV DSMAVGDQLS LCTGGCEAIV DSGTSLITGP SVEVKALQKA
     IGAFPLIQGE YMVNCDTVPS LPVISFTVGG QVYTLTGEQY ILKVTQAGKT MCLSGFMGLD
     IPAPAGPLWI LGDVFMGQYY TVFDRDANRV GFAKAK