CATS_HUMAN
ID CATS_HUMAN Reviewed; 331 AA.
AC P25774; B4DWC9; D3DV05; Q5T5I0; Q6FHS5; Q9BUG3;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Cathepsin S;
DE EC=3.4.22.27;
DE Flags: Precursor;
GN Name=CTSS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-161.
RC TISSUE=Alveolar macrophage;
RX PubMed=1373132; DOI=10.1016/s0021-9258(18)42513-6;
RA Shi G.-P., Munger J.S., Meara J.P., Rich D.H., Chapman H.A.;
RT "Molecular cloning and expression of human alveolar macrophage cathepsin S,
RT an elastinolytic cysteine protease.";
RL J. Biol. Chem. 267:7258-7262(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 115-129, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Testis;
RX PubMed=1377692; DOI=10.1016/s0021-9258(18)42271-5;
RA Wiederanders B., Broemme D., Kirschke H., von Figura K., Schmidt B.,
RA Peters C.;
RT "Phylogenetic conservation of cysteine proteinases. Cloning and expression
RT of a cDNA coding for human cathepsin S.";
RL J. Biol. Chem. 267:13708-13713(1992).
RN [3]
RP SEQUENCE REVISION TO 211.
RA Wiederanders B., Broemme D., Kirschke H., von Figura K., Schmidt B.,
RA Peters C.;
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-161.
RX PubMed=8157683; DOI=10.1016/s0021-9258(19)78156-3;
RA Shi G.-P., Webb A.C., Foster K.E., Knoll J.H.M., Lemere C.A., Munger J.S.,
RA Chapman H.A.;
RT "Human cathepsin S: chromosomal localization, gene structure, and tissue
RT distribution.";
RL J. Biol. Chem. 269:11530-11536(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TRP-113.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP TRP-113.
RC TISSUE=Placenta, and Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TRP-113.
RC TISSUE=Pancreas;
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 [10]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-104, AND MUTAGENESIS OF ASN-104.
RX PubMed=9524075; DOI=10.1515/bchm.1998.379.2.219;
RA Nissler K., Kreusch S., Rommerskirch W., Strubel W., Weber E.,
RA Wiederanders B.;
RT "Sorting of non-glycosylated human procathepsin S in mammalian cells.";
RL Biol. Chem. 379:219-224(1998).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30612035; DOI=10.1016/j.isci.2018.12.015;
RA Baranov M.V., Bianchi F., Schirmacher A., van Aart M.A.C., Maassen S.,
RA Muntjewerff E.M., Dingjan I., Ter Beest M., Verdoes M., Keyser S.G.L.,
RA Bertozzi C.R., Diederichsen U., van den Bogaart G.;
RT "The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major
RT Histocompatibility Complex Class II Antigen Presentation.";
RL IScience 11:160-177(2019).
RN [15]
RP 3D-STRUCTURE MODELING OF 115-331.
RX PubMed=9876921; DOI=10.1093/protein/11.11.1007;
RA Fengler A., Brandt W.;
RT "Three-dimensional structures of the cysteine proteases cathepsins K and S
RT deduced by knowledge-based modelling and active site characteristics.";
RL Protein Eng. 11:1007-1013(1998).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 115-331.
RX PubMed=11856830; DOI=10.1107/s0907444901021825;
RA Turkenburg J.P., Lamers M.B., Brzozowski A.M., Wright L.M., Hubbard R.E.,
RA Sturt S.L., Williams D.H.;
RT "Structure of a Cys25-->Ser mutant of human cathepsin S.";
RL Acta Crystallogr. D 58:451-455(2002).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 112-331 IN COMPLEX WITH INHIBITOR,
RP AND DISULFIDE BONDS.
RX PubMed=17469812; DOI=10.1021/jm070111+;
RA Inagaki H., Tsuruoka H., Hornsby M., Lesley S.A., Spraggon G., Ellman J.A.;
RT "Characterization and optimization of selective, nonpeptidic inhibitors of
RT cathepsin S with an unprecedented binding mode.";
RL J. Med. Chem. 50:2693-2699(2007).
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 (PubMed:30612035). The bond-specificity of this
CC proteinase is in part similar to the specificities of cathepsin L.
CC {ECO:0000269|PubMed:30612035}.
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 -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17469812}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:1377692}. Secreted
CC {ECO:0000269|PubMed:9524075}. Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:30612035}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25774-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25774-2; Sequence=VSP_042712;
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}.
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DR EMBL; S93414; AAB22005.1; -; mRNA.
DR EMBL; M86553; AAA35655.1; -; mRNA.
DR EMBL; M90696; AAC37592.1; -; mRNA.
