Details for: CTSG

Gene ID: 1511

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: CTSG

Ensembl ID: ENSG00000100448

Description: cathepsin G

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • promyelocyte CL0000836
    CSI 19.52
    rCSI 28.16%
    PRS 97.56
  • granulocyte monocyte progenitor cell CL0000557
    CSI 12.41
    rCSI 10.74%
    PRS 97.87
  • common dendritic progenitor CL0001029
    CSI 8.93
    rCSI 11.21%
    PRS 98.72
  • common myeloid progenitor CL0000049
    CSI 8.23
    rCSI 6.65%
    PRS 97.97
  • basal cell of epidermis CL0002187
    CSI 6.49
    rCSI 11.5%
    PRS 76.7
  • promonocyte CL0000559
    CSI 6.32
    rCSI 10.82%
    PRS 97.66
  • basophil CL0000767
    CSI 5.93
    rCSI 12.54%
    PRS 98.01
  • mast cell CL0000097
    CSI 5.09
    rCSI 10.99%
    PRS 92.82
  • granulocyte CL0000094
    CSI 4.69
    rCSI 7.17%
    PRS 98.36
  • progenitor cell CL0011026
    CSI 4.52
    rCSI 9.61%
    PRS 93.15
  • neutrophil CL0000775
    CSI 4.15
    rCSI 23.21%
    PRS 94.54
  • eosinophil CL0000771
    CSI 1.02
    rCSI 6.72%
    PRS 99.05
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.77
    rCSI 4%
    PRS 99.37
  • myelocyte CL0002193
    CSI 0.6
    rCSI 3.91%
    PRS 98.55

