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Granzyme B is a serine protease most commonly found in the granules of cytotoxic lymphocytes (CTLs), natural killer cells (NK cells) and cytotoxic T cells. It is secreted by these cells along with the pore forming protein perforin to mediate apoptosis in target cells. Granzyme B has also more recently found to be produced by a wide range of non-cytotoxic cells ranging from basophils and mast cells to smooth muscle cells. The secondary functions of granzyme B are also numerous. Granzyme B has shown to be involved in inducing inflammation by stimulating cytokine release and is also involved in extracellular matrix remodelling. Elevated levels of granzyme B are also implicated in a number of autoimmune diseases, several skin diseases, and type 1 diabetes. ==Structure== Granzyme B is encoded by GZMB on chromosome 14q.11.2 which is 3.2kb long consisting of 4 introns and 5 exons. It is one of the most abundant granzymes of which there are 5 in humans and 10 in mice.〔 Granzyme B is thought to have evolved from a granzyme H related precursor and is more effective at lower concentrations than the other granzymes. The enzyme is initially in an inactive precursor zymogen form, with an additional amino terminal peptide sequence.〔 This sequence can be cleaved by cathepsin C, removing 2 amino acids. Cathepsin H has also been reported to activate granzyme B.〔 Granzyme B's structure consists of two 6 stranded β sheets with 3 trans domain segments. In the granules of cytotoxic lymphocytes the enzyme can exist in two glycosylated forms. The high mannose form weighs 32kDa and the complex form, 35kDa.〔 Granzyme B contains the catalytic triad histidine-aspartic acid-serine in its active site and preferentially cleaves after an aspartic acid residue situated in the P1 position. The aspartic acid residue to be cleaved associates with an arginine residue in the enzyme's binding pocket. Granzyme B is active at a neutral pH and is therefore inactive in the acidic CTL granules. The enzyme is also rendered inactive when bound by serglycin in the granules to avoid apoptosis triggering inside the cytotoxic T cells themselves. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Granzyme B」の詳細全文を読む スポンサード リンク
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