Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases - An expanding Nudt family
Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases - An expanding Nudt family
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DOI：
10.1074/jbc.275.17.12730
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发表时间：
2000-04-28
影响因子：
4.8
通讯作者：
Shears, SB
中科院分区：
文献类型：
--
作者：
Caffrey, JJ;Safrany, ST;Shears, SB
由钙离子和环核苷酸调节的酶对“高能”的二磷酸肌醇多磷酸的周转被认为是一种调节的分子开关活动。目标进程可能包括细胞内贩运。继我们早些时候在巴多聚磷酸磷酸水解酶(HDIPP1)下鉴定了一个原型人(D)后，我们现在描述了新的21 kDa人类亚型hDIPP2α和hDIPP2β，仅通过hDIPP2β含有一个额外的氨基酸(Gln(86))来区分彼此。还鉴定了大鼠和小鼠的候选DIPP2α和DIPP2β同源物。催化活性的排序为hDIPP1；hDIPP2α&gT；hDIPP2β。HDIPP异构体的差异表达可能为分子开关的响应时间提供灵活性。HDIPP1和hDIPP2s之间76%的同源性包括一个新出现的特征序列的保守，即带有Gx(2)Gx(6)G羧基延伸的nudt(Mut)基序。Northern和Western分析表明，hDIPP2s的表达是广泛的，但受到非典型调控；这些蛋白是从多个3‘-非翻译区长度不同的mRNA翻译而来的，这是因为利用了一系列可供选择的(规范和非规范)多聚腺苷酸化信号。因此，细胞可以招募复杂的分子过程来调节二磷酸肌醇多聚磷酸的周转。
The turnover of the "high energy" diphosphoinositol polyphosphates by Ca2+- and cyclic nucleotide-modulated enzymes is considered a regulatory, molecular switching activity. Target processes may include intracellular trafficking. Following our earlier identification of a prototype human (d) under bar iphospho (i) under bar nositol-(p) under bar olyphosphate phosphohydrolase (hDIPP1), we now describe new 21-kDa human isoforms, hDIPP2 alpha and hDIPP2 beta, distinguished from each other solely by hDIPP2 beta possessing one additional amino acid (Gln(86)). Candidate DIPP2 alpha and DIPP2 beta homologues in rat and mouse were also identified. The rank order for catalytic activity is hDIPP1 > hDIPP2 alpha > hDIPP2 beta. Differential expression of hDIPP isoforms may provide flexibility in response times of the molecular switches. The 76% identity between hDIPP1 and the hDIPP2s includes conservation of an emerging signature sequence, namely, a Nudt (MutT) motif with a GX(2)GX(6)G carboxy extension. Northern and Western analyses indicate expression of hDIPP2s is broad but atypically controlled; these proteins are translated from multiple mRNAs that differ in the length of the 3'-untranslated region because of utilization of an array of alternative (canonical and noncanonical) polyadenylation signals. Thus, cells can recruit sophisticated molecular processes to regulate diphosphoinositol polyphosphate turnover.