Introduction to Protein Posttranslational Modifications (PTMs)

  • Xiucong BaoEmail author
Part of the Springer Theses book series (Springer Theses)


In the ‘central dogma’ of molecular biology, genetic information stored in DNA can be transcribed into mRNAs and eventually translated into proteins to fulfill their biological functions.


  1. 1.
    Walsh CT, Garneau-Tsodikova S, Gatto GJ, Jr. (2005) Protein posttranslational modifications: the chemistry of proteome diversifications. Angewandte Chem 44:7342–7372.
  2. 2.
    Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336. Scholar
  3. 3.
    Maniatis T, Tasic B (2002) Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418:236–243. Scholar
  4. 4.
    Walsh C (2006) Posttranslational modification of proteins: expanding nature’s inventory. Roberts and Company Publishers, Englewood, COGoogle Scholar
  5. 5.
    Greer EL, Shi Y (2012) Histone methylation: a dynamic mark in health, disease and inheritance Nature reviews. Genetics 13:343–357
  6. 6.
    Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of rna synthesis. Proc Natl Acad Sci USA 51:786–794. Scholar
  7. 7.
    Mann M, Ong SE, Gronborg M, Steen H, Jensen ON, Pandey A (2002) Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome. Trends Biotechnol 20:261–268CrossRefGoogle Scholar
  8. 8.
    Paik WK, Paik DC, Kim S (2007) Historical review: the field of protein methylation. Trends Biochem Sci 32:146–152. Scholar
  9. 9.
    Smith BC, Denu JM (2009) Chemical mechanisms of histone lysine and arginine modifications. Biochem Biophys Acta 1789:45–57. Scholar
  10. 10.
    Adams JA (2001) Kinetic and catalytic mechanisms of protein kinases. Chem Rev 101:2271–2290CrossRefGoogle Scholar
  11. 11.
    Jiang J et al (2012) Investigation of the acetylation mechanism by GCN5 histone acetyltransferase PloS One 7:e36660. Scholar
  12. 12.
    Okazaki IJ, Moss J (1996) Mono-ADP-ribosylation: a reversible posttranslational modification of proteins. Adv Pharmacol 35:247–280CrossRefGoogle Scholar
  13. 13.
    Cohen P (2000) The regulation of protein function by multisite phosphorylation–a 25 year update. Trends Biochem Sci 25:596–601CrossRefGoogle Scholar
  14. 14.
    Ubersax JA, Ferrell JE Jr (2007) Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol 8:530–541. Scholar
  15. 15.
    Eberharter A, Becker PB (2002) Histone acetylation: a switch between repressive and permissive chromatin. Second Rev Ser Chromatin Dyn EMBO Rep 3:224–229. Scholar
  16. 16.
    Soutoglou E, Katrakili N, Talianidis I (2000) Acetylation regulates transcription factor activity at multiple levels. Mol Cell 5:745–751CrossRefGoogle Scholar
  17. 17.
    Anderson KA, Hirschey MD (2012) Mitochondrial protein acetylation regulates metabolism. Essays Biochem 52:23–35. Scholar
  18. 18.
    Resh MD (2013) Covalent lipid modifications of proteins. Curr Biol CB 23:R431–R435. Scholar
  19. 19.
    Hochstrasser M (1996) Ubiquitin-dependent protein degradation. Ann Rev Genet 30:405–439. Scholar
  20. 20.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705. Scholar
  21. 21.
    Tan S, Davey CA (2011) Nucleosome structural studies. Curr Opin Struct Biol 21:128–136. Scholar
  22. 22.
    Sarma K, Reinberg D (2005) Histone variants meet their match. Nat Rev Mol Cell Biol 6:139–149. Scholar
  23. 23.
    Gutierrez JL, Chandy M, Carrozza MJ, Workman JL (2007) Activation domains drive nucleosome eviction by SWI/SNF. EMBO J 26:730–740. Scholar
  24. 24.
    Huang H, Lin S, Garcia BA, Zhao Y (2015) Quantitative proteomic analysis of histone modifications. Chem Rev 115:2376–2418. Scholar
  25. 25.
    Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Ann Rev Biochem 70:81–120. Scholar
  26. 26.
    Sauve AA, Wolberger C, Schramm VL, Boeke JD (2006) The biochemistry of sirtuins. Annu Rev Biochem 75:435–465. Scholar
  27. 27.
    Falkenberg KJ, Johnstone RW (2014) Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Disc 13:673–691. Scholar
  28. 28.
    Bowman GD, Poirier MG (2015) Post-translational modifications of histones that influence nucleosome dynamics. Chem Rev 115:2274–2295. Scholar
  29. 29.
    Allan J, Harborne N, Rau DC, Gould H (1982) Participation of core histone “tails” in the stabilization of the chromatin solenoid. J Cell Biol 93:285–297CrossRefGoogle Scholar
  30. 30.
    Fletcher TM, Hansen JC (1995) Core histone tail domains mediate oligonucleosome folding and nucleosomal DNA organization through distinct molecular mechanisms. J Biol Chem 270:25359–25362CrossRefGoogle Scholar
  31. 31.
    Simpson RT (1978) Structure of chromatin containing extensively acetylated H3 and H4. Cell 13:691–699CrossRefGoogle Scholar
  32. 32.
    Neumann H et al (2009) A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell 36:153–163. Scholar
  33. 33.
    Tropberger P et al (2013) Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer. Cell 152:859–872
  34. 34.
    Manohar M et al (2009) Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding. J Biol Chem 284:23312–23321. Scholar
  35. 35.
    Chatterjee N et al (2015) Histone acetylation near the nucleosome dyad axis enhances nucleosome disassembly by RSC and SWI/SNF. Mol Cell Biol 35:4083–4092. Scholar
  36. 36.
    Ye J et al (2005) Histone H4 lysine 91 acetylation a core domain modification associated with chromatin assembly. Mol Cell 18:123–130. Scholar
  37. 37.
    Musselman CA, Lalonde ME, Cote J, Kutateladze TG (2012) Perceiving the epigenetic landscape through histone readers. Nat Struct Mol Biol 19:1218–1227. Scholar
  38. 38.
    Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM (1999) Structure and ligand of a histone acetyltransferase bromodomain. Nature 399:491–496. Scholar
  39. 39.
    Syntichaki P, Topalidou I, Thireos G (2000) The Gcn5 bromodomain co-ordinates nucleosome remodelling. Nature 404:414–417. Scholar
  40. 40.
    Jacobson RH, Ladurner AG, King DS, Tjian R (2000) Structure and function of a human TAFII250 double bromodomain module. Science 288:1422–1425CrossRefGoogle Scholar
  41. 41.
    Kasten M, Szerlong H, Erdjument-Bromage H, Tempst P, Werner M, Cairns BR (2004) Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14. EMBO J 23:1348–1359. Scholar
  42. 42.
    Nielsen PR et al (2002) Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416:103–107. Scholar
  43. 43.
    Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120. Scholar
  44. 44.
    Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124. Scholar
  45. 45.
    Vermeulen M et al (2007) Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131:58–69. Scholar
  46. 46.
    Flanagan JF et al (2005) Double chromodomains cooperate to recognize the methylated histone H3 tail. Nature 438:1181–1185. Scholar
  47. 47.
    Phillips DM (1963) The presence of acetyl groups of histones. Biochem J 87:258–263CrossRefGoogle Scholar
  48. 48.
    L’Hernault SW, Rosenbaum JL (1985) Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24:473–478CrossRefGoogle Scholar
  49. 49.
    Gu W, Roeder RG (1997) Activation of p 53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain Cell 90:595–606Google Scholar
  50. 50.
    Kiernan RE et al (1999) HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J 18:6106–6118. Scholar
  51. 51.
    Ott M, Schnolzer M, Garnica J, Fischle W, Emiliani S, Rackwitz HR, Verdin E (1999) Acetylation of the HIV-1 Tat protein by p 300 is important for its transcriptional activity. Curr Biol CB 9:1489–1492CrossRefGoogle Scholar
  52. 52.
    Kim SC et al (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23:607–618. Scholar
  53. 53.
    Choudhary C et al (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840. Scholar
  54. 54.
    Millar CB, Kurdistani SK, Grunstein M (2004) Acetylation of yeast histone H4 lysine 16: a switch for protein interactions in heterochromatin and euchromatin. Cold Spring Harb Symp Quant Biol 69:193–200.
  55. 55.
    Ge Z, Nair D, Guan X, Rastogi N, Freitas MA, Parthun MR (2013) Sites of acetylation on newly synthesized histone H4 are required for chromatin assembly and DNA damage response signaling. Mol Cell Biol 33:3286–3298.
  56. 56.
    Yuan J, Pu MT, Zhang ZG, Lou ZK (2009) Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8:1747–1753. Scholar
  57. 57.
    Tamburini BA, Tyler JK (2005) Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair. Mol Cell Biol 25:4903–4913. Scholar
  58. 58.
    Luo J, Li M, Tang Y, Laszkowska M, Roeder RG, Gu W (2004) Acetylation of p 53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci U S A 101:2259–2264CrossRefGoogle Scholar
  59. 59.
    Lamonica JM, Vakoc CR, Blobel GA (2006) Acetylation of GATA-1 is required for chromatin occupancy. Blood 108:3736–3738.
  60. 60.
    Ott M et al. (2004) Tat acetylation: a regulatory switch between early and late phases in HIV transcription elongation. Novartis Found Symp 259:182–193; discussion 193–186, 223–185Google Scholar
  61. 61.
    Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–851CrossRefGoogle Scholar
  62. 62.
    Massuda ES et al (1997) Regulated expression of the diphtheria toxin A chain by a tumor-specific chimeric transcription factor results in selective toxicity for alveolar rhabdomyosarcoma cells. Proc Natl Acad Sci USA 94:14701–14706CrossRefGoogle Scholar
  63. 63.
    Marmorstein R (2001) Structure and function of histone acetyltransferases. Cell Mol Life Sci CMLS 58:693–703CrossRefGoogle Scholar
  64. 64.
    Marmorstein R, Roth SY (2001) Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev 11:155–161CrossRefGoogle Scholar
  65. 65.
    Dokmanovic M, Clarke C, Marks PA (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res MCR 5:981–989. Scholar
  66. 66.
    Marks PA, Xu WS (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107:600–608. Scholar
  67. 67.
    Liu Z, Yang T, Li X, Peng T, Hang HC, Li XD (2015) Integrative chemical biology approaches for identification and characterization of “erasers” for fatty-acid-acylated lysine residues within proteins. Angew Chem 54:1149–1152. Scholar
  68. 68.
    Bao X et al (2014) Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach eLife 3.
  69. 69.
    Du J et al (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase Science 334:806–809.
  70. 70.
    Tan M et al (2014) Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab 19:605–617.
  71. 71.
    Peng C et al (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics MCP 10(M111):012658. Scholar
  72. 72.
    Jiang H et al (2013) SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496:110–113. Scholar
  73. 73.
    Ryall JG et al (2015) The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Cell Stem Cell 16:171–183. Scholar
  74. 74.
    Nakahata Y et al (2008) The NAD +-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–340. Scholar
  75. 75.
    Vaziri H et al (2001) hSIR2(SIRT1) functions as an NAD-dependent p 53 deacetylase. Cell 107:149–159Google Scholar
  76. 76.
    Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 282:6823–6832.
  77. 77.
    North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003) The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 11:437–444CrossRefGoogle Scholar
  78. 78.
    North BJ, Verdin E (2007) Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis. PloS one 2:e784
  79. 79.
    Teng YB et al (2015) Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies. Sci Rep 5:8529. Scholar
  80. 80.
    Hirschey MD, Shimazu T, Huang JY, Schwer B, Verdin E (2011) SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism. Cold Spring Harb Symp Quant Biol 76:267–277.
  81. 81.
    Hirschey MD et al (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–125. Scholar
  82. 82.
    Mahlknecht U, Voelter-Mahlknecht S (2011) Genomic organization and localization of the NAD-dependent histone deacetylase gene sirtuin 3 (Sirt3) in the mouse. Int J Oncol 38:813–822. Scholar
  83. 83.
    Scher MB, Vaquero A, Reinberg D (2007) SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 21:920–928.
  84. 84.
    Iwahara T, Bonasio R, Narendra V, Reinberg D (2012) SIRT3 functions in the nucleus in the control of stress-related gene expression. Mol Cell Biol 32:5022–5034.
  85. 85.
    Ahuja N et al (2007) Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem 282:33583–33592.
  86. 86.
    Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009) SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560–570.
  87. 87.
    Nishida Y et al (2015) SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol Cell 59:321–332. Scholar
  88. 88.
    Park J et al (2013) SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell 50:919–930. Scholar
  89. 89.
    Van Meter M, Kashyap M, Rezazadeh S, Geneva AJ, Morello TD, Seluanov A, Gorbunova V (2014) SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun 5:5011. Scholar
  90. 90.
    Mao Z et al (2011) SIRT6 promotes DNA repair under stress by activating PARP1. Science 332:1443–1446. Scholar
  91. 91.
    Liszt G, Ford E, Kurtev M, Guarente L (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem 280:21313–21320.
  92. 92.
    Kawahara TL et al (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136:62–74.
  93. 93.
    Michishita E et al (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nat 452:492–496.
  94. 94.
    Barber MF et al (2012) SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nat 487:114–118.
  95. 95.
    Kiran S, Chatterjee N, Singh S, Kaul SC, Wadhwa R, Ramakrishna G (2013) Intracellular distribution of human SIRT7 and mapping of the nuclear/nucleolar localization signal. FEBS J 280:3451–3466.
  96. 96.
    Filippakopoulos P, Knapp S (2014) Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Disc 13:337–356. Scholar
  97. 97.
    Cherasse Y et al (2007) The p 300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP. Nucleic Acids Res 35:5954–5965.
  98. 98.
    Cao F et al (2014) Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol Cell 53:247–261. Scholar
  99. 99.
    Meyers RE, Sharp PA (1993) TATA-binding protein and associated factors in polymerase II and polymerase III transcription. Mol Cell Biol 13:7953–7960CrossRefGoogle Scholar
  100. 100.
    Wu SY, Chiang CM (2001) TATA-binding protein-associated factors enhance the recruitment of RNA polymerase II by transcriptional activators. J Biol Chem 276:34235–34243. Scholar
  101. 101.
    Lange M et al (2008) Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. Genes Dev 22:2370–2384. Scholar
  102. 102.
    Zeng L, Zhang Q, Li S, Plotnikov AN, Walsh MJ, Zhou MM (2010) Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature 466:258–262. Scholar
  103. 103.
    Li Y et al (2014) AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation. Cell 159:558–571. Scholar
  104. 104.
    Boussouar F, Jamshidikia M, Morozumi Y, Rousseaux S, Khochbin S (2013) Malignant genome reprogramming by ATAD2. Biochim Biophys Acta 1829:1010–1014. Scholar
  105. 105.
    Vangamudi B et al (2015) The SMARCA2/4 ATPase domain surpasses the bromodomain as a drug target in SWI/SNF-mutant cancers: insights from cDNA rescue and PFI-3 inhibitor studies. Cancer Res 75:3865–3878. Scholar
  106. 106.
    Moriniere J et al (2009) Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461:664–668. Scholar
  107. 107.
    Cavellan E, Asp P, Percipalle P, Farrants AK (2006) The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear proteins in transcription. J Biol Chem 281:16264–16271. Scholar
  108. 108.
    Fairbridge NA, Dawe CE, Niri FH, Kooistra MK, King-Jones K, McDermid HE (2010) Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors Birth defects research Part A. Clin Mol Teratol 88:619–625. Scholar
  109. 109.
    Huang H, Rambaldi I, Daniels E, Featherstone M (2003) Expression of the Wdr9 gene and protein products during mouse development developmental. Dyn Official Publ Am Assoc Anatomists 227:608–614. Scholar
  110. 110.
    An S, Yeo KJ, Jeon YH, Song JJ (2011) Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J Biol Chem 286:8369–8374. Scholar
  111. 111.
    Gregory GD et al (2007) Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol Cell Biol 27:8466–8479. Scholar
  112. 112.
    LeRoy G, Rickards B, Flint SJ (2008) The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell 30:51–60. Scholar
  113. 113.
    Venturini L et al (1999) TIF1gamma, a novel member of the transcriptional intermediary factor 1 family. Oncogene 18:1209–1217. Scholar
  114. 114.
    Sanchez R, Zhou MM (2009) The role of human bromodomains in chromatin biology and gene transcription. Curr Opin Drug Disc Dev 12:659–665Google Scholar
  115. 115.
    Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (2009) Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons. Dev Biol 329:176–190. Scholar
  116. 116.
    Muller P, Kuttenkeuler D, Gesellchen V, Zeidler MP, Boutros M (2005) Identification of JAK/STAT signalling components by genome-wide RNA interference. Nature 436:871–875. Scholar
  117. 117.
    Field M et al (2007) Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly. Am J Hum Genet 81:367–374. Scholar
  118. 118.
    Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR (2013) Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet 45:592–601. Scholar
  119. 119.
    Reisman D, Glaros S, Thompson EA (2009) The SWI/SNF complex and cancer. Oncogene 28:1653–1668.
  120. 120.
    Kaburagi Y et al (2007) Role of IRS and PHIP on insulin-induced tyrosine phosphorylation and distribution of IRS proteins. Cell Struct Function 32:69–78CrossRefGoogle Scholar
  121. 121.
    Farhang-Fallah J, Yin X, Trentin G, Cheng AM, Rozakis-Adcock M (2000) Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein. J Biol Chem 275:40492–40497. Scholar
  122. 122.
    Zhou Y, Santoro R, Grummt I (2002) The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J 21:4632–4640CrossRefGoogle Scholar
  123. 123.
    Santoro R, Li J, Grummt I (2002) The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription. Nat Genet 32:393–396. Scholar
  124. 124.
    Yan K et al (2016) The chromatin regulator BRPF3 preferentially activates the HBO1 acetyltransferase but is dispensable for mouse development and survival. J Biol Chem 291:2647–2663.
  125. 125.
    Zhang Z, Tan M, Xie Z, Dai L, Chen Y, Zhao Y (2011) Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol 7:58–63. Scholar
  126. 126.
    Colak G et al (2013) Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli. Mol Cell Proteomics MCP 12:3509–3520. Scholar
  127. 127.
    Rosen R, Becher D, Buttner K, Biran D, Hecker M, Ron EZ (2004) Probing the active site of homoserine trans-succinylase. FEBS Lett 577:386–392. Scholar
  128. 128.
    Kawai Y, Fujii H, Okada M, Tsuchie Y, Uchida K, Osawa T (2006) Formation of Nepsilon-(succinyl)lysine in vivo: a novel marker for docosahexaenoic acid-derived protein modification. J Lipid Res 47:1386–1398.
  129. 129.
    Repetto B, Tzagoloff A (1989) Structure and regulation of KGD1, the structural gene for yeast alpha-ketoglutarate dehydrogenase. Mol Cell Biol 9:2695–2705CrossRefGoogle Scholar
  130. 130.
    Przybyla-Zawislak B, Dennis RA, Zakharkin SO, McCammon MT (1998) Genes of succinyl-CoA ligase from Saccharomyces cerevisiae. Eur J Biochem/FEBS 258:736–743CrossRefGoogle Scholar
  131. 131.
    Weinert BT, Scholz C, Wagner SA, Iesmantavicius V, Su D, Daniel JA, Choudhary C (2013) Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep 4:842–851. Scholar
  132. 132.
    Tannahill GM et al (2013) Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496:238–242. Scholar
  133. 133.
    Rardin MJ et al (2013) SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab 18:920–933. Scholar
  134. 134.
    Xie L et al (2015) First succinyl-proteome profiling of extensively drug-resistant Mycobacterium tuberculosis revealed involvement of succinylation in cellular physiology. J Proteome Res 14:107–119. Scholar
  135. 135.
    Yang M et al (2015) Succinylome analysis reveals the involvement of lysine succinylation in metabolism in pathogenic Mycobacterium tuberculosis. Mol Cell Proteomics MCP 14:796–811. Scholar
  136. 136.
    Li X et al (2014) Systematic identification of the lysine succinylation in the protozoan parasite Toxoplasma gondii. J Proteome Res 13:6087–6095. Scholar
  137. 137.
    Xie Z et al (2012) Lysine succinylation and lysine malonylation in histones. Mol Cell Proteomics MCP 11:100–107. Scholar
  138. 138.
    Wagner GR, Payne RM (2013) Widespread and enzyme-independent Nepsilon-acetylation and Nepsilon-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem 288:29036–29045. Scholar
  139. 139.
    Grammel M, Hang HC (2013) Chemical reporters for biological discovery. Nat Chem Biol 9:475–484. Scholar
  140. 140.
    Bao X, Zhao Q, Yang T, Fung YM, Li XD (2013) A chemical probe for lysine malonylation. Angew Chem 52:4883–4886. Scholar
  141. 141.
    Berg JM, Tymoczko JL, Stryer L (2002) Acetyl coenzyme A carboxylase plays a key role in controlling fatty acid metabolism, 5th edn. Biochemistry, New YorkGoogle Scholar
  142. 142.
    Gaertig J, Cruz MA, Bowen J, Gu L, Pennock DG, Gorovsky MA (1995) Acetylation of lysine 40 in alpha-tubulin is not essential in Tetrahymena thermophila. J Cell Biol 129:1301–1310CrossRefGoogle Scholar
  143. 143.
    Saggerson D (2008) Malonyl-CoA, a key signaling molecule in mammalian cells. Ann Rev Nutr 28:253–272. Scholar
  144. 144.
    Abu-Elheiga L, Oh W, Kordari P, Wakil SJ (2003) Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci U S A 100:10207–10212. Scholar
  145. 145.
    de Wit MC et al (2006) Brain abnormalities in a case of malonyl-CoA decarboxylase deficiency. Mol Genet Metab 87:102–106. Scholar
  146. 146.
    Du Y et al (2015) Lysine malonylation is elevated in type 2 diabetic mouse models and enriched in metabolic associated proteins. Mol Cell Proteomics MCP 14:227–236. Scholar
  147. 147.
    Colak G et al (2015) Proteomic and biochemical studies of lysine malonylation suggest Its malonic aciduria-associated regulatory role in mitochondrial function and fatty Acid oxidation. Mol Cell Proteomics MCP 14:3056–3071. Scholar
  148. 148.
    Lu C, Thompson CB (2012) Metabolic regulation of epigenetics. Cell metabolism 16:9–17. Scholar
  149. 149.
    Tan M et al (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146:1016–1028.
  150. 150.
    Montellier E, Rousseaux S, Zhao Y, Khochbin S (2012) Histone crotonylation specifically marks the haploid male germ cell gene expression program: post-meiotic male-specific gene expression. BioEssays News Rev Mol Cell Dev Biol 34:187–193.
  151. 151.
    Flynn EM, Huang OW, Poy F, Oppikofer M, Bellon SF, Tang Y, Cochran AG (2015) A subset of human bromodomains recognizes butyryllysine and crotonyllysine histone peptide modifications. Structure 23:1801–1814. Scholar
  152. 152.
    Sabari BR et al (2015) Intracellular crotonyl-CoA stimulates transcription through p 300-catalyzed histone crotonylation. Mol Cell 58:203–215. Scholar
  153. 153.
    Wang ZG, Lv N, Bi WZ, Zhang JL, Ni JZ (2015) Development of the affinity materials for phosphorylated proteins/peptides enrichment in phosphoproteomics analysis. ACS applied materials & interfaces 7:8377–8392. Scholar
  154. 154.
    Andersson L, Porath J (1986) Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. Anal Biochem 154:250–254Google Scholar
  155. 155.
    Schmidt A, Csaszar E, Ammerer G, Mechtler K (2008) Enhanced detection and identification of multiply phosphorylated peptides using TiO2 enrichment in combination with MALDI TOF/TOF MS. Proteomics 8:4577–4592.
  156. 156.
    Rush J et al (2005) Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 23:94–101. Scholar
  157. 157.
    Bergstrom Lind S et al (2008) Immunoaffinity enrichments followed by mass spectrometric detection for studying global protein tyrosine phosphorylation. J Proteome Res 7:2897–2910. Scholar
  158. 158.
    Carlson SM, Gozani O (2014) Emerging technologies to map the protein methylome. J Mol Biol 426:3350–3362. Scholar
  159. 159.
    Geoghegan V, Guo A, Trudgian D, Thomas B, Acuto O (2015) Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling. Nat Commun 6:6758. Scholar
  160. 160.
    Sletten EM, Bertozzi CR (2009) Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem 48:6974–6998. Scholar
  161. 161.
    Resh MD (2006) Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol 2:584–590. Scholar
  162. 162.
    Hang HC, Wilson JP, Charron G (2011) Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking. Acc Chem Res 44:699–708. Scholar
  163. 163.
    Kho Y et al (2004) A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. Proc Natl Acad Sci USA 101:12479–12484. Scholar
  164. 164.
    Charron G, Tsou LK, Maguire W, Yount JS, Hang HC (2011) Alkynyl-farnesol reporters for detection of protein S-prenylation in cells. Mol BioSyst 7:67–73. Scholar
  165. 165.
    DeGraw AJ, Palsuledesai C, Ochocki JD, Dozier JK, Lenevich S, Rashidian M, Distefano MD (2010) Evaluation of alkyne-modified isoprenoids as chemical reporters of protein prenylation. Chem Biol Drug Des 76:460–471. Scholar
  166. 166.
    Burnaevskiy N et al (2013) Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ. Nature 496:106–109. Scholar
  167. 167.
    Peng T, Hang HC (2015) Bifunctional fatty acid chemical reporter for analyzing S-palmitoylated membrane protein-protein interactions in mammalian cells. J Am Chem Soc 137:556–559. Scholar
  168. 168.
    Zaro BW, Yang YY, Hang HC, Pratt MR (2011) Chemical reporters for fluorescent detection and identification of O-GlcNAc-modified proteins reveal glycosylation of the ubiquitin ligase NEDD4–1. Proc Natl Acad Sci U S A 108:8146–8151. Scholar
  169. 169.
    Westcott NP, Hang HC (2014) Chemical reporters for exploring ADP-ribosylation and AMPylation at the host-pathogen interface. Curr Opin Chem Biol 23:56–62. Scholar
  170. 170.
    Grammel M, Luong P, Orth K, Hang HC (2011) A chemical reporter for protein AMPylation. J Am Chem Soc 133:17103–17105. Scholar
  171. 171.
    Thinon E, Hang HC (2015) Chemical reporters for exploring protein acylation. Biochem Soc Trans 43:253–261. Scholar
  172. 172.
    Young KH (1998) Yeast two-hybrid: so many interactions, (in) so little time. Biol Reprod 58:302–311CrossRefGoogle Scholar
  173. 173.
    Adams PD, Seeholzer S, Ohh M (2002) Identification of associated proteins by coimmunoprecipitation. In: Golemis E (ed) Protein-Protein Interactions. A Molecular Cloning Manual, CSHL Press, New YorkGoogle Scholar
  174. 174.
    Li X, Kapoor TM (2010) Approach to profile proteins that recognize post-translationally modified histone “tails”. J Am Chem Soc 132:2504–2505. Scholar
  175. 175.
    Li X, Foley EA, Molloy KR, Li Y, Chait BT, Kapoor TM (2012) Quantitative chemical proteomics approach to identify post-translational modification-mediated protein-protein interactions. J Am Chem Soc 134:1982–1985. Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of ChemistryThe University of Hong KongHong KongChina

Personalised recommendations