Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
Hum Genomics. 2009 Oct;4(1):43-55. doi: 10.1186/1479-7364-4-1-43.
The 'A-disintegrin and metalloproteinase' ( ADAM ) and 'A-disintegrin and metalloproteinase with thrombospondin motifs' ( ADAMTS ) genes make up two similar, yet distinct, gene families. The human and mouse genomes contain 21 and 24 putatively functional protein-coding ADAM genes, respectively, and 24 versus 32 putatively functional protein-coding ADAMTS genes, respectively. Analysis of evolutionary divergence shows that both families are unique. Each of the two families can be separated, if need be, into groups of more closely related members: six subfamilies for ADAM , four subfamilies for ADAMTS. The presence of both disintegrin and peptidase domains within the ADAM and ADAMTS proteins implies multiple biological roles within the cell. Membrane-anchored ADAM proteins are best known for their role in activating zymogens--including tumour necrosis factor-alpha, epidermal growth factor (EGF) and amyloid precursor protein (APP). ADAM proteins can also participate in cell adhesion via their interaction with integrins in neighbouring cells. ADAMTS are secreted proteins that participate in extracellular matrix maintenance by way of their cleavage of procollagen and proteoglycans. ADAMTS proteins also are involved in coagulation by cleaving von Willibrand factor precursor protein. ADAM and ADAMTS proteins participate in a wide range of cellular processes, including cell adhesion and migration, ectodomain shedding, proteolysis, development, ovulation and angiogenesis. Because these enzymes are believed to play an important role in a number of pathologies, including Alzheimer's disease, rheumatoid arthritis, atherosclerosis, asthma and cancer progression, the products of the ADAM and ADAMTS genes represent promising drug targets for the prevention and management of a number of human diseases.
“解整合素和金属蛋白酶”（ADAM）和“解整合素和金属蛋白酶与血小板反应蛋白基序”（ADAMTS）基因组成两个相似但不同的基因家族。人类和鼠基因组分别包含 21 个和 24 个推定的具有功能的蛋白编码 ADAM 基因，分别包含 24 个和 32 个推定的具有功能的蛋白编码 ADAMTS 基因。进化分歧分析表明，这两个家族都是独特的。如果需要，可以将这两个家族分别分为更密切相关的成员组：ADAM 有六个亚家族，ADAMTS 有四个亚家族。ADAM 和 ADAMTS 蛋白内的整合素和肽酶结构域的存在暗示了细胞内的多种生物学作用。膜锚定 ADAM 蛋白以其在激活酶原中的作用而闻名，包括肿瘤坏死因子-α、表皮生长因子（EGF）和淀粉样前体蛋白（APP）。ADAM 蛋白还可以通过与相邻细胞中的整合素相互作用参与细胞黏附。ADAMTS 是分泌蛋白，通过切割前胶原和蛋白聚糖参与细胞外基质的维持。ADAMTS 蛋白还通过切割 von Willebrand 因子前体蛋白参与凝血。ADAM 和 ADAMTS 蛋白参与多种细胞过程，包括细胞黏附和迁移、外显子脱落、蛋白水解、发育、排卵和血管生成。由于这些酶被认为在许多病理学中发挥重要作用，包括阿尔茨海默病、类风湿关节炎、动脉粥样硬化、哮喘和癌症进展，ADAM 和 ADAMTS 基因的产物代表了预防和管理许多人类疾病的有前途的药物靶点。
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