Davis Melissa J, Hanson Kelly A, Clark Francis, Fink J Lynn, Zhang Fasheng, Kasukawa Takeya, Kai Chikatoshi, Kawai Jun, Carninci Piero, Hayashizaki Yoshihide, Teasdale Rohan D
Institute for Molecular Bioscience and ARC Centre in Bioinformatics, University of Queensland, St. Lucia, Queensland, Australia.
PLoS Genet. 2006 Apr;2(4):e46. doi: 10.1371/journal.pgen.0020046. Epub 2006 Apr 28.
Membrane organization describes the orientation of a protein with respect to the membrane and can be determined by the presence, or absence, and organization within the protein sequence of two features: endoplasmic reticulum signal peptides and alpha-helical transmembrane domains. These features allow protein sequences to be classified into one of five membrane organization categories: soluble intracellular proteins, soluble secreted proteins, type I membrane proteins, type II membrane proteins, and multi-spanning membrane proteins. Generation of protein isoforms with variable membrane organizations can change a protein's subcellular localization or association with the membrane. Application of MemO, a membrane organization annotation pipeline, to the FANTOM3 Isoform Protein Sequence mouse protein set revealed that within the 8,032 transcriptional units (TUs) with multiple protein isoforms, 573 had variation in their use of signal peptides, 1,527 had variation in their use of transmembrane domains, and 615 generated protein isoforms from distinct membrane organization classes. The mechanisms underlying these transcript variations were analyzed. While TUs were identified encoding all pairwise combinations of membrane organization categories, the most common was conversion of membrane proteins to soluble proteins. Observed within our high-confidence set were 156 TUs predicted to generate both extracellular soluble and membrane proteins, and 217 TUs generating both intracellular soluble and membrane proteins. The differential use of endoplasmic reticulum signal peptides and transmembrane domains is a common occurrence within the variable protein output of TUs. The generation of protein isoforms that are targeted to multiple subcellular locations represents a major functional consequence of transcript variation within the mouse transcriptome.
膜组织描述了蛋白质相对于膜的方向，可通过蛋白质序列中两种特征的存在与否及其组织形式来确定：内质网信号肽和α-螺旋跨膜结构域。这些特征使蛋白质序列能够被分类为五种膜组织类别之一：可溶性细胞内蛋白质、可溶性分泌蛋白质、I型膜蛋白、II型膜蛋白和多跨膜蛋白。具有可变膜组织的蛋白质异构体的产生可以改变蛋白质的亚细胞定位或与膜的结合。将膜组织注释管道MemO应用于FANTOM3异构体蛋白质序列小鼠蛋白质集，结果显示，在具有多种蛋白质异构体的8032个转录单位（TU）中，573个在信号肽的使用上存在差异，1527个在跨膜结构域的使用上存在差异，615个产生了来自不同膜组织类别的蛋白质异构体。对这些转录本变异的潜在机制进行了分析。虽然鉴定出的TU编码了膜组织类别的所有成对组合，但最常见的是膜蛋白向可溶性蛋白的转化。在我们的高可信度数据集中观察到，有156个TU预计会产生细胞外可溶性蛋白和膜蛋白，217个TU会产生细胞内可溶性蛋白和膜蛋白。内质网信号肽和跨膜结构域的差异使用在TU的可变蛋白质输出中很常见。产生靶向多个亚细胞位置的蛋白质异构体代表了小鼠转录组中转录本变异的一个主要功能后果。
