BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Post-translational Modifications and Their Biological Functions: Proteomic Analysis and Systematic Approaches

  • Seo, Ja-Won (Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University) ;
  • Lee, Kong-Joo (Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University)
  • Published : 2004.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.

Keywords

References

  1. Andersen, J. S., Svensson, B. and Roepstorff, P. (1996) Electrospray ionization and matrix assisted laser desorption/ ionization mass spectrometry: powerful analytical tools in recombinant protein chemistry. Nat. Biotechnol. 14, 449-457. https://doi.org/10.1038/nbt0496-449
  2. Annan, R. S. and Carr, S. A. (1996) Phosphopeptide analysis by matrix-assisted laser desorption time-of-flight mass spectrometry. Anal. Chem. 68, 3413-3421. https://doi.org/10.1021/ac960221g
  3. Baenziger, J. U. (2003) A major step on the road to understanding a unique posttranslational modification and its role in a genetic disease. Cell 113, 421-422. https://doi.org/10.1016/S0092-8674(03)00354-4
  4. Burlingame, A. L. (1996) Characterization of protein glycosylation by mass spectrometry. Curr. Opin. Biotechnol. 7, 4-10. https://doi.org/10.1016/S0958-1669(96)80088-7
  5. Carr, S. A., Huddleston, M. J. and Annan, R. S. (1996) Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. Anal. Biochem. 239, 180-192. https://doi.org/10.1006/abio.1996.0313
  6. Chiarugi, P. and Cirri, P. (2003) Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal transduction. Trends Biochem. Sci. 28, 509-514. https://doi.org/10.1016/S0968-0004(03)00174-9
  7. Daniels, M. A., Hogquist, K. A. and Jameson, S. C. (2002) Sweet 'n' sour: the impact of differential glycosylation on T cell responses. Nat. Immunol. 3, 903-910. https://doi.org/10.1038/ni1002-903
  8. Figeys, D., Gygi, S. P., Zhang, Y., Watts, J., Gu, M. and Aebersold, R. (1998) Electrophoresis combined with novel mass spectrometry techniques: powerful tools for the analysis of proteins and proteomes. Electrophoresis 19, 1811-1818. https://doi.org/10.1002/elps.1150191045
  9. Fratelli, M., Demol, H., Puype, M., Casagrande, S., Eberini, I., Salmona, M., Bonetto, V., Mengozzi, M., Duffieux, F., Miclet, E., Bachi, A., Vandekerckhove, J., Gianazza, E. and Ghezzi, P. (2002) Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc. Natl. Acad. Sci. USA 99, 3505-3510. https://doi.org/10.1073/pnas.052592699
  10. Freiman, R. N. and Tjian, R. (2003) Regulating the regulators: lysine modifications make their mark. Cell 112, 11-17. https://doi.org/10.1016/S0092-8674(02)01278-3
  11. Georgiou, G. (2002) How to flip the (redox) switch. Cell 111, 607-610. https://doi.org/10.1016/S0092-8674(02)01165-0
  12. Gianazza, E., Celentano, F., Magenes, S., Ettori, C. and Righetti, P. G. (1989) Formulations for immobilized pH gradients including pH extremes. Electrophoresis 10, 806-808. https://doi.org/10.1002/elps.1150101115
  13. Giasson, B. I. and Lee, V. M. (2003) Are ubiquitination pathways central to Parkinson's disease? Cell 114, 1-8. https://doi.org/10.1016/S0092-8674(03)00509-9
  14. Gobom, J., Nordhoff, E., Mirgorodskaya, E., Ekman, R. and Roepstorff, P. (1999) Sample purification and preparation technique based on nano-scale reversed-phase columns for the sensitive analysis of complex peptide mixtures by matrixassisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 34, 105-116. https://doi.org/10.1002/(SICI)1096-9888(199902)34:2<105::AID-JMS768>3.0.CO;2-4
  15. Harvey, D. J., Kuster, B. and Naven, T. J. (1998) Perspectives in the glycosciences--matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of carbohydrates. Glycoconj. J. 15, 333-338. https://doi.org/10.1023/A:1006913616252
  16. Jensen, O. N., Stensballe, A. and Andersen, S. (2000) Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off-line mass spectrometry analysis. Proteomics 1, 207-222.
