CPLM-009560

Genbank Nucleotide ID

Protein Synonyms/Alias

Hist1h4a; Hist1h4b; Hist1h4c; Hist1h4d; Hist1h4f; Hist1h4h; Hist1h4i; Hist1h4j; Hist1h4k; Hist1h4m; Hist2h4a; Hist4h4

H4-53; H4-12; Hist2h4

Mus musculus (Mouse)

Position	Peptide	Type	References
6	**MSGRGKGGKGLGK	acetylation	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]
6	**MSGRGKGGKGLGK	methylation	[5]
9	SGRGKGGKGLGKGGA	acetylation	[1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]
9	SGRGKGGKGLGKGGA	crotonylation	[15]
13	KGGKGLGKGGAKRHR	acetylation	[1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17]
17	GLGKGGAKRHRKVLR	acetylation	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16]
17	GLGKGGAKRHRKVLR	crotonylation	[15]
17	GLGKGGAKRHRKVLR	methylation	[5]
17	GLGKGGAKRHRKVLR	propionylation	[5]
21	GGAKRHRKVLRDNIQ	acetylation	[4, 5]
21	GGAKRHRKVLRDNIQ	methylation	[5]
32	DNIQGITKPAIRRLA	acetylation	[3, 6, 7, 8, 11]
32	DNIQGITKPAIRRLA	succinylation	[11, 18]
32	DNIQGITKPAIRRLA	succinylation	[11]
32	DNIQGITKPAIRRLA	ubiquitination	[19]
34	IQGITKPAIRRLARR	crotonylation	[15]
60	EETRGVLKVFLENVI	acetylation	[7]
78	VTYTEHAKRKTVTAM	acetylation	[5, 6, 7, 8, 11, 14]
78	VTYTEHAKRKTVTAM	succinylation	[11, 18]
80	YTEHAKRKTVTAMDV	acetylation	[5, 7]
80	YTEHAKRKTVTAMDV	succinylation	[18]
92	MDVVYALKRQGRTLY	acetylation	[5, 6, 7, 11]
92	MDVVYALKRQGRTLY	crotonylation	[5]
92	MDVVYALKRQGRTLY	succinylation	[11, 18]
92	MDVVYALKRQGRTLY	ubiquitination	[19]

[1] Peptide mass mapping of acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors.
Ren C, Zhang L, Freitas MA, Ghoshal K, Parthun MR, Jacob ST.
J Am Soc Mass Spectrom. 2005 Oct;16(10):1641-53. [PMID: 16099169]
[2] 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]
[3] 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]
[4] Comprehensive mapping of post-translational modifications on synaptic, nuclear, and histone proteins in the adult mouse brain.
Tweedie-Cullen RY, Reck JM, Mansuy IM.
J Proteome Res. 2009 Nov;8(11):4966-82. [PMID: 19737024]
[5] Identification of combinatorial patterns of post-translational modifications on individual histones in the mouse brain.
Tweedie-Cullen RY, Brunner AM, Grossmann J, Mohanna S, Sichau D, Nanni P, Panse C, Mansuy IM.
PLoS One. 2012;7(5):e36980. [PMID: 22693562]
[6] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
Simon GM, Cheng J, Gordon JI.
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
[7] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
[8] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
[9] 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]
[10] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
[11] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
[12] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
[13] Regulation of histone acetylation during meiotic maturation in mouse oocytes.
Akiyama T, Kim JM, Nagata M, Aoki F.
Mol Reprod Dev. 2004 Oct;69(2):222-7. [PMID: 15293224]
[14] Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
Masri S, Patel VR, Eckel-Mahan KL, Peleg S, Forne I, Ladurner AG, Baldi P, Imhof A, Sassone-Corsi P.
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44. [PMID: 23341599]
[15] 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]
[16] The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
Yang L, Vaitheesvaran B, Hartil K, Robinson AJ, Hoopmann MR, Eng JK, Kurland IJ, Bruce JE.
J Proteome Res. 2011 Sep 2;10(9):4134-49. [PMID: 21728379]
[17] Chaperone-mediated acetylation of histones by Rtt109 identified by quantitative proteomics.
Abshiru N, Ippersiel K, Tang Y, Yuan H, Marmorstein R, Verreault A, Thibault P.
J Proteomics. 2013 Apr 9;81:80-90. [PMID: 23036725]
[18] 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]
[19] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]

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.

DNA_BIND 17 21
MOD_RES 2 2 N-acetylserine (By similarity).
MOD_RES 2 2 Phosphoserine.
MOD_RES 4 4 Asymmetric dimethylarginine; by PRMT1;
MOD_RES 4 4 Citrulline; alternate (By similarity).
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 (By
MOD_RES 17 17 N6-acetyllysine; alternate.
MOD_RES 17 17 N6-crotonyl-L-lysine; alternate.
MOD_RES 21 21 N6,N6,N6-trimethyllysine; alternate.
MOD_RES 21 21 N6,N6-dimethyllysine; alternate (By
MOD_RES 21 21 N6-methyllysine; alternate (By
MOD_RES 32 32 N6-acetyllysine (By similarity).
MOD_RES 48 48 Phosphoserine; by PAK2 (By similarity).
MOD_RES 52 52 Phosphotyrosine.
MOD_RES 89 89 Phosphotyrosine.
MOD_RES 92 92 N6-acetyllysine; alternate (By
CROSSLNK 92 92 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; Chromosome; Citrullination; Complete proteome; DNA-binding; Isopeptide bond; Methylation; Nucleosome core; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0015629; C:actin cytoskeleton; IEA:Compara.
GO:0005730; C:nucleolus; IEA:Compara.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0000786; C:nucleosome; ISS:UniProtKB.
GO:0003677; F:DNA binding; ISS:UniProtKB.
GO:0045653; P:negative regulation of megakaryocyte differentiation; IEA:Compara.
GO:0006334; P:nucleosome assembly; ISS:UniProtKB.

IPR009072; Histone-fold.
IPR007125; Histone_core_D.
IPR001951; Histone_H4.
IPR019809; Histone_H4_CS.