General Information of Target

Target ID LDTP02271
Target Name Cathepsin G (CTSG)
Gene Name CTSG
Gene ID 1511
Synonyms
Cathepsin G; CG; EC 3.4.21.20) [Cleaved into: Cathepsin G, C-terminal truncated form]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVL
TAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRR
NRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYD
PRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRT
TMRSFKLLDQMETPL
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Peptidase S1 family
Subcellular location
Cell membrane
Function
Serine protease with trypsin- and chymotrypsin-like specificity. Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of its protease activity. Prefers Phe and Tyr residues in the P1 position of substrates but also cleaves efficiently after Trp and Leu. Shows a preference for negatively charged amino acids in the P2' position and for aliphatic amino acids both upstream and downstream of the cleavage site. Required for recruitment and activation of platelets which is mediated by the F2RL3/PAR4 platelet receptor. Binds reversibly to and stimulates B cells and CD4(+) and CD8(+) T cells. Also binds reversibly to natural killer (NK) cells and enhances NK cell cytotoxicity through its protease activity. Cleaves complement C3. Cleaves vimentin. Cleaves thrombin receptor F2R/PAR1 and acts as either an agonist or an inhibitor, depending on the F2R cleavage site. Cleavage of F2R at '41-Arg-|-Ser-42' results in receptor activation while cleavage at '55-Phe-|-Trp-56' results in inhibition of receptor activation. Cleaves the synovial mucin-type protein PRG4/lubricin. Cleaves and activates IL36G which promotes expression of chemokines CXCL1 and CXLC8 in keratinocytes. Cleaves IL33 into mature forms which have greater activity than the unprocessed form. Cleaves coagulation factor F8 to produce a partially activated form. Also cleaves and activates coagulation factor F10. Cleaves leukocyte cell surface protein SPN/CD43 to releases its extracellular domain and trigger its intramembrane proteolysis by gamma-secretase, releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus. Cleaves CCL5/RANTES to produce RANTES(4-68) lacking the N-terminal three amino acids which exhibits reduced chemotactic and antiviral activities. During apoptosis, cleaves SMARCA2/BRM to produce a 160 kDa cleavage product which localizes to the cytosol. Cleaves myelin basic protein MBP in B cell lysosomes at '224-Phe-|-Lys-225' and '248-Phe-|-Ser-249', degrading the major immunogenic MBP epitope and preventing the activation of MBP-specific autoreactive T cells. Cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce peptides which act on neutrophil N-formyl peptide receptors to enhance the release of CXCL2. Acts as a ligand for the N-formyl peptide receptor FPR1, enhancing phagocyte chemotaxis. Has antibacterial activity against the Gram-negative bacteria N.gonorrhoeae and P.aeruginosa. Likely to act against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2. Exhibits potent antimicrobial activity against the Gram-positive bacterium L.monocytogenes. Has antibacterial activity against the Gram-positive bacterium S.aureus and degrades S.aureus biofilms, allowing polymorphonuclear leukocytes to penetrate the biofilm and phagocytose bacteria. Has antibacterial activity against M.tuberculosis. Mediates CASP4 activation induced by the Td92 surface protein of the periodontal pathogen T.denticola, causing production and secretion of IL1A and leading to pyroptosis of gingival fibroblasts.
TTD ID
T86385
Uniprot ID
P08311
DrugMap ID
TTQAJF1
Ensemble ID
ENST00000216336.3
HGNC ID
HGNC:2532
ChEMBL ID
CHEMBL4071

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C49(2.50); C207(1.42)  LDD3334  [1]
4-Iodoacetamidophenylacetylene
 Probe Info 
N.A.  LDD0038  [2]
IA-alkyne
 Probe Info 
N.A.  LDD0166  [3]
Lodoacetamide azide
 Probe Info 
C142(0.00); C49(0.00)  LDD0037  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 JURL-MK1 C207(1.01)  LDD2410  [1]
 LDCM0023  KB03 K052 C142(1.44)  LDD2844  [1]
 LDCM0024  KB05 MOLM-16 C49(2.50); C207(1.42)  LDD3334  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cysteine-rich tail protein 1 (CYSRT1) CYSRT1 family A8MQ03
Keratin, type I cuticular Ha1 (KRT31) Intermediate filament family Q15323
Notch homolog 2 N-terminal-like protein A (NOTCH2NLA) NOTCH family Q7Z3S9
PRKCA-binding protein (PICK1) . Q9NRD5

The Drug(s) Related To This Target

Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Jnj-10311795 Small molecular drug D01YIO
Investigative
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
1,3-dibenzyl-[1,3]Diazetidine-2,4-dione Small molecular drug D0F2YC
Bis-napthyl Beta-ketophosphonic Acid Small molecular drug D05EGR
Pmid22595175c4g Small molecular drug D0C1NP
2-[3-({Methyl[1-(2-naphthoyl)Piperidin-4-yl]Amino}Carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic Acid . DB04016
Patented
Click To Hide/Show 9 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Peptide Analog 55 Peptide D0IL0Y
Peptide Analog 56 Peptide D0O8MI
Peptide Analog 58 Peptide D0ZA3S
Peptide Analog 60 Peptide D0K2RX
Peptide Analog 61 Peptide D09ZUJ
Peptide Analog 70 Peptide D0M6WD
Peptide Analog 57 Small molecular drug D0R7UI
Peptide Analog 59 Small molecular drug D00TCL
Peptide Analog 62 Small molecular drug D0ZW9O
Discontinued
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Aloxistatin Small molecular drug D0NJ1A
Dermolastin Small molecular drug D0B9EH

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060