CTSS
Cathepsin S
Also known as: CATS_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P25774
- Gene
- CTSS
- Ensembl
- ENSG00000163131
- Chromosome
- 1
- Canonical length
- 331 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Vesicles
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
The preproprotein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. The mature protein cleaves the invariant chain of MHC class II molecules in endolysosomal compartments and enables the formation of antigen-MHC class II complexes and the proper display of extracellular antigenic peptides by MHC-II. The mature protein also functions as an elastase over a broad pH range. When secreted from cells, this protein can remodel components of the extracellular matrix such as elastin, collagen, and fibronectin. This gene is implicated in the pathology of many inflammatory and autoimmune diseases and, given its elastase activity, plays a significant role in some pulmonary diseases. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2020]
Canonical amino-acid sequenceUniProt
331 residues, UniProt reviewed canonical sequence.
>P25774|CTSS
1 MKRLVCVLLV CSSAVAQLHK DPTLDHHWHL WKKTYGKQYK EKNEEAVRRL IWEKNLKFVM
61 LHNLEHSMGM HSYDLGMNHL GDMTSEEVMS LMSSLRVPSQ WQRNITYKSN PNRILPDSVD
121 WREKGCVTEV KYQGSCGACW AFSAVGALEA QLKLKTGKLV SLSAQNLVDC STEKYGNKGC
181 NGGFMTTAFQ YIIDNKGIDS DASYPYKAMD QKCQYDSKYR AATCSKYTEL PYGREDVLKE
241 AVANKGPVSV GVDARHPSFF LYRSGVYYEP SCTQNVNHGV LVVGYGDLNG KEYWLVKNSW
301 GHNFGEEGYI RMARNKGNHC GIASFPSYPE ILocalizationUniProt · AlphaFold · HPA
Whether an antibody against CTSS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.26
- Highest tissue expression
- 128 nTPM
Expression across tissuesHPA
Tissue
- spleen: 128 nTPM
- bone marrow: 122 nTPM
- appendix: 82 nTPM
- colon: 78 nTPM
- lung: 70 nTPM
- lymph node: 67 nTPM
Single-cell type
- kupffer cells: 2,999 nCPM
- monocytes: 2,663 nCPM
- neutrophils: 1,730 nCPM
- macrophages: 1,043 nCPM
- neutrophil progenitors: 829 nCPM
- cdc: 622 nCPM
Immune cell
- total PBMC: 2,556 nTPM
- classical monocyte: 2,462 nTPM
- intermediate monocyte: 1,718 nTPM
- non-classical monocyte: 1,642 nTPM
- neutrophil: 1,016 nTPM
- myeloid DC: 565 nTPM
Brain region
- white matter: 36 nTPM
- medulla oblongata: 27 nTPM
- pons: 26 nTPM
- thalamus: 25 nTPM
- spinal cord: 20 nTPM
- choroid plexus: 18 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CTSS.
Disease | ImmuneIEDB
Conditions an epitope on CTSS was assayed in.
- type 1 diabetes mellitus T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.53
- gnomAD pLI
- 0.34
- gnomAD missense Z
- 2.24
- DepMap mean gene effect
- -0.04
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adaptive immune response
- antigen processing and presentation
- antigen processing and presentation of exogenous peptide antigen via MHC class II
- antigen processing and presentation of peptide antigen
- basement membrane disassembly
- cellular response to thyroid hormone stimulus
- collagen catabolic process
- extracellular matrix disassembly
- immune response
- positive regulation of cation channel activity
- protein processing
- proteolysis
- proteolysis involved in protein catabolic process
- regulation of antigen processing and presentation
- response to acidic pH
- toll-like receptor signaling pathway
Molecular functions
- collagen binding
- cysteine-type endopeptidase activity
- cysteine-type peptidase activity
- fibronectin binding
- laminin binding
- peptidase activity
- proteoglycan binding
- serine-type endopeptidase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Cysteine peptidase, cysteine active site
- Peptidase C1A, papain C-terminal
- Peptidase C1A
- Cathepsin propeptide inhibitor domain (I29)
- Cysteine peptidase, histidine active site
- Cysteine peptidase, asparagine active site
- Papain-like cysteine peptidase superfamily
- Papain-like cysteine endopeptidase
- Papain family cysteine protease
- Cathepsin propeptide inhibitor domain (I29)
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CTSS as an antibody target. Whether an autoantibody or antibody against CTSS could matter depends on whether native CTSS is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CTSS is annotated as secreted, so native CTSS circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- This gene is implicated in the pathology of many inflammatory and autoimmune diseases and, given its elastase activity, plays a significant role in some pulmonary diseases.
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