Cathepsin G 

Cathepsin G is a pH-dependent serine protease. Cathepsin G hydrolyzes diverse synthetic and protein substrates and remodels extracellular matrix. Cathepsin G exerts immunomodulatory effects via recruiting phagocytes, enhancing T cell motility, activating ERK1/2 and p38 MAPK signaling, and mediating PKCζ membrane translocation. Cathepsin G regulates inflammatory responses by cleaving inflammatory mediators. Cathepsin G participates in vascular regulation by converting angiotensin I to angiotensin II. Cathepsin G induces PAR4-dependent platelet activation, facilitates platelet-neutrophil aggregation, and mediates VITT-related NETosis, thrombus formation. Cathepsin G can be used for the research of immune thrombotic thrombocytopenia, cardiovascular disease, and select autoimmune and inflammatory diseases^{[1][2][3][4][5][6]}.

Cathepsin G selectively hydrolyzes specific chymotrypsin-like substrates with characteristic kinetic properties for Bz-Tyr-OEt, but is inactive against trypsin, elastase and several chymotrypsin substrates. It exhibits optimal activity at pH 7.5-8.0 toward azo-casein and Bz-DL-Phe-2-ONap^[1].
Cathepsin G activity is differentially modulated by salts and inhibitors, and is immunologically identical to human leukocyte and neutrophil chymotrypsin-like enzymes. Its activity is promoted by MgCl2, NaCl and KCl, suppressed by CaCl2 and Na2SO4, and completely eliminated by high-concentration NaSCN without persistent functional impairment^[1].
Cathepsin G localizes to the granule fraction (44% of total activity) and undisrupted cell fraction in normal human peripheral blood neutrophils and is released in a dose-dependent manner from stimulated neutrophils, confirming its lysosomal granule localization^[2].
Cathepsin G efficiently generates angiotensin II and hydrolyzes the synthetic substrate BTEE, and shows identical electrophoretic mobility and antigenic identity to the angiotensin II-generating protease^[2].
Cathepsin G (10 μM; 20 min) mediates VITT plasma-induced prothrombotic responses, including platelet-dependent thrombus growth in healthy human whole blood under laminar flow, as well as neutrophil-platelet-based NET formation, tissue factor production and thrombin generation^[3].
Cathepsin G acts as a low-affinity agonist of human FPR with a K_d/EC₅₀ of 85 nM, activating chemotaxis and specific intracellular signaling pathways in human phagocytes and increasing T cell random motility^[4].
Cathepsin G (0-10 μg/mL; 0-30 minutes) potently activates washed human platelets, inducing concentration-dependent degranulation, up-regulation of P-selectin, GPIIb/IIIa complex, and GPIV, and near-complete down-regulation of GPIb^[5].
Cathepsin G modulates chemokine activity through proteolytic processing to produce chemoattractants for neutrophils, monocytes and antigen-presenting cells, and activates protease-activated receptor 4 and protease-activated receptor 2 to exert pro-inflammatory and pro-thrombotic effects in vitro^[6].
Cathepsin G regulates antigen processing and presentation to modulate T cell activation and immune responses, increases endothelial and epithelial cell permeability by disrupting junctional proteins, and activates pro-matrix metalloproteinases to mediate matrix remodeling and angiogenesis^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cathepsin G loss-of-function mutations confer resistance to collagen-induced arthritis and reduce tubular cell apoptosis and collagen deposition in renal ischemia/reperfusion injury in mice^[6].
Cathepsin G dose-dependently promotes antigen-specific antibody production via Th1 and Th2 pathways in BALB/c mice, and its inhibition or downregulation improves beta cell function, reduces CD4⁺ T cell activation and delays diabetes progression in non-obese diabetic mice^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

26815.87

C₁₁₆₃H₁₈₈₃N₃₈₃O₃₂₇S₁₁

107200-92-0

Liquid

Ile-Ile-Gly-Gly-Arg-Glu-Ser-Arg-Pro-His-Ser-Arg-Pro-Tyr-Met-Ala-Tyr-Leu-Gln-Ile-Gln-Ser-Pro-Ala-Gly-Gln-Ser-Arg-Cys-Gly-Gly-Phe-Leu-Val-Arg-Glu-Asp-Phe-Val-Leu-Thr-Ala-Ala-His-Cys-Trp-Gly-Ser-Asn-Ile-Asn-Val-Thr-Leu-Gly-Ala-His-Asn-Ile-Gln-Arg-Arg-Glu-Asn-Thr-Gln-Gln-His-Ile-Thr-Ala-Arg-Arg-Ala-Ile-Arg-His-Pro-Gln-Tyr-Asn-Gln-Arg-Thr-Ile-Gln-Asn-Asp-Ile-Met-Leu-Leu-Gln-Leu-Ser-Arg-Arg-Val-Arg-Arg-Asn-Arg-Asn-Val-Asn-Pro-Val-Ala-Leu-Pro-Arg-Ala-Gln-Glu-Gly-Leu-Arg-Pro-Gly-Thr-Leu-Cys-Thr-Val-Ala-Gly-Trp-Gly-Arg-Val-Ser-Met-Arg-Arg-Gly-Thr-Asp-Thr-Leu-Arg-Glu-Val-Gln-Leu-Arg-Val-Gln-Arg-Asp-Arg-Trp-Cys-Leu-Arg-Ile-Phe-Gly-Ser-Tyr-Asp-Pro-Arg-Arg-Gln-Ile-Cys-Val-Gly-Asp-Arg-Arg-Glu-Arg-Lys-Ala-Ala-Phe-Lys-Gly-Asp-Ser-Gly-Gly-Pro-Leu-Leu-Cys-Asn-Asn-Val-Ala-His-Gly-Ile-Val-Ser-Tyr-Gly-Lys-Ser-Ser-Gly-Val-Pro-Pro-Glu-Val-Phe-Thr-Arg-Val-Ser-Ser-Phe-Leu-Pro-Trp-Ile-Arg-Thr-Thr-Met-Arg-Ser-Phe-Lys-Leu-Leu-Asp-Gln-Met-Glu-Thr-Pro-Leu

IIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRWCLRIFGSYDPRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRTTMRSFKLLDQMETPL

Room temperature in continental US; may vary elsewhere.

• [1]. Starkey PM. Human cathepsin G: catalytic and immunological properties. Biochemical Journal, 1976, 155(2): 273-278.

  [2]. Tonnesen MG, et al. Identification of a human neutrophil angiotension II-generating protease as cathepsin G. J Clin Invest. 1982;69(1):25-30.

  [3]. Carnevale R, et al. PAD4-Induced NETosis Via Cathepsin G-Mediated Platelet-Neutrophil Interaction in ChAdOx1 Vaccine-Induced Thrombosis-Brief Report. Arterioscler Thromb Vasc Biol. 2023;43(10):e396-e403.  [Content Brief]

  [4]. Migeotte I, et al. Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev. 2006;17(6):501-519.

  [5]. LaRosa CA, et al. Human neutrophil cathepsin G is a potent platelet activator. J Vasc Surg. 1994;19(2):306-319.  [Content Brief]

  [6]. Gao S, et al. Cathepsin G and Its Role in Inflammation and Autoimmune Diseases. Arch Rheumatol. 2018;33(4):498-504. Published 2018 Jan 22.  [Content Brief]