A Comprehensive Analysis On Human Protein Ubiquitination Sites Affected By NsSNPs

Protein ubiquitylation is one of the most important post-translational modifications, which playsimportant regulatory roles in many cell processes, such as signal transduction, cell cycle process, cellproliferation and cell differentiation. Ubiquitylation site, a specific lysine was considered as thebinding site between ubiquitin and target protein. The loss of Ubiquitylation site will result inabnormal process of protein ubiquitylation, which further leads to corresponding diseases. A Non-synonymous single nucleotide variations (nsSNPs) is the most direct cause of losing ubiquitylationsite, therefore it’s very important in studying related diseases. In this study, we mainly focus onanalysis of non-synonymous single nucleotide variations (nsSNPs), which lead to the loss of theprotein ubiquitylation site. The main research work and innovative results were summarized asfollows:Firstly, for further annotation and analysis, we collected all proteins that lost one or moreubiquitylation sites due to nsSNPs. Data analysis and data mining work had been done based on thosehigh throughput data of protein ubiquitylation sites in Homo sapiens. We found that there are870unique nsSNPs lead to the loss of ubiquitylation sites in744proteins. As a result, these nsSNPs datawere included in our dataset.Secondly, from perspective of protein sequence, structure, and GO analysis, we had donebioinformatics analysis of change of ubiquitination sites caused by nsSNPs. Our analysis resultsreveal that those proteins in our dataset mainly tend to gather in cytoplasm and the molecularfunctions of these proteins are mainly involved in enzymes’ activity; in Pathway analysis forfunctional of the protein dataset, we had found that these proteins act as important roles in thedevelopment and progression of many diseases, which show the importance of those ubiquitinationproteins. In the process of analyzing data of ubiquitination sites, we had found that secondarystructure where ubiquitination sites are located in are mainly α-helix, the mutational ubiquitinationsites are more tended to hydrophilic amino acid and exposing to the surface of protein they belong to.For declaring effect on proteins caused by nsSNPs, we implemented molecular dynamics simulationof protein SOX9with method of molecular dynamics simulation to analysis the SOX9‘s dynamicstructural properties. By analyzing of residues of protein before and after mutation, we found that,after mutation, RMSD of sites and entire domain where the nsSNPs locate in both show higher valuethan before, which leads to instability of corresponding protein structure. Finally, in view of the K residues involved in a variety of post-translational modificationactivities and K occupies an important position in the protein post-translational modification sites, soin this study we established ModLysSNP, a Genetic mutation database of human protein Lys-modification sites which provides a user-friendly interface for querying the database, includingAcetylation Lys-modification sites, Methylation Lys-modification sites, Sumoylation Lys-modification sites and Ubiquitylation Lys-modification sites, and the detail annotation on variations.ModLysSNP focuses on non-synonymous single nucleotide polymorphisms (nsSNPs) which arecoding mutation that introduce amino acid changes in their corresponding proteins and can serves as abridge between genomic data and proteomic studies.