DR EMBL; U07374; AAB60643.2; -; Genomic_DNA.
DR EMBL; U07370; AAB60643.2; JOINED; Genomic_DNA.
DR EMBL; U07371; AAB60643.2; JOINED; Genomic_DNA.
DR EMBL; U07372; AAB60643.2; JOINED; Genomic_DNA.
DR EMBL; U07373; AAB60643.2; JOINED; Genomic_DNA.
DR EMBL; CR541676; CAG46477.1; -; mRNA.
DR EMBL; AK301472; BAG62991.1; -; mRNA.
DR EMBL; AK314482; BAG37086.1; -; mRNA.
DR EMBL; AL356292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53518.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53519.1; -; Genomic_DNA.
DR EMBL; BC002642; AAH02642.1; -; mRNA.
DR CCDS; CCDS55634.1; -. [P25774-2]
DR CCDS; CCDS968.1; -. [P25774-1]
DR PIR; A42482; A42482.
DR RefSeq; NP_001186668.1; NM_001199739.1. [P25774-2]
DR RefSeq; NP_004070.3; NM_004079.4. [P25774-1]
DR PDB; 1GLO; X-ray; 2.20 A; A=115-331.
DR PDB; 1MS6; X-ray; 1.90 A; A=115-331.
DR PDB; 1NPZ; X-ray; 2.00 A; A/B=115-331.
DR PDB; 1NQC; X-ray; 1.80 A; A=115-331.
DR PDB; 2C0Y; X-ray; 2.10 A; A=17-331.
DR PDB; 2F1G; X-ray; 1.90 A; A/B=112-331.
DR PDB; 2FQ9; X-ray; 1.65 A; A/B=114-331.
DR PDB; 2FRA; X-ray; 1.90 A; A/B=114-330.
DR PDB; 2FRQ; X-ray; 1.60 A; A/B=114-331.
DR PDB; 2FT2; X-ray; 1.70 A; A/B=114-331.
DR PDB; 2FUD; X-ray; 1.95 A; A/B=114-331.
DR PDB; 2FYE; X-ray; 2.20 A; A=115-331.
DR PDB; 2G6D; X-ray; 2.50 A; A=115-331.
DR PDB; 2G7Y; X-ray; 2.00 A; A/B=114-330.
DR PDB; 2H7J; X-ray; 1.50 A; A/B=112-331.
DR PDB; 2HH5; X-ray; 1.80 A; A/B=112-331.
DR PDB; 2HHN; X-ray; 1.55 A; A/B=112-331.
DR PDB; 2HXZ; X-ray; 1.90 A; A/B/C=112-331.
DR PDB; 2OP3; X-ray; 1.60 A; A/B=112-331.
DR PDB; 2R9M; X-ray; 1.97 A; A/B=115-331.
DR PDB; 2R9N; X-ray; 2.00 A; A/B=115-331.
DR PDB; 2R9O; X-ray; 2.00 A; A/B=115-331.
DR PDB; 3IEJ; X-ray; 2.18 A; A/B=115-331.
DR PDB; 3N3G; X-ray; 1.60 A; A/B=115-331.
DR PDB; 3N4C; X-ray; 1.90 A; A/B=115-331.
DR PDB; 3OVX; X-ray; 1.49 A; A/B=114-331.
DR PDB; 4P6E; X-ray; 1.80 A; A/B=109-331.
DR PDB; 4P6G; X-ray; 1.58 A; A/B/C/D=114-331.
DR PDB; 5QBU; X-ray; 2.78 A; A/B=114-331.
DR PDB; 5QBV; X-ray; 1.80 A; A/B=115-331.
DR PDB; 5QBW; X-ray; 3.01 A; A=114-331.
DR PDB; 5QBX; X-ray; 2.10 A; A/B=114-331.
DR PDB; 5QBY; X-ray; 2.25 A; A/B=114-331.
DR PDB; 5QBZ; X-ray; 2.80 A; A=114-331.
DR PDB; 5QC0; X-ray; 1.90 A; A/B=114-331.
DR PDB; 5QC1; X-ray; 2.08 A; A/B=114-331.
DR PDB; 5QC2; X-ray; 2.26 A; A/B=114-331.
DR PDB; 5QC3; X-ray; 2.00 A; A/B=114-331.
DR PDB; 5QC4; X-ray; 2.00 A; A/B=115-331.
DR PDB; 5QC5; X-ray; 2.40 A; A/B=114-331.
DR PDB; 5QC6; X-ray; 2.10 A; A/B=114-331.
DR PDB; 5QC7; X-ray; 1.90 A; A/B=114-331.
