CTSG

Description

The CTSG (cathepsin G) is a protein-coding gene located on chromosome 14.

Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.

== Structure ==

=== Gene === The CTSG gene is located at chromosome 14q11.2, consisting of 5 exons. Each residue of the catalytic triad is located on a separate exon. Five polymorphisms have been identified by scanning the entire coding region. Cathepsin G is one of those homologous protease that evolved from a common ancestor by gene duplication.

=== Protein === Cathepsin G is a 255-amino-acid-residue protein including an 18-residue signal peptide, a two-residue activation peptide at the N-terminus and a carboxy terminal extension. The activity of cathepsin G depends on a catalytic triad composed of aspartate, histidine and serine residues which are widely separated in the primary sequence but close to each other at the active site of the enzyme in the tertiary structure.

== Function == Cathepsin G has a specificity similar to that of chymotrypsin C, but it is most closely related to other immune serine proteases, such as neutrophil elastase and the granzymes.

Cathepsin G (CTSG) is a serine protease exhibiting trypsin- and chymotrypsin-like specificity. It displays antibacterial activity against both Gram-negative and Gram-positive bacteria, independent of its protease activity. It preferentially cleaves after Phe and Tyr residues in the P1 position of substrates but can also efficiently cleave after Trp and Leu. CTSG 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. CTSG plays a crucial role in the recruitment and activation of platelets, mediated by the F2RL3/PAR4 platelet receptor. It binds reversibly to and stimulates B cells, CD4(+) and CD8(+) T cells. CTSG also binds reversibly to natural killer (NK) cells and enhances NK cell cytotoxicity through its protease activity. CTSG cleaves complement C3, vimentin, and thrombin receptor F2R/PAR1. Cleavage of F2R at '41-Arg-|-Ser-42' activates the receptor, while cleavage at '55-Phe-|-Trp-56' inhibits receptor activation. It cleaves the synovial mucin-type protein PRG4/lubricin, activates IL36G, promoting the expression of chemokines CXCL1 and CXLC8 in keratinocytes. CTSG cleaves IL33 into mature forms with greater activity than the unprocessed form. It cleaves coagulation factor F8, generating a partially activated form and activates coagulation factor F10. CTSG cleaves the leukocyte cell surface protein SPN/CD43, releasing its extracellular domain and triggering its intramembrane proteolysis by gamma-secretase, releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus. It cleaves CCL5/RANTES, producing RANTES(4-68) lacking the N-terminal three amino acids, which exhibits reduced chemotactic and antiviral activities. During apoptosis, CTSG cleaves SMARCA2/BRM, producing a 160 kDa cleavage product that localizes to the cytosol. It cleaves myelin basic protein MBP in B cell lysosomes, degrading the major immunogenic MBP epitope and preventing the activation of MBP-specific autoreactive T cells. CTSG cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce peptides that act on neutrophil N-formyl peptide receptors to enhance the release of CXCL2. It acts as a ligand for the N-formyl peptide receptor FPR1, enhancing phagocyte chemotaxis. CTSG exhibits antibacterial activity against the Gram-negative bacteria N.gonorrhoeae and P.aeruginosa, potentially acting against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2. It demonstrates potent antimicrobial activity against the Gram-positive bacterium L.monocytogenes, exhibits antibacterial activity against the Gram-positive bacterium S.aureus, and degrades S.aureus biofilms, allowing polymorphonuclear leukocytes to penetrate the biofilm and phagocytose bacteria. CTSG also displays antibacterial activity against M.tuberculosis. It mediates CASP4 activation induced by the Td92 surface protein of the periodontal pathogen T.denticola, leading to the production and secretion of IL1A and subsequent pyroptosis of gingival fibroblasts. CTSG interacts with CASP4, an interaction promoted by the Td92 surface protein of the periodontal pathogen T.denticola, leading to CASP4 activation. It also interacts with M.tuberculosis protein Rv3364c and S.aureus EapH1, where EapH1 acts as a reversible inhibitor of CTSG activity.

CTSG is also known as CATG, CG.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing