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Protein

Cathepsin S

Gene

CTSS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L.

Catalytic activityi

Similar to cathepsin L, but with much less activity on Z-Phe-Arg-|-NHMec, and more activity on the Z-Val-Val-Arg-|-Xaa compound.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei139By similarity1
Active sitei278By similarity1
Active sitei298By similarity1

GO - Molecular functioni

  • collagen binding Source: BHF-UCL
  • cysteine-type endopeptidase activity Source: CAFA
  • fibronectin binding Source: BHF-UCL
  • laminin binding Source: BHF-UCL
  • proteoglycan binding Source: BHF-UCL
  • serine-type endopeptidase activity Source: Reactome

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • antigen processing and presentation Source: UniProtKB
  • antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  • antigen processing and presentation of peptide antigen Source: CACAO
  • basement membrane disassembly Source: BHF-UCL
  • cellular response to thyroid hormone stimulus Source: UniProtKB
  • collagen catabolic process Source: BHF-UCL
  • extracellular matrix disassembly Source: Reactome
  • immune response Source: ProtInc
  • neutrophil degranulation Source: Reactome
  • positive regulation of cation channel activity Source: CACAO
  • protein processing Source: CACAO
  • proteolysis Source: CAFA
  • proteolysis involved in cellular protein catabolic process Source: BHF-UCL
  • response to acidic pH Source: CACAO
  • toll-like receptor signaling pathway Source: Reactome

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease

Enzyme and pathway databases

BRENDAi3.4.22.27 2681
ReactomeiR-HSA-1236977 Endosomal/Vacuolar pathway
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-2132295 MHC class II antigen presentation
R-HSA-6798695 Neutrophil degranulation
SIGNORiP25774

Protein family/group databases

MEROPSiI29.004

Names & Taxonomyi

Protein namesi
Recommended name:
Cathepsin S (EC:3.4.22.27)
Gene namesi
Name:CTSS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163131.10
HGNCiHGNC:2545 CTSS
MIMi116845 gene
neXtProtiNX_P25774

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1520
OpenTargetsiENSG00000163131
PharmGKBiPA27041

Chemistry databases

ChEMBLiCHEMBL2954
DrugBankiDB08195 (1R)-2-[(CYANOMETHYL)AMINO]-1-({[2-(DIFLUOROMETHOXY)BENZYL]SULFONYL}METHYL)-2-OXOETHYL MORPHOLINE-4-CARBOXYLATE
DB03837 Morpholine-4-Carboxylic Acid (1-(3-Benzenesulfonyl-1-Phenethylallylcarbamoyl)-3-Methylbutyl)-Amide
DB03984 Morpholine-4-Carboxylic Acid [1-(2-Benzylsulfanyl-1-Formyl-Ethylcarbamoyl)-2-Phenyl-Ethyl]-Amide
DB03767 Morpholine-4-Carboxylic Acid [1s-(2-Benzyloxy-1r-Cyano-Ethylcarbamoyl)-3-Methyl-Butyl]Amide
DB08752 N-[(1S)-2-[(4-cyano-1-methylpiperidin-4-yl)amino]-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide
DB08755 N-[(1S)-2-{[(1R)-2-(benzyloxy)-1-cyano-1-methylethyl]amino}-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide
GuidetoPHARMACOLOGYi2353

Polymorphism and mutation databases

BioMutaiCTSS
DMDMi88984046

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000002631317 – 114Activation peptideAdd BLAST98
ChainiPRO_0000026314115 – 331Cathepsin SAdd BLAST217

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi126 ↔ 2241 Publication
Disulfide bondi136 ↔ 1801 Publication
Disulfide bondi170 ↔ 2131 Publication
Disulfide bondi272 ↔ 3201 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP25774
MaxQBiP25774
PaxDbiP25774
PeptideAtlasiP25774
PRIDEiP25774
ProteomicsDBi54285
54286 [P25774-2]

PTM databases

iPTMnetiP25774
PhosphoSitePlusiP25774

Miscellaneous databases

PMAP-CutDBiP25774

Expressioni

Gene expression databases

BgeeiENSG00000163131
CleanExiHS_CTSS
ExpressionAtlasiP25774 baseline and differential
GenevisibleiP25774 HS

