Granzyme K (GrK) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is encoded by the ''GZMK''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

on chromosome 5 in humans.

Granzyme Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infe ...

s are a family of

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...

s which have various intracellular and extracellular roles. GrK is found in granules of

natural killer Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are par ...

(NK) cells and cytotoxic T lymphocytes (CTLs), and is traditionally described as being cytotoxic towards targeted foreign, infected, or cancerous cells. NK cells and CTLs can induce apoptosis through the granule secretory pathway, which involves the secretion of granzymes along with

perforin Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs). ...

immunological synapse In immunology, an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell, B cell, or natural killer cell. The interface was originally named after the neurona ...

s. Intracellularly, GrK may cleave a variety of substrates, such as the nucleosome assembly protein (NAP), HMG2, and Ape1 in the ER-associated SET complex, along with other targets that have downstream cytotoxic effects. Compared to ''in vitro'' studies of GrK cytotoxicity in rats and humans, ''in vitro'' mouse studies show no cytotoxic potential in the absence of perforin, making the role of GrK controversial. ''In vitro'' studies show potential extracellular targets for GrK such as the cleavage and activation of protease activated receptors (PAR)-1 and PAR-2. Grk binds lipopolysaccharides (LPS) ''in vitro'' separately from GrK's catalytic activity. Both PAR and LPS activation by GrK induce cytokine production in human ''in vitro'' studies. GrK is important in bacterial and viral infection control. GrK-expressing CD8+ T cells may be associated with inflammation and aging.

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Further reading