Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Histone H4  

UniProtKB / Swiss-Prot ID :  H4_HUMAN

Gene Name (Synonyms) : 
HIST1H4A, H4/A, H4FA
HIST1H4B, H4/I, H4FI
HIST1H4C, H4/G, H4FG
HIST1H4D, H4/B, H4FB
HIST1H4E, H4/J, H4FJ
HIST1H4F, H4/C, H4FC
HIST1H4H, H4/H, H4FH
HIST1H4I, H4/M, H4FM
HIST1H4J, H4/E, H4FE
HIST1H4K, H4/D, H4FD
HIST1H4L, H4/K, H4FK
HIST2H4A, H4/N, H4F2, H4FN, HIST2H4
HIST2H4B, H4/O, H4FO
HIST4H4  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Nucleus. Chromosome. 

Protein Function :  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. 

Protein Sequence MSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDA...
Predicted Secondary Structure CCCCCCCCCHHHHHHHHHHHHHHHHHHHCCCHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH...
Protein Variant
LocationDescription
64E -> Q (in a breast cancer sample;somatic mutation).
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-acetylserine.---MSGRGK
---CCCCCC
36.88UniProtKB
Link-
2Phosphoserine---MSGRGK
---CCCCCC
36.88PhosphoELM
Link-
2Phosphoserine---MSGRGK
---CCCCCC
36.88Phosphositeplus
Link-
2Phosphoserine.---MSGRGK
---CCCCCC
36.88UniProtKB
Link-
45-methylarginine-MSGRGKGG
-CCCCCCCC
36.02Phosphositeplus
Link-
4Asymmetric dimethylarginine; by PRMT1;alternate.-MSGRGKGG
-CCCCCCCC
36.02UniProtKB
Link-
4Citrulline; alternate.-MSGRGKGG
-CCCCCCCC
36.02UniProtKB
Link-
4N2,N2-dimethylarginine-MSGRGKGG
-CCCCCCCC
36.02Phosphositeplus
Link-
4Omega-N-methylarginine; by PRMT1;alternate.-MSGRGKGG
-CCCCCCCC
36.02UniProtKB
Link-
6N6-acetyllysineSGRGKGGKG
CCCCCCCCH
64.23HPRD
Link-
6N6-acetyllysineSGRGKGGKG
CCCCCCCCH
64.23HPRD
Link-
6N6-acetyllysineSGRGKGGKG
CCCCCCCCH
64.23Phosphositeplus
Link-
6N6-acetyllysine.SGRGKGGKG
CCCCCCCCH
64.23UniProtKB
Link-
9N6-acetyllysineGKGGKGLGK
CCCCCHHHH
60.68HPRD
Link-
9N6-acetyllysineGKGGKGLGK
CCCCCHHHH
60.68HPRD
Link-
9N6-acetyllysineGKGGKGLGK
CCCCCHHHH
60.68Phosphositeplus
Link-
9N6-acetyllysine.GKGGKGLGK
CCCCCHHHH
60.68UniProtKB
Link-
13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)KGLGKGGAK
CHHHHHHHH
60.25Phosphositeplus
Link-
13N6-acetyllysineKGLGKGGAK
CHHHHHHHH
60.25HPRD
Link-
13N6-acetyllysineKGLGKGGAK
CHHHHHHHH
60.25HPRD
Link-
13N6-acetyllysineKGLGKGGAK
CHHHHHHHH
60.25Phosphositeplus
Link-
13N6-acetyllysine.KGLGKGGAK
CHHHHHHHH
60.25UniProtKB
Link-
17N6-acetyllysineKGGAKRHRK
HHHHHHHHH
52.60HPRD
Link
17N6-acetyllysineKGGAKRHRK
HHHHHHHHH
52.60HPRD
Link
17N6-acetyllysineKGGAKRHRK
HHHHHHHHH
52.60Phosphositeplus
Link
17N6-acetyllysine.KGGAKRHRK
HHHHHHHHH
52.60UniProtKB
Link
21N6,N6,N6-trimethyllysineKRHRKVLRD
HHHHHHHHH
39.22Phosphositeplus
Link
21N6,N6,N6-trimethyllysine; alternate.KRHRKVLRD
HHHHHHHHH
39.22UniProtKB
Link
21N6,N6-dimethyllysineKRHRKVLRD
HHHHHHHHH
39.22Phosphositeplus
Link
21N6,N6-dimethyllysine; alternate.KRHRKVLRD
HHHHHHHHH
39.22UniProtKB
Link
21N6-acetyllysineKRHRKVLRD
HHHHHHHHH
39.22Phosphositeplus
Link
21N6-methylated lysineKRHRKVLRD
HHHHHHHHH
39.22HPRD
Link
21N6-methyllysineKRHRKVLRD
HHHHHHHHH
39.22Phosphositeplus
Link
21N6-methyllysineKRHRKVLRD
HHHHHHHHH
39.22SysPTM
Link
21N6-methyllysine; alternate.KRHRKVLRD
HHHHHHHHH
39.22UniProtKB
Link
32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)QGITKPAIR
HCCCHHHHH
30.45Phosphositeplus
Link-
32N6,N6-dimethyllysineQGITKPAIR
HCCCHHHHH
30.45Phosphositeplus
Link-
32N6-acetyllysineQGITKPAIR
HCCCHHHHH
30.45HPRD
Link-
32N6-acetyllysineQGITKPAIR
HCCCHHHHH
30.45Phosphositeplus
Link-
32N6-acetyllysine.QGITKPAIR
HCCCHHHHH
30.45UniProtKB
Link-
32N6-methyllysineQGITKPAIR
HCCCHHHHH
30.45Phosphositeplus
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42HPRD
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42HPRD
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42HPRD
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42PhosphoELM
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42Phosphositeplus
Link-
48PhosphoserineVKRISGLIY
HHHHHHHHH
31.42SysPTM
Link-
48Phosphoserine; by PAK2.VKRISGLIY
HHHHHHHHH
31.42UniProtKB
Link-
52PhosphotyrosineSGLIYEETR
HHHHHHHHH
16.86HPRD
Link-
52PhosphotyrosineSGLIYEETR
HHHHHHHHH
16.86PhosphoELM
Link-
52PhosphotyrosineSGLIYEETR
HHHHHHHHH
16.86Phosphositeplus
Link-
52Phosphotyrosine.SGLIYEETR
HHHHHHHHH
16.86UniProtKB
Link-
565-methylarginineYEETRGVLK
HHHHHHHHH
36.18Phosphositeplus
Link-
56N2,N2-dimethylarginineYEETRGVLK
HHHHHHHHH
36.18Phosphositeplus
Link-
60Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)RGVLKVFLE
HHHHHHHHH
28.65Phosphositeplus
Link-
60N6,N6-dimethyllysineRGVLKVFLE
HHHHHHHHH
28.65Phosphositeplus
Link-
60N6-acetyllysineRGVLKVFLE
HHHHHHHHH
28.65HPRD
Link-
60N6-acetyllysineRGVLKVFLE
HHHHHHHHH
28.65Phosphositeplus
Link-
60N6-acetyllysine.RGVLKVFLE
HHHHHHHHH
28.65UniProtKB
Link-
60N6-methyllysineRGVLKVFLE
HHHHHHHHH
28.65MeMo
Link-
60N6-methyllysineRGVLKVFLE
HHHHHHHHH
28.65Phosphositeplus
Link-
73PhosphotyrosineDAVTYTEHA
HHHCCCCCH
11.97Phosphositeplus
Link-
78Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)TEHAKRKTV
CCCHHHHHH
57.23Phosphositeplus
Link-
78N6-acetyllysineTEHAKRKTV
CCCHHHHHH
57.23Phosphositeplus
Link-
78N6-methyllysineTEHAKRKTV
CCCHHHHHH
57.23Phosphositeplus
Link-
80Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HAKRKTVTA
CHHHHHHHH
46.79Phosphositeplus
Link-
80N6-acetyllysine.HAKRKTVTA
CHHHHHHHH
46.79UniProtKB
Link-
81PhosphothreonineAKRKTVTAM
HHHHHHHHH
27.41HPRD
Link-
81PhosphothreonineAKRKTVTAM
HHHHHHHHH
27.41Phosphositeplus
Link-
83PhosphothreonineRKTVTAMDV
HHHHHHHHH
22.84HPRD
Link-
83PhosphothreonineRKTVTAMDV
HHHHHHHHH
22.84Phosphositeplus
Link-
89PhosphotyrosineMDVVYALKR
HHHHHHHHH
13.18HPRD
Link-
89PhosphotyrosineMDVVYALKR
HHHHHHHHH
13.18PhosphoELM
Link-
89PhosphotyrosineMDVVYALKR
HHHHHHHHH
13.18Phosphositeplus
Link-
89Phosphotyrosine.MDVVYALKR
HHHHHHHHH
13.18UniProtKB
Link-
92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VYALKRQGR
HHHHHHCCC
34.21Phosphositeplus
Link-
92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate.VYALKRQGR
HHHHHHCCC
34.21UniProtKB
Link-
92N6-acetyllysineVYALKRQGR
HHHHHHCCC
34.21Phosphositeplus
Link-
92N6-acetyllysine; alternate.VYALKRQGR
HHHHHHCCC
34.21UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
JHD3A_HUMANdirect interactionMINT-2829876MINT16415788
JHD3A_HUMANdirect interactionMINT-2830405MINT16415788
JHD3A_HUMANdirect interactionMINT-2829504MINT16415788
TNR1A_HUMANphysical interactionMINT-49356MINT14743216
BRCA1_HUMANphysical interactionMINT-2490745MINT16628214
1433Z_HUMANphysical interactionMINT-3296655MINT15161933