  17. Jeong, J. W., Bae, M. K., Ahn, M. Y., Kim, S. H., Sohn, T. K., Bae, M. H., Yoo, M. A., Song, E. J., Lee, K. J. and Kim, K. W. (2002) Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 111, 709-720. https://doi.org/10.1016/S0092-8674(02)01085-1
  18. Kim, H. J., Song, E. J. and Lee, K. J. (2002) Proteomic analysis of protein phosphorylations in heat shock response and thermotolerance. J. Biol. Chem. 277, 23193-23207. https://doi.org/10.1074/jbc.M201007200
  19. Kim, J. Y., Kim, K. W., Kwon, H. J., Lee, D. W. and Yoo, J. S. (2002) Probing lysine acetylation with a modification-specific marker ion using high-performance liquid chromatography/electrospray-mass spectrometry with collision-induced dissociation. Anal. Chem. 74, 5443-5449. https://doi.org/10.1021/ac0256080
  20. Kim, Y. M., Song, E. J., Kim, H. J. and Lee, K. J. (2003) Proteomic analysis of tyrosine phosphorylations in vascular endothelial growth factor- and reactive oxygen species-mediated signaling pathway of endothelial cells. J. Biol. Chem. Submitted.
  21. Kouzarides, T. (2000) Acetylation: a regulatory modification to rival phosphorylation? EMBO J. 19, 1176-1179.
  22. Kuncewicz, T., Sheta, E. A., Goldknopf, I. L. and Kone, B. C. (2003) Proteomic analysis of s-nitrosylated proteins in mesangial cells. Mol. Cell. Proteomics 2, 156-163. https://doi.org/10.1074/mcp.M300003-MCP200
  23. Kussmann, M., Lassing, U., Sturmer, C. A., Przybylski, M. and Roepstorff, P. (1997) Matrix-assisted laser desorption/ionization mass spectrometric peptide mapping of the neural cell adhesion protein neurolin purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis or acidic precipitation. J. Mass. Spectrom. 32, 483-493. https://doi.org/10.1002/(SICI)1096-9888(199705)32:5<483::AID-JMS502>3.0.CO;2-J
  24. Kuster, B. and Mann, M. (1999) $^{18}O$-labeling of N-glycosylation sites to improve the identification of gel-separated glycoproteins using peptide mass mapping and database searching. Anal. Chem. 71, 1431-1440. https://doi.org/10.1021/ac981012u
  25. Kuster, B., Wheeler, S. F., Hunter, A. P., Dwek, R. A. and Harvey, D. J. (1997) Sequencing of N-linked oligosaccharides directly from protein gels: in-gel deglycosylation followed by matrixassisted laser desorption/ionization mass spectrometry and normal-phase high-performance liquid chromatography. Anal. Biochem. 250, 82-101. https://doi.org/10.1006/abio.1997.2199
  26. Linder, M. E. and Deschenes, R. J. (2003) New insights into the mechanisms of protein palmitoylation. Biochemistry 42, 4311-4320. https://doi.org/10.1021/bi034159a
  27. Mann, M. and Jensen, O. N. (2003) Proteomic analysis of posttranslational modifications. Nat. Biotechnol. 21, 255-261. https://doi.org/10.1038/nbt0303-255
  28. Mortz, E., Sareneva, T., Haebel, S., Julkunen, I. and Roepstorff, P. (1996) Mass spectrometric characterization of glycosylated interferon-gamma variants separated by gel electrophoresis. Electrophoresis 17, 925-931. https://doi.org/10.1002/elps.1150170514
  29. Neubauer, G. and Mann, M. (1999) Mapping of phosphorylation sites of gel-isolated proteins by nanoelectrospray tandem mass spectrometry: potentials and limitations. Anal. Chem. 71, 235-242.
  30. Packer, N. H., Ball, M. S. and Devine, P. L. (1999) Glycoprotein detection of 2-D separated proteins. Methods Mol. Biol. 112, 341-352.
