Cathepsin S

Function

Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules and MHC class II antigen presentation. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L. Elicits itch by mediating cleavage and activation of MRGPRX1 (By similarity).

Classification

Family (Pfam)

PF08246 Inhibitor_I29, PF00112 Peptidase_C1

InterPro

Papain-like_cys_pep_sf, Pept_asp_AS, Pept_cys_AS, Pept_his_AS, Peptidase_C1A, Peptidase_C1A_C, Peptidase_C1A_papain-like, Prot_inhib_I29

Functional cluster

Secreted Hydrolases & Toxins

Experimental structures · PDB · 62

• 1GLO X-ray 2.20A
• 1MS6 X-ray 1.90A
• 1NPZ X-ray 2.00A
• 1NQC X-ray 1.80A
• 2C0Y X-ray 2.10A
• 2F1G X-ray 1.90A
• 2FQ9 X-ray 1.65A
• 2FRA X-ray 1.90A
• 2FRQ X-ray 1.60A
• 2FT2 X-ray 1.70A
• 2FUD X-ray 1.95A
• 2FYE X-ray 2.20A
• … and 50 more

A predicted model is available from AlphaFold.

Gene Ontology · 34

• GO:0036021 endolysosome lumen
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:1904813 ficolin-1-rich granule lumen
• GO:0005770 late endosome
• GO:0043202 lysosomal lumen
• GO:0005764 lysosome
• GO:0045335 phagocytic vesicle
• GO:1904724 tertiary granule lumen
• GO:0005518 collagen binding
• GO:0004197 cysteine-type endopeptidase activity
• GO:0008234 cysteine-type peptidase activity
• GO:0001968 fibronectin binding
• GO:0043236 laminin binding
• GO:0008233 peptidase activity
• GO:0043394 proteoglycan binding
• GO:0004252 serine-type endopeptidase activity
• GO:0002250 adaptive immune response
• GO:0019882 antigen processing and presentation
• GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II
• GO:0048002 antigen processing and presentation of peptide antigen
• GO:0034769 basement membrane disassembly
• GO:0097067 cellular response to thyroid hormone stimulus
• GO:0030574 collagen catabolic process
• GO:0022617 extracellular matrix disassembly
• GO:0006955 immune response
• GO:2001259 positive regulation of cation channel activity
• GO:0016485 protein processing
• GO:0006508 proteolysis
• GO:0051603 proteolysis involved in protein catabolic process
• GO:0002577 regulation of antigen processing and presentation
• GO:0010447 response to acidic pH
• GO:0002224 toll-like receptor signaling pathway

Drugs targeting this protein · 1

• PETESICATIB inhibitor

Related proteins · sequence + function similarity

• Cathepsin S 0.99
• Cathepsin S 0.98
• Cathepsin S 0.97
• Cathepsin S 0.94
• Cathepsin K 0.94
• Cathepsin S 0.94
• Cathepsin K 0.93
• Cathepsin K 0.93
• Cathepsin K 0.93
• Cathepsin K 0.93
• Cathepsin K 0.93
• Cathepsin K 0.93

Co-cited proteins · studied together in the literature

• 1-phosphatidylinositol 3-phosphate 5-kinase 1 shared papers

Literature · 14 cited papers

• The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation. IScience · 2019
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Characterization and optimization of selective, nonpeptidic inhibitors of cathepsin S with an unprecedented binding mode. J. Med. Chem. · 2007
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Structure of a Cys25-->Ser mutant of human cathepsin S. Acta Crystallogr. D · 2002
• Three-dimensional structures of the cysteine proteases cathepsins K and S deduced by knowledge-based modelling and active site characteristics. Protein Eng. · 1998
• Sorting of non-glycosylated human procathepsin S in mammalian cells. Biol. Chem. · 1998
• Human cathepsin S: chromosomal localization, gene structure, and tissue distribution. J. Biol. Chem. · 1994
• … and 2 more in the literature graph