TP53B_HUMANdirect interactionMINT-2829895MINT16415788
TP53B_HUMANdirect interactionMINT-2830357MINT16415788
TP53B_HUMANdirect interactionMINT-2829576MINT16415788
TP53B_HUMANdirect interactionMINT-2829624MINT16415788
M3K1_HUMANphysical interactionMINT-48337MINT14743216
Q402F7_HUMANphysical interactionMINT-4950280MINT17599839
Q402F7_HUMANphysical interactionMINT-4950315MINT17599839
TAF12_HUMANphysical interaction
physical interaction
DIP:149EDIP8598932
8598932
LMBTL_HUMANdirect interaction
direct interaction
direct interaction
EBI-1265536
EBI-1265150
EBI-1
intact17540172
17540172
17540172
H14_HUMANdirect interactionEBI-1265536
intact17540172
GA45A_HUMANin vitro
in vivo
HPRD:13662HPRD11498536
10022855
HDAC8_HUMANin vitroHPRD:13662HPRD10926844
SAP30_HUMANin vivoHPRD:13662HPRD9651585
UBC9_HUMANin vitro
in vivo
HPRD:13662HPRD14578449
H2B1J_HUMANENSP00000348258STRING
H2A2C_HUMANENSP00000348258STRING
H32_HUMANENSP00000348258STRING
H2B2E_HUMANENSP00000348258STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Histone H4 acetylation distinguishes coding regions of the humangenome from heterochromatin in a differentiation-dependent buttranscription-independent manner.";
O'Neill L.P., Turner B.M.;
EMBO J. 14:3946-3957(1995).
Cited for: ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
"Histone H4 acetylation in human cells. Frequency of acetylation atdifferent sites defined by immunolabeling with site-specificantibodies.";
Turner B.M., O'Neill L.P., Allan I.M.;
FEBS Lett. 253:141-145(1989).
Cited for: ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
"Substrate and functional diversity of lysine acetylation revealed bya proteomics survey.";
Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T.,Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
Mol. Cell 23:607-618(2006).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9; LYS-13 AND LYS-17,AND MASS SPECTROMETRY.
"Characterization of histones H2A and H2B variants and their post-translational modifications by mass spectrometry.";
Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J.;
Mol. Cell. Proteomics 5:541-552(2006).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9 AND LYS-13,METHYLATION AT LYS-21, PHOSPHORYLATION AT SER-2, AND MASSSPECTROMETRY.
"Certain and progressive methylation of histone H4 at lysine 20 duringthe cell cycle.";
Pesavento J.J., Yang H., Kelleher N.L., Mizzen C.A.;
Mol. Cell. Biol. 28:468-486(2008).
Cited for: ACETYLATION AT SER-2; LYS-13 AND LYS-17, PHOSPHORYLATION AT SER-2, ANDMETHYLATION AT LYS-21.
"BBAP monoubiquitylates histone H4 at lysine 91 and selectivelymodulates the DNA damage response.";
Yan Q., Dutt S., Xu R., Graves K., Juszczynski P., Manis J.P.,Shipp M.A.;
Mol. Cell 36:110-120(2009).
Cited for: ACETYLATION AT LYS-92, AND UBIQUITINATION AT LYS-92.
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9; LYS-13; LYS-17;LYS-32 AND LYS-60, AND MASS SPECTROMETRY.
Methylation
ReferencePubMed
"Methylation of histone H4 at arginine 3 occurs in vivo and ismediated by the nuclear receptor coactivator PRMT1.";
Strahl B.D., Briggs S.D., Brame C.J., Caldwell J.A., Koh S.S., Ma H.,Cook R.G., Shabanowitz J., Hunt D.F., Stallcup M.R., Allis C.D.;
Curr. Biol. 11:996-1000(2001).
Cited for: METHYLATION AT ARG-4.
