First Insight into the Human Liver Proteome from PROTEOMESKY-LIVERHu 1.0, a Publicly Available Database

Abstract

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 HLP and the 11 104 PEGs represented in the HLT 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 (100 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.