A systematic identification of species-specific protein succinylation sites using joint element features information

Lysine succinylation, an important type of protein posttranslational modification, plays significant roles in many cellular processes. Accurate identification of succinylation sites can facilitate our understanding about the molecular mechanism and potential roles of lysine succinylation. However, even in well-studied systems, a majority of the succinylation sites remain undetected because the traditional experimental approaches to succinylation site identification are often costly, time-consuming, and laborious. In silico approach, on the other hand, is potentially an alternative strategy to predict succinylation substrates. In this paper, a novel computational predictor SuccinSite2.0 was developed for predicting generic and species-specific protein succinylation sites. This predictor takes the composition of profile-based amino acid and orthogonal binary features, which were used to train a random forest classifier. We demonstrated that the proposed SuccinSite2.0 predictor outperformed other currently existing implementations on a complementarily independent dataset. Furthermore, the important features that make visible contributions to species-specific and cross-species-specific prediction of protein succinylation site were analyzed. The proposed predictor is anticipated to be a useful computational resource for lysine succinylation site prediction. The integrated species-specific online tool of SuccinSite2.0 is publicly accessible.

[1]  Li-na Wang,et al.  Accurate in silico prediction of species-specific methylation sites based on information gain feature optimization , 2016, Bioinform..

[2]  Longxiang Xie,et al.  Proteomic analysis of lysine succinylation of the human pathogen Histoplasma capsulatum. , 2017, Journal of proteomics.

[3]  Zhongyi Cheng,et al.  Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis* , 2015, Molecular & Cellular Proteomics.

[4]  V. Vacic,et al.  Identification, analysis, and prediction of protein ubiquitination sites , 2010, Proteins.

[5]  Md. Nurul Haque Mollah,et al.  SuccinSite: a computational tool for the prediction of protein succinylation sites by exploiting the amino acid patterns and properties. , 2016, Molecular bioSystems.

[6]  S. Liang,et al.  Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii , 2014, Parasites & Vectors.

[7]  Zhiqiang Ma,et al.  Accurate in silico identification of protein succinylation sites using an iterative semi-supervised learning technique. , 2015, Journal of theoretical biology.

[8]  Sebastian A. Wagner,et al.  Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. , 2013, Cell reports.

[9]  Geoffrey I. Webb,et al.  Accurate in silico identification of species-specific acetylation sites by integrating protein sequence-derived and functional features , 2014, Scientific Reports.

[10]  Shao-Ping Shi,et al.  SuccFind: a novel succinylation sites online prediction tool via enhanced characteristic strategy , 2015, Bioinform..

[11]  Hening Lin,et al.  Identification of Lysine Succinylation Substrates and the Succinylation Regulatory Enzyme CobB in Escherichia coli* , 2013, Molecular & Cellular Proteomics.

[12]  Ziding Zhang,et al.  Using Weakly Conserved Motifs Hidden in Secretion Signals to Identify Type-III Effectors from Bacterial Pathogen Genomes , 2013, PloS one.

[13]  C. Chen,et al.  Quantitative global proteome and lysine succinylome analyses provide insights into metabolic regulation and lymph node metastasis in gastric cancer , 2017, Scientific Reports.

[14]  Ying Gao,et al.  Bioinformatics Applications Note Sequence Analysis Cd-hit Suite: a Web Server for Clustering and Comparing Biological Sequences , 2022 .

[15]  Vladimir Vacic,et al.  Two Sample Logo: a graphical representation of the differences between two sets of sequence alignments , 2006, Bioinform..

[16]  Johan Auwerx,et al.  Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase , 2011, Science.

[17]  T. Tsunoda,et al.  SucStruct: Prediction of succinylated lysine residues by using structural properties of amino acids. , 2017, Analytical biochemistry.

[18]  Ling-Yun Wu,et al.  iSuc-PseAAC: predicting lysine succinylation in proteins by incorporating peptide position-specific propensity , 2015, Scientific Reports.

[19]  Zhihong Zhang,et al.  Identification of lysine succinylation as a new post-translational modification. , 2011, Nature chemical biology.

[20]  Ziding Zhang,et al.  Prediction of mucin-type O-glycosylation sites in mammalian proteins using the composition of k-spaced amino acid pairs , 2008, BMC Bioinformatics.

[21]  Michael Gribskov,et al.  Use of Receiver Operating Characteristic (ROC) Analysis to Evaluate Sequence Matching , 1996, Comput. Chem..

[22]  Yingming Zhao,et al.  SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. , 2013, Molecular cell.

[23]  Kuo-Chen Chou,et al.  iSuc-PseOpt: Identifying lysine succinylation sites in proteins by incorporating sequence-coupling effects into pseudo components and optimizing imbalanced training dataset. , 2016, Analytical biochemistry.

[24]  J. Boeke,et al.  Lysine Succinylation and Lysine Malonylation in Histones* , 2012, Molecular & Cellular Proteomics.

[25]  Albert Y. Zomaya,et al.  SiteSeek: Post-translational modification analysis using adaptive locality-effective kernel methods and new profiles , 2008, BMC Bioinformatics.

[26]  Kuo-Chen Chou,et al.  pSuc-Lys: Predict lysine succinylation sites in proteins with PseAAC and ensemble random forest approach. , 2016, Journal of theoretical biology.

[27]  Weibo Jin,et al.  Proteome-Wide Identification of Lysine Succinylation in the Proteins of Tomato (Solanum lycopersicum) , 2016, PloS one.

[28]  Jinyan Li,et al.  Computational Identification of Protein Pupylation Sites by Using Profile-Based Composition of k-Spaced Amino Acid Pairs , 2015, PloS one.

[29]  Lukasz A. Kurgan,et al.  Prediction of integral membrane protein type by collocated hydrophobic amino acid pairs , 2009, J. Comput. Chem..

[30]  Chunaram Choudhary,et al.  Proteome-Wide Mapping of the Drosophila Acetylome Demonstrates a High Degree of Conservation of Lysine Acetylation , 2011, Science Signaling.

[31]  Yingming Zhao,et al.  Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. , 2014, Cell metabolism.

[32]  Eliora Z Ron,et al.  Probing the active site of homoserine trans‐succinylase , 2004, FEBS letters.

[33]  Ping Mu,et al.  Global analysis of protein lysine succinylation profiles in common wheat , 2017, BMC Genomics.