Ubiquitin and Ubiquitin-Like Conjugations in Complex Diseases: A Computational Perspective

  • Tianshun Gao
  • Zexian Liu
  • Yongbo Wang
  • Yu XueEmail author
Part of the Translational Bioinformatics book series (TRBIO, volume 4)


As one class of most essential and common post-translational modifications (PTMs), ubiquitin and ubiquitin-like (Ub/UBL) conjugations play an important role in almost all aspects of biological processes, and aberrances in the conjugation systems are highly involved in numerous complex diseases. Identification of the Ub/UBL-associated enzymes, substrates and sites is fundamental for understanding the molecular mechanisms of Ub/UBL conjugations, and provides a potential reservoir for discovering disease biomarkers and drug targets. Besides experimental identifications, computational analysis of Ub/UBL conjugations has also emerged as an attractive field. In this chapter, we first summarized the cutting-edge experimental techniques in the large-scale identification of Ub/UBL conjugation substrates, and further emphasized the importance of computational efforts by introducing online databases and predictors for Ub/UBL conjugations. Although computational analysis of Ub/UBL conjugations is still immature, we believe more and more efforts will be paid in the near future.


Ubiquitin and ubiquitin-like conjugation Ubiquitination Sumoylation Proteomics Small cell lung cancer 



This work was supported by grants from the National Basic Research Program (973 project) (2012CB910101, and 2013CB933903), Natural Science Foundation of China (31171263 and 81272578), and International Science and Technology Cooperation Program of China (0S2013ZR0003).


  1. Aghajan M, Jonai N, Flick K, Fu F, Luo M, Cai X, Ouni I, Pierce N, Tang X, Lomenick B, et al. Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase. Nat Biotechnol. 2010;28:738–42.PubMedCrossRefGoogle Scholar
  2. Bedford L, Lowe J, Dick LR, Mayer RJ, Brownell JE. Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat Rev Drug Discov. 2011;10:29–46.PubMedCrossRefGoogle Scholar
  3. Bogunovic D, Boisson-Dupuis S, Casanova JL. ISG15: leading a double life as a secreted molecule. Exp Mol Med. 2013;45:e18.PubMedCrossRefGoogle Scholar
  4. Bonacci T, Roignot J, Soubeyran P. Protein ubiquitylation in pancreatic cancer. ScientificWorldJournal. 2010;10:1462–72.PubMedCrossRefGoogle Scholar
  5. Bourgeois-Daigneault MC, Thibodeau J. Autoregulation of MARCH1 expression by dimerization and autoubiquitination. J Immunol. 2012;188:4959–70.PubMedCrossRefGoogle Scholar
  6. Bustos D, Bakalarski CE, Yang Y, Peng J, Kirkpatrick DS. Characterizing ubiquitination sites by peptide based immunoaffinity enrichment. Mol Cell Proteomics. 2012.Google Scholar
  7. Chasapis CT, Spyroulias GA. RING finger E(3) ubiquitin ligases: structure and drug discovery. Curr Pharm Des. 2009;15:3716–31.PubMedCrossRefGoogle Scholar
  8. Chau V, Tobias JW, Bachmair A, Marriott D, Ecker DJ, Gonda DK, Varshavsky A. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989;243:1576–83.PubMedCrossRefGoogle Scholar
  9. Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011a;11:239–53.PubMedCrossRefGoogle Scholar
  10. Chen Q, Xie W, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D, Corral LG, Krenitsky VP, Xu W. Moutouh-de Parseval L et al. Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood. 2008;111:4690–9.PubMedCrossRefGoogle Scholar
  11. Chen X, Qiu JD, Shi SP, Suo SB, Huang SY, Liang RP. Incorporating key position and amino acid residue features to identify general and species-specific ubiquitin conjugation sites. Bioinformatics. 2013.Google Scholar
  12. Chen Z, Chen YZ, Wang XF, Wang C, Yan RX, Zhang Z. Prediction of ubiquitination sites by using the composition of k-spaced amino acid pairs. PLoS ONE. 2011b;6:e22930.PubMedCrossRefGoogle Scholar
  13. Chen Z, Zhou Y, Song J, Zhang Z. hCKSAAP_UbSite: Improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties. Biochim Biophys Acta. 2013.Google Scholar
