Details for: CTSO

Gene ID: 1519

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CTSO

Ensembl ID: ENSG00000256043

Description: cathepsin O

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • plasmacytoid dendritic cell, human CL0001058
    CSI 10.45
    rCSI 7.3%
    PRS 96.65
  • naive B cell CL0000788
    CSI 5.63
    rCSI 4.83%
    PRS 96.66
  • fibroblast of lung CL0002553
    CSI 3.68
    rCSI 3.43%
    PRS 95.66
  • mucosal invariant T cell CL0000940
    CSI 3.49
    rCSI 2.82%
    PRS 97.39
  • bronchus fibroblast of lung CL2000093
    CSI 3.16
    rCSI 2.56%
    PRS 94.35
  • Kupffer cell CL0000091
    CSI 2.99
    rCSI 6.83%
    PRS 95.54
  • epithelial cell of lung CL0000082
    CSI 2.89
    rCSI 2.4%
    PRS 95.48
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.83
    rCSI 4.52%
    PRS 95.92
  • hepatic stellate cell CL0000632
    CSI 2.79
    rCSI 10.47%
    PRS 92.06
  • multi-ciliated epithelial cell CL0005012
    CSI 2.78
    rCSI 2.78%
    PRS 90.09
  • hepatocyte CL0000182
    CSI 2.75
    rCSI 4.93%
    PRS 93.06
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.6
    rCSI 2%
    PRS 96.79
  • intestinal epithelial cell CL0002563
    CSI 2.32
    rCSI 2.42%
    PRS 92.72
  • ciliated epithelial cell CL0000067
    CSI 2.19
    rCSI 1.92%
    PRS 87.92
  • dendritic cell, human CL0001056
    CSI 1.88
    rCSI 2.88%
    PRS 97.78
  • placental villous trophoblast CL2000060
    CSI 1.66
    rCSI 2.56%
    PRS 93.07
  • blood vessel smooth muscle cell CL0019018
    CSI 1.55
    rCSI 12.61%
    PRS 93.63
  • keratocyte CL0002363
    CSI 1.53
    rCSI 3.69%
    PRS 95.15
  • vascular associated smooth muscle cell CL0000359
    CSI 1.53
    rCSI 4.95%
    PRS 93.5
  • mesenchymal cell CL0008019
    CSI 0.92
    rCSI 2.33%
    PRS 91.49
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.81
    rCSI 2.35%
    PRS 94.08
  • podocyte CL0000653
    CSI 0.77
    rCSI 3.41%
    PRS 94.53

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CTSO](/details-gene/1519), or Cathepsin O, is a protein-coding gene that encodes a cysteine-type endopeptidase. Functionally, it is involved in [proteolysis](/details-go/GO:0006508) and is localized to both the [lysosome](/details-go/GO:0005764) and the [extracellular space](/details-go/GO:0005615). Its expression pattern suggests a significant role within the immune system, particularly in antigen-presenting cells. **Overall**, it shows the highest significance as a marker for [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 10.45) and [naive B cell](/details-cell/CL0000788) (CSI: 5.63), consistent with its involvement in the [Adaptive immune system](/details-reactome/R-HSA-1280218) and [Mhc class ii antigen presentation](/details-reactome/R-HSA-2132295) pathways. The gene also shows notable expression in various non-immune cell types, including [fibroblast of lung](/details-cell/CL0002553) and [epithelial cell of lung](/details-cell/CL0000082), indicating potentially broader roles in tissue homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [CTSO](/details-gene/1519) highlights its dual role in both the immune system and general tissue biology. Its most significant expression is found in key cell types of the adaptive immune system. It serves as a defining marker for [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and is also highly significant in [naive B cell](/details-cell/CL0000788), [mucosal invariant T cell](/details-cell/CL0000940), [Kupffer cell](/details-cell/CL0000091), and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396). This strong association with antigen-presenting cells and lymphocytes underscores its importance in immune surveillance and response. Beyond the immune compartment, [CTSO](/details-gene/1519) demonstrates a widespread, albeit lower, significance in various stromal and epithelial cells. This includes notable expression in [fibroblast of lung](/details-cell/CL0002553), [epithelial cell of lung](/details-cell/CL0000082), [hepatic stellate cell](/details-cell/CL0000632), and [hepatocyte](/details-cell/CL0000182). This broader expression pattern suggests that in addition to its specialized immunological functions, [CTSO](/details-gene/1519) may participate in more fundamental cellular processes, such as protein turnover or tissue remodeling in multiple organs. Initial cloning and expression analysis from a breast carcinoma also point to its relevance outside of hematopoietic lineages [Link](https://doi.org/10.1016/s0021-9258(18)47135-9). ## Pathways and Molecular Function Functionally, [CTSO](/details-gene/1519) is annotated with [cysteine-type endopeptidase activity](/details-go/GO:0004197), enabling it to perform [proteolysis](/details-go/GO:0006508). This catalytic activity is central to its biological roles. The gene's involvement in the [Mhc class ii antigen presentation](/details-reactome/R-HSA-2132295) pathway is a direct consequence of this function, where it likely participates in the lysosomal degradation of foreign proteins into peptides suitable for loading onto MHC class II molecules. This is highly consistent with its prominent expression in professional antigen-presenting cells like [dendritic cell, human](/details-cell/CL0001056) and [Kupffer cell](/details-cell/CL0000091). The dual localization of the CTSO protein to the [lysosome](/details-go/GO:0005764) and the [extracellular space](/details-go/GO:0005615) suggests it has both intracellular and extracellular functions. Intracellularly, it contributes to protein catabolism within the lysosome. Extracellularly, it may be involved in remodeling the extracellular matrix or processing cell surface proteins, a function that could be particularly relevant in the context of its expression in [fibroblast of lung](/details-cell/CL0002553) and [hepatic stellate cell](/details-cell/CL0000632). ## Research Directions Based on its function and expression profile, [CTSO](/details-gene/1519) presents several avenues for future research, particularly concerning its precise roles in immunity and tissue biology. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and its function as a protease, it is hypothesized that **[CTSO](/details-gene/1519) is a specialized lysosomal protease critical for processing viral or self-antigens for MHC class II presentation in pDCs, thereby shaping the T-cell response in antiviral immunity and autoimmunity.** 2. Considering its expression in stromal cells like [fibroblast of lung](/details-cell/CL0002553) and its secretion into the [extracellular space](/details-go/GO:0005615), a second hypothesis is that **extracellular [CTSO](/details-gene/1519) contributes to pathological tissue remodeling in diseases like pulmonary fibrosis by degrading specific extracellular matrix components, promoting fibroblast activation and migration.** **Experimental Approach:** To test the first hypothesis regarding the role of [CTSO](/details-gene/1519) in antigen presentation, a compelling experiment would be to use CRISPR-Cas9 to knock out [CTSO](/details-gene/1519) in primary human pDCs or a relevant cell line. These knockout cells, alongside wild-type controls, would be pulsed with a model viral protein (e.g., influenza hemagglutinin). The repertoire of peptides bound to MHC class II molecules could then be analyzed using immunopeptidomics (elution followed by mass spectrometry). A significant alteration in the presented peptide landscape in knockout cells would provide direct evidence for the role of [CTSO](/details-gene/1519) in processing that specific antigen. This could be complemented with functional assays measuring the ability of these pDCs to activate antigen-specific T helper cells. **Therapeutic Potential:** As an enzyme, [CTSO](/details-gene/1519) is a potentially druggable target. Given its role in antigen presentation, **inhibition** of CTSO could be a therapeutic strategy in autoimmune diseases driven by aberrant T-cell responses, such as systemic lupus erythematosus, where pDCs are known to play a pathogenic role. A specific small-molecule inhibitor could reduce the presentation of self-antigens, thereby dampening the autoimmune reaction. However, its expression in non-immune cells raises the possibility of off-target effects, suggesting that targeted delivery or careful patient selection would be crucial for minimizing adverse events.

Genular Protein ID: 1789404409

Symbol: CATO_HUMAN

Name: Cathepsin O

UniProtKB Accession Codes:

P43234

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 2 Ensembl 2 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7929457

Title: Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues.

PubMed ID: 7929457

DOI: 10.1016/s0021-9258(18)47135-9

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 321
  • Mass: 35958
  • Checksum: F48011ECA9E0BC45
  • Sequence:
    • MDVRALPWLP WLLWLLCRGG GDADSRAPFT PTWPRSRERE AAAFRESLNR HRYLNSLFPS 
ENSTAFYGIN QFSYLFPEEF KAIYLRSKPS KFPRYSAEVH MSIPNVSLPL RFDWRDKQVV 
TQVRNQQMCG GCWAFSVVGA VESAYAIKGK PLEDLSVQQV IDCSYNNYGC NGGSTLNALN 
WLNKMQVKLV KDSEYPFKAQ NGLCHYFSGS HSGFSIKGYS AYDFSDQEDE MAKALLTFGP 
LVVIVDAVSW QDYLGGIIQH HCSSGEANHA VLITGFDKTG STPYWIVRNS WGSSWGVDGY 
AHVKMGSNVC GIADSVSSIF V