ID   CATD_SHEEP              Reviewed;         365 AA.
AC   Q9MZS8;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 108.
DE   RecName: Full=Cathepsin D;
DE            EC=3.4.23.5;
DE   Flags: Precursor; Fragment;
GN   Name=CTSD;
OS   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT CONCL ASN-268.
RC   STRAIN=White Swedish Landrace;
RX   PubMed=10856224; DOI=10.1093/emboj/19.12.2786;
RA   Tyynela J., Sohar I., Sleat D.E., Gin R.M., Donnelly R.J., Baumann M.,
RA   Haltia M., Lobel P.;
RT   "A mutation in the ovine cathepsin D gene causes a congenital lysosomal
RT   storage disease with profound neurodegeneration.";
RL   EMBO J. 19:2786-2792(2000).
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: Occurs as a mixture of both a single chain form and two types
CC       of two chain (light and heavy) forms. Interacts with ADAM30; this leads
CC       to activation of CTSD (By similarity). Interacts with GRN; stabilizes
CC       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   -!- DISEASE: Note=Defects in CTSD are a cause of congenital ovine neuronal
CC       ceroid lipofuscinosis (CONCL). CONCL is an autosomal recessive
CC       disorder. Newborn lambs are weak, trembling, and unable to rise and
CC       support their bodies. However, they are able to vocalize, support their
CC       heads, and to suckle if bottle-fed. At autopsy, the brains of affected
CC       lambs are strikingly small. The deep layers of the cerebral cortex show
CC       pronounced neuronal loss, reactive astrocytosis, and infiltration of
CC       macrophages. There is severe degeneration of hippocampal pyramidal
CC       neurons.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   EMBL; AF164143; AAF80494.1; -; mRNA.
DR   AlphaFoldDB; Q9MZS8; -.
DR   SMR; Q9MZS8; -.
DR   STRING; 9940.ENSOARP00000004202; -.
DR   MEROPS; A01.009; -.
DR   PRIDE; Q9MZS8; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   Proteomes; UP000002356; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
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; 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; IPR033144; Cathepsin_D.
DR   InterPro; IPR033121; PEPTIDASE_A1.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR   PANTHER; PTHR47966; PTHR47966; 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; Disease variant; Disulfide bond; Glycoprotein;
KW   Hydrolase; Lysosome; Protease; Reference proteome; Secreted; Zymogen.
FT   PROPEP          <1..39
FT                   /note="Activation peptide"
FT                   /id="PRO_0000025964"
FT   CHAIN           40..>365
FT                   /note="Cathepsin D"
FT                   /id="PRO_0000025965"
FT   DOMAIN          54..>365
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        72
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        268
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   CARBOHYD        109
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        66..135
FT                   /evidence="ECO:0000250"
FT   DISULFID        85..92
FT                   /evidence="ECO:0000250"
FT   DISULFID        259..263
FT                   /evidence="ECO:0000250"
FT   DISULFID        302..339
FT                   /evidence="ECO:0000250"
FT   VARIANT         268
FT                   /note="D -> N (in CONCL; inactive)"
FT                   /evidence="ECO:0000269|PubMed:10856224"
FT   NON_TER         1
FT   NON_TER         365
SQ   SEQUENCE   365 AA;  39815 MW;  76A7BFE5BC45E9CB CRC64;
     LHKFTSNRRT MSEAMGPVEH LIAKGPISKY ATREPAVRQG PIPELLTNYM DAQYYGEIGI
     GTPPQCFTVV FDTGSANLWV PSIHCKLLDI ACWVHHKYNS DKSSTYVKNG TTFDIHYGSG
     SLSGYLSQDT VSVPCNPSSS SPGGVTVQRQ TFGEAIKQPG VVFIAAKFDG ILGMAYPRIS
     VNNVLPVFDN LMRQKLVDKN VFSFFLNRDP KAQPGEELML GGTDSKYYRG SLTYHNVTRQ
     AYWQIHMDQL DVGSSLTVCK GGCEAIVDTG TSLMVGPVDE VRELHKAIGA VPLIQGEYMI
     PCEKVSSLPQ VTLKLGGKDY TLSPEDYTLK VSQAGTTVCL SGFMGMDIPP PGGPLWILGD
     VFIGR