CATD_RAT
ID CATD_RAT Reviewed; 407 AA.
AC P24268;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Cathepsin D;
DE EC=3.4.23.5;
DE Contains:
DE RecName: Full=Cathepsin D 12 kDa light chain;
DE Contains:
DE RecName: Full=Cathepsin D 9 kDa light chain;
DE Contains:
DE RecName: Full=Cathepsin D 34 kDa heavy chain;
DE Contains:
DE RecName: Full=Cathepsin D 30 kDa heavy chain;
DE Flags: Precursor;
GN Name=Ctsd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pituitary;
RX PubMed=2243802; DOI=10.1093/nar/18.21.6445;
RA Birch N.P., Loh Y.P.;
RT "Cloning, sequence and expression of rat cathepsin D.";
RL Nucleic Acids Res. 18:6445-6445(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 65-74; 118-127 AND 165-174,
RP AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=1883350; DOI=10.1016/0006-291x(91)91353-e;
RA Fujita H., Tanaka Y., Noguchi Y., Kono A., Himeno M., Kato K.;
RT "Isolation and sequencing of a cDNA clone encoding rat liver lysosomal
RT cathepsin D and the structure of three forms of mature enzymes.";
RL Biochem. Biophys. Res. Commun. 179:190-196(1991).
RN [3]
RP PROTEIN SEQUENCE OF 134-170.
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 PROTEIN SEQUENCE OF 35-62; 65-72; 172-189; 222-248; 283-304 AND 309-348,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-258, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
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 (PubMed:1883350). Interacts with
CC ADAM30; this leads to activation of CTSD (By similarity).
CC {ECO:0000250|UniProtKB:P07339, ECO:0000269|PubMed:1883350}.
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 EMBL; X54467; CAA38349.1; -; mRNA.
DR PIR; S13111; KHRTD.
DR PDB; 5UX4; X-ray; 2.81 A; A/B=21-407.
DR PDBsum; 5UX4; -.
DR AlphaFoldDB; P24268; -.
DR SMR; P24268; -.
DR IntAct; P24268; 1.
DR STRING; 10116.ENSRNOP00000027407; -.
DR MEROPS; A01.009; -.
DR GlyGen; P24268; 2 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; P24268; -.
DR PhosphoSitePlus; P24268; -.
DR SwissPalm; P24268; -.
DR jPOST; P24268; -.
DR PaxDb; P24268; -.
DR PRIDE; P24268; -.
DR UCSC; RGD:621511; rat.
DR RGD; 621511; Ctsd.
DR eggNOG; KOG1339; Eukaryota.
DR InParanoid; P24268; -.
DR PhylomeDB; P24268; -.
DR BRENDA; 3.4.23.5; 5301.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P24268; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR GO; GO:0005764; C:lysosome; IDA:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISO:RGD.
DR GO; GO:0070001; F:aspartic-type peptidase activity; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; IDA:RGD.
DR GO; GO:0016787; F:hydrolase activity; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0000045; P:autophagosome assembly; ISO:RGD.
DR GO; GO:0042159; P:lipoprotein catabolic process; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0070201; P:regulation of establishment of protein localization; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
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 3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Lysosome; Protease; Reference proteome; Secreted;
KW Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..64
FT /note="Activation peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025958"
FT CHAIN 65..407
FT /note="Cathepsin D"
FT /id="PRO_0000025959"
FT CHAIN 65..164
FT /note="Cathepsin D 12 kDa light chain"
FT /id="PRO_0000025960"
FT CHAIN 65..117
FT /note="Cathepsin D 9 kDa light chain"
FT /id="PRO_0000025961"
FT CHAIN 118..407
FT /note="Cathepsin D 34 kDa heavy chain"
FT /id="PRO_0000025962"
FT CHAIN 165..407
FT /note="Cathepsin D 30 kDa heavy chain"
FT /id="PRO_0000025963"
FT DOMAIN 79..402
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT DISULFID 91..160
FT /evidence="ECO:0000250"
FT DISULFID 110..117
FT /evidence="ECO:0000250"
FT DISULFID 281..285
FT /evidence="ECO:0000250"
FT DISULFID 324..361
FT /evidence="ECO:0000250"
FT CONFLICT 15
FT /note="D -> A (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="D -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="K -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="K -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 146..159
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 167..179
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 209..215
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 234..244
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 262..265
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 300..309
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 349..353
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 360..367
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:5UX4"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 388..393
FT /evidence="ECO:0007829|PDB:5UX4"
FT TURN 394..397
FT /evidence="ECO:0007829|PDB:5UX4"
FT STRAND 398..404
FT /evidence="ECO:0007829|PDB:5UX4"
SQ SEQUENCE 407 AA; 44681 MW; C423AD4104D95F84 CRC64;
MQTPGVLLLI LGLLDASSSA LIRIPLRKFT SIRRTMTEVG GSVEDLILKG PITKYSMQSS
PRTKEPVSEL LKNYLDAQYY GEIGIGTPPQ CFTVVFDTGS SNLWVPSIHC KLLDIACWVH
HKYNSDKSST YVKNGTSFDI HYGSGSLSGY LSQDTVSVPC KSDLGGIKVE KQIFGEATKQ
PGVVFIAAKF DGILGMGYPF ISVNKVLPVF DNLMKQKLVE KNIFSFYLNR DPTGQPGGEL
MLGGTDSRYY HGELSYLNVT RKAYWQVHMD QLEVGSELTL CKGGCEAIVD TGTSLLVGPV
DEVKELQKAI GAVPLIQGEY MIPCEKVSSL PIITFKLGGQ NYELHPEKYI LKVSQAGKTI
CLSGFMGMDI PPPSGPLWIL GDVFIGCYYT VFDREYNRVG FAKAATL
