First Insight into the Human Liver Proteome from PROTEOMESKY-LIVERHu 1.0, a Publicly Available Database
First Insight into the Human Liver Proteome from PROTEOMESKY-LIVERHu 1.0, a Publicly Available Database
复制标题
从公开数据库 PROTEOMESKY-LIVERHu 1.0 首次洞察人类肝脏蛋白质组
DOI：
10.1021/pr900532r
复制
发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Cui, Tuo
中科院分区：
文献类型：
--
作者：
Jiang, Ying;Ying, Wantao;Cui, Tuo
在此，我们报告了成人肝脏的蛋白质组和转录组图谱，并进行了初步分析。总的来说，人类肝脏蛋白质组（HLP）数据集包括6788个识别的蛋白质，其中至少有两个肽匹配在95%的置信度，包括3721个新发现的蛋白质在肝脏。人类肝脏转录组（HLT）数据集由11205个表达基因组成。HLP是人类器官中最大的蛋白质组数据集，也是蛋白质组与来自同一样本的转录组之间的第一个直接关联。虽然目前很难完全覆盖HLP，但基于这一数据集可以明确得出以下几个结论：（1）从IPI Human v3.07中的20 070个PEG和整合的人类转录组数据库中的19 478个PEGS中鉴定出由HILP代表的5816个蛋白质编码基因（PEG）和由HILT代表的11 104个PEG，分别(2)与HLP对应的基因的染色体分布模式与HLT高度一致。一些染色体区域，如16p13.3，19q13.31，19q13.42和Xq28，表现出特别高密度的肝脏特异性基因，这些基因在该器官中执行与正常生理学或/和病理学相关的重要功能。(3)HLP跨越6个数量级的相对蛋白质丰度和78%的蛋白质落在这个范围的中间。在新发现的肝脏蛋白质中，82.5%是低丰度的。(4)参与代谢、转运和凝血的蛋白质以及含有代谢、转运和生物合成活性结构域的蛋白质在肝脏中显着富集。(5)KEGG中的94条代谢途径都有不同程度的涉及。其中，48条途径，特别是参与碳水化合物和氨基酸代谢的途径，80%以上的组分蛋白已被检测到。肝脏特异性途径，如参与胆汁酸和胆红素代谢以及生物转化的途径，被确定具有非常高的覆盖率。细胞色素P450家族共有31个成员，其中4个是首次在人类肝脏中观察到的。(6)参与能量代谢和蛋白质及胆汁酸分泌的转运蛋白非常丰富。三种离子通道在肝脏中首次被描述。(7)HLP数据集中有800种与信号转导相关的蛋白质，主要参与细胞识别、定位、通讯和炎症。涉及葡萄糖和脂肪酸调节的胰岛素和脂肪细胞因子途径也被高度覆盖。(8)转录因子（总共309种）以相对低的检测率和丰度被识别;然而，调节与运输、代谢和生物合成相关的基因表达的转录因子以相对高的覆盖率被检测到，并且它们的靶基因的蛋白质产物（总共1100种），例如代谢酶和血浆蛋白，也被鉴定。(9)人肝脏和血浆蛋白质组之间的重叠在凝血/抗凝/纤维蛋白溶解和补体系统中特别值得注意。肝脏和血浆中凝血蛋白的丰度之间存在显著的正线性相关。
Herein, we report proteome and transcriptome profiles of the human adult liver and present an initial analysis. Overall, the human liver proteome (HLP) data set comprises 6788 identified proteins with at least two peptides matches at 95% confidence, including 3721 proteins newly identified in liver. The human liver transcriptome (HLT) data set consists of 11 205 expressed genes. The HLP is the largest proteome data set for a human organ and is the first direct association between a proteome and its transcriptome derived from the same sample. Although it is hard to approach complete coverage of the HLP currently, several conclusions based on this data set are clearly reached: (1) The 5816 protein-encoding genes (PEGs) represented by the HILP and the 11 104 PEGs represented in the HILT have been identified from 20 070 PEGs in IPI Human v3.07 and 19 478 PEGS in the integrated human transcriptome database, respectively. (2) The patterns of chromosomal distribution of the genes corresponding to the HLP are highly consistent with those of the HLT. Some chromosomal regions, such as 16p13.3, 19q13.31, 19q13.42, and Xq28, exhibit particularly high densities of liver-specific genes, which perform the important functions related to normal physiology or/and pathology in this organ. (3) The HLP spans 6 orders of magnitude in relative protein abundance and 78% of the proteins fall in the middle of this range. Of newly identified liver proteins, 82.5% are of low abundance. (4) Proteins involving in metabolism, transport, and coagulation and those containing active domains for metabolism, transport, and biosynthesis are significantly enriched in liver. (5) All 94 metabolic pathways in KEGG are touched to different extent. Of which, for 48 pathways, particularly those involved in metabolism of carbohydrates and amino acids, more than 80% of the component proteins have been detected. The liver-specific pathways, such as those participating in metabolism of bile acid and bilirubin and in biotransformation, are identified with remarkably high coverage. A total of 31 members of the cytochrome P450 family are identified, four of which have been observed for the first time in human liver. (6) Transport proteins involved in energy metabolism and secretion of both protein and bile acid are highly abundant. Three ion channels are described for the first time in liver. (7) The 800 proteins related to signal transduction and primarily involved in cellular recognition, localization, communication, and inflammation are present in the HLP data set. Insulin and adipocytokine pathways, which are involved in the regulation of glucose and fatty acids, are highly covered. (8) Transcription factors (309 in total) have been recognized at relatively low detection rates and abundance; however, transcription factors regulating gene expression related to transport, metabolism, and biosynthesis are detected at relatively higher coverage and the protein products of their target genes (1100 in total), such as metabolic enzymes and plasma proteins, are also identified. (9) The overlap between the human liver and plasma proteomes is particularly noteworthy in the coagulation/anticoagulation/fibrinolysis and complement system. There is a significantly positive linear correlation between the abundance of coagulator proteins in liver and plasma.