Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin
Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin
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DOI：
10.1186/1741-7007-7-50
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发表时间：
2009-08-13
期刊：
影响因子：
5.4
通讯作者：
Schioth, Helgi B.
中科院分区：
文献类型：
--
作者：
Almen, Markus Sallman;Nordstrom, Karl J. V.;Schioth, Helgi B.
背景资料：膜蛋白在介导细胞与周围环境的相互作用中形成关键节点，这是大多数药物靶点是膜蛋白的主要原因之一。结果：在这里，我们挖掘了人类蛋白质组，并确定了膜蛋白质组子集使用三个预测工具的α-螺旋：Phobius，TMHMM和SOSUI。通过将该数据集与人类基因组进行比对，将其简化为非冗余集，然后使用我们自己的交互式ISODATA算法进行聚类。基因被分类，每个蛋白质组都是人工管理的，虚拟地评估簇的每个序列，与一系列数据库和其他资源进行系统比较。我们鉴定了6，718种人类膜蛋白，并将其中大多数分为234个家族，其中151个属于三个主要功能组：受体（63组，1，352个成员），转运蛋白（89组，817个成员）或酶（7组，533个成员）。此外，还确定了74个杂项小组，697名成员。有趣的是，我们发现41%的膜蛋白是单线态，与任何人类蛋白质家族没有明显的联系或身份。我们的研究结果确定了人类膜蛋白质组与单细胞生物之间的主要差异，并且我们还显示出对不同功能类别的某些膜拓扑结构的强烈偏好：77%的所有转运蛋白具有六个以上的螺旋，而60%的具有酶功能的蛋白质和88%的受体（不是GPCR）只有一个跨膜α-螺旋。此外，我们已经确定和新的基因家族和现有family.Conclusion的新成员的特点：在这里，我们提出了最详细的路线图的基因数量和家庭，我们的知识，这是一个重要的一步，对整个人类蛋白质组的整体分类。我们估计，27%的总人类蛋白质组是α-螺旋跨膜蛋白，并提供了一个扩展的分类连同膜蛋白质组的功能，结构和进化特征的深入调查。
Background: Membrane proteins form key nodes in mediating the cell's interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins.Results: Here we mined the human proteome and identified the membrane proteome subset using three prediction tools for alpha-helices: Phobius, TMHMM, and SOSUI. This dataset was reduced to a non-redundant set by aligning it to the human genome and then clustered with our own interactive implementation of the ISODATA algorithm. The genes were classified and each protein group was manually curated, virtually evaluating each sequence of the clusters, applying systematic comparisons with a range of databases and other resources. We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups: receptors (63 groups, 1,352 members), transporters (89 groups, 817 members) or enzymes (7 groups, 533 members). Also, 74 miscellaneous groups with 697 members were determined. Interestingly, we find that 41% of the membrane proteins are singlets with no apparent affiliation or identity to any human protein family. Our results identify major differences between the human membrane proteome and the ones in unicellular organisms and we also show a strong bias towards certain membrane topologies for different functional classes: 77% of all transporters have more than six helices while 60% of proteins with an enzymatic function and 88% receptors, that are not GPCRs, have only one single membrane spanning alpha-helix. Further, we have identified and characterized new gene families and novel members of existing families.Conclusion: Here we present the most detailed roadmap of gene numbers and families to our knowledge, which is an important step towards an overall classification of the entire human proteome. We estimate that 27% of the total human proteome are alpha-helical transmembrane proteins and provide an extended classification together with in-depth investigations of the membrane proteome's functional, structural, and evolutionary features.