Organism-specific databases

HPAiCAB000460
HPA002988

Interactioni

Subunit structurei

Monomer.1 Publication

GO - Molecular functioni

  • fibronectin binding Source: BHF-UCL
  • laminin binding Source: BHF-UCL
  • proteoglycan binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107900, 3 interactors
DIPiDIP-61077N
IntActiP25774, 7 interactors
STRINGi9606.ENSP00000357981

Chemistry databases

BindingDBiP25774

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 24Combined sources3
Helixi25 – 35Combined sources11
Helixi44 – 67Combined sources24
Beta strandi72 – 75Combined sources4
Helixi79 – 82Combined sources4
Helixi85 – 91Combined sources7
Helixi100 – 102Combined sources3
Helixi121 – 124Combined sources4
Beta strandi135 – 137Combined sources3
Helixi139 – 156Combined sources18
Helixi164 – 170Combined sources7
Helixi173 – 175Combined sources3
Helixi179 – 181Combined sources3
Helixi185 – 195Combined sources11
Beta strandi198 – 200Combined sources3
Turni201 – 203Combined sources3
Helixi217 – 219Combined sources3
Beta strandi220 – 222Combined sources3
Beta strandi226 – 229Combined sources4
Helixi235 – 244Combined sources10
Beta strandi248 – 252Combined sources5
Helixi257 – 261Combined sources5
Beta strandi264 – 267Combined sources4
Beta strandi278 – 288Combined sources11
Beta strandi291 – 297Combined sources7
Turni302 – 305Combined sources4
Beta strandi309 – 313Combined sources5
Beta strandi315 – 318Combined sources4
Helixi319 – 321Combined sources3
Turni322 – 324Combined sources3
Beta strandi327 – 330Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BXFmodel-A115-331[»]
1GLOX-ray2.20A115-331[»]
1MS6X-ray1.90A115-331[»]
1NPZX-ray2.00A/B115-331[»]
1NQCX-ray1.80A115-331[»]
2C0YX-ray2.10A17-331[»]
2F1GX-ray1.90A/B112-331[»]
2FQ9X-ray1.65A/B114-331[»]
2FRAX-ray1.90A/B114-330[»]
2FRQX-ray1.60A/B114-331[»]
2FT2X-ray1.70A/B114-331[»]
2FUDX-ray1.95A/B114-331[»]
2FYEX-ray2.20A115-331[»]
2G6DX-ray2.50A115-331[»]
2G7YX-ray2.00A/B114-330[»]
2H7JX-ray1.50A/B112-331[»]
2HH5X-ray1.80A/B112-331[»]
2HHNX-ray1.55A/B112-331[»]
2HXZX-ray1.90A/B/C112-331[»]
2OP3X-ray1.60A/B112-331[»]
2R9MX-ray1.97A/B115-331[»]
2R9NX-ray2.00A/B115-331[»]
2R9OX-ray2.00A/B115-331[»]
3IEJX-ray2.18A/B115-331[»]
3N3GX-ray1.60A/B115-331[»]
3N4CX-ray1.90A/B115-331[»]
3OVXX-ray1.49A/B114-331[»]
4P6EX-ray1.80A/B109-331[»]
4P6GX-ray1.58A/B/C/D114-331[»]
5QBUX-ray2.78A/B114-331[»]
5QBVX-ray1.80A/B115-331[»]
5QBWX-ray3.01A114-331[»]
5QBXX-ray2.10A/B114-331[»]
5QBYX-ray2.25A/B114-331[»]
5QBZX-ray2.80A114-331[»]
5QC0X-ray1.90A/B114-331[»]
5QC1X-ray2.08A/B114-331[»]
5QC2X-ray2.26A/B114-331[»]
5QC3X-ray2.00A/B114-331[»]
5QC4X-ray2.00A/B115-331[»]
5QC5X-ray2.40A/B114-331[»]
5QC6X-ray2.10A/B114-331[»]
5QC7X-ray1.90A/B114-331[»]
5QC8X-ray1.74A/B114-331[»]
5QC9X-ray2.00A/B114-331[»]
5QCAX-ray2.29A/B114-331[»]
5QCBX-ray2.20A/B114-331[»]
5QCCX-ray1.80A/B114-331[»]
5QCDX-ray1.95A114-331[»]
5QCEX-ray2.78A/B114-331[»]
5QCFX-ray2.10A114-331[»]
5QCGX-ray2.69A/B114-331[»]
5QCHX-ray2.20A/B/C/D114-331[»]
5QCIX-ray2.18A114-331[»]
5QCJX-ray2.00A/B/C114-331[»]
ProteinModelPortaliP25774
SMRiP25774
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP25774