  31. Packer, N. H., Lawson, M. A., Jardine, D. R., Sanchez, J. C. and Gooley, A. A. (1998) Analyzing glycoproteins separated by two-dimensional gel electrophoresis. Electrophoresis 19, 981-988. https://doi.org/10.1002/elps.1150190613
  32. Pawson, T. (2002) Regulation and targets of receptor tyrosine kinases. Eur. J. Cancer Suppl 5, S3-10. https://doi.org/10.1016/S0959-8049(02)80597-4
  33. Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D. and Gygi, S. P. (2003) A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 21, 921-926. https://doi.org/10.1038/nbt849
  34. Salomon, A. R., Ficarro, S. B., Brill, L. M., Brinker, A., Phung, Q. T., Ericson, C., Sauer, K., Brock, A., Horn, D. M., Schultz, P. G. and Peters, E. C. (2003) Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc. Natl. Acad. Sci. USA 100, 443-448.
  35. Schopfer, F. J., Baker, P. R. and Freeman, B. A. (2003) NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response? Trends Biochem. Sci. 28, 646-654. https://doi.org/10.1016/j.tibs.2003.10.006
  36. Schwartz, D. C. and Hochstrasser, M. (2003) A superfamily of protein tags: ubiquitin, SUMO and related modifiers. Trends Biochem. Sci. 28, 321-328. https://doi.org/10.1016/S0968-0004(03)00113-0
  37. Schwartz, J. H. (2003) Ubiquitination, protein turnover, and longterm synaptic plasticity. Sci. STKE. 190, pe26.
  38. Seeler, J. S. and Dejean, A. (2003) Nuclear and unclear functions of SUMO. Nat. Rev. Mol. Cell. Biol. 4, 690-699. https://doi.org/10.1038/nrm1200
  39. Sherrier, D. J. and Prime, T. A. (1999) Glycosylphosphatidylinositol- anchored cell-surface proteins from Arabidopsis. Electrophoresis 10, 2027-2035.
  40. Soskic, V., Gorlach, M., Poznanovic, S., Boehmer, F. D. and Godovac-Zimmermann, J. (1999) Functional proteomics analysis of signal transduction pathways of the platelet-derived growth factor beta receptor. Biochemistry 38, 1757-1764. https://doi.org/10.1021/bi982093r
  41. Spangfort, M. D., Ipsen, H., Sparholt, S. H., Aasmul-Olsen, S., Larsen, M. R., Mortz, E., Roepstorff, P. and Larsen, J. N. (1996) Characterization of purified recombinant Bet v 1 with authentic N-terminus, cloned in fusion with maltose-binding protein. Protein Expr. Purif. 8, 365-373. https://doi.org/10.1006/prep.1996.0112
  42. van Montfort, R. L., Congreve, M., Tisi, D., Carr, R. and Jhoti, H. (2003) Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature 423, 773-777. https://doi.org/10.1038/nature01681
  43. Wells, L., Whalen, S. A. and Hart, G. W. (2003) O-GlcNAc: a regulatory post-translational modification. Biochem. Biophys. Res. Commun. 302, 435-441. https://doi.org/10.1016/S0006-291X(03)00175-X
  44. Whelan, S. A. and Hart, G. W. (2003) Proteomic approaches to analyze the dynamic relationships between nucleocytoplasmic protein glycosylation and phosphorylation. Circ. Res. 93, 1047-1058. https://doi.org/10.1161/01.RES.0000103190.20260.37
  45. Woo, H. A., Chae, H. Z., Hwang, S. C., Yang, K. S., Kang, S. W., Kim, K. and Rhee, S. G. (2003) Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation. Science 300, 653-656. https://doi.org/10.1126/science.1080273
  46. Yan, J. X., Sanchez, J. C., Binz, P. A., Williams, K. L. and Hochstrasser, D. F. (1999) Method for identification and quantitative analysis of protein lysine methylation using matrixassisted laser desorption/ionization--time-of-flight mass spectrometry and amino acid analysis. Electrophoresis 20, 749-754. https://doi.org/10.1002/(SICI)1522-2683(19990101)20:4/5<749::AID-ELPS749>3.0.CO;2-V
