P62805 (H4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H4

Gene names

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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	103 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Subunit structure	The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
Subcellular location	Nucleus. Chromosome.
Post-translational modification	Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin. Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation. Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3). Monomethylation is performed by SET8. Trimethylation is performed by SUV420H1 and SUV420H2 and induces gene silencing. Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.28 Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4. Ref.28 Ref.36 Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me). Ref.27 Ref.30 Sumoylated, which is associated with transcriptional repression. Ref.22 Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. Ref.35
Sequence similarities	Belongs to the histone H4 family.
Sequence caution	The sequence AAI28106.1 differs from that shown. Reason: Frameshift at position 3.

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
PTM	Acetylation Citrullination Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	CENP-A containing nucleosome assembly at centromere Traceable author statement. Source: Reactome negative regulation of megakaryocyte differentiation Inferred from direct assay PubMed 18474616. Source: UniProtKB phosphatidylinositol-mediated signaling Non-traceable author statement PubMed 15504738. Source: UniProtKB telomere maintenance Traceable author statement. Source: Reactome
Cellular_component	actin cytoskeleton Inferred from direct assay. Source: HPA extracellular region Traceable author statement. Source: Reactome nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome nucleosome Traceable author statement Ref.2. Source: UniProtKB
Molecular_function	DNA binding Traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BPTF	Q12830	3	EBI-302023,EBI-1560273
BPTF	Q12830-4	16	EBI-302023,EBI-4288838
CENPA	P49450	4	EBI-302023,EBI-1751979
HAT1	O14929	4	EBI-302023,EBI-2339359
L3MBTL1	Q9Y468	3	EBI-302023,EBI-1265089
MCM2	P49736	3	EBI-302023,EBI-374819
MCM3	P25205	2	EBI-302023,EBI-355153
MCM5	P33992	2	EBI-302023,EBI-359410
PRMT5	O14744	3	EBI-302023,EBI-351098
RBBP7	Q16576	4	EBI-302023,EBI-352227
SETD8	Q9NQR1	4	EBI-302023,EBI-1268946

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 103

102

Histone H4

PRO_0000158320

Regions

DNA binding

17 – 21

5

Ref.17

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.28

Modified residue

2

1

Phosphoserine Ref.28

Modified residue

4

1

Asymmetric dimethylarginine; by PRMT1; alternate Ref.19 Ref.20 Ref.23

Modified residue

4

1

Citrulline; alternate

Modified residue

4

1

Omega-N-methylarginine; by PRMT1; alternate Ref.19 Ref.20 Ref.23

Modified residue

4

1

Symmetric dimethylarginine; by PRMT5 and PRMT7; alternate By similarity

Modified residue

6

1

N6-acetyllysine; alternate Ref.16 Ref.18 Ref.32

Modified residue

6

1

N6-crotonyl-L-lysine; alternate Ref.35

Modified residue

9

1

N6-acetyllysine; alternate Ref.16 Ref.18 Ref.32

Modified residue

9

1

N6-crotonyl-L-lysine; alternate Ref.35

Modified residue

13

1

N6-acetyllysine; alternate Ref.16 Ref.18 Ref.28 Ref.32

Modified residue

13

1

N6-crotonyl-L-lysine; alternate Ref.35

Modified residue

17

1

N6-acetyllysine; alternate Ref.16 Ref.18 Ref.28 Ref.32

Modified residue

17

1

N6-crotonyl-L-lysine; alternate By similarity

Modified residue

21

1

N6,N6,N6-trimethyllysine; alternate Ref.21 Ref.24 Ref.28

Modified residue

21

1

N6,N6-dimethyllysine; alternate Ref.21 Ref.24 Ref.28

Modified residue

21

1

N6-methyllysine; alternate Ref.21 Ref.24 Ref.28

Modified residue

32

1

N6-acetyllysine Ref.32

Modified residue

48

1

Phosphoserine; by PAK2 Ref.26 Ref.29 Ref.31 Ref.33 Ref.36 Ref.37

Modified residue

52

1

Phosphotyrosine Ref.25 Ref.33

Modified residue

89

1

Phosphotyrosine By similarity

Modified residue

92

1

N6-acetyllysine; alternate Ref.30

Cross-link

92

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.30

Natural variations

Natural variant

64

1

E → Q in a breast cancer sample; somatic mutation. Ref.39

VAR_036206

Experimental info

Sequence conflict

71

1

V → A in AAH67496. Ref.14

Sequence conflict

77

1

A → P in CAG46986. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

103

Helix Strand Turn

Details...

Beta strand

5 – 8

4

Beta strand

21 – 23

3

Beta strand

28 – 30

3

Helix

32 – 41

10

Helix

49 – 76

28

Beta strand

80 – 82

3

Helix

84 – 91

8

Beta strand

94 – 96

3

Turn

97 – 102

6

Sequences

	Sequence		Length	Mass (Da)
	P62805 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: A9E5DFD3F8B97598	FASTA	103	11,367
	10 20 30 40 50 60 MSGRGKGGKG LGKGGAKRHR KVLRDNIQGI TKPAIRRLAR RGGVKRISGL IYEETRGVLK 70 80 90 100 VFLENVIRDA VTYTEHAKRK TVTAMDVVYA LKRQGRTLYG FGG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and in vitro transcription of a human H4 histone gene." Sierra F., Stein G., Stein J. Nucleic Acids Res. 11:7069-7086(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene." Pauli U., Chrysogelos S., Stein G., Stein J., Nick H. Science 236:1308-1311(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Isolation and characterization of two human H1 histone genes within clusters of core histone genes." Albig W., Kardalinou E., Drabent B., Zimmer A., Doenecke D. Genomics 10:940-948(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"Association of histone H4 genes with the mammalian testis-specific H1t histone gene." Drabent B., Kardalinou E., Bode C., Doenecke D. DNA Cell Biol. 14:591-597(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Characterization of the H1.5 gene completes the set of human H1 subtype genes." Albig W., Meergans T., Doenecke D. Gene 184:141-148(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The human histone gene cluster at the D6S105 locus." Albig W., Doenecke D. Hum. Genet. 101:284-294(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Human histone gene organization: nonregular arrangement within a large cluster." Albig W., Kioschis P., Poustka A., Meergans K., Doenecke D. Genomics 40:314-322(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"The human and mouse replication-dependent histone genes." Marzluff W.F., Gongidi P., Woods K.R., Jin J., Maltais L.J. Genomics 80:487-498(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H4A; HIST1H4B; HIST1H4C; HIST1H4D; HIST1H4E; HIST1H4F; HIST1H4H; HIST1H4I; HIST1H4J; HIST1H4K; HIST1H4L; HIST2H4A AND HIST4H4).
[9]	"A recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma results in replacement of the 5' regulatory region of BCL6 with a novel H4 histone gene." Akasaka T., Miura I., Takahashi N., Akasaka H., Yonetani N., Ohno H., Fukuhara S., Okuma M. Cancer Res. 57:7-12(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"Functional characterization of a human histone gene cluster duplication." Braastad C.D., Hovhannisyan H., van Wijnen A.J., Stein J.L., Stein G.S. Gene 342:35-40(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[11]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (HIST1H4F; HIST1H4H AND HIST2H4A).
[12]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (HIST1H4A; HIST1H4B; HIST1H4C; HIST1H4D; HIST1H4E; HIST1H4F; HIST1H4H; HIST1H4I; HIST1H4J; HIST1H4K AND HIST1H4L).
[13]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum, Eye and Placenta.
[15]	Bienvenut W.V. Submitted (MAR-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 25-36; 47-56; 61-78 AND 81-93, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[16]	"Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner." O'Neill L.P., Turner B.M. EMBO J. 14:3946-3957(1995) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
[17]	"A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA." Ebralidse K.K., Grachev S.A., Mirzabekov A.D. Nature 331:365-367(1988) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING REGION.
[18]	"Histone H4 acetylation in human cells. Frequency of acetylation at different sites defined by immunolabeling with site-specific antibodies." Turner B.M., O'Neill L.P., Allan I.M. FEBS Lett. 253:141-145(1989) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
[19]	"Methylation of histone H4 at arginine 3 occurs in vivo and is mediated 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) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT ARG-4.
[20]	"Methylation of histone H4 at arginine 3 facilitating transcriptional activation 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) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT ARG-4.
[21]	"PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 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) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT LYS-21.
[22]	"Histone sumoylation is associated with transcriptional repression." Shiio Y., Eisenman R.N. Proc. Natl. Acad. Sci. U.S.A. 100:13225-13230(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[23]	"Human PAD4 regulates histone arginine methylation levels via demethylimination." 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) [PubMed] [Europe PMC] [Abstract] Cited for: CITRULLINATION AT ARG-4, METHYLATION AT ARG-4.
[24]	"SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone 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) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT LYS-21.
[25]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-52, MASS SPECTROMETRY.
[26]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage." Wang H., Zhai L., Xu J., Joo H.-Y., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y. Mol. Cell 22:383-394(2006) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[28]	"Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle." Pesavento J.J., Yang H., Kelleher N.L., Mizzen C.A. Mol. Cell. Biol. 28:468-486(2008) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT SER-2; LYS-13 AND LYS-17, PHOSPHORYLATION AT SER-2, METHYLATION AT LYS-21.
[29]	"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) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[30]	"BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates 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) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-92, UBIQUITINATION AT LYS-92.
[31]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals 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) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[32]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9; LYS-13; LYS-17 AND LYS-32, MASS SPECTROMETRY.
[33]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48 AND TYR-52, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[34]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]	"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 J.S., 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 146:1016-1028(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CROTONYLATION AT LYS-6; LYS-9 AND LYS-13.
[36]	"Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome assembly." Kang B., Pu M., Hu G., Wen W., Dong Z., Zhao K., Stillman B., Zhang Z. Genes Dev. 25:1359-1364(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-48.
[37]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, MASS SPECTROMETRY.
[38]	"Alteration of the nucleosomal DNA path in the crystal structure of a human nucleosome core particle." Tsunaka Y., Kajimura N., Tate S., Morikawa K. Nucleic Acids Res. 33:3424-3434(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[39]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-64.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00038 Genomic DNA. Translation: CAA24918.1. Sequence problems.
M16707 Genomic DNA. Translation: AAA52652.1.
M60749 Genomic DNA. Translation: AAA63188.1.
X60481 Genomic DNA. Translation: CAA43011.1.
X60482 Genomic DNA. Translation: CAA43012.1.
X60483 Genomic DNA. Translation: CAA43013.1.
X60484 Genomic DNA. Translation: CAA43014.1.
X60486 Genomic DNA. Translation: CAA43016.1.
X60487 Genomic DNA. Translation: CAA43017.1.
X67081 Genomic DNA. Translation: CAA47464.1.
Z80787 Genomic DNA. Translation: CAB02549.1.
X83548 Genomic DNA. Translation: CAA58538.1.
AF525682 Genomic DNA. Translation: AAM83108.1.
AY128653 Genomic DNA. Translation: AAN01438.1.
AY128654 Genomic DNA. Translation: AAN01439.1.
AY128655 Genomic DNA. Translation: AAN01440.1.
AY128656 Genomic DNA. Translation: AAN01441.1.
AY128657 Genomic DNA. Translation: AAN01442.1.
AY128658 Genomic DNA. Translation: AAN01443.1.
AY128659 Genomic DNA. Translation: AAN01444.1.
AY128661 Genomic DNA. Translation: AAN01446.1.
AY128662 Genomic DNA. Translation: AAN01447.1.
AY128663 Genomic DNA. Translation: AAN01448.1.
AY128664 Genomic DNA. Translation: AAN01449.1.
AY128665 Genomic DNA. Translation: AAN01450.1.
AB000905 Genomic DNA. Translation: BAA19208.1.
AY648850 Genomic DNA. Translation: AAT68253.1.
CR542169 mRNA. Translation: CAG46966.1.
CR542172 mRNA. Translation: CAG46969.1.
CR542180 mRNA. Translation: CAG46977.1.
CR542187 mRNA. Translation: CAG46984.1.
CR542189 mRNA. Translation: CAG46986.1.
AL021807 Genomic DNA. Translation: CAA16946.1.
AL021917 Genomic DNA. Translation: CAC69642.1.
AL031777 Genomic DNA. Translation: CAC03414.1.
AL031777 Genomic DNA. Translation: CAC03418.1.
AL049822 Genomic DNA. Translation: CAC03426.1.
AL049822 Genomic DNA. Translation: CAC03427.1.
AL353759 Genomic DNA. Translation: CAC04128.1.
Z98744 Genomic DNA. Translation: CAD24074.1.
AL591493 Genomic DNA. Translation: CAI12560.1.
AL591493 Genomic DNA. Translation: CAI12567.1.
CH471087 Genomic DNA. Translation: EAW55509.1.
CH471087 Genomic DNA. Translation: EAW55510.1.
CH471087 Genomic DNA. Translation: EAW55538.1.
CH471087 Genomic DNA. Translation: EAW55549.1.
CH471087 Genomic DNA. Translation: EAW55555.1.
CH471094 Genomic DNA. Translation: EAW96325.1.
CH471081 Genomic DNA. Translation: EAX03086.1.
CH471081 Genomic DNA. Translation: EAX03111.1.
CH471081 Genomic DNA. Translation: EAX03112.1.
CH471081 Genomic DNA. Translation: EAX03121.1.
BC017361 mRNA. Translation: AAH17361.1.
BC054014 mRNA. Translation: AAH54014.1.
BC066248 mRNA. Translation: AAH66248.1.
BC066249 mRNA. Translation: AAH66249.1.
BC066250 mRNA. Translation: AAH66250.1.
BC067495 mRNA. Translation: AAH67495.1.
BC067496 mRNA. Translation: AAH67496.1.
BC067497 mRNA. Translation: AAH67497.1.
BC069288 mRNA. Translation: AAH69288.1.
BC069392 mRNA. Translation: AAH69392.1.
BC069467 mRNA. Translation: AAH69467.1.
BC069654 mRNA. Translation: AAH69654.1.
BC093763 mRNA. Translation: AAH93763.1.
BC093765 mRNA. Translation: AAH93765.1.
BC093969 mRNA. Translation: AAH93969.1.
BC111093 mRNA. Translation: AAI11094.1.
BC111434 mRNA. Translation: AAI11435.1.
BC112193 mRNA. Translation: AAI12194.1.
BC120939 mRNA. Translation: AAI20940.1.
BC128104 mRNA. Translation: AAI28105.1.
BC128105 mRNA. Translation: AAI28106.1. Frameshift.
BC130558 mRNA. Translation: AAI30559.1.
BC130560 mRNA. Translation: AAI30561.1.
BC143045 mRNA. Translation: AAI43046.1.

IPI

IPI00453473.

PIR

HSHU4. D40335.

RefSeq

NP_001029249.1. NM_001034077.4.
NP_003486.1. NM_003495.2.
NP_003529.1. NM_003538.3.
NP_003530.1. NM_003539.3.
NP_003531.1. NM_003540.3.
NP_003532.1. NM_003541.2.
NP_003533.1. NM_003542.3.
NP_003534.1. NM_003543.3.
NP_003535.1. NM_003544.2.
NP_003536.1. NM_003545.3.
NP_003537.1. NM_003546.2.
NP_003539.1. NM_003548.2.
NP_068803.1. NM_021968.3.
NP_778224.1. NM_175054.2.

UniGene

Hs.143080.
Hs.247816.
Hs.248172.
Hs.248178.
Hs.248179.
Hs.278483.
Hs.46423.
Hs.528055.
Hs.533295.
Hs.55468.
Hs.591790.
Hs.655235.
Hs.662174.
Hs.706635.
Hs.718935.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BQZ	X-ray	1.50	B/F	18-26	[»]
2CV5	X-ray	2.50	B/F	1-103	[»]
2LVM	NMR	-	B	15-28	[»]
2RNY	NMR	-	B	14-28	[»]
2RS9	NMR	-	A	2-11	[»]
3A6N	X-ray	2.70	B/F	1-103	[»]
3AFA	X-ray	2.50	B/F	1-103	[»]
3AN2	X-ray	3.60	B/F	1-103	[»]
3AV1	X-ray	2.50	B/F	1-103	[»]
3AV2	X-ray	2.80	B/F	1-103	[»]
3AYW	X-ray	2.90	B/F	1-103	[»]
3AZE	X-ray	3.00	B/F	1-103	[»]
3AZF	X-ray	2.70	B/F	1-103	[»]
3AZG	X-ray	2.40	B/F	1-103	[»]
3AZH	X-ray	3.49	B/F	1-103	[»]
3AZI	X-ray	2.70	B/F	1-103	[»]
3AZJ	X-ray	2.89	B/F	1-103	[»]
3AZK	X-ray	3.20	B/F	1-103	[»]
3AZL	X-ray	2.70	B/F	1-103	[»]
3AZM	X-ray	2.89	B/F	1-103	[»]
3AZN	X-ray	3.00	B/F	1-103	[»]
3CFS	X-ray	2.40	E	28-42	[»]
3CFV	X-ray	2.60	E/F	25-42	[»]
3F9W	X-ray	1.60	E/F/G/H	16-25	[»]
3F9X	X-ray	1.25	E/F/G/H	16-25	[»]
3F9Y	X-ray	1.50	E/F	16-25	[»]
3F9Z	X-ray	1.60	E/F/G/H	16-25	[»]
3NQJ	X-ray	2.10	B	21-103	[»]
3NQU	X-ray	2.50	B	1-103	[»]
3O36	X-ray	1.70	D/E	15-20	[»]
3QZS	X-ray	1.80	C/D	13-22	[»]
3QZT	X-ray	1.50	B	13-22	[»]
3QZV	X-ray	2.00	C	8-18	[»]
3R45	X-ray	2.60	B	1-103	[»]
3UVW	X-ray	1.37	B	2-12	[»]
3UVX	X-ray	1.91	B	12-22	[»]
3UVY	X-ray	2.02	B	16-26	[»]
3UW9	X-ray	2.30	E/F	8-18	[»]
4GQB	X-ray	2.06	C	2-22	[»]
4H9N	X-ray	1.95	B	2-103	[»]
4H9O	X-ray	2.05	B	2-103	[»]
4H9P	X-ray	2.20	B	2-103	[»]
4H9Q	X-ray	1.95	B	2-103	[»]
4H9R	X-ray	2.20	B	2-103	[»]
4H9S	X-ray	2.60	C/D	21-103	[»]
4HGA	X-ray	2.80	C	1-103	[»]

ProteinModelPortal

P62805.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33079N.

IntAct

P62805. 71 interactions.

MINT

MINT-276350.

STRING

9606.ENSP00000289352.

PTM databases

PhosphoSite

P62805.

2D gel databases

SWISS-2DPAGE

P62805.

Proteomic databases

PaxDb

P62805.

PeptideAtlas

P62805.

PRIDE

P62805.

Protocols and materials databases

DNASU

8294.
8360.
8362.
8363.
8364.
8365.
8366.
8367.
8368.
8370.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000289352; ENSP00000289352; ENSG00000158406.
ENST00000340756; ENSP00000343282; ENSG00000188987.
ENST00000354348; ENSP00000346316; ENSG00000198339.
ENST00000355057; ENSP00000347168; ENSG00000197238.
ENST00000355981; ENSP00000348258; ENSG00000198558.
ENST00000357549; ENSP00000350159; ENSG00000197914.
ENST00000358064; ENSP00000350767; ENSG00000197837.
ENST00000359907; ENSP00000352980; ENSG00000196176.
ENST00000360441; ENSP00000353624; ENSG00000198518.
ENST00000369157; ENSP00000358153; ENSG00000182217.
ENST00000369165; ENSP00000358162; ENSG00000183941.
ENST00000377364; ENSP00000366581; ENSG00000124529.
ENST00000377727; ENSP00000366956; ENSG00000158406.
ENST00000377745; ENSP00000366974; ENSG00000198327.
ENST00000377803; ENSP00000367034; ENSG00000197061.
ENST00000392932; ENSP00000376663; ENSG00000182217.
ENST00000392933; ENSP00000376664; ENSG00000182217.
ENST00000392938; ENSP00000376668; ENSG00000183941.
ENST00000392939; ENSP00000376669; ENSG00000183941.
ENST00000539745; ENSP00000443017; ENSG00000197837.

GeneID

121504.
554313.
8294.
8359.
8360.
8361.
8362.
8363.
8364.
8365.
8366.
8367.
8368.
8370.

