ID   CATS_MOUSE              Reviewed;         340 AA.
AC   O70370; E9QK18; O54973;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Cathepsin S;
DE            EC=3.4.22.27;
DE   Flags: Precursor;
GN   Name=Ctss; Synonyms=Cats;
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 [GENOMIC DNA / MRNA].
RC   STRAIN=129/Sv, and BALB/cJ; TISSUE=Brain;
RA   Doh-ura K.;
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Spleen;
RA   Rommerskirch W.;
RL   Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 144-306, AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J; TISSUE=Cartilage;
RX   PubMed=10395917; DOI=10.1016/s0167-4781(99)00068-8;
RA   Soederstroem M., Salminen H., Glumoff V., Kirschke H., Aro H., Vuorio E.;
RT   "Cathepsin expression during skeletal development.";
RL   Biochim. Biophys. Acta 1446:35-46(1999).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 296-340.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=9516475; DOI=10.1074/jbc.273.13.7691;
RA   Dandoy-Dron F., Guillo F., Benboudjema L., Deslys J.-P., Lasmesas C.,
RA   Dormont D., Tovey M.G., Dron M.;
RT   "Gene expression in scrapie. Cloning of a new scrapie-responsive gene and
RT   the identification of increased levels of seven other mRNA transcripts.";
RL   J. Biol. Chem. 273:7691-7697(1998).
RN   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=9545226; DOI=10.1126/science.280.5362.450;
RA   Nakagawa T., Roth W., Wong P., Nelson A., Farr A., Deussing J.,
RA   Villadangos J.A., Ploegh H., Peters C., Rudensky A.Y.;
RT   "Cathepsin L: critical role in Ii degradation and CD4 T cell selection in
RT   the thymus.";
RL   Science 280:450-453(1998).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Liver, Lung, Spleen, and Testis;
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).
CC   -!- FUNCTION: Thiol protease. Key protease responsible for the removal of
CC       the invariant chain from MHC class II molecules and MHC class II
CC       antigen presentation. The bond-specificity of this proteinase is in
CC       part similar to the specificities of cathepsin L.
CC       {ECO:0000250|UniProtKB:P25774}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Similar to cathepsin L, but with much less activity on Z-Phe-
CC         Arg-|-NHMec, and more activity on the Z-Val-Val-Arg-|-Xaa compound.;
CC         EC=3.4.22.27;
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P25774}. Secreted
CC       {ECO:0000250|UniProtKB:P25774}. Cytoplasmic vesicle, phagosome
CC       {ECO:0000250|UniProtKB:P25774}.
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest expression found in
CC       non-skeletal tissues. Relatively high levels found in skeletal tissues.
CC       Expressed in spleen, B cells, dendritic cells and macrophages
CC       (PubMed:9545226). {ECO:0000269|PubMed:10395917,
CC       ECO:0000269|PubMed:9545226}.
CC   -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC       ECO:0000255|PROSITE-ProRule:PRU10090}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA05360.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF051732; AAC05781.1; -; Genomic_DNA.
DR   EMBL; AF051727; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF051728; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF051729; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF051726; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF051730; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF051731; AAC05781.1; JOINED; Genomic_DNA.
DR   EMBL; AF038546; AAB94925.1; -; mRNA.
DR   EMBL; AJ002386; CAA05360.1; ALT_FRAME; mRNA.
DR   EMBL; AC092203; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Y18466; CAA77184.1; -; mRNA.
DR   EMBL; AJ223208; CAA11182.1; -; mRNA.
DR   CCDS; CCDS50992.1; -.
DR   RefSeq; NP_067256.4; NM_021281.3.
DR   PDB; 4BPV; X-ray; 2.00 A; A/B/C/D/E/K=116-340.
DR   PDB; 4BQV; X-ray; 1.70 A; A/B/C/D/E/F/G/H=116-340.
DR   PDB; 4BS5; X-ray; 1.25 A; A=116-340.
DR   PDB; 4BS6; X-ray; 1.20 A; A/B=116-340.
