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Protein

Cathepsin S

Gene

CTSS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 and cathepsin N.

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: BHF-UCL
  • 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
  • positive regulation of cation channel activity Source: CACAO
  • protein processing Source: CACAO
  • proteolysis Source: CACAO
  • proteolysis involved in cellular protein catabolic process Source: BHF-UCL
  • response to acidic pH Source: CACAO
  • toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Enzyme and pathway databases

BioCyciZFISH:HS08791-MONOMER.
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.

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

HGNCiHGNC:2545. CTSS.

Subcellular locationi

GO - Cellular componenti

  • endolysosome lumen Source: Reactome
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1520.
OpenTargetsiENSG00000163131.
PharmGKBiPA27041.

Chemistry databases

ChEMBLiCHEMBL2954.
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...)Sequence 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.

PTM databases

iPTMnetiP25774.
PhosphoSitePlusiP25774.

Miscellaneous databases

PMAP-CutDBP25774.

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

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

Protein-protein interaction databases

BioGridi107900. 3 interactors.
DIPiDIP-61077N.
IntActiP25774. 2 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
Turni301 – 303Combined sources3
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[»]
3KWNX-ray2.10A/B115-331[»]
3MPEX-ray2.25A/B114-331[»]
3MPFX-ray1.80A/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[»]
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.
GeneTreeiENSGT00760000118871.
HOGENOMiHOG000230774.
HOVERGENiHBG011513.
InParanoidiP25774.
KOiK01368.
OMAiKATDQKC.
OrthoDBiEOG091G0AKT.
PhylomeDBiP25774.
TreeFamiTF313739.

Family and domain databases

InterProiIPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR013201. Prot_inhib_I29.
[Graphical view]
PANTHERiPTHR12411. PTHR12411. 1 hit.
PfamiPF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSiPR00705. PAPAIN.
SMARTiSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEiPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]

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 → W.3 PublicationsCorresponds to variant rs2230061dbSNPEnsembl.1
Natural variantiVAR_025386161S → T.2 PublicationsCorresponds to variant rs1059604dbSNPEnsembl.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. Translation: CAI13657.1.
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

Cross-referencesi

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. Translation: CAI13657.1.
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.

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[»]
3KWNX-ray2.10A/B115-331[»]
3MPEX-ray2.25A/B114-331[»]
3MPFX-ray1.80A/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[»]
ProteinModelPortaliP25774.
SMRiP25774.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107900. 3 interactors.
DIPiDIP-61077N.
IntActiP25774. 2 interactors.
STRINGi9606.ENSP00000357981.

Chemistry databases

BindingDBiP25774.
ChEMBLiCHEMBL2954.
GuidetoPHARMACOLOGYi2353.

Protein family/group databases

MEROPSiI29.004.

PTM databases

iPTMnetiP25774.
PhosphoSitePlusiP25774.

Polymorphism and mutation databases

BioMutaiCTSS.
DMDMi88984046.

Proteomic databases

EPDiP25774.
MaxQBiP25774.
PaxDbiP25774.
PeptideAtlasiP25774.
PRIDEiP25774.

Protocols and materials databases

DNASUi1520.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1520.
DisGeNETi1520.
GeneCardsiCTSS.
HGNCiHGNC:2545. CTSS.
HPAiCAB000460.
HPA002988.
MIMi116845. gene.
neXtProtiNX_P25774.
OpenTargetsiENSG00000163131.
PharmGKBiPA27041.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1543. Eukaryota.
COG4870. LUCA.
GeneTreeiENSGT00760000118871.
HOGENOMiHOG000230774.
HOVERGENiHBG011513.
InParanoidiP25774.
KOiK01368.
OMAiKATDQKC.
OrthoDBiEOG091G0AKT.
PhylomeDBiP25774.
TreeFamiTF313739.

Enzyme and pathway databases

BioCyciZFISH:HS08791-MONOMER.
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.

Miscellaneous databases

ChiTaRSiCTSS. human.
EvolutionaryTraceiP25774.
GeneWikiiCathepsin_S.
GenomeRNAii1520.
PMAP-CutDBP25774.
PROiP25774.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163131.
CleanExiHS_CTSS.
ExpressionAtlasiP25774. baseline and differential.
GenevisibleiP25774. HS.

Family and domain databases

InterProiIPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR013201. Prot_inhib_I29.
[Graphical view]
PANTHERiPTHR12411. PTHR12411. 1 hit.
PfamiPF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSiPR00705. PAPAIN.
SMARTiSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEiPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCATS_HUMAN
AccessioniPrimary (citable) accession number: P25774
Secondary accession number(s): B4DWC9
, D3DV05, Q5T5I0, Q6FHS5, Q9BUG3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: February 21, 2006
Last modified: November 30, 2016
This is version 173 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.