CATD_MOUSE
ID CATD_MOUSE Reviewed; 410 AA.
AC P18242;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Cathepsin D;
DE EC=3.4.23.5;
DE Flags: Precursor;
GN Name=Ctsd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=2263503; DOI=10.1093/nar/18.23.7184;
RA Diedrich J.F., Staskus K.A., Retzel E.F., Haase A.T.;
RT "Nucleotide sequence of a cDNA encoding mouse cathepsin D.";
RL Nucleic Acids Res. 18:7184-7184(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2374732; DOI=10.1093/nar/18.13.4008;
RA Grusby M.J., Mitchell S.C., Glimcher L.H.;
RT "Molecular cloning of mouse cathepsin D.";
RL Nucleic Acids Res. 18:4008-4008(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=8011168; DOI=10.1089/dna.1994.13.419;
RA Hetman M., Perschl A., Saftig P., von Figura K., Peters C.;
RT "Mouse cathepsin D gene: molecular organization, characterization of the
RT promoter, and chromosomal localization.";
RL DNA Cell Biol. 13:419-427(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-261.
RC TISSUE=Epidermis;
RX PubMed=16170054; DOI=10.1074/mcp.m500203-mcp200;
RA Uematsu R., Furukawa J., Nakagawa H., Shinohara Y., Deguchi K., Monde K.,
RA Nishimura S.;
RT "High throughput quantitative glycomics and glycoform-focused proteomics of
RT murine dermis and epidermis.";
RL Mol. Cell. Proteomics 4:1977-1989(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH GRN.
RX PubMed=28453791; DOI=10.1093/hmg/ddx162;
RA Beel S., Moisse M., Damme M., De Muynck L., Robberecht W.,
RA Van Den Bosch L., Saftig P., Van Damme P.;
RT "Progranulin functions as a cathepsin D chaperone to stimulate axonal
RT outgrowth in vivo.";
RL Hum. Mol. Genet. 26:2850-2863(2017).
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 (PubMed:28453791).
CC {ECO:0000250|UniProtKB:P07339, ECO:0000269|PubMed:28453791}.
CC -!- SUBCELLULAR LOCATION: Lysosome. Melanosome {ECO:0000250}. Secreted,
CC extracellular space {ECO:0000250}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P07339,
CC ECO:0000269|PubMed:16170054}.
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; X53337; CAA37423.1; -; mRNA.
DR EMBL; X52886; CAA37067.1; -; mRNA.
DR EMBL; X68378; CAA48453.1; -; Genomic_DNA.
DR EMBL; X68379; CAA48453.1; JOINED; Genomic_DNA.
DR EMBL; X68380; CAA48453.1; JOINED; Genomic_DNA.
DR EMBL; X68381; CAA48453.1; JOINED; Genomic_DNA.
DR EMBL; X68382; CAA48453.1; JOINED; Genomic_DNA.
DR EMBL; X68383; CAA48453.1; JOINED; Genomic_DNA.
DR EMBL; BC054758; AAH54758.1; -; mRNA.
DR EMBL; BC057931; AAH57931.1; -; mRNA.
DR CCDS; CCDS22029.1; -.
DR PIR; I48278; KHMSD.
DR RefSeq; NP_034113.1; NM_009983.2.
DR AlphaFoldDB; P18242; -.
DR SMR; P18242; -.
DR BioGRID; 198970; 8.
DR IntAct; P18242; 11.
DR MINT; P18242; -.
DR STRING; 10090.ENSMUSP00000121203; -.
DR MEROPS; A01.009; -.
DR GlyConnect; 2190; 10 N-Linked glycans (2 sites).
DR GlyGen; P18242; 2 sites, 10 N-linked glycans (2 sites).
DR iPTMnet; P18242; -.
DR PhosphoSitePlus; P18242; -.
DR CPTAC; non-CPTAC-3403; -.
DR CPTAC; non-CPTAC-3695; -.
DR EPD; P18242; -.
DR jPOST; P18242; -.
DR PaxDb; P18242; -.
DR PeptideAtlas; P18242; -.
DR PRIDE; P18242; -.
DR ProteomicsDB; 265551; -.
DR DNASU; 13033; -.
DR Ensembl; ENSMUST00000151120; ENSMUSP00000121203; ENSMUSG00000007891.
DR GeneID; 13033; -.
DR KEGG; mmu:13033; -.
DR UCSC; uc009kmv.1; mouse.
DR CTD; 1509; -.
DR MGI; MGI:88562; Ctsd.
DR VEuPathDB; HostDB:ENSMUSG00000007891; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000155733; -.
DR HOGENOM; CLU_013253_3_1_1; -.
DR InParanoid; P18242; -.
DR OMA; DKSHYTG; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; P18242; -.
DR TreeFam; TF314990; -.
DR BRENDA; 3.4.23.5; 3474.
DR Reactome; R-MMU-1442490; Collagen degradation.
DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-MMU-2132295; MHC class II antigen presentation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 13033; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Ctsd; mouse.
DR PRO; PR:P18242; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P18242; protein.
DR Bgee; ENSMUSG00000007891; Expressed in choroid plexus of fourth ventricle and 275 other tissues.
DR ExpressionAtlas; P18242; baseline and differential.
DR Genevisible; P18242; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:MGI.
DR GO; GO:0070001; F:aspartic-type peptidase activity; IMP:ARUK-UCL.
DR GO; GO:0004175; F:endopeptidase activity; IDA:MGI.
DR GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; IMP:MGI.
DR GO; GO:0042159; P:lipoprotein catabolic process; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR GO; GO:0070201; P:regulation of establishment of protein localization; ISO:MGI.
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; Disulfide bond; Glycoprotein; Hydrolase; Lysosome;
KW Protease; Reference proteome; Secreted; 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_0000025953"
FT CHAIN 65..410
FT /note="Cathepsin D"
FT /id="PRO_0000025954"
FT DOMAIN 79..405
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 293
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000269|PubMed:16170054"
FT DISULFID 91..160
FT /evidence="ECO:0000250"
FT DISULFID 110..117
FT /evidence="ECO:0000250"
FT DISULFID 284..288
FT /evidence="ECO:0000250"
FT DISULFID 327..364
FT /evidence="ECO:0000250"
SQ SEQUENCE 410 AA; 44954 MW; DC4928EC46928BF0 CRC64;
MKTPGVLLLI LGLLASSSFA IIRIPLRKFT SIRRTMTEVG GSVEDLILKG PITKYSMQSS
PKTTEPVSEL LKNYLDAQYY GDIGIGTPPQ CFTVVFDTGS SNLWVPSIHC KILDIACWVH
HKYNSDKSST YVKNGTSFDI HYGSGSLSGY LSQDTVSVPC KSDQSKARGI KVEKQIFGEA
TKQPGIVFVA AKFDGILGMG YPHISVNNVL PVFDNLMQQK LVDKNIFSFY LNRDPEGQPG
GELMLGGTDS KYYHGELSYL NVTRKAYWQV HMDQLEVGNE LTLCKGGCEA IVDTGTSLLV
GPVEEVKELQ KAIGAVPLIQ GEYMIPCEKV SSLPTVYLKL GGKNYELHPD KYILKVSQGG
KTICLSGFMG MDIPPPSGPL WILGDVFIGS YYTVFDRDNN RVGFANAVVL