DR PDB; 5QC8; X-ray; 1.74 A; A/B=114-331.
DR PDB; 5QC9; X-ray; 2.00 A; A/B=114-331.
DR PDB; 5QCA; X-ray; 2.29 A; A/B=114-331.
DR PDB; 5QCB; X-ray; 2.20 A; A/B=114-331.
DR PDB; 5QCC; X-ray; 1.80 A; A/B=114-331.
DR PDB; 5QCD; X-ray; 1.95 A; A=114-331.
DR PDB; 5QCE; X-ray; 2.78 A; A/B=114-331.
DR PDB; 5QCF; X-ray; 2.10 A; A=114-331.
DR PDB; 5QCG; X-ray; 2.69 A; A/B=114-331.
DR PDB; 5QCH; X-ray; 2.20 A; A/B/C/D=114-331.
DR PDB; 5QCI; X-ray; 2.18 A; A=114-331.
DR PDB; 5QCJ; X-ray; 2.00 A; A/B/C=114-331.
DR PDB; 6YYN; X-ray; 2.22 A; AAA/BBB=113-331.
DR PDB; 6YYO; X-ray; 1.50 A; AAA/BBB=113-331.
DR PDB; 6YYP; X-ray; 2.05 A; AAA/BBB=113-331.
DR PDB; 6YYQ; X-ray; 2.51 A; AAA/BBB/CCC/DDD=113-331.
DR PDB; 6YYR; X-ray; 1.30 A; AAA/BBB=113-331.
DR PDBsum; 1GLO; -.
DR PDBsum; 1MS6; -.
DR PDBsum; 1NPZ; -.
DR PDBsum; 1NQC; -.
DR PDBsum; 2C0Y; -.
DR PDBsum; 2F1G; -.
DR PDBsum; 2FQ9; -.
DR PDBsum; 2FRA; -.
DR PDBsum; 2FRQ; -.
DR PDBsum; 2FT2; -.
DR PDBsum; 2FUD; -.
DR PDBsum; 2FYE; -.
DR PDBsum; 2G6D; -.
DR PDBsum; 2G7Y; -.
DR PDBsum; 2H7J; -.
DR PDBsum; 2HH5; -.
DR PDBsum; 2HHN; -.
DR PDBsum; 2HXZ; -.
DR PDBsum; 2OP3; -.
DR PDBsum; 2R9M; -.
DR PDBsum; 2R9N; -.
DR PDBsum; 2R9O; -.
DR PDBsum; 3IEJ; -.
DR PDBsum; 3N3G; -.
DR PDBsum; 3N4C; -.
DR PDBsum; 3OVX; -.
DR PDBsum; 4P6E; -.
DR PDBsum; 4P6G; -.
DR PDBsum; 5QBU; -.
DR PDBsum; 5QBV; -.
DR PDBsum; 5QBW; -.
DR PDBsum; 5QBX; -.
DR PDBsum; 5QBY; -.
DR PDBsum; 5QBZ; -.
DR PDBsum; 5QC0; -.
DR PDBsum; 5QC1; -.
DR PDBsum; 5QC2; -.
DR PDBsum; 5QC3; -.
DR PDBsum; 5QC4; -.
DR PDBsum; 5QC5; -.
DR PDBsum; 5QC6; -.
DR PDBsum; 5QC7; -.
DR PDBsum; 5QC8; -.
DR PDBsum; 5QC9; -.
DR PDBsum; 5QCA; -.
DR PDBsum; 5QCB; -.
DR PDBsum; 5QCC; -.
DR PDBsum; 5QCD; -.
DR PDBsum; 5QCE; -.
DR PDBsum; 5QCF; -.
DR PDBsum; 5QCG; -.
DR PDBsum; 5QCH; -.
DR PDBsum; 5QCI; -.
DR PDBsum; 5QCJ; -.
DR PDBsum; 6YYN; -.
DR PDBsum; 6YYO; -.
DR PDBsum; 6YYP; -.
DR PDBsum; 6YYQ; -.
DR PDBsum; 6YYR; -.
DR AlphaFoldDB; P25774; -.
DR SMR; P25774; -.
DR BioGRID; 107900; 133.
DR DIP; DIP-61077N; -.
DR IntAct; P25774; 8.
DR STRING; 9606.ENSP00000357981; -.
DR BindingDB; P25774; -.
DR ChEMBL; CHEMBL2954; -.
DR DrugBank; DB08195; (1R)-2-[(CYANOMETHYL)AMINO]-1-({[2-(DIFLUOROMETHOXY)BENZYL]SULFONYL}METHYL)-2-OXOETHYL MORPHOLINE-4-CARBOXYLATE.