  14. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009;33:275–86.PubMedCrossRefGoogle Scholar
  15. Chernorudskiy AL, Garcia A, Eremin EV, Shorina AS, Kondratieva EV, Gainullin MR. UbiProt: a database of ubiquitylated proteins. BMC Bioinformatics. 2007;8:126.PubMedCrossRefGoogle Scholar
  16. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell. 1994;79:13–21.PubMedCrossRefGoogle Scholar
  17. Cohen P, Tcherpakov M. Will the ubiquitin system furnish as many drug targets as protein kinases? Cell. 2010;143:686–93.PubMedCrossRefGoogle Scholar
  18. Conrad C, Podolsky MJ, Cusack JC. Antiproteasomal agents in rectal cancer. Anticancer Drugs. 2011;22:341–50.PubMedCrossRefGoogle Scholar
  19. Coornaert B, Carpentier I, Beyaert R. A20: central gatekeeper in inflammation and immunity. J Biol Chem. 2009;284:8217–21.PubMedCrossRefGoogle Scholar
  20. Dahlmann B. Role of proteasomes in disease. BMC Biochem. 2007;8 Suppl 1:S3.PubMedCrossRefGoogle Scholar
  21. Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Mol Cell Proteomics. 2011;10:M110 003590.Google Scholar
  22. Day IN, Thompson RJ. UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein. Prog Neurobiol. 2010;90:327–62.PubMedCrossRefGoogle Scholar
  23. Deng H, Liang H, Jankovic J. F-box only protein 7 gene in parkinsonian-pyramidal disease. JAMA Neurol. 2013;70:20–4.PubMedCrossRefGoogle Scholar
  24. Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D. Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics. 2007;7:868–74.PubMedCrossRefGoogle Scholar
  25. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399–434.PubMedCrossRefGoogle Scholar
  26. Du H, Huang X, Wang S, Wu Y, Xu W, Li M. PSMA7, a potential biomarker of diseases. Protein Pept Lett. 2009a;16:486–9.PubMedCrossRefGoogle Scholar
  27. Du Y, Xu N, Lu M, Li T. hUbiquitome: a database of experimentally verified ubiquitination cascades in humans. Database (Oxford). 2011;2011:bar055.Google Scholar
  28. Du Z, Zhou X, Li L, Su Z. plantsUPS: a database of plants’ ubiquitin proteasome system. BMC Genomics. 2009b;10:227.PubMedCrossRefGoogle Scholar
  29. Duncan K, Schafer G, Vava A, Parker MI, Zerbini LF. Targeting neddylation in cancer therapy. Future Oncol. 2012;8:1461–70.PubMedCrossRefGoogle Scholar
  30. Escobar M, Velez M, Belalcazar A, Santos ES, Raez LE. The role of proteasome inhibition in nonsmall cell lung cancer. J Biomed Biotechnol. 2011;2011:806506.PubMedCrossRefGoogle Scholar
  31. Festa RA, McAllister F, Pearce MJ, Mintseris J, Burns KE, Gygi SP, Darwin KH. Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected]. PLoS ONE. 2010;5:e8589.PubMedCrossRefGoogle Scholar
  32. Flick K, Ouni I, Wohlschlegel JA, Capati C, McDonald WH, Yates JR, Kaiser P. Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat Cell Biol. 2004;6:634–41.PubMedCrossRefGoogle Scholar
  33. Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, Jia M, Shepherd R, Leung K, Menzies A, et al. COSMIC: mining complete cancer genomes in the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2011;39:D945–50.PubMedCrossRefGoogle Scholar
  34. Gao T, Liu Z, Wang Y, Cheng H, Yang Q, Guo A, Ren J, Xue Y. UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation. Nucleic Acids Res. 2013;41:D445–51.PubMedCrossRefGoogle Scholar
  35. Geng F, Wenzel S, Tansey WP. Ubiquitin and proteasomes in transcription. Annu Rev Biochem. 2012;81:177–201.PubMedCrossRefGoogle Scholar
  36. Giannakopoulos NV, Luo JK, Papov V, Zou W, Lenschow DJ, Jacobs BS, Borden EC, Li J, Virgin HW, Zhang DE. Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun. 2005;336:496–506.PubMedCrossRefGoogle Scholar
  37. Han Y, Lee H, Park JC, Yi GS. E3Net: a system for exploring E3-mediated regulatory networks of cellular functions. Mol Cell Proteomics. 2012;11:O111 014076.Google Scholar
  38. Hegde AN, Upadhya SC. The ubiquitin-proteasome pathway in health and disease of the nervous system. Trends Neurosci. 2007;30:587–95.PubMedCrossRefGoogle Scholar
