Counting the zinc-proteins encoded in the human genome
Counting the zinc-proteins encoded in the human genome
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DOI：
10.1021/pr050361j
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Rosato, A
中科院分区：
文献类型：
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作者：
Andreini, C;Banci, L;Rosato, A
金属蛋白是一种能够结合一种或多种金属离子的蛋白质，这些金属离子可能是其生物功能、活性调节或结构目的所必需的。基因组测序项目已经提供了大量的蛋白质初级序列，但是，尽管通过丰富且不断增加的生物信息学工具组合已经实现了几种不同的详细分析和注释，金属结合特性仍然难以预测和实验研究。因此，目前对金属蛋白的认识是片面的。目前的生物信息学研究提出了一种策略来回答人类基因组中编码的多少蛋白质和哪些蛋白质可能需要锌来实现其生理功能。这是通过多种方法的结合来实现的，其中包括：(i)在蛋白质组中搜索锌结合模式，然后从所有可用的x射线数据中获得锌结合模式；00使用基于从Pfam数据库中获得的已知金属蛋白的多个序列比对的金属结合蛋白结构域文库；（iii）挖掘人类基因序列的注释，这是基于任何类型的可用信息。结果发现，人类蛋白质组中有1684个蛋白被三种方法独立鉴定为锌蛋白，746个蛋白被两种方法鉴定，777个蛋白仅被一种方法鉴定。假设通过至少两种方法鉴定的所有蛋白质都是真正的锌结合蛋白，并检查通过一种方法鉴定的蛋白质，可以提出大约2800个人类蛋白质在体内是潜在的锌结合蛋白，相当于人类蛋白质组的10%，不确定度为400个序列。现有的功能信息表明，绝大多数人类锌结合蛋白参与基因表达的调节。人类中最丰富的一类锌结合蛋白是锌指蛋白，其中Cys(4)和Cys(2)His(2)是最常见的配合环境类型。
Metalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, or for regulation of their activities or for structural purposes. Genome sequencing projects have provided a huge number of protein primary sequences, but, even though several different elaborate analyses and annotations have been enabled by a rich and ever-increasing portfolio of bioinformatic tools, metal-binding properties remain difficult to predict as well as to investigate experimentally. Consequently, the present knowledge about metalloproteins is only partial. The present bioinformatic research proposes a strategy to answer the question of how many and which proteins encoded in the human genome may require zinc for their physiological function. This is achieved by a combination of approaches, which include: (i) searching in the proteome for the zinc-binding patterns that, on their turn, are obtained from all available X-ray data; 00 using libraries of metal-binding protein domains based on multiple sequence alignments of known metalloproteins obtained from the Pfam database; and (iii) mining the annotations of human gene sequences, which are based on any type of information available. It is found that 1684 proteins in the human proteome are independently identified by all three approaches as zinc-proteins, 746 are identified by two, and 777 are identified by only one method. By assuming that all proteins identified by at least two approaches are truly zinc-binding and inspecting the proteins identified by a single method, it can be proposed that ca. 2800 human proteins are potentially zinc-binding in vivo, corresponding to 10% of the human proteome, with an uncertainty of 400 sequences. Available functional information suggests that the large majority of human zinc-binding proteins are involved in the regulation of gene expression. The most abundant class of zinc-binding proteins in humans is that of zinc-fingers, with Cys(4) and Cys(2)His(2) being the most common types of coordination environment.