FAT: a novel domain in PIK-related kinases
FAT: a novel domain in PIK-related kinases
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DOI：
10.1016/s0968-0004(00)01563-2
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发表时间：
2000-05-01
影响因子：
13.8
通讯作者：
Sonnhammer, ELL
中科院分区：
文献类型：
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作者：
Bosotti, R;Isacchi, A;Sonnhammer, ELL
磷脂酰肌醇激酶存在于所有真核生物中，在磷脂酰肌醇（PI）信号通路中发挥重要作用1。除了PI-激酶结构域之外，这些蛋白质中的大多数具有许多辅助结构域，通常参与蛋白质-蛋白质相互作用，其指定在给定途径中的作用。图1a中示出了这种域组织的一些示例。最近，PI激酶超家族的一个新的亚家族已经出现，称为PIK相关的2，3。尽管这些蛋白质很大（2000-4000个氨基酸），但它们仅在约300个氨基酸的激酶结构域中与经典PI激酶具有相似性。PIK相关家族的成员在功能上似乎不同，因为它们中没有一个被证明磷酸化脂质，如PI;相反，许多具有Ser/Thr蛋白激酶活性4 -7。尽管有这种功能上的差异，我们将这个结构域称为PI-激酶结构域。许多PIK相关蛋白参与细胞周期检查点控制[例如ATM、ATR、DNA-PK、ESR 1和Rad 3（综述见参考文献8）]。功能障碍可导致一系列疾病，包括免疫缺陷、神经系统疾病和癌症9。之前已经注意到，PIK相关家族的成员在极端C末端共享一个独特的基序10，我们称之为FATC。然而，已经证明难以在大的N-末端部分中定义共享结构域。虽然
Phosphatidylinositol kinases are found in all eukaryotes and serve important functions in phosphatidylinositol (PI) signaling pathways1. In addition to the PI-kinase domain, most of these proteins have a number of accessory domains, usually involved in protein–protein interactions, that specify the role in a given pathway. A few examples of such domain organizations are shown in Fig. 1a. Recently, a new subfamily of the PI-kinase superfamily has emerged, called PIK-related2, 3. Although these proteins are large (2000–4000 amino acids), they only share similarity to classical PI kinases in the~ 300-amino-acid kinase domain.Members of the PIK-related family appear functionally distinct, as none of them has been shown to phosphorylate lipids, such as PI; instead, many have Ser/Thr protein kinase activity4–7. Despite this functional disparity, we will refer to this domain as the PI-kinase domain. Many PIK-related proteins are involved in cell-cycle checkpoint control [eg ATM, ATR, DNA-PK, ESR1 and Rad3 (reviewed in Ref. 8)]. Dysfunction can result in a range of diseases, including immunodeficiency, neurological disorder and cancer9. It has previously been noted that members of the PIK-related family share a unique motif at the extreme C terminus10, which we call FATC. However, it has proved difficult to define shared domains in the large N-terminal portions. Although