CATD_PIG
ID CATD_PIG Reviewed; 345 AA.
AC P00795;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 2.
DT 03-AUG-2022, entry version 127.
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP PROTEIN SEQUENCE OF 1-98, AND SUBUNIT.
RC TISSUE=Spleen;
RX PubMed=6406481; DOI=10.1016/s0021-9258(18)32429-3;
RA Takahashi T., Tang J.;
RT "Amino acid sequence of porcine spleen cathepsin D light chain.";
RL J. Biol. Chem. 258:6435-6443(1983).
RN [2]
RP PROTEIN SEQUENCE OF 104-345, AND SUBUNIT.
RC TISSUE=Spleen;
RX PubMed=6587385; DOI=10.1073/pnas.81.12.3703;
RA Shewale J.G., Tang J.;
RT "Amino acid sequence of porcine spleen cathepsin D.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:3703-3707(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 74-148.
RX PubMed=3182800; DOI=10.1016/s0021-9258(18)37621-x;
RA Yonezawa S., Takahashi T., Wang X., Wong R.N.S., Hartsuck J.A., Tang J.;
RT "Structures at the proteolytic processing region of cathepsin D.";
RL J. Biol. Chem. 263:16504-16511(1988).
RN [4]
RP STRUCTURE OF CARBOHYDRATES.
RX PubMed=6422853; DOI=10.1016/0003-9861(84)90128-0;
RA Nakao Y., Kozutsumi Y., Kawasaki T., Yamashina I., van Halbeek H.,
RA Vliegenthart J.F.G.;
RT "Oligosaccharides on cathepsin D from porcine spleen.";
RL Arch. Biochem. Biophys. 229:43-54(1984).
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 (PubMed:6406481,
CC PubMed:6587385). Interacts with ADAM30; this leads to activation of
CC CTSD (By similarity). Interacts with GRN; stabilizes CTSD; increases
CC its proteolytic activity (By similarity).
CC {ECO:0000250|UniProtKB:P07339, ECO:0000250|UniProtKB:P18242,
CC ECO:0000269|PubMed:6406481, ECO:0000269|PubMed:6587385}.
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; A92425; KHPGD.
DR AlphaFoldDB; P00795; -.
DR SMR; P00795; -.
DR MEROPS; A01.009; -.
DR PeptideAtlas; P00795; -.
DR PRIDE; P00795; -.
DR InParanoid; P00795; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
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 Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Lysosome; Protease; Reference proteome; Secreted; Zymogen.
FT CHAIN 1..98
FT /note="Cathepsin D light chain"
FT /evidence="ECO:0000269|PubMed:6406481"
FT /id="PRO_0000025955"
FT PROPEP 99..103
FT /evidence="ECO:0000269|PubMed:6587385"
FT /id="PRO_0000025956"
FT CHAIN 104..345
FT /note="Cathepsin D heavy chain"
FT /evidence="ECO:0000269|PubMed:6587385"
FT /id="PRO_0000025957"
FT DOMAIN 15..342
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 33
FT ACT_SITE 230
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 46..53
FT DISULFID 221..225
FT DISULFID 264..301
FT VARIANT 234
FT /note="S -> K"
FT VARIANT 247
FT /note="G -> Q"
FT CONFLICT 89
FT /note="Missing (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="C -> S (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 345 AA; 37295 MW; B3E72C11787F14E2 CRC64;
GPIPEVLKNY MDAQYYGEIG IGTPPQCFTV VFDTGSSNLW VPSIHCKLLD IACWIHHKYN
SGKSSTYVKN GTTFAIHYGS GSLSGYLSSQ DTVSVPCNSA LSGVGGIKVE RQTFGEATKQ
PGLTFIAAKF DGILGMAYPR ISVNNVVPVF DNLMQQKLVD KDIFSFYLNR DPGAQPGGEL
MLGGIDSKYY KGSLDYHNVT RKAYWQIHMN QVAVGSSLTL CKGGCEAIVD TGTSLIVGQP
EEVRELGKAI GAVPLIQGEY MIPCEKVPSL PDVTVTLGGK KYKLSSENYT LKVSQAGQTI
CLSGFMGMDI PPPGGPLWIL GDVFIGRYYT VFDRDLNRVG LAEAA