DR   PDB; 4BSQ; X-ray; 1.96 A; A=116-340.
DR   PDB; 4MZO; X-ray; 1.47 A; A/B/C/D/E/F/G/H=116-340.
DR   PDB; 4MZS; X-ray; 1.85 A; A/B=116-340.
DR   PDBsum; 4BPV; -.
DR   PDBsum; 4BQV; -.
DR   PDBsum; 4BS5; -.
DR   PDBsum; 4BS6; -.
DR   PDBsum; 4BSQ; -.
DR   PDBsum; 4MZO; -.
DR   PDBsum; 4MZS; -.
DR   AlphaFoldDB; O70370; -.
DR   SMR; O70370; -.
DR   BioGRID; 198976; 2.
DR   STRING; 10090.ENSMUSP00000015667; -.
DR   BindingDB; O70370; -.
DR   ChEMBL; CHEMBL4098; -.
DR   GuidetoPHARMACOLOGY; 2353; -.
DR   MEROPS; C01.034; -.
DR   GlyCosmos; O70370; 1 site, No reported glycans.
DR   GlyGen; O70370; 1 site.
DR   iPTMnet; O70370; -.
DR   PhosphoSitePlus; O70370; -.
DR   SwissPalm; O70370; -.
DR   CPTAC; non-CPTAC-3897; -.
DR   EPD; O70370; -.
DR   MaxQB; O70370; -.
DR   PaxDb; 10090-ENSMUSP00000015667; -.
DR   ProteomicsDB; 265335; -.
DR   Antibodypedia; 849; 500 antibodies from 36 providers.
DR   DNASU; 13040; -.
DR   Ensembl; ENSMUST00000116304.3; ENSMUSP00000112006.3; ENSMUSG00000038642.11.
DR   GeneID; 13040; -.
DR   KEGG; mmu:13040; -.
DR   UCSC; uc008qjz.3; mouse.
DR   AGR; MGI:107341; -.
DR   CTD; 1520; -.
DR   MGI; MGI:107341; Ctss.
DR   VEuPathDB; HostDB:ENSMUSG00000038642; -.
DR   eggNOG; KOG1543; Eukaryota.
DR   GeneTree; ENSGT00940000155176; -.
DR   HOGENOM; CLU_012184_1_2_1; -.
DR   InParanoid; O70370; -.
DR   OMA; ETCCCAK; -.
DR   OrthoDB; 5472948at2759; -.
DR   BRENDA; 3.4.22.27; 3474.
DR   Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR   Reactome; R-MMU-2022090; Assembly of collagen fibrils and other multimeric structures.
DR   Reactome; R-MMU-2132295; MHC class II antigen presentation.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   BioGRID-ORCS; 13040; 2 hits in 72 CRISPR screens.
DR   ChiTaRS; Ctss; mouse.
DR   PRO; PR:O70370; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; O70370; Protein.
DR   Bgee; ENSMUSG00000038642; Expressed in stroma of bone marrow and 246 other cell types or tissues.
DR   ExpressionAtlas; O70370; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0031905; C:early endosome lumen; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005770; C:late endosome; ISO:MGI.
DR   GO; GO:0005764; C:lysosome; IDA:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR   GO; GO:0005518; F:collagen binding; ISO:MGI.
DR   GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IBA:GO_Central.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; EXP:Reactome.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; ISO:MGI.
DR   GO; GO:0001968; F:fibronectin binding; ISO:MGI.
DR   GO; GO:0043236; F:laminin binding; ISO:MGI.
DR   GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR   GO; GO:0043394; F:proteoglycan binding; ISO:MGI.
DR   GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; ISS:UniProtKB.
DR   GO; GO:0048002; P:antigen processing and presentation of peptide antigen; ISO:MGI.
DR   GO; GO:0034769; P:basement membrane disassembly; IMP:BHF-UCL.
DR   GO; GO:0045453; P:bone resorption; ISO:MGI.
DR   GO; GO:0030574; P:collagen catabolic process; ISO:MGI.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:2001259; P:positive regulation of cation channel activity; IDA:CACAO.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IGI:MGI.
DR   GO; GO:0016485; P:protein processing; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; IDA:MGI.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP:BHF-UCL.
DR   GO; GO:0010447; P:response to acidic pH; ISO:MGI.
DR   CDD; cd02248; Peptidase_C1A; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR025661; Pept_asp_AS.
DR   InterPro; IPR000169; Pept_cys_AS.
DR   InterPro; IPR025660; Pept_his_AS.
DR   InterPro; IPR013128; Peptidase_C1A.
DR   InterPro; IPR000668; Peptidase_C1A_C.
DR   InterPro; IPR039417; Peptidase_C1A_papain-like.
DR   InterPro; IPR013201; Prot_inhib_I29.
DR   PANTHER; PTHR12411:SF525; CATHEPSIN S; 1.
DR   PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1.
DR   Pfam; PF08246; Inhibitor_I29; 1.
DR   Pfam; PF00112; Peptidase_C1; 1.
DR   PRINTS; PR00705; PAPAIN.
DR   SMART; SM00848; Inhibitor_I29; 1.
DR   SMART; SM00645; Pept_C1; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR   PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR   PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
DR   Genevisible; O70370; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Hydrolase;
KW   Lysosome; Protease; Reference proteome; Secreted; Signal; Thiol protease;
KW   Zymogen.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   PROPEP          18..122
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000026315"
FT   CHAIN           123..340
FT                   /note="Cathepsin S"
FT                   /id="PRO_0000026316"
FT   ACT_SITE        147
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        287
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        307
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        134..233
FT                   /evidence="ECO:0000250"
FT   DISULFID        144..189
FT                   /evidence="ECO:0000250"
FT   DISULFID        178..222
FT                   /evidence="ECO:0000250"
FT   DISULFID        281..329
FT                   /evidence="ECO:0000250"
FT   CONFLICT        34
FT                   /note="Y -> H (in Ref. 2; CAA05360)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        97
FT                   /note="L -> S (in Ref. 1; AAB94925/AAC05781)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        106
FT                   /note="P -> S (in Ref. 1; AAB94925/AAC05781)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        146
FT                   /note="A -> S (in Ref. 3; CAA77184)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        218
FT                   /note="T -> M (in Ref. 1; AAB94925 and 2; CAA05360)"
FT                   /evidence="ECO:0000305"
FT   HELIX           129..132
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           147..164
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           172..178
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   TURN            182..184
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           188..190
FT                   /evidence="ECO:0007829|PDB:4MZO"
FT   HELIX           194..204
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          207..209
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   TURN            210..212
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           226..228
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          229..231
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          234..238
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           244..253
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          257..261
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           266..270
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          273..276
FT                   /evidence="ECO:0007829|PDB:4MZO"
FT   STRAND          287..297
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          300..306
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          318..322
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          324..327
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   HELIX           328..330
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   TURN            331..333
FT                   /evidence="ECO:0007829|PDB:4BS6"
FT   STRAND          336..339
FT                   /evidence="ECO:0007829|PDB:4BS6"
SQ   SEQUENCE   340 AA;  38475 MW;  10550C5106318C47 CRC64;
     MRAPGHAAIR WLFWMPLVCS VAMEQLQRDP TLDYHWDLWK KTHEKEYKDK NEEEVRRLIW
     EKNLKFIMIH NLEYSMGMHT YQVGMNDMGD MTNEEILCRM GALRIPRQSP KTVTFRSYSN
     RTLPDTVDWR EKGCVTEVKY QGSCGACWAF SAVGALEGQL KLKTGKLISL SAQNLVDCSN
     EEKYGNKGCG GGYMTEAFQY IIDNGGIEAD ASYPYKATDE KCHYNSKNRA ATCSRYIQLP
     FGDEDALKEA VATKGPVSVG IDASHSSFFF YKSGVYDDPS CTGNVNHGVL VVGYGTLDGK
     DYWLVKNSWG LNFGDQGYIR MARNNKNHCG IASYCSYPEI
//