  47. Yano, H., Kuroda, S. and Buchanan, B. B. (2002) Disulfide proteome in the analysis of protein function and structure. Proteomics 2, 1090-1096. https://doi.org/10.1002/1615-9861(200209)2:9<1067::AID-PROT1067>3.0.CO;2-2

Cited by

  1. Charge profiling and stability testing of biosimilar by capillary isoelectric focusing vol.35, pp.10, 2014, https://doi.org/10.1002/elps.201300471
  2. Signatures of Natural Selection on Mutations of Residues with Multiple Posttranslational Modifications vol.31, pp.7, 2014, https://doi.org/10.1093/molbev/msu137
  3. The challenge to quantify proteins with charge trains due to isoforms or conformers vol.33, pp.2, 2012, https://doi.org/10.1002/elps.201100321
  4. An overview of proteomics approaches applied to biopharmaceuticals and cyclotides research vol.93, 2013, https://doi.org/10.1016/j.jprot.2013.06.009
  5. SUMO proteases: uncovering the roles of deSUMOylation in plants vol.67, pp.9, 2016, https://doi.org/10.1093/jxb/erw092
  6. Where Do Phosphosites Come from and Where Do They Go after Gene Duplication? vol.2012, 2012, https://doi.org/10.1155/2012/843167
  7. Post-translational events and modifications regulating plant enzymes involved in isoprenoid precursor biosynthesis vol.203-204, 2013, https://doi.org/10.1016/j.plantsci.2012.12.008
  8. A conserved SUMOylation signaling for cell cycle control in a holocentric species Bombyx mori vol.51, 2014, https://doi.org/10.1016/j.ibmb.2014.05.008
  9. Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2003-2004 vol.28, pp.2, 2009, https://doi.org/10.1002/mas.20192
  10. Histaminylation of glutamine residues is a novel posttranslational modification implicated in G-protein signaling vol.586, pp.21, 2012, https://doi.org/10.1016/j.febslet.2012.09.027
  11. dbPTM 2016: 10-year anniversary of a resource for post-translational modification of proteins vol.44, pp.D1, 2016, https://doi.org/10.1093/nar/gkv1240
  12. Identification of SUMO Targets by a Novel Proteomic Approach in PlantsF vol.55, pp.1, 2013, https://doi.org/10.1111/jipb.12012
  13. WITHDRAWN: Major proteins from the seminal plasma of adult Santa Ines rams 2011, https://doi.org/10.1016/j.anireprosci.2011.05.001
  14. The Clinical Significance of Posttranslational Modification of Autoantigens vol.47, pp.1, 2014, https://doi.org/10.1007/s12016-014-8424-0
  15. Nonsynonymous Single-Nucleotide Variations on Some Posttranslational Modifications of Human Proteins and the Association with Diseases vol.2015, 2015, https://doi.org/10.1155/2015/124630
  16. Charge heterogeneity of a therapeutic monoclonal antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin vol.1217, pp.45, 2010, https://doi.org/10.1016/j.chroma.2010.09.022
  17. Proteomics and Metabolomics: Two Emerging Areas for Legume Improvement vol.6, 2015, https://doi.org/10.3389/fpls.2015.01116
  18. Functional analysis of proteins and protein species using shotgun proteomics and linear mathematics vol.41, pp.2, 2011, https://doi.org/10.1007/s00726-010-0669-1
  19. The Combination of Lectin Affinity Chromatography, Gel Electrophoresis and Mass Spectrometry in the Study of Plant Glycoproteome: Preliminary Insights vol.73, pp.S1, 2011, https://doi.org/10.1007/s10337-010-1846-9
  20. Mechanistic Study of the Deamidation Reaction of Glutamine: A Computational Approach vol.118, pp.9, 2014, https://doi.org/10.1021/jp4107266
  21. In vivo subcellular localization of Mal de Río Cuarto virus (MRCV) non-structural proteins in insect cells reveals their putative functions vol.430, pp.2, 2012, https://doi.org/10.1016/j.virol.2012.04.016
  22. Sumoylation May Play an Important Role in Modification of Large Number of Proteins Associated with Heat Stress in Plants vol.84, pp.3, 2014, https://doi.org/10.1007/s40011-013-0249-8
