Abstract
Protein-protein interactions are fundamental for all biological phenomena, and protein-protein interaction networks provide a global view of the interactions. The hub proteins, with many interaction partners, play vital roles in the networks. We investigated the subcellular localizations of proteins in the human network, and found that the ones localized in multiple subcellular compartments, especially the nucleus/cytoplasm proteins (NCP), the cytoplasm/cell membrane proteins (CMP), and the nucleus/cytoplasm/cell membrane proteins (NCMP), tend to be hubs. Examinations of keywords suggested that among NCP, those related to post-translational modifications and transcription functions are the major contributors to the large number of interactions. These types of proteins are characterized by a multi-domain architecture and intrinsic disorder. A survey of the typical hub proteins with prominent numbers of interaction partners in the type revealed that most are either transcription factors or co-regulators involved in signaling pathways. They translocate from the cytoplasm to the nucleus, triggered by the phosphorylation and/or ubiquitination of intrinsically disordered regions. Among CMP and NCMP, the contributors to the numerous interactions are related to either kinase or ubiquitin ligase activity. Many of them reside on the cytoplasmic side of the cell membrane, and act as the upstream regulators of signaling pathways. Overall, these hub proteins function to transfer external signals to the nucleus, through the cell membrane and the cytoplasm. Our analysis suggests that multiple-localization is a crucial concept to characterize groups of hub proteins and their biological functions in cellular information processing.
Highlights
Eukaryotic cells are composed of many subcellular compartments, and each provides a specific environment for proteins to function [1]
We investigated the subcellular localizations of proteins in the human network, and found that the ones localized in multiple subcellular compartments, especially the nucleus/cytoplasm proteins (NCP), the cytoplasm/cell membrane proteins (CMP), and the nucleus/cytoplasm/cell membrane proteins (NCMP), tend to be hubs
Referring to the Uniprot accession, we assigned each of the Human Protein Reference Database (HPRD) proteins to the Uniprot entry [25], in which the subcellular localization was described while allowing doi:10.1371/journal.pone.0156455.g001
Summary
Eukaryotic cells are composed of many subcellular compartments, and each provides a specific environment for proteins to function [1]. Many metabolic reactions are conducted by a variety of enzymes. They are engaged in catabolism and anabolism, using ATP supplied by mitochondria. Membranes surround the cell and separate it from the outside environment. All of the materials required by a cell are imported through the cell membranes by transporter or pump proteins. Receptors receive various signals from the environment outside the cell, and transmit them to the inside. These examples indicate the strong relationships between the subcellular localization of a protein and its function.
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