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1543 Eukaryota
COG4870 LUCA
GeneTreeiENSGT00900000140823
HOGENOMiHOG000230774
HOVERGENiHBG011513
InParanoidiP25774
KOiK01368
OMAiKYQGSCG
OrthoDBiEOG091G0AKT
PhylomeDBiP25774
TreeFamiTF313739

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR025661 Pept_asp_AS
IPR000169 Pept_cys_AS
IPR025660 Pept_his_AS
IPR013128 Peptidase_C1A
IPR000668 Peptidase_C1A_C
IPR013201 Prot_inhib_I29
PANTHERiPTHR12411 PTHR12411, 1 hit
PfamiView protein in Pfam
PF08246 Inhibitor_I29, 1 hit
PF00112 Peptidase_C1, 1 hit
PRINTSiPR00705 PAPAIN
SMARTiView protein in SMART
SM00848 Inhibitor_I29, 1 hit
SM00645 Pept_C1, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00640 THIOL_PROTEASE_ASN, 1 hit
PS00139 THIOL_PROTEASE_CYS, 1 hit
PS00639 THIOL_PROTEASE_HIS, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P25774-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKRLVCVLLV CSSAVAQLHK DPTLDHHWHL WKKTYGKQYK EKNEEAVRRL
60 70 80 90 100
IWEKNLKFVM LHNLEHSMGM HSYDLGMNHL GDMTSEEVMS LMSSLRVPSQ
110 120 130 140 150
WQRNITYKSN PNRILPDSVD WREKGCVTEV KYQGSCGACW AFSAVGALEA
160 170 180 190 200
QLKLKTGKLV SLSAQNLVDC STEKYGNKGC NGGFMTTAFQ YIIDNKGIDS
210 220 230 240 250
DASYPYKAMD QKCQYDSKYR AATCSKYTEL PYGREDVLKE AVANKGPVSV
260 270 280 290 300
GVDARHPSFF LYRSGVYYEP SCTQNVNHGV LVVGYGDLNG KEYWLVKNSW
310 320 330
GHNFGEEGYI RMARNKGNHC GIASFPSYPE I
Length:331
Mass (Da):37,496
Last modified:February 21, 2006 - v3
Checksum:i86093619DB6F0269
GO
Isoform 2 (identifier: P25774-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     84-133: Missing.

Note: No experimental confirmation available.
Show »
Length:281
Mass (Da):31,626
Checksum:iC0445894FAD89713
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti92M → T (PubMed:1373132).Curated1
Sequence conflicti92M → T (PubMed:8157683).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025385113R → W3 PublicationsCorresponds to variant dbSNP:rs2230061Ensembl.1
Natural variantiVAR_025386161S → T2 PublicationsCorresponds to variant dbSNP:rs1059604Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04271284 – 133Missing in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S93414 mRNA Translation: AAB22005.1
M86553 mRNA Translation: AAA35655.1
M90696 mRNA Translation: AAC37592.1
U07374
, U07370, U07371, U07372, U07373 Genomic DNA Translation: AAB60643.2
CR541676 mRNA Translation: CAG46477.1
AK301472 mRNA Translation: BAG62991.1
AK314482 mRNA Translation: BAG37086.1
AL356292 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53518.1
CH471121 Genomic DNA Translation: EAW53519.1
BC002642 mRNA Translation: AAH02642.1
CCDSiCCDS55634.1 [P25774-2]
CCDS968.1 [P25774-1]
PIRiA42482
RefSeqiNP_001186668.1, NM_001199739.1 [P25774-2]
NP_004070.3, NM_004079.4 [P25774-1]
UniGeneiHs.181301

Genome annotation databases

EnsembliENST00000368985; ENSP00000357981; ENSG00000163131 [P25774-1]
ENST00000448301; ENSP00000408414; ENSG00000163131 [P25774-2]
GeneIDi1520
KEGGihsa:1520
UCSCiuc001evn.3 human [P25774-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCATS_HUMAN
AccessioniPrimary (citable) accession number: P25774
Secondary accession number(s): B4DWC9
, D3DV05, Q5T5I0, Q6FHS5, Q9BUG3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: February 21, 2006
Last modified: June 20, 2018
This is version 185 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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