Abstract

Motivation

   Protein ubiquitination is one of the important post-translational
   modifications by attaching ubiquitin to specific lysine (K) residues in
   target proteins, and plays important regulatory roles in many cell
   processes. Recent studies indicated that abnormal protein
   ubiquitination have been implicated in many diseases by degradation of
   many key regulatory proteins including tumor suppressor, oncoprotein,
   and cell cycle regulator. The detailed information of protein
   ubiquitination sites is useful for scientists to investigate the
   mechanism of many cell activities and related diseases.

Results

   In this study we established mUbiSida for mammalian Ubiquitination Site
   Database, which provides a scientific community with a comprehensive,
   freely and high-quality accessible resource of mammalian protein
   ubiquitination sites. In mUbiSida, we deposited about 35,494
   experimentally validated ubiquitinated proteins with 110,976
   ubiquitination sites from five species. The mUbiSiDa can also provide
   blast function to predict novel protein ubiquitination sites in other
   species by blast the query sequence in the deposit sequences in
   mUbiSiDa. The mUbiSiDa was designed to be a widely used tool for
   biologists and biomedical researchers with a user-friendly interface,
   and facilitate the further research of protein ubiquitination,
   biological networks and functional proteomics. The mUbiSiDa database is
   freely available at [35]http://reprod.njmu.edu.cn/mUbiSiDa.

Introduction

   Protein ubiquitination, known as the important protein
   post-translational modification of targeting proteins by ubiquitins for
   their subsequent degradation in the ATP-dependent ubiquitin proteasome
   system (UPS), plays an important role in cell activity [36][1]–[37][5].
   Currently, many regulatory functions of protein ubiquitination have
   been discovered, including the regulation of DNA repair and
   transcription, control of signal transduction, and implication of
   endocytosis and sorting. There are also sufficient evidences showing
   that the deregulation of protein ubiquitination have been implicated in
   many diseases by degradation of many key regulatory proteins, including
   tumor suppressor, oncoprotein, and cell cycle regulator
   [38][6]–[39][8]. Therefore protein ubiquitination has captured the
   attention of researchers in life science fields.

   Protein ubiquitination is implemented by ubiquitin binding to the
   lysine site of a target protein. The location, numbers, and
   distribution of ubiquitination site are important information for
   scientists to investigate the mechanism of UPS and relevant diseases
   [40][9], [41][10]. Therefore recently scientists began to focus on
   collecting and managing the available protein ubiquitination
   information. The current available ubiquitination database like UbiProt
   provides information almost exclusively on yeast protein ubiquitination
   due to the previous experimental limits [42][11]. For human,
   hUbiquitome mainly focused on the relationship between ubiquination
   enzymes and substrates, and only 279 substrates were included in the
   database [43][12]. With the recent new technology advances, such as
   proteomic technology, mass spectrometry technology, the growing number
   of the experimentally confirmed ubiquitination sites of mammalian
   protein laid the solid basis for investigating the regulatory mechanism
   of protein stability. Therefore it is imperative for scientific
   community to construct the comprehensive database for depositing and
   retrieving mammalian protein ubiquitination sites.

   Consequently, in this study we constructed a user-friendly database,
   mUbiSida, which meets the above requirements. The dataset in mUbiSiDa
   are mainly collected from published papers. In total, we searched and
   obtained 104 references containing experimentally validated 35,494