Get3 in yeast or TRC40 in mammals is an ATPase that, in eukaryotes, is a central element of the GET or TRC pathway involved in the targeting of tail-anchored proteins. Get3 has also been shown to possess chaperone holdase activity. A bioinformatic assessment was performed across all domains of life on functionally important regions of Get3 including the TRC40-insert and the hydrophobic groove essential for tail-anchored protein binding. We find that such a hydrophobic groove is much more common in bacterial Get3 homologs than previously appreciated based on a directed comparison of bacterial ArsA and yeast Get3. Furthermore, our analysis shows that the region containing the TRC40-insert varies in length and methionine content to an unexpected extent within eukaryotes and also between different phylogenetic groups. In fact, since the TRC40-insert is present in all domains of life, we suggest that its presence does not automatically predict a tail-anchored protein targeting function. This opens up a new perspective on the function of organellar Get3 homologs in plants which feature the TRC40-insert but have not been demonstrated to function in tail-anchored protein targeting. Our analysis also highlights a large diversity of the ways Get3 homologs dimerize. Thus, based on the structural features of Get3 homologs, these proteins may have an unexplored functional diversity in all domains of life.

中文翻译：

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Get3样伴侣的自然历史。

酵母或哺乳动物TRC40中的Get3是一个ATPase，在真核生物中，它是GET或TRC途径中涉及尾锚蛋白靶向的核心元素。Get3还显示具有伴侣蛋白保持酶活性。在生命的所有领域中，对Get3的功能重要区域（包括TRC40插入片段和尾部锚定蛋白结合所必需的疏水性凹槽）进行了生物信息学评估。我们发现，基于细菌ArsA和酵母Get3的直接比较，这种疏水性凹槽在细菌Get3同源物中比以前认识到的要普遍得多。此外，我们的分析表明，包含TRC40插入片段的区域的长度和蛋氨酸含量在真核生物内部以及不同的系统发生群体之间的变化程度出乎意料。事实上，由于TRC40插入物存在于生活的所有领域，我们建议其存在并不自动预测尾锚蛋白靶向功能。这为具有TRC40插入但未证明在尾锚蛋白靶向中起作用的植物中的细胞器Get3同源物的功能开辟了新的视角。我们的分析还强调了Get3同源物二聚化方式的多样性。因此，基于Get3同源物的结构特征，这些蛋白质可能在生命的所有域中都具有未开发的功能多样性。这为以TRC40插入为特征但尚未证明在尾锚蛋白靶向中起作用的植物中的细胞器Get3同源物的功能开辟了新的视角。我们的分析还强调了Get3同源物二聚化方式的多样性。因此，基于Get3同源物的结构特征，这些蛋白质可能在生命的所有域中都具有未开发的功能多样性。这为以TRC40插入为特征但尚未证明在尾锚蛋白靶向中起作用的植物中的细胞器Get3同源物的功能开辟了新的视角。我们的分析还强调了Get3同源物二聚化方式的多样性。因此，基于Get3同源物的结构特征，这些蛋白质可能在生命的所有域中都具有未开发的功能多样性。