DR DrugBank; DB08611; 2-[(2',3',4'-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB03837; Morpholine-4-Carboxylic Acid (1-(3-Benzenesulfonyl-1-Phenethylallylcarbamoyl)-3-Methylbutyl)-Amide.
DR DrugBank; DB03984; Morpholine-4-Carboxylic Acid [1-(2-Benzylsulfanyl-1-Formyl-Ethylcarbamoyl)-2-Phenyl-Ethyl]-Amide.
DR DrugBank; DB03767; Morpholine-4-Carboxylic Acid [1s-(2-Benzyloxy-1r-Cyano-Ethylcarbamoyl)-3-Methyl-Butyl]Amide.
DR DrugBank; DB07587; N-(1-CYANOCYCLOPROPYL)-3-({[(2S)-5-OXOPYRROLIDIN-2-YL]METHYL}SULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)ETHYL]-L-ALANINAMIDE.
DR DrugBank; DB07878; N-[(1S)-1-{1-[(1R,3E)-1-ACETYLPENT-3-EN-1-YL]-1H-1,2,3-TRIAZOL-4-YL}-1,2-DIMETHYLPROPYL]BENZAMIDE.
DR DrugBank; DB08752; N-[(1S)-2-[(4-cyano-1-methylpiperidin-4-yl)amino]-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide.
DR DrugBank; DB08755; N-[(1S)-2-{[(1R)-2-(benzyloxy)-1-cyano-1-methylethyl]amino}-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide.
DR DrugBank; DB07589; N-[1-(AMINOMETHYL)CYCLOPROPYL]-3-(BENZYLSULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-HYDROXYPHENYL)ETHYL]-L-ALANINAMIDE.
DR DrugBank; DB07520; N-[1-(AMINOMETHYL)CYCLOPROPYL]-3-(MORPHOLIN-4-YLSULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)ETHYL]-L-ALANINAMIDE.
DR DrugBank; DB07839; N~2~-1,3-BENZOXAZOL-2-YL-3-CYCLOHEXYL-N-{2-[(4-METHOXYPHENYL)AMINO]ETHYL}-L-ALANINAMIDE.
DR DrugCentral; P25774; -.
DR GuidetoPHARMACOLOGY; 2353; -.
DR MEROPS; C01.034; -.
DR MEROPS; I29.004; -.
DR GlyGen; P25774; 3 sites.
DR iPTMnet; P25774; -.
DR PhosphoSitePlus; P25774; -.
DR BioMuta; CTSS; -.
DR DMDM; 88984046; -.
DR EPD; P25774; -.
DR jPOST; P25774; -.
DR MassIVE; P25774; -.
DR MaxQB; P25774; -.
DR PaxDb; P25774; -.
DR PeptideAtlas; P25774; -.
DR PRIDE; P25774; -.
DR ProteomicsDB; 54285; -. [P25774-1]
DR ProteomicsDB; 54286; -. [P25774-2]
DR ABCD; P25774; 1 sequenced antibody.
DR Antibodypedia; 849; 468 antibodies from 36 providers.
DR DNASU; 1520; -.
DR Ensembl; ENST00000368985.8; ENSP00000357981.3; ENSG00000163131.12. [P25774-1]
DR Ensembl; ENST00000472977.7; ENSP00000475176.2; ENSG00000163131.12. [P25774-1]
DR Ensembl; ENST00000607427.2; ENSP00000475557.2; ENSG00000163131.12. [P25774-1]
DR Ensembl; ENST00000680288.1; ENSP00000506001.1; ENSG00000163131.12. [P25774-2]
DR Ensembl; ENST00000681444.1; ENSP00000505359.1; ENSG00000163131.12. [P25774-1]
DR GeneID; 1520; -.
DR KEGG; hsa:1520; -.
DR MANE-Select; ENST00000368985.8; ENSP00000357981.3; NM_004079.5; NP_004070.3.
DR UCSC; uc001evn.3; human. [P25774-1]
DR CTD; 1520; -.
DR DisGeNET; 1520; -.
DR GeneCards; CTSS; -.
DR HGNC; HGNC:2545; CTSS.
DR HPA; ENSG00000163131; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 116845; gene.
DR neXtProt; NX_P25774; -.
DR OpenTargets; ENSG00000163131; -.
DR PharmGKB; PA27041; -.
DR VEuPathDB; HostDB:ENSG00000163131; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000155176; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; P25774; -.
DR OMA; EMDGAFQ; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; P25774; -.
DR TreeFam; TF313739; -.
