ID   CATD_BOVIN              Reviewed;         390 AA.
AC   P80209; Q9TS27;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   27-APR-2001, sequence version 2.
DT   03-AUG-2022, entry version 128.
DE   RecName: Full=Cathepsin D;
DE            EC=3.4.23.5;
DE   Flags: Precursor;
GN   Name=CTSD;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   PROTEIN SEQUENCE OF 1-48.
RC   TISSUE=Milk;
RX   PubMed=8454061; DOI=10.1016/0014-5793(93)80036-t;
RA   Larsen L.B., Boisen A., Petersen T.E.;
RT   "Procathepsin D cannot autoactivate to cathepsin D at acid pH.";
RL   FEBS Lett. 319:54-58(1993).
RN   [2]
RP   PROTEIN SEQUENCE OF 45-390, AND X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS).
RC   TISSUE=Liver;
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).
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. {ECO:0000250|UniProtKB:P07339}.
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. Interacts with
CC       ADAM30; this leads to activation of CTSD. Interacts with GRN;
CC       stabilizes CTSD; increases its proteolytic activity (By similarity).
CC       {ECO:0000250|UniProtKB:P07339, ECO:0000250|UniProtKB:P18242}.
CC   -!- SUBCELLULAR LOCATION: Lysosome. Melanosome {ECO:0000250}. Secreted,
CC       extracellular space {ECO:0000250}.
CC   -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P07339}.
CC   -!- PTM: Undergoes proteolytic cleavage and activation by ADAM30.
CC       {ECO:0000250|UniProtKB:P07339}.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   PIR; S32383; S32383.
DR   STRING; 9913.ENSBTAP00000010022; -.
DR   BindingDB; P80209; -.
DR   ChEMBL; CHEMBL4106; -.
DR   MEROPS; A01.009; -.
DR   PaxDb; P80209; -.
DR   PeptideAtlas; P80209; -.
DR   PRIDE; P80209; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   InParanoid; P80209; -.
DR   OrthoDB; 1619495at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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; Secreted; Zymogen.
FT   PROPEP          1..44
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:8467789"
FT                   /id="PRO_0000025947"
FT   CHAIN           45..390
FT                   /note="Cathepsin D"
FT                   /id="PRO_0000025948"
FT   DOMAIN          59..385
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        77
FT   ACT_SITE        273
FT   CARBOHYD        114
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        71..140
FT   DISULFID        90..97
FT   DISULFID        264..268
FT   DISULFID        307..344
SQ   SEQUENCE   390 AA;  42491 MW;  5B38AA1C33C48D35 CRC64;
     VIRIPLHKFT SIRRTMSEAA GXVXXLIAKG PISKYATGEP AVRQGPIPEL LKNYMDAQYY
     GEIGIGTPPQ CFTVVFDTGS ANLWVPSIHC KLLDIACWTH RKYNSDKSST YVKNGTTFDI
     HYGSGSLSGY LSQDTVSVPC NPSSSSPGGV TVQRQTFGEA IKQPGVVFIA AKFDGILGMA
     YPRISVNNVL PVFDNLMQQK LVDKNVFSFF LNRDPKAQPG GELMLGGTDS KYYRGSLMFH
     NVTRQAYWQI HMDQLDVGSS LTVCKGGCEA IVDTGTSLIV GPVEEVRELQ KAIGAVPLIQ
     GEYMIPCEKV SSLPEVTVKL GGKDYALSPE DYALKVSQAE TTVCLSGFMG MDIPPPGGPL
     WILGDVFIGR YYTVFDRDQN RVGLAEAARL