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 [CTSG](/details-gene/1511), or Cathepsin G, is a protein-coding gene located on chromosome 14q12 that encodes a highly reactive serine protease. This enzyme is a critical component of the innate immune system, primarily stored within the azurophil granules of myeloid cells ([GO:0035578](https://www.ebi.ac.uk/QuickGO/term/GO:0035578)). Expression data from an **Overall** context reveals that [CTSG](/details-gene/1511) is a defining marker for the myeloid lineage, showing exceptionally high significance in precursor cells such as the [promyelocyte](/details-cell/CL0000836) (CSI: 19.52) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 12.41), as well as in mature effector cells like the [neutrophil](/details-cell/CL0000775). Functionally, [CTSG](/details-gene/1511) is involved in host defense through direct antimicrobial activity ([GO:0019731](https://www.ebi.ac.uk/QuickGO/term/GO:0019731)), tissue remodeling via extracellular matrix degradation ([GO:0022617](https://www.ebi.ac.uk/QuickGO/term/GO:0022617)), and modulation of inflammatory responses, including platelet activation ([GO:0030168](https://www.ebi.ac.uk/QuickGO/term/GO:0030168)). ## Cellular Roles and Expression Landscape The expression profile of [CTSG](/details-gene/1511) firmly establishes its role as a key protein in the development and function of the myeloid branch of the hematopoietic system. Its significance is highest in the earliest stages of myelopoiesis, including in the [common myeloid progenitor](/details-cell/CL0000049) and the [granulocyte monocyte progenitor cell](/details-cell/CL0000557). This high-level expression is maintained and peaks during intermediate differentiation in the [promyelocyte](/details-cell/CL0000836), the stage at which primary (azurophil) granules are synthesized. In mature circulating cells, [CTSG](/details-gene/1511) remains a significant marker for several innate immune effector cells. It is highly characteristic of [basophil](/details-cell/CL0000767)s, [mast cell](/details-cell/CL0000097)s, and [granulocyte](/details-cell/CL0000094)s, particularly [neutrophil](/details-cell/CL0000775)s, where it is a major constituent of granules released upon activation ([R-HSA-6798695](https://reactome.org/content/detail/R-HSA-6798695)). This expression pattern is consistent with its function as a ready-to-deploy weapon against invading pathogens and as a modulator of the inflammatory microenvironment. Interestingly, a high significance score is also noted in the [basal cell of epidermis](/details-cell/CL0002187), suggesting a potential, less-characterized role in cutaneous defense or homeostasis. ## Pathways and Molecular Function Functionally, [CTSG](/details-gene/1511) operates primarily as a serine-type endopeptidase ([GO:0004252](https://www.ebi.ac.uk/QuickGO/term/GO:0004252)). Its biological activities are broad and central to innate immunity and inflammation. * **Host Defense:** [CTSG](/details-gene/1511) is integral to the [Innate immune system](/details-gene/R-HSA-168249) ([R-HSA-168249](https://reactome.org/content/detail/R-HSA-168249)). It participates directly in antimicrobial responses, including the defense against gram-positive ([GO:0050830](https://www.ebi.ac.uk/QuickGO/term/GO:0050830)) and gram-negative ([GO:0050829](https://www.ebi.ac.uk/QuickGO/term/GO:0050829)) bacteria. Studies have identified its direct bactericidal activity against various pathogens ([Link](https://doi.org/10.1073/pnas.86.14.5610), [Link](https://doi.org/10.1099/00221287-136-6-997)). This is supported by its inclusion in the [Antimicrobial peptides](/details-gene/R-HSA-6803157) pathway ([R-HSA-6803157](https://reactome.org/content/detail/R-HSA-6803157)). * **Inflammation and Tissue Remodeling:** Upon [neutrophil](/details-cell/CL0000775) degranulation, [CTSG](/details-gene/1511) is released into the extracellular space where it can cleave a wide range of substrates. It contributes to the [Degradation of the extracellular matrix](/details-gene/R-HSA-1474228) ([R-HSA-1474228](https://reactome.org/content/detail/R-HSA-1474228)), which facilitates immune cell migration but can also cause tissue damage if unregulated. Furthermore, it modulates inflammatory signaling by processing cytokines ([GO:0019221](https://www.ebi.ac.uk/QuickGO/term/GO:0019221)) and chemoattractants, contributing to [monocyte chemotaxis](/details-cell/GO:0002548) ([GO:0002548](https://www.ebi.ac.uk/QuickGO/term/GO:0002548)). * **Hemostasis and Thrombosis:** [CTSG](/details-gene/1511) is a potent platelet agonist ([Link](https://doi.org/10.1042/bj2510293)), directly linking the innate immune response with coagulation. Its ability to induce [platelet activation](/details-cell/GO:0030168) ([GO:0030168](https://www.ebi.ac.uk/QuickGO/term/GO:0030168)) highlights its role in the pathophysiology of thrombo-inflammatory conditions. * **Hormone Processing:** Beyond immunity, [CTSG](/details-gene/1511) is involved in peptide hormone metabolism, notably in the [Metabolism of angiotensinogen to angiotensins](/details-gene/R-HSA-2022377) ([R-HSA-2022377](https://reactome.org/content/detail/R-HSA-2022377)), suggesting a potential role in blood pressure regulation. ## Research Directions Based on its expression profile and known functions, several research avenues for [CTSG](/details-gene/1511) can be proposed. 1. **Role in Myeloid Differentiation:** The exceptionally high expression of [CTSG](/details-gene/1511) in myeloid progenitor cells, such as the [promyelocyte](/details-cell/CL0000836), suggests it may be more than just a cargo protein for mature cells. It is hypothesized that [CTSG](/details-gene/1511) plays an active enzymatic role within progenitor cells, possibly by processing key transcription factors or cell surface receptors that guide granulocytic differentiation. 2. **Contribution to Thrombo-inflammation:** Given its potent platelet-activating properties ([Link](https://doi.org/10.1042/bj2510293)) and its role in extracellular matrix degradation, it is hypothesized that uncontrolled [CTSG](/details-gene/1511) activity at sites of vascular injury or chronic inflammation is a key driver of immunothrombosis, contributing to pathologies like atherosclerosis, deep vein thrombosis, and lung injury. 3. **Function in Epidermal Biology:** The significant expression in the [basal cell of epidermis](/details-cell/CL0002187) is intriguing and warrants investigation. It is hypothesized that epidermal [CTSG](/details-gene/1511) serves as a localized, non-hematopoietic component of the skin's innate defense system, potentially involved in processing antimicrobial peptides or modulating keratinocyte proliferation and differentiation during wound healing. * **Experimental Approach:** To test the first hypothesis regarding its role in differentiation, a compelling experiment would be to use CRISPR-Cas9 to knock out [CTSG](/details-gene/1511) in primary human CD34+ hematopoietic stem and progenitor cells. These modified cells could then be cultured *in vitro* under conditions that promote myeloid differentiation. The impact of [CTSG](/details-gene/1511) loss could be assessed by single-cell RNA sequencing (scRNA-seq) and flow cytometry at various time points to determine if the differentiation trajectory is skewed, delayed, or arrested, and to identify potential molecular pathways that are perturbed. * **Therapeutic Potential:** As an extracellular protease with a central role in inflammation and tissue destruction, [CTSG](/details-gene/1511) is an attractive therapeutic target. Its activity is implicated in the pathology of numerous inflammatory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and rheumatoid arthritis. Therefore, the development of potent and specific small-molecule or antibody-based **inhibitors** of [CTSG](/details-gene/1511) represents a promising strategy to mitigate neutrophil-driven tissue damage and modulate inflammation in these conditions. The high specificity of its expression to the myeloid lineage suggests that systemic inhibition may have a favorable safety profile with limited off-target effects.