KEGG

hsa:121504.
hsa:554313.
hsa:8294.
hsa:8359.
hsa:8360.
hsa:8361.
hsa:8362.
hsa:8363.
hsa:8364.
hsa:8365.
hsa:8366.
hsa:8367.
hsa:8368.
hsa:8370.

UCSC

uc001ess.3. human.

Organism-specific databases

CTD

121504.
554313.
8294.
8359.
8360.
8361.
8362.
8363.
8364.
8365.
8366.
8367.
8368.
8370.

GeneCards

GC01M149830.
GC01P149804.
GC06M026027.
GC06M026188.
GC06M026281.
GC06M027798.
GC06M027845.
GC06P026021.
GC06P026104.
GC06P026204.
GC06P026240.
GC06P027107.
GC06P027791.
GC12M014920.

HGNC

HGNC:4781. HIST1H4A.
HGNC:4789. HIST1H4B.
HGNC:4787. HIST1H4C.
HGNC:4782. HIST1H4D.
HGNC:4790. HIST1H4E.
HGNC:4783. HIST1H4F.
HGNC:4788. HIST1H4H.
HGNC:4793. HIST1H4I.
HGNC:4785. HIST1H4J.
HGNC:4784. HIST1H4K.
HGNC:4791. HIST1H4L.
HGNC:4794. HIST2H4A.
HGNC:29607. HIST2H4B.
HGNC:20510. HIST4H4.

HPA

CAB011503.
CAB021887.
CAB037279.
HPA042201.

MIM

142750. gene.
602822. gene.
602823. gene.
602824. gene.
602825. gene.
602826. gene.
602827. gene.
602828. gene.
602829. gene.
602830. gene.
602831. gene.
602833. gene.
615069. gene.

neXtProt

NX_P62805.

PharmGKB

PA29169.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2036.

HOGENOM

HOG000234654.

HOVERGEN

HBG051878.

InParanoid

P62805.

KO

K11254.

OMA

TAMDIVY.

OrthoDB

EOG4KD6NP.

PhylomeDB

P62805.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classiii_pathway. Signaling events mediated by HDAC Class III.

Reactome

REACT_111183. Meiosis.
REACT_115566. Cell Cycle.
REACT_116125. Disease.

Gene expression databases

ArrayExpress

P62805.

Bgee

P62805.

CleanEx

HS_HIST1H4A.
HS_HIST1H4B.
HS_HIST1H4C.
HS_HIST1H4D.
HS_HIST1H4E.
HS_HIST1H4F.
HS_HIST1H4H.
HS_HIST1H4I.
HS_HIST1H4L.
HS_HIST2H4A.
HS_HIST2H4B.
HS_HIST4H4.

Genevestigator

P62805.

GermOnline

ENSG00000124529. Homo sapiens.
ENSG00000158406. Homo sapiens.
ENSG00000182217. Homo sapiens.
ENSG00000183941. Homo sapiens.
ENSG00000188987. Homo sapiens.
ENSG00000196176. Homo sapiens.
ENSG00000197061. Homo sapiens.
ENSG00000197238. Homo sapiens.
ENSG00000197914. Homo sapiens.
ENSG00000198327. Homo sapiens.
ENSG00000198339. Homo sapiens.
ENSG00000198518. Homo sapiens.
ENSG00000198558. Homo sapiens.

Family and domain databases

Gene3D

1.10.20.10. 1 hit.

InterPro

IPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR001951. Histone_H4.
IPR019809. Histone_H4_CS.
[Graphical view]

PANTHER

PTHR10484. PTHR10484. 1 hit.

Pfam

PF00125. Histone. 1 hit.
[Graphical view]

PRINTS

PR00623. HISTONEH4.

SMART

SM00417. H4. 1 hit.
[Graphical view]

SUPFAM

SSF47113. Histone-fold. 1 hit.

PROSITE

PS00047. HISTONE_H4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5876.

EvolutionaryTrace

P62805.

NextBio

31093.

SOURCE

Search...

Entry information

Entry name

H4_HUMAN

Accession

Primary (citable) accession number: P62805
Secondary accession number(s): A2VCL0 , P02304, P02305, Q6DRA9, Q6FGB8, Q6NWP7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.