  39. Hicke L. Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol. 2001;2:195–201.PubMedCrossRefGoogle Scholar
  40. Hochrainer K, Lipp J. Ubiquitylation within signaling pathways in- and outside of inflammation. Thromb Haemost. 2007;97:370–7.PubMedGoogle Scholar
  41. Hochstrasser M. Origin and function of ubiquitin-like proteins. Nature. 2009;458:422–9.PubMedCrossRefGoogle Scholar
  42. House CM, Hancock NC, Moller A, Cromer BA, Fedorov V, Bowtell DD, Parker MW, Polekhina G. Elucidation of the substrate binding site of Siah ubiquitin ligase. Structure. 2006;14:695–701.PubMedCrossRefGoogle Scholar
  43. Humbard MA, Miranda HV, Lim JM, Krause DJ, Pritz JR, Zhou G, Chen S, Wells L, Maupin-Furlow JA. Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii. Nature. 2010;463:54–60.PubMedCrossRefGoogle Scholar
  44. Hutchins AP, Liu S, Diez D, Miranda-Saavedra D. The repertoires of ubiquitinating and deubiquitinating enzymes in eukaryotic genomes. Mol Biol Evol. 2013;30:1172–87.PubMedCrossRefGoogle Scholar
  45. Irminger-Finger I. BARD1, a possible biomarker for breast and ovarian cancer. Gynecol Oncol. 2010;117:211–5.PubMedCrossRefGoogle Scholar
  46. Iyer LM, Burroughs AM, Aravind L. The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like beta-grasp domains. Genome Biol. 2006;7:R60.PubMedCrossRefGoogle Scholar
  47. Jeram SM, Srikumar T, Pedrioli PG, Raught B. Using mass spectrometry to identify ubiquitin and ubiquitin-like protein conjugation sites. Proteomics. 2009;9:922–34.PubMedCrossRefGoogle Scholar
  48. Jones J, Wu K, Yang Y, Guerrero C, Nillegoda N, Pan ZQ, Huang L. A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins. J Proteome Res. 2008;7:1274–87.PubMedCrossRefGoogle Scholar
  49. Kaelin WG. Von Hippel-Lindau disease. Annu Rev Pathol. 2007;2:145–73.CrossRefGoogle Scholar
  50. Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 2012;40:D109–14.PubMedCrossRefGoogle Scholar
  51. Kang C, Yi GS. Identification of ubiquitin/ubiquitin-like protein modification from tandem mass spectra with various PTMs. BMC Bioinform. 2011;12 Suppl 14:S8.CrossRefGoogle Scholar
  52. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell. 2011;44:325–40.PubMedCrossRefGoogle Scholar
  53. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, et al. DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. Nucleic Acids Res. 2011;39:D1035–41.PubMedCrossRefGoogle Scholar
  54. Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR. Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. J Biol Chem. 2011a;286:41530–8.PubMedCrossRefGoogle Scholar
  55. Lee TY, Chen SA, Hung HY, Ou YY. Incorporating distant sequence features and radial basis function networks to identify ubiquitin conjugation sites. PLoS ONE. 2011b;6:e17331.PubMedCrossRefGoogle Scholar
  56. Lee WC, Lee M, Jung JW, Kim KP, Kim D. SCUD: Saccharomyces cerevisiae ubiquitination database. BMC Genomics. 2008;9:440.PubMedCrossRefGoogle Scholar
  57. Lehman NL. The ubiquitin proteasome system in neuropathology. Acta Neuropathol. 2009;118:329–47.PubMedCrossRefGoogle Scholar
  58. Li H, Xing X, Ding G, Li Q, Wang C, Xie L, Zeng R, Li Y. SysPTM: a systematic resource for proteomic research on post-translational modifications. Mol Cell Proteomics. 2009;8:1839–49.PubMedCrossRefGoogle Scholar
  59. Lin H, Lin Q, Liu M, Lin Y, Wang X, Chen H, Xia Z, Lu B, Ding F, Wu Q et al. PKA/Smurf1 signaling-mediated stabilization of Nur77 is required for anticancer drug cisplatin-induced apoptosis. Oncogene. 2013.Google Scholar
  60. Linehan WM, Bratslavsky G, Pinto PA, Schmidt LS, Neckers L, Bottaro DP, Srinivasan R. Molecular diagnosis and therapy of kidney cancer. Annu Rev Med. 2010;61:329–43.PubMedCrossRefGoogle Scholar
  61. Liu Z, Ma Q, Cao J, Gao X, Ren J, Xue Y. GPS-PUP: computational prediction of pupylation sites in prokaryotic proteins. Mol BioSyst. 2011;7:2737–40.PubMedCrossRefGoogle Scholar
  62. Liu Z, Yuan F, Ren J, Cao J, Zhou Y, Yang Q, Xue Y. GPS-ARM: computational analysis of the APC/C recognition motif by predicting D-boxes and KEN-boxes. PLoS ONE. 2012;7:e34370.PubMedCrossRefGoogle Scholar