Genular Protein ID: 3261836550

Symbol: CATG_HUMAN

Name: Cathepsin G

UniProtKB Accession Codes:

P08311 Q6IBJ6 Q9UCA5 Q9UCU6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 GO 41 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 14 PDBsum 14 PIR 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 9 RefSeq 1 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3304423

Title: Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases.

PubMed ID: 3304423

DOI: 10.1021/bi00382a032

PubMed ID: 2569462

Title: Genomic organization and chromosomal localization of the human cathepsin G gene.

PubMed ID: 2569462

DOI: 10.1016/s0021-9258(18)80012-6

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

PubMed ID: 8194606

Title: Identification of the U-937 membrane-associated proteinase interacting with the V3 loop of HIV-1 gp120 as cathepsin G.

PubMed ID: 8194606

DOI: 10.1016/0014-5793(94)00410-2

PubMed ID: 3799965

Title: Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil cathepsin G from normal donors.

PubMed ID: 3799965

DOI: 10.1016/0003-2697(86)90612-3

PubMed ID: 2501794

Title: Antibiotic proteins of human polymorphonuclear leukocytes.

PubMed ID: 2501794

DOI: 10.1073/pnas.86.14.5610

PubMed ID: 1861080

Title: Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G.

PubMed ID: 1861080

PubMed ID: 7897245

Title: Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis.

PubMed ID: 7897245

DOI: 10.1016/0022-1759(94)00295-8

PubMed ID: 26274980

Title: Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G.

PubMed ID: 26274980

DOI: 10.3390/biom5031832

PubMed ID: 3390156

Title: Cathepsin G is a strong platelet agonist released by neutrophils.

PubMed ID: 3390156

DOI: 10.1042/bj2510293

PubMed ID: 2383548

Title: An unusual specificity in the activation of neutrophil serine proteinase zymogens.

PubMed ID: 2383548

DOI: 10.1021/bi00474a013

PubMed ID: 2116408

Title: Identification of the primary antimicrobial domains in human neutrophil cathepsin G.

PubMed ID: 2116408

DOI: 10.1016/s0021-9258(18)77388-2

PubMed ID: 2117044

Title: Listericidal activity of human neutrophil cathepsin G.

PubMed ID: 2117044

DOI: 10.1099/00221287-136-6-997

PubMed ID: 2126324

Title: Molecular mechanism for the antigonococcal action of lysosomal cathepsin G.

PubMed ID: 2126324

DOI: 10.1111/j.1365-2958.1990.tb00706.x

PubMed ID: 1937776

Title: Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa.

PubMed ID: 1937776

DOI: 10.1128/iai.59.11.4193-4200.1991

PubMed ID: 7842483

Title: Stimulation of human lymphocytes by cathepsin G.

PubMed ID: 7842483

DOI: 10.1016/0008-8749(95)80005-4

PubMed ID: 7744748

Title: Proteolysis of the human platelet and endothelial cell thrombin receptor by neutrophil-derived cathepsin G.

PubMed ID: 7744748

DOI: 10.1074/jbc.270.19.11168

PubMed ID: 7499346

Title: Human cathepsin G lacking functional glycosylation site is proteolytically processed and targeted for storage in granules after transfection to the rat basophilic/mast cell line RBL or the murine myeloid cell line 32D.

PubMed ID: 7499346

DOI: 10.1074/jbc.270.47.28413

PubMed ID: 8920993

Title: Activation of Mac-1 (CD11b/CD18)-bound factor X by released cathepsin G defines an alternative pathway of leucocyte initiation of coagulation.

PubMed ID: 8920993

DOI: 10.1042/bj3190873

PubMed ID: 9000539

Title: Cathepsin G binds to human lymphocytes.

PubMed ID: 9000539

DOI: 10.1002/jlb.61.1.73

PubMed ID: 9536127

Title: Cathepsin G enhances human natural killer cytotoxicity.

PubMed ID: 9536127

DOI: 10.1046/j.1365-2567.1998.00397.x

PubMed ID: 10702240

Title: Cathepsin G activates protease-activated receptor-4 in human platelets.