  23. Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia vol.14, pp.1, 2014, https://doi.org/10.1186/1471-2253-14-3
  24. Deciphering the human nucleolar proteome vol.25, pp.2, 2006, https://doi.org/10.1002/mas.20067
  25. Determination of phosphoserine/threonine by nano ultra-performance liquid chromatography–tandem mass spectrometry coupled with microscale labeling vol.443, pp.2, 2013, https://doi.org/10.1016/j.ab.2013.08.022
  26. Analysis of differentially expressed novel post-translational modifications of plasma apolipoprotein E in Taiwanese females with breast cancer vol.126, 2015, https://doi.org/10.1016/j.jprot.2015.05.038
  27. Novel post-digest isotope coded protein labeling method for phospho- and glycoproteome analysis vol.73, pp.10, 2010, https://doi.org/10.1016/j.jprot.2010.06.003
  28. Functional proteomics inCiona intestinalis: A breakthrough in the exploration of the molecular and cellular mechanism of ascidian development vol.236, pp.7, 2007, https://doi.org/10.1002/dvdy.21121
  29. Fluorescence-Based Cloning of a Protein Tyrosine Kinase with a Yeast Tribrid System vol.6, pp.8, 2005, https://doi.org/10.1002/cbic.200500047
  30. Review seed biopharmaceutical cyclic peptides: From discovery to applications vol.104, pp.6, 2015, https://doi.org/10.1002/bip.22741
  31. Challenges in design and characterization of ligand-targeted drug delivery systems vol.164, pp.2, 2012, https://doi.org/10.1016/j.jconrel.2012.05.052
  32. Reverse engineering and verification of gene networks: Principles, assumptions, and limitations of present methods and future perspectives vol.144, pp.3, 2009, https://doi.org/10.1016/j.jbiotec.2009.07.013
  33. Optimization of apolipoprotein-B-100 sequence coverage by liquid chromatography–tandem mass spectrometry for the future study of its posttranslational modifications vol.411, pp.1, 2011, https://doi.org/10.1016/j.ab.2010.11.039
  34. Comparative analysis of boar seminal plasma proteome from different freezability ejaculates and identification of Fibronectin 1 as sperm freezability marker vol.3, pp.2, 2015, https://doi.org/10.1111/andr.12009
  35. Cadmium Stress Responses inBrassica juncea: Hints from Proteomics and Metabolomics vol.12, pp.11, 2013, https://doi.org/10.1021/pr400793e
  36. Clinical Neuroproteomics and Biomarkers vol.70, pp.3, 2012, https://doi.org/10.1227/NEU.0b013e3182333a26
  37. Wound outcome in combat injuries is associated with a unique set of protein biomarkers vol.11, pp.1, 2013, https://doi.org/10.1186/1479-5876-11-281
  38. Proteomics and low-temperature studies: bridging the gap between gene expression and metabolism vol.126, pp.1, 2006, https://doi.org/10.1111/j.1399-3054.2006.00617.x
  39. Biological Insights into Therapeutic Protein Modifications throughout Trafficking and Their Biopharmaceutical Applications vol.2013, 2013, https://doi.org/10.1155/2013/273086
  40. “Without Ub I am nothing”: NEMO as a multifunctional player in ubiquitin-mediated control of NF-κB activation vol.67, pp.18, 2010, https://doi.org/10.1007/s00018-010-0404-9
  41. Development and validation of a rapid capillary zone electrophoresis method for determining charge variants of mAb vol.906, 2012, https://doi.org/10.1016/j.jchromb.2012.08.022
  42. Unraveling the Phosphoproteome Dynamics in Mammal Mitochondria from a Network Perspective vol.12, pp.10, 2013, https://doi.org/10.1021/pr4003917
  43. A New Strategy for Early Diagnosis of Type 2 Diabetes by Standard-Free, Label-Free LC-MS/MS Quantification of Glycated Peptides vol.62, pp.11, 2013, https://doi.org/10.2337/db13-0347
  44. Characterization and expression of Rubisco activase genes in Ipomoea batatas vol.40, pp.11, 2013, https://doi.org/10.1007/s11033-013-2744-7
  45. Co-ordination of osmotic stress responses through osmosensing and signal transduction events in fishes vol.76, pp.8, 2010, https://doi.org/10.1111/j.1095-8649.2010.02590.x
  46. Protein variety and functional diversity: Swiss-Prot annotation in its biological context vol.328, pp.10-11, 2005, https://doi.org/10.1016/j.crvi.2005.06.001
  47. Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects vol.83, pp.1, 2015, https://doi.org/10.1002/prot.24605
  48. An innovative strategy for sulfopeptides analysis using MALDI-TOF MS reflectron positive ion mode vol.12, pp.14, 2012, https://doi.org/10.1002/pmic.201100525
  49. Systemic and Cell-Type Specific Profiling of Molecular Changes in Parkinson`s Disease vol.4, pp.3, 2012, https://doi.org/10.4051/ibc.2012.4.3.0006
  50. Sweet and Sour: The Impact of Differential Glycosylation in Cancer Cells Undergoing Epithelial–Mesenchymal Transition vol.4, 2014, https://doi.org/10.3389/fonc.2014.00059
  51. Proteomic investigation of 1,6-dimethoxyhexane testicular toxicity vol.24, pp.2, 2007, https://doi.org/10.1016/j.etap.2007.04.001
  52. Calcineurin-mediated YB-1 Dephosphorylation Regulates CCL5 Expression during Monocyte Differentiation vol.289, pp.31, 2014, https://doi.org/10.1074/jbc.M114.562991
  53. Neuron-specific protein interactions of Drosophila CASK-β are revealed by mass spectrometry vol.7, 2014, https://doi.org/10.3389/fnmol.2014.00058
  54. The major cystic fibrosis causing mutation exhibits defective propensity for phosphorylation vol.15, pp.2-3, 2015, https://doi.org/10.1002/pmic.201400218
  55. Transcreener™: screening enzymes involved in covalent regulation vol.10, pp.1, 2006, https://doi.org/10.1517/14728222.10.1.179
  56. An Arginine-rich Motif of Ring Finger Protein 4 (RNF4) Oversees the Recruitment and Degradation of the Phosphorylated and SUMOylated Krüppel-associated Box Domain-associated Protein 1 (KAP1)/TRIM28 Protein during Genotoxic Stress vol.289, pp.30, 2014, https://doi.org/10.1074/jbc.M114.555672
  57. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes vol.2010, 2010, https://doi.org/10.1155/2010/130781
  58. Metodologías fosfoproteómicas útiles en estudios clínicos vol.27, pp.1, 2008, https://doi.org/10.1016/S0213-9626(08)70047-7
  59. Specific changes in total and mitochondrial proteomes are associated with higher levels of heterosis in maize hybrids vol.72, pp.1, 2012, https://doi.org/10.1111/j.1365-313X.2012.05056.x
  60. Exploring Pathogenic Mechanisms ofBotrytis cinereaSecretome under Different Ambient pH Based on Comparative Proteomic Analysis vol.11, pp.8, 2012, https://doi.org/10.1021/pr300365f
  61. topPTM: a new module of dbPTM for identifying functional post-translational modifications in transmembrane proteins vol.42, pp.D1, 2014, https://doi.org/10.1093/nar/gkt1221
  62. Transcriptional regulation by the Set7 lysine methyltransferase vol.8, pp.4, 2013, https://doi.org/10.4161/epi.24234
  63. Role and challenges of proteomics in pharma and biotech: technical, scientific and commercial perspective vol.3, pp.2, 2006, https://doi.org/10.1586/14789450.3.2.179
  64. Integration of an on-line protein digestion microreactor to a nanoelectrospray emitter for peptide mapping vol.359, pp.2, 2006, https://doi.org/10.1016/j.ab.2006.09.005
  65. Facile identification of photocleavable reactive metabolites and oxidative stress biomarkers in proteins via mass spectrometry vol.403, pp.8, 2012, https://doi.org/10.1007/s00216-012-5867-0
  66. Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation vol.46, pp.1, 2016, https://doi.org/10.4070/kcj.2016.46.1.1
  67. Current approaches for global post-translational modification discovery and mass spectrometric analysis vol.627, pp.1, 2008, https://doi.org/10.1016/j.aca.2008.03.032
  68. Using bioinformatics to predict the functional impact of SNVs vol.27, pp.4, 2011, https://doi.org/10.1093/bioinformatics/btq695
  69. NMR localization of the O-mycoloylation on PorH, a channel forming peptide fromCorynebacterium glutamicum vol.587, pp.22, 2013, https://doi.org/10.1016/j.febslet.2013.09.032
  70. Quality assurance of monoclonal antibody pharmaceuticals based on their charge variants using microchip isoelectric focusing method vol.1309, 2013, https://doi.org/10.1016/j.chroma.2013.08.021
  71. The expression and localization of a novel protein phosphatase inhibitor 2810408A11Rik in mouse testis and sperm vol.26, pp.2, 2012, https://doi.org/10.1016/S1674-8301(12)60020-7
  72. Capillary electrophoresis at the omics level: Towards systems biology vol.27, pp.1, 2006, https://doi.org/10.1002/elps.200500511
  73. 2DE: The Phoenix of Proteomics vol.104, 2014, https://doi.org/10.1016/j.jprot.2014.03.035
  74. Phosphoproteomics analysis of a clinical Mycobacterium tuberculosis Beijing isolate: expanding the mycobacterial phosphoproteome catalog vol.6, 2015, https://doi.org/10.3389/fmicb.2015.00006
  75. Proteomic analysis in human breast cancer: Identification of a characteristic protein expression profile of malignant breast epithelium vol.6, pp.6, 2006, https://doi.org/10.1002/pmic.200500129
  76. Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications vol.2016, 2016, https://doi.org/10.1155/2016/1298473
  77. Analysis of the Structure and Stability of Erythropoietin by pH and Temperature Changes using Various LC/MS vol.34, pp.9, 2013, https://doi.org/10.5012/bkcs.2013.34.9.2663
  78. POSTMan (POST-translational modification analysis), a software application for PTM discovery vol.9, pp.5, 2009, https://doi.org/10.1002/pmic.200800500
  79. Translational control of eukaryotic gene expression vol.44, pp.4, 2009, https://doi.org/10.1080/10409230902882090
  80. Protein lysine acetylation in bacteria: Current state of the art vol.16, pp.2, 2016, https://doi.org/10.1002/pmic.201500258
  81. Differential protein expression during sperm maturation and capacitation in an hermaphroditic bivalve,Pecten maximus(Linnaeus, 1758) vol.82, pp.4, 2016, https://doi.org/10.1093/mollus/eyw028
  82. FragAnchor: A Large-Scale Predictor of Glycosylphosphatidylinositol Anchors in Eukaryote Protein Sequences by Qualitative Scoring vol.5, pp.2, 2007, https://doi.org/10.1016/S1672-0229(07)60022-9
  83. Global Survey of the Bovine Salivary Proteome: Integrating Multidimensional Prefractionation, Targeted, and Glycocapture Strategies vol.10, pp.11, 2011, https://doi.org/10.1021/pr200516d
  84. The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression vol.6, 2016, https://doi.org/10.3389/fonc.2016.00054
  85. SysPTM 2.0: an updated systematic resource for post-translational modification vol.2014, pp.0, 2014, https://doi.org/10.1093/database/bau025
  86. Biologically and diagenetically derived peptide modifications in moa collagens vol.282, pp.1808, 2015, https://doi.org/10.1098/rspb.2015.0015
  87. A high-resolution capillary isoelectric focusing method for the determination of therapeutic recombinant monoclonal antibody vol.34, pp.14, 2011, https://doi.org/10.1002/jssc.201100067
  88. Proteomics of regulated secretory organelles vol.28, pp.5, 2009, https://doi.org/10.1002/mas.20211