"Methylation of histone H4 at arginine 3 facilitating transcriptionalactivation by nuclear hormone receptor.";
Wang H., Huang Z.-Q., Xia L., Feng Q., Erdjument-Bromage H.,Strahl B.D., Briggs S.D., Allis C.D., Wong J., Tempst P., Zhang Y.;
Science 293:853-857(2001).
Cited for: METHYLATION AT ARG-4.
"PR-Set7 is a nucleosome-specific methyltransferase that modifieslysine 20 of histone H4 and is associated with silent chromatin.";
Nishioka K., Rice J.C., Sarma K., Erdjument-Bromage H., Werner J.,Wang Y., Chuikov S., Valenzuela P., Tempst P., Steward R., Lis J.T.,Allis C.D., Reinberg D.;
Mol. Cell 9:1201-1213(2002).
Cited for: METHYLATION AT LYS-21.
"Identifying and quantifying in vivo methylation sites by heavy methylSILAC.";
Ong S.E., Mittler G., Mann M.;
Nat. Methods 1:119-126(2004).
Cited for: METHYLATION [LARGE SCALE ANALYSIS] AT LYS-21, AND MASS SPECTROMETRY.
"Human PAD4 regulates histone arginine methylation levels viademethylimination.";
Wang Y., Wysocka J., Sayegh J., Lee Y.-H., Perlin J.R., Leonelli L.,Sonbuchner L.S., McDonald C.H., Cook R.G., Dou Y., Roeder R.G.,Clarke S., Stallcup M.R., Allis C.D., Coonrod S.A.;
Science 306:279-283(2004).
Cited for: CITRULLINATION AT ARG-4, AND METHYLATION AT ARG-4.
"SET8 recognizes the sequence RHRK20VLRDN within the N terminus ofhistone H4 and mono-methylates lysine 20.";
Yin Y., Liu C., Tsai S.N., Zhou B., Ngai S.M., Zhu G.;
J. Biol. Chem. 280:30025-30031(2005).
Cited for: METHYLATION AT LYS-21.
"Characterization of histones H2A and H2B variants and their post-translational modifications by mass spectrometry.";
Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J.;
Mol. Cell. Proteomics 5:541-552(2006).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9 AND LYS-13,METHYLATION AT LYS-21, PHOSPHORYLATION AT SER-2, AND MASSSPECTROMETRY.
"Certain and progressive methylation of histone H4 at lysine 20 duringthe cell cycle.";
Pesavento J.J., Yang H., Kelleher N.L., Mizzen C.A.;
Mol. Cell. Biol. 28:468-486(2008).
Cited for: ACETYLATION AT SER-2; LYS-13 AND LYS-17, PHOSPHORYLATION AT SER-2, ANDMETHYLATION AT LYS-21.
Phosphorylation
ReferencePubMed
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASSSPECTROMETRY.
"Characterization of histones H2A and H2B variants and their post-translational modifications by mass spectrometry.";
Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J.;
Mol. Cell. Proteomics 5:541-552(2006).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9 AND LYS-13,METHYLATION AT LYS-21, PHOSPHORYLATION AT SER-2, AND MASSSPECTROMETRY.
"Phosphoproteomic analysis of the human pituitary.";
Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
Pituitary 9:109-120(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASSSPECTROMETRY.
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-52 AND TYR-89, AND MASSSPECTROMETRY.
"Evaluation of the low-specificity protease elastase for large-scalephosphoproteome analysis.";
Wang B., Malik R., Nigg E.A., Korner R.;
Anal. Chem. 80:9526-9533(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASSSPECTROMETRY.
"Certain and progressive methylation of histone H4 at lysine 20 duringthe cell cycle.";
Pesavento J.J., Yang H., Kelleher N.L., Mizzen C.A.;
Mol. Cell. Biol. 28:468-486(2008).
Cited for: ACETYLATION AT SER-2; LYS-13 AND LYS-17, PHOSPHORYLATION AT SER-2, ANDMETHYLATION AT LYS-21.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASSSPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASSSPECTROMETRY.
"Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosomeassembly.";
Kang B., Pu M., Hu G., Wen W., Dong Z., Zhao K., Stillman B.,Zhang Z.;
Genes Dev. 25:1359-1364(2011).
Cited for: PHOSPHORYLATION AT SER-48.
Ubiquitylation
ReferencePubMed
"BBAP monoubiquitylates histone H4 at lysine 91 and selectivelymodulates the DNA damage response.";
Yan Q., Dutt S., Xu R., Graves K., Juszczynski P., Manis J.P.,Shipp M.A.;
Mol. Cell 36:110-120(2009).
Cited for: ACETYLATION AT LYS-92, AND UBIQUITINATION AT LYS-92.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures