CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009559
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
 CAA24918.1; AAA52652.1; AAA63188.1; CAA43011.1; CAA43012.1; CAA43013.1; CAA43014.1; CAA43016.1; CAA43017.1; CAA47464.1; CAB02549.1; CAA58538.1; AAM83108.1; AAN01438.1; AAN01439.1; AAN01440.1; AAN01441.1; AAN01442.1; AAN01443.1; AAN01444.1; AAN01446.1; AAN01447.1; AAN01448.1; AAN01449.1; AAN01450.1; BAA19208.1; AAT68253.1; CAG46966.1; CAG46969.1; CAG46977.1; CAG46984.1; CAG46986.1; CAA16946.1; CAC69642.1; CAC03414.1; CAC03418.1; CAC03426.1; CAC03427.1; CAC04128.1; CAD24074.1; CAI12560.1; CAI12567.1; EAW55509.1; EAW55510.1; EAW55538.1; EAW55549.1; EAW55555.1; EAW96325.1; EAX03086.1; EAX03111.1; EAX03112.1; EAX03121.1; AAH17361.1; AAH54014.1; AAH66248.1; AAH66249.1; AAH66250.1; AAH67495.1; AAH67496.1; AAH67497.1; AAH69288.1; AAH69392.1; AAH69467.1; AAH69654.1; AAH93763.1; AAH93765.1; AAH93969.1; AAI11094.1; AAI11435.1; AAI12194.1; AAI20940.1; AAI28105.1; AAI28106.1; AAI30559.1; AAI30561.1; AAI43046.1 
Protein Name
 Histone H4 
Protein Synonyms/Alias
  
Gene Name
 HIST1H4A; HIST1H4B; HIST1H4C; HIST1H4D; HIST1H4E; HIST1H4F; HIST1H4H; HIST1H4I; HIST1H4J; HIST1H4K; HIST1H4L; HIST2H4A; HIST2H4B; HIST4H4 
Gene Synonyms/Alias
 H4/A; H4FA; H4/I; H4FI; H4/G; H4FG; H4/B; H4FB; H4/J; H4FJ; H4/C; H4FC; H4/H; H4FH; H4/M; H4FM; H4/E; H4FE; H4/D; H4FD; H4/K; H4FK; H4/N; H4F2; H4FN; HIST2H4; H4/O; H4FO 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
6**MSGRGKGGKGLGKacetylation[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]
6**MSGRGKGGKGLGKbutyrylation[24]
6**MSGRGKGGKGLGKcrotonylation[25]
6**MSGRGKGGKGLGKpropionylation[24]
9SGRGKGGKGLGKGGAacetylation[1, 2, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 16, 17, 18, 19, 21, 22, 23, 26, 27]
9SGRGKGGKGLGKGGAbutyrylation[24]
9SGRGKGGKGLGKGGAcrotonylation[25]
9SGRGKGGKGLGKGGApropionylation[24]
13KGGKGLGKGGAKRHRacetylation[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 27, 28]
13KGGKGLGKGGAKRHRbutyrylation[24]
13KGGKGLGKGGAKRHRcrotonylation[25]
13KGGKGLGKGGAKRHRpropionylation[24]
13KGGKGLGKGGAKRHRsuccinylation[29]
13KGGKGLGKGGAKRHRsumoylation[30]
13KGGKGLGKGGAKRHRubiquitination[31]
17GLGKGGAKRHRKVLRacetylation[1, 2, 4, 5, 6, 7, 8, 9, 11, 13, 14, 16, 17, 19, 22, 23, 27, 28, 32, 33]
17GLGKGGAKRHRKVLRbutyrylation[24]
17GLGKGGAKRHRKVLRpropionylation[24]
21GGAKRHRKVLRDNIQmethylation[34, 35]
32DNIQGITKPAIRRLAacetylation[11, 16, 17, 21, 23]
32DNIQGITKPAIRRLAbutyrylation[24]
32DNIQGITKPAIRRLAmethylation[8]
32DNIQGITKPAIRRLApropionylation[24]
32DNIQGITKPAIRRLAsuccinylation[29]
32DNIQGITKPAIRRLAubiquitination[23, 31, 36, 37, 38, 39, 40, 41, 42, 43, 44]
45LARRGGVKRISGLIYbutyrylation[24]
45LARRGGVKRISGLIYpropionylation[24]
60EETRGVLKVFLENVIacetylation[16, 19]
60EETRGVLKVFLENVImethylation[45]
60EETRGVLKVFLENVIubiquitination[23, 31, 36, 38, 39, 40, 41, 42, 43, 44]
78VTYTEHAKRKTVTAMacetylation[21]
78VTYTEHAKRKTVTAMbutyrylation[24]
78VTYTEHAKRKTVTAMmethylation[8]
78VTYTEHAKRKTVTAMpropionylation[24]
78VTYTEHAKRKTVTAMsuccinylation[29]
78VTYTEHAKRKTVTAMubiquitination[23, 31, 38, 39, 40, 41, 43, 44]
80YTEHAKRKTVTAMDVacetylation[46]
80YTEHAKRKTVTAMDVbutyrylation[24]
80YTEHAKRKTVTAMDVmethylation[34]
80YTEHAKRKTVTAMDVpropionylation[24]
80YTEHAKRKTVTAMDVubiquitination[31, 38, 39]
92MDVVYALKRQGRTLYacetylation[21, 46]
92MDVVYALKRQGRTLYbutyrylation[24]
92MDVVYALKRQGRTLYpropionylation[24]
92MDVVYALKRQGRTLYsuccinylation[29]
92MDVVYALKRQGRTLYubiquitination[23, 31, 36, 39, 40, 41, 43, 44]
Reference
 [1] Patterns of histone acetylation.
 Thorne AW, Kmiciek D, Mitchelson K, Sautiere P, Crane-Robinson C.
 Eur J Biochem. 1990 Nov 13;193(3):701-13. [PMID: 2249688]
 [2] Histone H4 acetylation in human cells. Frequency of acetylation at different sites defined by immunolabeling with site-specific antibodies.
 Turner BM, O'Neill LP, Allan IM.
 FEBS Lett. 1989 Aug 14;253(1-2):141-5. [PMID: 2474456]
 [3] Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase.
 Verreault A, Kaufman PD, Kobayashi R, Stillman B.
 Curr Biol. 1998 Jan 15;8(2):96-108. [PMID: 9427644]
 [4] Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.
 Schiltz RL, Mizzen CA, Vassilev A, Cook RG, Allis CD, Nakatani Y.
 J Biol Chem. 1999 Jan 15;274(3):1189-92. [PMID: 9880483]
 [5] Tip60 acetylates six lysines of a specific class in core histones in vitro.
 Kimura A, Horikoshi M.
 Genes Cells. 1998 Dec;3(12):789-800. [PMID: 10096020]
 [6] Histone acetylation and deacetylation: identification of acetylation and methylation sites of HeLa histone H4 by mass spectrometry.
 Zhang K, Williams KE, Huang L, Yau P, Siino JS, Bradbury EM, Jones PR, Minch MJ, Burlingame AL.
 Mol Cell Proteomics. 2002 Jul;1(7):500-8. [PMID: 12239278]
 [7] Shotgun annotation of histone modifications: a new approach for streamlined characterization of proteins by top down mass spectrometry.
 Pesavento JJ, Kim YB, Taylor GK, Kelleher NL.
 J Am Chem Soc. 2004 Mar 24;126(11):3386-7. [PMID: 15025441]
 [8] Quantitative proteomic analysis of post-translational modifications of human histones.
 Beck HC, Nielsen EC, Matthiesen R, Jensen LH, Sehested M, Finn P, Grauslund M, Hansen AM, Jensen ON.
 Mol Cell Proteomics. 2006 Jul;5(7):1314-25. [PMID: 16627869]
 [9] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [10] Properties of the type B histone acetyltransferase Hat1: H4 tail interaction, site preference, and involvement in DNA repair.
 Benson LJ, Phillips JA, Gu Y, Parthun MR, Hoffman CS, Annunziato AT.
 J Biol Chem. 2007 Jan 12;282(2):836-42. [PMID: 17052979]
 [11] Organismal differences in post-translational modifications in histones H3 and H4.
 Garcia BA, Hake SB, Diaz RL, Kauer M, Morris SA, Recht J, Shabanowitz J, Mishra N, Strahl BD, Allis CD, Hunt DF.
 J Biol Chem. 2007 Mar 9;282(10):7641-55. [PMID: 17194708]
 [12] Histone H4 acetylation dynamics determined by stable isotope labeling with amino acids in cell culture and mass spectrometry.
 Su X, Zhang L, Lucas DM, Davis ME, Knapp AR, Green-Church KB, Marcucci G, Parthun MR, Byrd JC, Freitas MA.
 Anal Biochem. 2007 Apr 1;363(1):22-34. [PMID: 17286952]
 [13] Analysis of dynamic changes in post-translational modifications of human histones during cell cycle by mass spectrometry.
 Bonenfant D, Towbin H, Coulot M, Schindler P, Mueller DR, van Oostrum J.
 Mol Cell Proteomics. 2007 Nov;6(11):1917-32. [PMID: 17644761]
 [14] Combinatorial modification of human histone H4 quantitated by two-dimensional liquid chromatography coupled with top down mass spectrometry.
 Pesavento JJ, Bullock CR, LeDuc RD, Mizzen CA, Kelleher NL.
 J Biol Chem. 2008 May 30;283(22):14927-37. [PMID: 18381279]
 [15] Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.
 Iizuka M, Takahashi Y, Mizzen CA, Cook RG, Fujita M, Allis CD, Frierson HF Jr, Fukusato T, Smith MM.
 Gene. 2009 May 1;436(1-2):108-14. [PMID: 19393168]
 [16] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [17] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589]
 [18] Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex.
 Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC.
 J Biol Chem. 2010 Feb 12;285(7):4268-72. [PMID: 20018852]
 [19] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [20] Human histone acetyltransferase 1 protein preferentially acetylates H4 histone molecules in H3.1-H4 over H3.3-H4.
 Zhang H, Han J, Kang B, Burgess R, Zhang Z.
 J Biol Chem. 2012 Feb 24;287(9):6573-81. [PMID: 22228774]
 [21] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [22] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [23] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [24] Lysine propionylation and butyrylation are novel post-translational modifications in histones.
 Chen Y, Sprung R, Tang Y, Ball H, Sangras B, Kim SC, Falck JR, Peng J, Gu W, Zhao Y.
 Mol Cell Proteomics. 2007 May;6(5):812-9. [PMID: 17267393]
 [25] Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.
 Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, Zhao Y.
 Cell. 2011 Sep 16;146(6):1016-28. [PMID: 21925322]
 [26] Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo.
 Winkler GS, Kristjuhan A, Erdjument-Bromage H, Tempst P, Svejstrup JQ.
 Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3517-22. [PMID: 11904415]
 [27] Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.
 Marimuthu S, Chivukula RS, Alfonso LF, Moridani M, Hagen FK, Bhat GJ.
 Int J Oncol. 2011 Nov;39(5):1273-83. [PMID: 21743961]
 [28] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [29] Lysine succinylation and lysine malonylation in histones.
 Xie Z, Dai J, Dai L, Tan M, Cheng Z, Wu Y, Boeke JD, Zhao Y.
 Mol Cell Proteomics. 2012 May;11(5):100-7. [PMID: 22389435]
 [30] A novel proteomics approach to identify SUMOylated proteins and their modification sites in human cells.
 Galisson F, Mahrouche L, Courcelles M, Bonneil E, Meloche S, Chelbi-Alix MK, Thibault P.
 Mol Cell Proteomics. 2011 Feb;10(2):M110.004796. [PMID: 21098080]
 [31] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [32] hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells.
 Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A, Akhtar A.
 Mol Cell Biol. 2005 Aug;25(15):6798-810. [PMID: 16024812]
 [33] Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure.
 Jo WJ, Ren X, Chu F, Aleshin M, Wintz H, Burlingame A, Smith MT, Vulpe CD, Zhang L.
 Toxicol Appl Pharmacol. 2009 Dec 15;241(3):294-302. [PMID: 19732783]
 [34] Update on activities at the Universal Protein Resource (UniProt) in 2013.
 e="String">UniProt Consortium.
 Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. [PMID: 23161681]
 [35] Large-scale global identification of protein lysine methylation in vivo.
 Cao XJ, Arnaudo AM, Garcia BA.
 Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510]
 [36] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [37] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [38] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [39] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [40] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [41] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [42] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [43] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [44] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [45] Identification of novel histone post-translational modifications by peptide mass fingerprinting.
 Zhang L, Eugeni EE, Parthun MR, Freitas MA.
 Chromosoma. 2003 Aug;112(2):77-86. [PMID: 12937907]
 [46] HAT4, a Golgi apparatus-anchored B-type histone acetyltransferase, acetylates free histone H4 and facilitates chromatin assembly.
 Yang X, Yu W, Shi L, Sun L, Liang J, Yi X, Li Q, Zhang Y, Yang F, Han X, Zhang D, Yang J, Yao Z, Shang Y.
 Mol Cell. 2011 Oct 7;44(1):39-50. [PMID: 21981917
Functional Description
 Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. 
Sequence Annotation
 DNA_BIND 17 21
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 2 2 Phosphoserine.
 MOD_RES 4 4 Asymmetric dimethylarginine; by PRMT1;
 MOD_RES 4 4 Citrulline; alternate.
 MOD_RES 4 4 Omega-N-methylarginine; by PRMT1;
 MOD_RES 4 4 Symmetric dimethylarginine; by PRMT5 and
 MOD_RES 6 6 N6-acetyllysine; alternate.
 MOD_RES 6 6 N6-crotonyl-L-lysine; alternate.
 MOD_RES 9 9 N6-acetyllysine; alternate.
 MOD_RES 9 9 N6-crotonyl-L-lysine; alternate.
 MOD_RES 13 13 N6-acetyllysine; alternate.
 MOD_RES 13 13 N6-crotonyl-L-lysine; alternate.
 MOD_RES 17 17 N6-acetyllysine; alternate.
 MOD_RES 17 17 N6-crotonyl-L-lysine; alternate (By
 MOD_RES 21 21 N6,N6,N6-trimethyllysine; alternate.
 MOD_RES 21 21 N6,N6-dimethyllysine; alternate.
 MOD_RES 21 21 N6-methyllysine; alternate.
 MOD_RES 32 32 N6-acetyllysine.
 MOD_RES 48 48 Phosphoserine; by PAK2.
 MOD_RES 52 52 Phosphotyrosine.
 MOD_RES 89 89 Phosphotyrosine (By similarity).
 MOD_RES 92 92 N6-acetyllysine; alternate.
 CROSSLNK 92 92 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Chromosome; Citrullination; Complete proteome; Direct protein sequencing; DNA-binding; Isopeptide bond; Methylation; Nucleosome core; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 103 AA 
Protein Sequence
MSGRGKGGKG LGKGGAKRHR KVLRDNIQGI TKPAIRRLAR RGGVKRISGL IYEETRGVLK 60
VFLENVIRDA VTYTEHAKRK TVTAMDVVYA LKRQGRTLYG FGG 103 
Gene Ontology
 GO:0015629; C:actin cytoskeleton; IDA:HPA.
 GO:0005576; C:extracellular region; TAS:Reactome.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0000786; C:nucleosome; TAS:UniProtKB.
 GO:0003677; F:DNA binding; TAS:UniProtKB.
 GO:0034080; P:CENP-A containing nucleosome assembly at centromere; TAS:Reactome.
 GO:0045653; P:negative regulation of megakaryocyte differentiation; IDA:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
 GO:0000723; P:telomere maintenance; TAS:Reactome. 
Interpro
 IPR009072; Histone-fold.
 IPR007125; Histone_core_D.
 IPR001951; Histone_H4.
 IPR019809; Histone_H4_CS. 
Pfam
 PF00125; Histone 
SMART
 SM00417; H4 
PROSITE
 PS00047; HISTONE_H4 
PRINTS
 PR00623; HISTONEH4.