  63. Lu CT, Huang KY, Su MG, Lee TY, Bretana NA, Chang WC, Chen YJ, Huang HD. DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications. Nucleic Acids Res. 2013;41:D295–305.PubMedCrossRefGoogle Scholar
  64. Magrane M, Consortium U. UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford). 2011;2011:bar009.Google Scholar
  65. Mandel SA, Fishman-Jacob T, Youdim MB. Modeling sporadic Parkinson’s disease by silencing the ubiquitin E3 ligase component, SKP1A. Parkinsonism Relat Disord. 2009;15(Suppl 3):S148–51.PubMedCrossRefGoogle Scholar
  66. Maor R, Jones A, Nuhse TS, Studholme DJ, Peck SC, Shirasu K. Multidimensional protein identification technology (MudPIT) analysis of ubiquitinated proteins in plants. Mol Cell Proteomics. 2007;6:601–10.PubMedCrossRefGoogle Scholar
  67. Meierhofer D, Wang X, Huang L, Kaiser P. Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res. 2008;7:4566–76.PubMedCrossRefGoogle Scholar
  68. Melino G, Gallagher E, Aqeilan RI, Knight R, Peschiaroli A, Rossi M, Scialpi F, Malatesta M, Zocchi L, Browne G, et al. Itch: a HECT-type E3 ligase regulating immunity, skin and cancer. Cell Death Differ. 2008;15:1103–12.PubMedCrossRefGoogle Scholar
  69. Muller S, Briand JP, Van Regenmortel MH. Presence of antibodies to ubiquitin during the autoimmune response associated with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1988;85:8176–80.PubMedCrossRefGoogle Scholar
  70. Nakajima H, Fujiwara H, Furuichi Y, Tanaka K, Shimbara N. A novel small-molecule inhibitor of NF-kappaB signaling. Biochem Biophys Res Commun. 2008;368:1007–13.PubMedCrossRefGoogle Scholar
  71. Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, et al. Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell. 2008;134:668–78.PubMedCrossRefGoogle Scholar
  72. Ohki Y, Funatsu N, Konishi N, Chiba T. The mechanism of poly-NEDD8 chain formation in vitro. Biochem Biophys Res Commun. 2009;381:443–7.PubMedCrossRefGoogle Scholar
  73. Orlicky S, Tang X, Neduva V, Elowe N, Brown ED, Sicheri F, Tyers M. An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase. Nat Biotechnol. 2010;28:733–7.PubMedCrossRefGoogle Scholar
  74. Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI. Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin. J Proteome Res. 2012;11:796–807.PubMedCrossRefGoogle Scholar
  75. Osula O, Swatkoski S, Cotter RJ. Identification of protein SUMOylation sites by mass spectrometry using combined microwave-assisted aspartic acid cleavage and tryptic digestion. J Mass Spectrom. 2012;47:644–54.PubMedCrossRefGoogle Scholar
  76. Peng J, Schwartz D, Elias JE, Thoreen CC, Cheng D, Marsischky G, Roelofs J, Finley D, Gygi SP. A proteomics approach to understanding protein ubiquitination. Nat Biotechnol. 2003;21:921–6.PubMedCrossRefGoogle Scholar
  77. Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM. Identification, analysis, and prediction of protein ubiquitination sites. Proteins. 2010;78:365–80.PubMedCrossRefGoogle Scholar
  78. Rape M, Reddy SK, Kirschner MW. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell. 2006;124:89–103.PubMedCrossRefGoogle Scholar
  79. Ren J, Gao X, Jin C, Zhu M, Wang X, Shaw A, Wen L, Yao X, Xue Y. Systematic study of protein sumoylation: Development of a site-specific predictor of SUMOsp 2.0. Proteomics. 2009;9:3409–12.PubMedCrossRefGoogle Scholar
  80. Rufini A, Fortuni S, Arcuri G, Condo I, Serio D, Incani O, Malisan F, Ventura N, Testi R. Preventing the ubiquitin-proteasome-dependent degradation of frataxin, the protein defective in Friedreich’s ataxia. Hum Mol Genet. 2011;20:1253–61.PubMedCrossRefGoogle Scholar
  81. Sadowski M, Sarcevic B. Mechanisms of mono- and poly-ubiquitination: Ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine. Cell Div. 2010;5:19.PubMedCrossRefGoogle Scholar
  82. Scheffner M, Staub O. HECT E3 s and human disease. BMC Biochem. 2007;8(Suppl 1):S6.PubMedCrossRefGoogle Scholar
  83. Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J. A data set of human endogenous protein ubiquitination sites. Mol Cell Proteomics. 2011;10:M110 002089.Google Scholar
  84. Shi Y, Xu P, Qin J. Ubiquitinated proteome: ready for global? Mol Cell Proteomics. 2011;10:R110 006882.Google Scholar
  85. Singhal S, Taylor MC, Baker RT. Deubiquitylating enzymes and disease. BMC Biochem. 2008;9(Suppl 1):S3.PubMedCrossRefGoogle Scholar
  86. Sohns W, van Veen TA, van der Heyden MA. Regulatory roles of the ubiquitin-proteasome system in cardiomyocyte apoptosis. Curr Mol Med. 2010;10:1–13.PubMedCrossRefGoogle Scholar
  87. Starita LM, Lo RS, Eng JK, von Haller PD, Fields S. Sites of ubiquitin attachment in Saccharomyces cerevisiae. Proteomics. 2012;12:236–40.PubMedCrossRefGoogle Scholar
  88. Striebel F, Imkamp F, Sutter M, Steiner M, Mamedov A, Weber-Ban E. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nat Struct Mol Biol. 2009;16:647–51.PubMedCrossRefGoogle Scholar
  89. Teng S, Luo H, Wang L. Predicting protein sumoylation sites from sequence features. Amino Acids. 2012;43:447–55.PubMedCrossRefGoogle Scholar
  90. Tung CW. PupDB: a database of pupylated proteins. BMC Bioinformatics. 2012;13:40.PubMedCrossRefGoogle Scholar
  91. Tung CW, Ho SY. Computational identification of ubiquitylation sites from protein sequences. BMC Bioinform. 2008;9:310.CrossRefGoogle Scholar
  92. Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA. Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition. Mol Cell Proteomics. 2012;11:148–59.PubMedCrossRefGoogle Scholar
  93. Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA. Refined preparation and use of anti-diglycine remnant (K-epsilon-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Mol Cell Proteomics. 2013;12:825–31.PubMedCrossRefGoogle Scholar
  94. Ulrich HD. The fast-growing business of SUMO chains. Mol Cell. 2008;32:301–5.PubMedCrossRefGoogle Scholar
  95. van der Veen AG, Ploegh HL. Ubiquitin-like proteins. Annu Rev Biochem. 2012;81:323–57.PubMedCrossRefGoogle Scholar
  96. Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol Cell Proteomics. 2011;10:M111 013284.Google Scholar
  97. Wagner SA, Beli P, Weinert BT, Scholz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C. Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues. Mol Cell Proteomics. 2012;11:1578–85.PubMedCrossRefGoogle Scholar
  98. Wang D, Xu W, McGrath SC, Patterson C, Neckers L, Cotter RJ. Direct identification of ubiquitination sites on ubiquitin-conjugated CHIP using MALDI mass spectrometry. J Proteome Res. 2005;4:1554–60.PubMedCrossRefGoogle Scholar
  99. Wang J. Cardiac function and disease: emerging role of small ubiquitin-related modifier. Wiley Interdiscip Rev Syst Biol Med. 2011;3:446–57.PubMedCrossRefGoogle Scholar
  100. Wong CS, Moller A. Siah: a promising anticancer target. Cancer Res. 2013;73:2400–6.PubMedCrossRefGoogle Scholar
  101. Xu J, He Y, Qiang B, Yuan J, Peng X, Pan XM. A novel method for high accuracy sumoylation site prediction from protein sequences. BMC Bioinform. 2008;9:8.CrossRefGoogle Scholar
  102. Xue Y, Ren J, Gao X, Jin C, Wen L, Yao X. GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy. Mol Cell Proteomics. 2008;7:1598–608.PubMedCrossRefGoogle Scholar
  103. Xue Y, Zhou F, Fu C, Xu Y, Yao X. SUMOsp: a web server for sumoylation site prediction. Nucleic Acids Res. 2006;34:W254–7.PubMedCrossRefGoogle Scholar
  104. Xue Y, Zhou F, Zhu M, Ahmed K, Chen G, Yao X. GPS: a comprehensive www server for phosphorylation sites prediction. Nucleic Acids Res. 2005;33:W184–7.PubMedCrossRefGoogle Scholar
  105. Yunus AA, Lima CD. Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway. Nat Struct Mol Biol. 2006;13:491–9.PubMedCrossRefGoogle Scholar
  106. Zhao C, Collins MN, Hsiang TY, Krug RM. Interferon-induced ISG15 pathway: an ongoing virus-host battle. Trends Microbiol. 2013;21:181–6.PubMedCrossRefGoogle Scholar
  107. Zhong Q, Gao W, Du F, Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005;121:1085–95.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations