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Granzyme K (GrK) is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that is encoded by the ''GZMK''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
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 infec ...
s are a family of serine proteases which have various intracellular and extracellular roles. GrK is found in granules of
natural killer Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...
(NK) cells and
cytotoxic T lymphocytes A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
(CTLs), and is traditionally described as 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 is a protein that in humans is encoded by the ''PRF1'' gene and the ''Prf1'' gene in mice. Function Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK ce ...
at
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/B cell or Natural Killer cell. The interface was originally named after the neuronal syn ...
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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