  89. Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway vol.21, pp.3, 2016, https://doi.org/10.1007/s10495-015-1207-0
  90. The Equilibrative Nucleoside Transporter (ENT1) can be phosphorylated at multiple sites by PKC and PKA vol.28, pp.6, 2011, https://doi.org/10.3109/09687688.2011.604861
  91. Radiolabelled proteomics to determine differential functioning ofAccumulibacterduring the anaerobic and aerobic phases of a bioreactor operating for enhanced biological phosphorus removal vol.11, pp.12, 2009, https://doi.org/10.1111/j.1462-2920.2009.02007.x
  92. Proteomic dissection of plant development vol.6, pp.14, 2006, https://doi.org/10.1002/pmic.200500851
  93. Proteome analysis ofPueraria mirificatubers collected in different seasons vol.80, pp.6, 2016, https://doi.org/10.1080/09168451.2016.1141035
  94. Hyaluronidase from the venom of the social wasp Polybia paulista (Hymenoptera, Vespidae): Cloning, structural modeling, purification, and immunological analysis vol.64, 2013, https://doi.org/10.1016/j.toxicon.2012.12.019
  95. Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase vol.280, pp.11, 2013, https://doi.org/10.1111/febs.12275
  96. Phosphorylation of Ser-80 of VP1 and Ser-254 of VP2 is essential for human BK virus propagation in tissue culture vol.92, pp.11, 2011, https://doi.org/10.1099/vir.0.033282-0
  97. Proteomic Analysis of the Defense Response of Wheat to the Powdery Mildew Fungus, Blumeria graminis f. sp. tritici vol.33, pp.6, 2014, https://doi.org/10.1007/s10930-014-9583-9
  98. Differences in phosphorylation of phosphoglucomutase 1 in beef steaks from the longissimus dorsi with high or low star probe values vol.96, pp.1, 2014, https://doi.org/10.1016/j.meatsci.2013.07.017
  99. Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins vol.16, pp.12, 2005, https://doi.org/10.1016/j.jasms.2005.08.008
  100. A novel molecular dynamics approach to evaluate the effect of phosphorylation on multimeric protein interface: the αB-Crystallin case study vol.17, pp.S4, 2016, https://doi.org/10.1186/s12859-016-0909-9
  101. Structural and functional analysis of phosphorylation-specific binders of the kinase ERK from designed ankyrin repeat protein libraries vol.109, pp.34, 2012, https://doi.org/10.1073/pnas.1205399109
  102. Proteomic analysis reveals the potential involvement of xylanase from Pyrenophora teres f. teres in net form net blotch disease of barley vol.43, pp.6, 2014, https://doi.org/10.1007/s13313-014-0314-7
  103. Rampant Purifying Selection Conserves Positions with Posttranslational Modifications in Human Proteins vol.28, pp.5, 2011, https://doi.org/10.1093/molbev/msr013
  104. Conserved and quickly evolving immunome genes have different evolutionary paths vol.33, pp.10, 2012, https://doi.org/10.1002/humu.22125
  105. Hydrogen–deuterium exchange mass spectrometry for determining protein structural changes in drug discovery vol.38, pp.10, 2015, https://doi.org/10.1007/s12272-015-0584-9
  106. Characterizing disease-associated changes in post-translational modifications by mass spectrometry vol.15, pp.3, 2018, https://doi.org/10.1080/14789450.2018.1433036
  107. Gears-In-Motion: The Interplay of WW and PPIase Domains in Pin1 vol.8, pp.2234-943X, 2018, https://doi.org/10.3389/fonc.2018.00469
  108. Utilizing Optimized Tools to Investigate PTM Crosstalk: Identifying Potential PTM Crosstalk of Acetylated Mitochondrial Proteins vol.6, pp.2, 2018, https://doi.org/10.3390/proteomes6020024
  109. Current trends in protein acetylation analysis vol.16, pp.2, 2019, https://doi.org/10.1080/14789450.2019.1559061