1. 重组蛋白
  2. Enzymes & Regulators
  3. ADAMs/ADAMTSs

ADAMs/ADAMTSs  (去整合素和金属蛋白酶)

ADAM(A Disintegrin and Metallo-proteinases)和ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) 是基质锌依赖的金属蛋白酶,它们一起被称为 adamalysins。ADAM 金属蛋白酶是跨膜和分泌蛋白,而 ADAMTS 是分泌形式。 Adamalysins 主要存在于细胞外基质 (ECM) 中,它们可以通过间隔域 (SD) 或血小板结合蛋白基序 (TS) 与细胞外基质连接。所有的adamalysins 最初都是作为前体合成的,其中大部分可以被 furin 激活。它们通过信号通路、细胞粘附和迁移等活动在细胞表型调控中发挥重要作用。 ADAMs 属于metzincin 超家族。ADAMs由前肽结构域、金属蛋白酶结构域、disintegrin 结构域、半胱氨酸富有结构域、EGF 样结构域、跨膜结构域和细胞质尾部组成。ADAMs 在细胞与细胞的相互作用 (如粘附和融合)、信号传递和重要细胞因子、细胞因子受体和其他靶细胞的蛋白质水解 (也称为外域脱落)中发挥着重要作用。因此,ADAMs 是发育和稳态中许多调控过程的基础,它们的功能失调与癌症、心血管疾病、哮喘和阿尔茨海默病等病理状态有关。 ADAMTSs (TS=thrombospondin motifs) 是 ADAMs 的一个亲缘家族,也属于 metzincin 蛋白酶超家族。ADAMTS在组织形态发生和病理生理重塑、炎症和血管生物学中有多种作用。

ADAM (A Disintegrin and Metallo-proteinases) and ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs), which together are known as adamalysins, are the matrix zinc-dependent metalloproteinases. ADAM metalloproteinases are transmembrane and secreted proteins while ADAMTS are secretion forms. Adamalysins are mainly localized in the extracellular matrix (ECM), with which they can be linked by spacer domain (SD) or thrombospondin motif (TS). All adamalysins are initially synthesized as precursors, and most of them can be activated by furin. They play an important role in the cell phenotype regulation via their activities in signaling pathways, cell adhesion and migration. The ADAMs belongs to the metzincin superfamily. ADAMs consists of a prodomain, a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. ADAMs have essential functions in cell-cell interactions (such as adhesion and fusion), in signaling, and in proteolysis (also termed ectodomain shedding) of important cytokines, cytokine receptors, and other targets. Thus, ADAMs are fundamental to many control processes in development and homeostasis, and they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. ADAMTSs (TS=thrombospondin motifs) is a related family of ADAMs that also belong to the metzincin protease superfamily. ADAMTS have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology.

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