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 ... See more...

Aliases for CTSS Gene

Aliases for CTSS Gene

  • Cathepsin S 2 3 4 5
  • EC 3.4.22.27 4 51
  • EC 3.4.22 51
  • CTSS 5

External Ids for CTSS Gene

Previous GeneCards Identifiers for CTSS Gene

  • GC01M148546
  • GC01M146449
  • GC01M147477
  • GC01M147919
  • GC01M147515
  • GC01M148969
  • GC01M150702
  • GC01M122080

Summaries for CTSS Gene

Entrez Gene Summary for CTSS 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]

GeneCards Summary for CTSS Gene

CTSS (Cathepsin S) is a Protein Coding gene. Diseases associated with CTSS include Dacryoadenitis. Among its related pathways are Lysosome and Degradation of the extracellular matrix. Gene Ontology (GO) annotations related to this gene include peptidase activity and cysteine-type peptidase activity. An important paralog of this gene is CTSK.

UniProtKB/Swiss-Prot Summary for CTSS Gene

  • 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.

Gene Wiki entry for CTSS Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CTSS Gene

Genomics for CTSS Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CTSS Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CTSS on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CTSS

Top Transcription factor binding sites by QIAGEN in the CTSS gene promoter:
  • AREB6
  • En-1
  • Evi-1
  • Ik-1
  • Ik-2
  • IRF-1
  • STAT5A
  • STAT5B
  • TBP

Genomic Locations for CTSS Gene

Genomic Locations for CTSS Gene
chr1:150,730,188-150,765,792
(GRCh38/hg38)
Size:
35,605 bases
Orientation:
Minus strand
chr1:150,702,672-150,738,433
(GRCh37/hg19)
Size:
35,762 bases
Orientation:
Minus strand

Genomic View for CTSS Gene

Genes around CTSS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CTSS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CTSS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CTSS Gene

Proteins for CTSS Gene

  • Protein details for CTSS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P25774-CATS_HUMAN
    Recommended name:
    Cathepsin S
    Protein Accession:
    P25774
    Secondary Accessions:
    • B4DWC9
    • D3DV05
    • Q5T5I0
    • Q6FHS5
    • Q9BUG3

    Protein attributes for CTSS Gene

    Size:
    331 amino acids
    Molecular mass:
    37496 Da
    Quaternary structure:
    • Monomer.

    Three dimensional structures from OCA and Proteopedia for CTSS Gene

    Alternative splice isoforms for CTSS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CTSS Gene

Selected DME Specific Peptides for CTSS Gene

P25774:
  • QNLVDCS
  • RRLIWEKNLK
  • VDWREKG
  • VLVVGYG
  • CWAFSAVGALE
  • QLKLKTGKL
  • PTLDHHW
  • LHNLEHSMGMHSY
  • DWREKGCVTEVKYQG
  • GDMTSEE
  • MNHLGDMT
  • GYIRMAR
  • YWLVKNS
  • KTGKLVSLS

Post-translational modifications for CTSS Gene

  • Glycosylation at Asn104
  • Modification sites at PhosphoSitePlus

Other Protein References for CTSS Gene

Antibody Products

Domains & Families for CTSS Gene

Gene Families for CTSS Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CTSS Gene

InterPro:
Blocks:
  • Papain cysteine protease (C1) family signature
  • Proteinase inhibitor I29, cathepsin propeptide
ProtoNet:

Suggested Antigen Peptide Sequences for CTSS Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50259, highly similar to Cathepsin S (EC 3.4.22.27) (B4DWC9_HUMAN)
  • Cathepsin S (CATS_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P25774

UniProtKB/Swiss-Prot:

CATS_HUMAN :
  • Belongs to the peptidase C1 family.
Family:
  • Belongs to the peptidase C1 family.
genes like me logo Genes that share domains with CTSS: view

Function for CTSS Gene

Molecular function for CTSS Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=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.; EC=3.4.22.27;.
GENATLAS Biochemistry:
cathepsin S,lysosomal cysteine proteinase,expressed in spleen,heart and lung,papain superfamily,specifically involved in MHCII-associated chain processing and peptide loading

Enzyme Numbers (IUBMB) for CTSS Gene

Phenotypes From GWAS Catalog for CTSS Gene

Gene Ontology (GO) - Molecular Function for CTSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001968 fibronectin binding IPI 22952693
GO:0004197 cysteine-type endopeptidase activity IDA,TAS --
GO:0005518 collagen binding IDA 22952693
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with CTSS: view
genes like me logo Genes that share phenotypes with CTSS: view

Animal Models for CTSS Gene

MGI Knock Outs for CTSS:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CTSS

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CTSS Gene

Localization for CTSS Gene

Subcellular locations from UniProtKB/Swiss-Prot for CTSS Gene

Lysosome. Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CTSS gene
Compartment Confidence
extracellular 5
lysosome 5
endosome 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CTSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA,IDA 9524075
GO:0005764 lysosome IBA,IDA 15196205
GO:0005770 late endosome IDA 22365146
GO:0036021 endolysosome lumen TAS --
genes like me logo Genes that share ontologies with CTSS: view

Pathways & Interactions for CTSS Gene

genes like me logo Genes that share pathways with CTSS: view

Pathways by source for CTSS Gene

2 GeneGo (Thomson Reuters) pathways for CTSS Gene
  • Bacterial infections in CF airways
  • Immune response Antigen presentation by MHC class II
1 GeneTex pathway for CTSS Gene

SIGNOR curated interactions for CTSS Gene

Inactivates:

Gene Ontology (GO) - Biological Process for CTSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002250 adaptive immune response IEP 15196205
GO:0006508 proteolysis IEA,IDA 12788072
GO:0006955 immune response TAS,IBA 21873635
GO:0010447 response to acidic pH IDA 22864553
genes like me logo Genes that share ontologies with CTSS: view

Drugs & Compounds for CTSS Gene

(17) Drugs for CTSS Gene - From: DrugBank, ApexBio, and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
(1R)-2-[(CYANOMETHYL)AMINO]-1-({[2-(DIFLUOROMETHOXY)BENZYL]SULFONYL}METHYL)-2-OXOETHYL MORPHOLINE-4-CARBOXYLATE Experimental Pharma Target 0
2-[(2',3',4'-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL Experimental Pharma Target 0
Morpholine-4-Carboxylic Acid (1-(3-Benzenesulfonyl-1-Phenethylallylcarbamoyl)-3-Methylbutyl)-Amide Experimental Pharma Target 0
Morpholine-4-Carboxylic Acid [1-(2-Benzylsulfanyl-1-Formyl-Ethylcarbamoyl)-2-Phenyl-Ethyl]-Amide Experimental Pharma Target 0

(3) ApexBio Compounds for CTSS Gene

Compound Action Cas Number
Cathepsin Inhibitor 1 Cathepsin inhibitor 225120-65-0
Cathepsin S inhibitor Blocks MHCII antigen presentation 1373215-15-6
E-64 Cysteine protease inhibitor,irriversible 66701-25-5
genes like me logo Genes that share compounds with CTSS: view

Drug Products

Transcripts for CTSS Gene

mRNA/cDNA for CTSS Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CTSS

Alternative Splicing Database (ASD) splice patterns (SP) for CTSS Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b · 9c ^ 10
SP1: - -
SP2: -
SP3:
SP4: - - -
SP5: -

Relevant External Links for CTSS Gene

GeneLoc Exon Structure for
CTSS

Expression for CTSS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CTSS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CTSS Gene

This gene is overexpressed in Whole Blood (x25.9) and Spleen (x4.3).

