Recombinant Human Granzyme K (GZMK)

Function

Serine protease that initiates the GZMK pathway of the complement system, a cascade of proteins directly activated by CD8(+) T-cells that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:3262682, PubMed:39814882, PubMed:39914456). GZMK is specifically secreted by CD8(+) T-cells and mediates both recognition and initiation steps of GZMK complement pathway (PubMed:39914456). First acts as a pattern recognition receptor, which specifically recognizes and binds heparan sulfate glycosaminoglycans on the pathogen surface to drive opsonization (PubMed:39914456). It then initiates the complement pathway cascade by catalyzing cleavage and activation of C2 and C4, the next components of the complement pathway (PubMed:39814882, PubMed:39914456). GZMK-mediated complement activation is an important contributor to tissue inflammation (PubMed:24711407, PubMed:33271118, PubMed:35704599, PubMed:39614076, PubMed:39814882, PubMed:39914456). Also able to cleave and activate F2R/PAR1 and PAR2/F2RL1, possibly promoting interleukin release (PubMed:21760880, PubMed:26936634, PubMed:35881628). May also regulate apoptosis by catalyzing cleavage and activation of BID, thereby promoting cytochrome C release from mitochrondria (PubMed:17308307)

Subcellular Location

Secreted; Cell surface; Cytoplasmic granule

Tissue Specificity

Specifically expressed by CD8(+) T-cells

• Przetak M.M. et al. Cloning of cDNA for human granzyme 3. — FEBS Lett. (1995)
• Sayers T.J. et al. Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3. — J. Leukoc. Biol. (1996)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hameed A. et al. Characterization of three serine esterases isolated from human IL-2 activated killer cells. — J. Immunol. (1988)
• Shi L. et al. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. — J. Exp. Med. (1992)
• Wilharm E. et al. Generation of catalytically active granzyme K from Escherichia coli inclusion bodies and identification of efficient granzyme K inhibitors in human plasma. — J. Biol. Chem. (1999)