Toward an understanding of the protein interaction network of the human liver

摘要

AbstractProteome-scale protein interaction maps are available for many organisms, ranging from bacteria, yeast, worms and flies to humans. These maps provide substantial new insights into systems biology, disease research and drug discovery. However, only a small fraction of the total number of human protein–protein interactions has been identified. In this study, we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology and establish a human liver protein interaction network (HLPN) composed of 3484 interactions among 2582 proteins. The data set has a validation rate of over 72% as determined by three independent biochemical or cellular assays. The network includes metabolic enzymes and liver-specific, liver-phenotype and liver-disease proteins that are individually critical for the maintenance of liver functions. The liver enriched proteins had significantly different topological properties and increased our understanding of the functional relationships among proteins in a liver-specific manner. Our data represent the first comprehensive description of a HLPN, which could be a valuable tool for understanding the functioning of the protein interaction network of the human liver.SynopsisAn extensive interaction network of human liver-expressed proteins is described, composed of 3484 interactions among 2582 proteins. Proteins associated with liver disease tend to be central and highly connected in the network.The interactions of a broad selection of human liver-expressed proteins were mapped by yeast two-hybrid technology, establishing a human liver protein interaction network composed of 3484 interactions among 2582 proteins.The data represent the first comprehensive description and analysis of the human liver protein interaction network.Proteins with known associations with liver diseases or phenotypes tend to be central and highly connected in the network, while liver-specific proteins and metabolic enzymes are preferentially connected to central proteins.