Protein differential expression in normal tissues from HIPED for CTSS Gene

This gene is overexpressed in Monocytes (12.2), Peripheral blood mononuclear cells (9.0), Spleen (6.3), and Nasal epithelium (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CTSS Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CTSS

SOURCE GeneReport for Unigene cluster for CTSS Gene:

Hs.181301

Evidence on tissue expression from TISSUES for CTSS Gene

  • Liver(4.6)
  • Pancreas(4.5)
  • Blood(4.5)
  • Intestine(4.2)
  • Nervous system(3.6)
  • Lung(3.3)
  • Spleen(3.3)
  • Lymph node(3.2)
  • Bone marrow(3)
  • Heart(2.6)
  • Muscle(2.5)
  • Stomach(2.5)
  • Skin(2.5)
  • Kidney(2.3)
  • Thyroid gland(2.1)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with CTSS: view

No data available for Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CTSS Gene

Orthologs for CTSS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CTSS Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CTSS 30 31
  • 99.5 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CTSS 30 31
  • 88.82 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CTSS 30 31
  • 87.11 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ctss 30
  • 81.45 (n)
Mouse
(Mus musculus)
Mammalia Ctss 30 17 31
  • 80.97 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CTSS 31
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CTSS 31
  • 73 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CTSS 30 31
  • 66.67 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CTSS 31
  • 64 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ctss 30
  • 67.98 (n)
African clawed frog
(Xenopus laevis)
Amphibia ctss-prov 30
Zebrafish
(Danio rerio)
Actinopterygii ctssb.1 30 31
  • 62.26 (n)
OneToMany
ctssb.2 31
  • 58 (a)
OneToMany
-- 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8503 30
Fruit Fly
(Drosophila melanogaster)
Insecta Cp1 32
  • 50 (a)
CG4847 32
  • 38 (a)
CG11459 32
  • 37 (a)
26-29kD-proteinase 32
  • 35 (a)
Worm
(Caenorhabditis elegans)
Secernentea cpl-1 32
  • 47 (a)
R09F10.1 32
  • 32 (a)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT4G11320 30
  • 51.52 (n)
Species where no ortholog for CTSS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for CTSS Gene

ENSEMBL:
Gene Tree for CTSS (if available)
TreeFam:
Gene Tree for CTSS (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CTSS: view image

Paralogs for CTSS Gene

Paralogs for CTSS Gene

genes like me logo Genes that share paralogs with CTSS: view

Variants for CTSS Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CTSS Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
731670 Benign: not provided 150,751,772(-) A/T INTRON_VARIANT
777937 Benign: not provided 150,747,785(-) C/A SYNONYMOUS_VARIANT
rs1059604 - p.Ser161Thr
rs2230061 - p.Arg113Trp

Additional dbSNP identifiers (rs#s) for CTSS Gene

Structural Variations from Database of Genomic Variants (DGV) for CTSS Gene

Variant ID Type Subtype PubMed ID
esv1299298 CNV deletion 17803354
esv1542672 CNV deletion 17803354
esv2717818 CNV deletion 23290073
esv3587511 CNV loss 21293372
nsv1006838 CNV gain 25217958
nsv1008381 CNV gain 25217958
nsv1076858 CNV deletion 25765185
nsv1144404 CNV deletion 24896259
nsv437169 CNV loss 16327808
nsv952803 CNV deletion 24416366

Variation tolerance for CTSS Gene

Residual Variation Intolerance Score: 33.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.13; 93.87% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CTSS Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CTSS

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CTSS Gene

Disorders for CTSS Gene

MalaCards: The human disease database

(1) MalaCards diseases for CTSS Gene - From: DISEASES

Disorder Aliases PubMed IDs
dacryoadenitis
  • dacryocystitis
- elite association - COSMIC cancer census association via MalaCards
Search CTSS in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CTSS

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CTSS: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CTSS Gene

Publications for CTSS Gene

  1. CTSS promoter -25G/A: not a risk factor for CHD in Chinese. (PMID: 19593952) Sun A … Ge J (Acta cardiologica 2009) 3 23 41
  2. Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. (PMID: 1373132) Shi GP … Chapman HA (The Journal of biological chemistry 1992) 2 3 4
  3. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  4. Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk. (PMID: 19336475) Drenos F … Hingorani AD (Human molecular genetics 2009) 3 41
  5. Oxidative stress, telomere length and biomarkers of physical aging in a cohort aged 79 years from the 1932 Scottish Mental Survey. (PMID: 18977241) Starr JM … Deary IJ (Mechanisms of ageing and development 2008) 3 41

Products for CTSS Gene