Genome-wide analysis of SPAK/OSR1 binding motifs

Genome-wide analysis of SPAK/OSR1 binding motifs
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DOI:
10.1152/physiolgenomics.00173.2006
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发表时间:
2007-01-17
影响因子:
4.6
通讯作者:
Gagnon, Kenneth B. E.
Gagnon, Kenneth B. E.
中科院分区:
生物学3区
文献类型:
--
作者:
Delpire, Eric;Gagnon, Kenneth B. E.

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基于与激酶SPAK(Ste20相关富含脯氨酸丙氨酸激酶)和OSR1(氧化应激反应1)相互作用的12个蛋白质基序序列的比对,我们对序列[S/G/V]RFx[V/I]xx[V/I/T/S]xx进行了全基因组搜索,其中x代表任何氨基酸。 “Mus musculus”搜索鉴定出 131 种小鼠蛋白,其中包含 137 个 SPAK/OSR1 推定结合基序。在人类、斑马鱼、果蝇和蠕虫中也发现了类似的数字。在人类搜索中还发现了略多于一半的含有 SPAK/OSR1 结合域的小鼠蛋白 (53%),而在斑马鱼搜索中也发现了类似的 17-18% 的常见命中。小鼠蛋白质可分为两大类:2/3 具有已确定的功能,而 1/3 是预测的或未知的功能。已知的蛋白质分为转运蛋白、其他膜蛋白、激酶、磷酸酶、细胞骨架、核糖体、核、酶等。对蛋白质序列中 SPAK/OSR1 结合基序位置的分析揭示了其在整个长度上的分布,但对于大量蛋白质来说,优先分布在最末端的氨基或羧基末端。对基序氨基酸组成的分析揭示了 5、6、7 和 8 位丝氨酸残基的优势。总之,我们的新搜索发现并证实了先前显示与激酶相互作用的 12 种蛋白质,并鉴定了小鼠蛋白质组中 SPAK 和 OSR1 的 119 个潜在新靶标。
Based on the alignment of 12 sequences of protein motifs that interact with the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress response 1), we performed genome-wide searches of the sequence [S/G/V]RFx[V/I]xx[V/I/T/S] xx, where x represents any amino acid. The "Mus musculus" search resulted in the identification of 131 mouse proteins containing 137 SPAK/OSR1 putative binding motifs. Similar numbers were found for human, zebrafish, fruit fly, and worm. A little more than half of the mouse proteins containing SPAK/OSR1 binding domains (53%) were also identified in the human search, whereas similar to 17-18% of these common hits were identified in the zebrafish search. The mouse proteins could be divided into two broad categories: 2/3 had an identified function, whereas 1/3 were either predicted or of unknown function. The known proteins were grouped as transport proteins, other membrane proteins, kinases, phosphatases, cytoskeletal, ribosomal, nuclear, enzymes, and others. Analysis of the location of the SPAK/OSR1 binding motif within the protein sequence revealed distribution throughout the entire length, but with preference to the extreme amino- or carboxyl termini for a large number of proteins. Analysis of the amino acid composition of the motifs revealed a preponderance of serine residues at positions 5, 6, 7, and 8. In summary, our new search found and thus confirms the 12 proteins previously shown to interact with the kinases and identifies 119 potential new targets for SPAK and OSR1 in the mouse proteome.