PubMed ID: 10702240

DOI: 10.1074/jbc.275.10.6819

PubMed ID: 11259672

Title: The human brm protein is cleaved during apoptosis: the role of cathepsin G.

PubMed ID: 11259672

DOI: 10.1073/pnas.071057398

PubMed ID: 15385470

Title: The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli.

PubMed ID: 15385470

DOI: 10.1128/iai.72.10.5712-5721.2004

PubMed ID: 15210802

Title: Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor.

PubMed ID: 15210802

DOI: 10.4049/jimmunol.173.1.428

PubMed ID: 15100291

Title: Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes.

PubMed ID: 15100291

DOI: 10.4049/jimmunol.172.9.5495

PubMed ID: 16963625

Title: N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related analogs into a truncated 4-68 variant.

PubMed ID: 16963625

DOI: 10.1189/jlb.0406290

PubMed ID: 18586676

Title: The cleavage of neutrophil leukosialin (CD43) by cathepsin G releases its extracellular domain and triggers its intramembrane proteolysis by presenilin/gamma-secretase.

PubMed ID: 18586676

DOI: 10.1074/jbc.m710286200

PubMed ID: 18217133

Title: Cathepsin G, a leukocyte protease, activates coagulation factor VIII.

PubMed ID: 18217133

DOI: 10.1160/th07-08-0495

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22275911

Title: Inhibition of the plasma-membrane-associated serine protease cathepsin G by Mycobacterium tuberculosis Rv3364c suppresses caspase-1 and pyroptosis in macrophages.

PubMed ID: 22275911

DOI: 10.3389/fmicb.2011.00281

PubMed ID: 22879591

Title: Cathepsin G-regulated release of formyl peptide receptor agonists modulate neutrophil effector functions.

PubMed ID: 22879591

DOI: 10.1074/jbc.m112.394452

PubMed ID: 22307629

Title: IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G.

PubMed ID: 22307629

DOI: 10.1073/pnas.1115884109

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 29077095

Title: Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts.

PubMed ID: 29077095

DOI: 10.1038/cdd.2017.167

PubMed ID: 29652924

Title: Extended cleavage specificity of human neutrophil cathepsin G: A low activity protease with dual chymase and tryptase-type specificities.

PubMed ID: 29652924

DOI: 10.1371/journal.pone.0195077

PubMed ID: 30804664

Title: Cathepsin G cleaves and activates IL-36gamma and promotes the inflammation of psoriasis.

PubMed ID: 30804664

DOI: 10.2147/dddt.s194765

PubMed ID: 32144329

Title: Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin.

PubMed ID: 32144329

DOI: 10.1038/s41598-020-61161-5

PubMed ID: 33589665

Title:

PubMed ID: 33589665

DOI: 10.1038/s41598-020-77619-5

PubMed ID: 32995850

Title: Cathepsin G Degrades Staphylococcus aureus Biofilms.

PubMed ID: 32995850

DOI: 10.1093/infdis/jiaa612

PubMed ID: 8896442

Title: The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.

PubMed ID: 8896442

DOI: 10.1002/j.1460-2075.1996.tb00933.x

PubMed ID: 11942800

Title: Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design.

PubMed ID: 11942800

DOI: 10.1021/ja017506h

PubMed ID: 15741158

Title: A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo.

PubMed ID: 15741158

DOI: 10.1074/jbc.m501302200

PubMed ID: 32303641

Title: Local structural plasticity of the Staphylococcus aureus evasion protein EapH1 enables engagement with multiple neutrophil serine proteases.

PubMed ID: 32303641

DOI: 10.1074/jbc.ra120.013601

PubMed ID: 8454293

Title: Sequence variant of the human cathepsin G gene.

PubMed ID: 8454293

DOI: 10.1007/bf00230230

Sequence Information:

  • Length: 255
  • Mass: 28837
  • Checksum: 6228E741E6A43889
  • Sequence:
    • MQPLLLLLAF LLPTGAEAGE IIGGRESRPH SRPYMAYLQI QSPAGQSRCG GFLVREDFVL 
TAAHCWGSNI NVTLGAHNIQ RRENTQQHIT ARRAIRHPQY NQRTIQNDIM LLQLSRRVRR 
NRNVNPVALP RAQEGLRPGT LCTVAGWGRV SMRRGTDTLR EVQLRVQRDR QCLRIFGSYD 
PRRQICVGDR RERKAAFKGD SGGPLLCNNV AHGIVSYGKS SGVPPEVFTR VSSFLPWIRT 
TMRSFKLLDQ METPL