DR BRENDA; 3.4.22.27; 2681.
DR PathwayCommons; P25774; -.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P25774; -.
DR SIGNOR; P25774; -.
DR BioGRID-ORCS; 1520; 8 hits in 1084 CRISPR screens.
DR ChiTaRS; CTSS; human.
DR EvolutionaryTrace; P25774; -.
DR GeneWiki; Cathepsin_S; -.
DR GenomeRNAi; 1520; -.
DR Pharos; P25774; Tchem.
DR PRO; PR:P25774; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P25774; protein.
DR Bgee; ENSG00000163131; Expressed in monocyte and 181 other tissues.
DR ExpressionAtlas; P25774; baseline and differential.
DR Genevisible; P25774; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0036021; C:endolysosome lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:ARUK-UCL.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0005518; F:collagen binding; IDA:BHF-UCL.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:CAFA.
DR GO; GO:0001968; F:fibronectin binding; IPI:BHF-UCL.
DR GO; GO:0043236; F:laminin binding; IDA:BHF-UCL.
DR GO; GO:0043394; F:proteoglycan binding; IPI:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0002250; P:adaptive immune response; IEP:UniProtKB.
DR GO; GO:0019882; P:antigen processing and presentation; TAS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0048002; P:antigen processing and presentation of peptide antigen; IDA:CACAO.
DR GO; GO:0034769; P:basement membrane disassembly; IDA:BHF-UCL.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IDA:BHF-UCL.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IDA:CACAO.
DR GO; GO:0016485; P:protein processing; IDA:CACAO.
DR GO; GO:0006508; P:proteolysis; IDA:CAFA.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0010447; P:response to acidic pH; IDA:CACAO.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome.
DR CDD; cd02248; Peptidase_C1A; 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; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
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; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Lysosome; Protease; Reference proteome; Secreted; Signal; Thiol protease;
KW Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..114
FT /note="Activation peptide"
FT /id="PRO_0000026313"
FT CHAIN 115..331
FT /note="Cathepsin S"
FT /id="PRO_0000026314"
FT ACT_SITE 139
FT /evidence="ECO:0000250"
FT ACT_SITE 278
FT /evidence="ECO:0000250"
FT ACT_SITE 298
FT /evidence="ECO:0000250"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:9524075"
FT DISULFID 126..224
FT /evidence="ECO:0000269|PubMed:17469812"
FT DISULFID 136..180
FT /evidence="ECO:0000269|PubMed:17469812"
FT DISULFID 170..213
FT /evidence="ECO:0000269|PubMed:17469812"
FT DISULFID 272..320
FT /evidence="ECO:0000269|PubMed:17469812"
FT VAR_SEQ 84..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042712"
FT VARIANT 113
FT /note="R -> W (in dbSNP:rs2230061)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_025385"
FT VARIANT 161
FT /note="S -> T (in dbSNP:rs1059604)"
FT /evidence="ECO:0000269|PubMed:1373132,
FT ECO:0000269|PubMed:8157683"
FT /id="VAR_025386"
FT MUTAGEN 104
FT /note="N->Q: Abolishes glycosylation."
FT /evidence="ECO:0000269|PubMed:9524075"
FT CONFLICT 92
FT /note="M -> T (in Ref. 1 and 4)"
FT /evidence="ECO:0000305"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 25..35
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 44..67
FT /evidence="ECO:0007829|PDB:2C0Y"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:2C0Y"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2HH5"
FT HELIX 139..156
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 164..170
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:3OVX"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 248..252
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 278..288
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:3OVX"
FT TURN 302..305
FT /evidence="ECO:0007829|PDB:5QCA"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:3OVX"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:3OVX"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:3OVX"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:3OVX"
SQ SEQUENCE 331 AA; 37496 MW; 86093619DB6F0269 CRC64;
MKRLVCVLLV CSSAVAQLHK DPTLDHHWHL WKKTYGKQYK EKNEEAVRRL IWEKNLKFVM
LHNLEHSMGM HSYDLGMNHL GDMTSEEVMS LMSSLRVPSQ WQRNITYKSN PNRILPDSVD
WREKGCVTEV KYQGSCGACW AFSAVGALEA QLKLKTGKLV SLSAQNLVDC STEKYGNKGC
NGGFMTTAFQ YIIDNKGIDS DASYPYKAMD QKCQYDSKYR AATCSKYTEL PYGREDVLKE
AVANKGPVSV GVDARHPSFF LYRSGVYYEP SCTQNVNHGV LVVGYGDLNG KEYWLVKNSW
GHNFGEEGYI RMARNKGNHC GIASFPSYPE I
