PLEKHA4,(5,6) bind PI3P

The second messenger phosphatidylinositol 3,4,5-trisphosphate
(PIP3, PtdIns(3,4,5)P) is generated by the action of phosphoinositide
3-kinase (PI3K) in response to growth factors and insulin and regulates a range of cellular processes. Proteins containing the plekstrin homology (PH) domain can interact specifically with PIP3 or its immediate breakdown product, phosphatidylinositol 3,4-diphosphate (PIP2, PtdIns(3,4)P). Proteins with a PH domain have also been found to bind to PIs other than PIP3 or PIP2. Pleckstrin homology domain-containing family A member 4 (PLEKHA4 aka PEPP1) is able to specifically bind phosphatidylinositol 3-phosphate (PI3P) but not other phosphoinositides (Dowler et al. 2000). Two related isoforms of
PLEKHA4, PLEKHA5 and 6 (PEPP2 and PEPP3), possess a very similar PH domain sequence, indicating that they may also interact with PI3P (Dowler et al. 2000, Yamada et al. 2012). These proteins may function as adaptor molecules since they possess no obvious catalytic moieties.

第二信使磷脂酰肌醇3,4,5-三磷酸（PIP3，磷脂酰肌醇（3,4,5）P）由磷脂酰肌醇3-激酶（PI3K）在生长因子和胰岛素的作用下生成，并调控一系列细胞过程。含有plekstrin同源（PH）结构域的蛋白质能够特异性地与PIP3或其直接分解产物磷脂酰肌醇3,4-二磷酸（PIP2，磷脂酰肌醇（3,4）P）相互作用。此外，也发现具有PH结构域的蛋白质能够与除PIP3或PIP2之外的磷脂酰肌醇（PIs）结合。Pleckstrin同源结构域家族A成员4（PLEKHA4，又称PEPP1）能够特异性地结合磷脂酰肌醇3磷酸（PI3P），但不能与其他磷脂酰肌醇结合（Dowler等人，2000年）。PLEKHA4的两个相关同源体PLEKHA5和6（PEPP2和PEPP3）具有非常相似的PH结构域序列，这表明它们也可能与PI3P相互作用（Dowler等人，2000年，Yamada等人，2012年）。这些蛋白质可能作为适配分子发挥作用，因为它们不具有明显的催化基团。