P04908 (H2A1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H2A type 1-B/E

Alternative name(s):
Histone H2A.2
Histone H2A/a
Histone H2A/m

Gene names

Name:	HIST1H2AB
Synonyms:	H2AFM
AND
Name:	HIST1H2AE
Synonyms:	H2AFA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	130 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	The chromatin-associated form is phosphorylated on Thr-121 during mitosis Probable. Ref.7 Ref.8 Ref.10 Ref.19 Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3. Monoubiquitination of Lys-120 by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Monoubiquitination and ionizing radiation-induced 'Lys-63'-linked ubiquitination are distinct events. Ref.9 Ref.12 Ref.13 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage By similarity.
Sequence similarities	Belongs to the histone H2A family.
Mass spectrometry	Molecular mass is 14037.9 Da from positions 2 - 130. Determined by ESI. Monoisotopic with N-acetylserine. Ref.15

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Ligand	DNA-binding
PTM	Acetylation Citrullination Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nucleosome assembly Non-traceable author statement. Source: UniProtKB
Cellular component	nucleosome Non-traceable author statement. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 130

129

Histone H2A type 1-B/E

PRO_0000055237

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.10 Ref.11 Ref.15

Modified residue

2

1

Phosphoserine; by RPS6KA5 By similarity

Modified residue

4

1

Citrulline; alternate

Modified residue

4

1

Symmetric dimethylarginine; alternate By similarity

Modified residue

6

1

N6-acetyllysine By similarity

Modified residue

121

1

Phosphothreonine Ref.7 Ref.19

Modified residue

123

1

Phosphoserine Ref.19

Cross-link

119

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.18

Cross-link

120

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9 Ref.12 Ref.13

Experimental info

Mutagenesis

2

1

S → A: Blocks the inhibition of transcription by RPS6KA5/MSK1. Ref.8

Sequence conflict

38 – 39

2

GN → AH in CAA24951. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

130

Helix Strand Turn

Details...

Helix

18 – 22

5

Helix

28 – 36

9

Turn

37 – 39

3

Beta strand

42 – 44

3

Helix

47 – 73

27

Beta strand

77 – 79

3

Helix

81 – 89

9

Helix

92 – 97

6

Turn

98 – 100

3

Beta strand

101 – 103

3

Helix

114 – 116

3

Sequences

	Sequence		Length	Mass (Da)
	P04908 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9CFE6184B2CC89F5	FASTA	130	14,135
	10 20 30 40 50 60 MSGRGKQGGK ARAKAKTRSS RAGLQFPVGR VHRLLRKGNY SERVGAGAPV YLAAVLEYLT 70 80 90 100 110 120 AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGR VTIAQGGVLP NIQAVLLPKK 130 TESHHKAKGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structure and expression of four cloned human histone genes." Zhong R., Roeder R.G., Heintz N. Nucleic Acids Res. 11:7409-7425(1983) [PubMed: 6647026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H2AB).
[2]	"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: 1916825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H2AE).
[3]	"The human histone gene cluster at the D6S105 locus." Albig W., Doenecke D. Hum. Genet. 101:284-294(1997) [PubMed: 9439656] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H2AE).
[4]	"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: 12408966] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H2AB AND HIST1H2AE).
[5]	"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: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (HIST1H2AE). Tissue: Liver.
[7]	"Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo." Aihara H., Nakagawa T., Yasui K., Ohta T., Hirose S., Dhomae N., Takio K., Kaneko M., Takeshima Y., Muramatsu M., Ito T. Genes Dev. 18:877-888(2004) [PubMed: 15078818] [Abstract] Cited for: PHOSPHORYLATION AT THR-121.
[8]	"Phosphorylation of histone H2A inhibits transcription on chromatin templates." Zhang Y., Griffin K., Mondal N., Parvin J.D. J. Biol. Chem. 279:21866-21872(2004) [PubMed: 15010469] [Abstract] Cited for: PHOSPHORYLATION AT SER-2, MUTAGENESIS OF SER-2.
[9]	"Role of histone H2A ubiquitination in Polycomb silencing." Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S., Zhang Y. Nature 431:873-878(2004) [PubMed: 15386022] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[10]	"Global regulation of post-translational modifications on core histones." Galasinski S.C., Louie D.F., Gloor K.K., Resing K.A., Ahn N.G. J. Biol. Chem. 277:2579-2588(2002) [PubMed: 11709551] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-2, ACETYLATION AT SER-2.
[11]	"Deimination of histone H2A and H4 at arginine 3 in HL-60 granulocytes." Hagiwara T., Hidaka Y., Yamada M. Biochemistry 44:5827-5834(2005) [PubMed: 15823041] [Abstract] Cited for: ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, MASS SPECTROMETRY.
[12]	"Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing." Cao R., Tsukada Y., Zhang Y. Mol. Cell 20:845-854(2005) [PubMed: 16359901] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[13]	"DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A." Bergink S., Salomons F.A., Hoogstraten D., Groothuis T.A.M., de Waard H., Wu J., Yuan L., Citterio E., Houtsmuller A.B., Neefjes J., Hoeijmakers J.H.J., Vermeulen W., Dantuma N.P. Genes Dev. 20:1343-1352(2006) [PubMed: 16702407] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[14]	"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) [PubMed: 16319397] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[15]	"Precise characterization of human histones in the H2A gene family by top down mass spectrometry." Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L. J. Proteome Res. 5:248-253(2006) [PubMed: 16457589] [Abstract] Cited for: MASS SPECTROMETRY, ACETYLATION AT SER-2.
[16]	"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins." Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J., Lukas C., Lukas J. Cell 131:887-900(2007) [PubMed: 18001824] [Abstract] Cited for: UBIQUITINATION.
[17]	"RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly." Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J. Cell 131:901-914(2007) [PubMed: 18001825] [Abstract] Cited for: UBIQUITINATION.
[18]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-119, MASS SPECTROMETRY.
[19]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-121 AND SER-123, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage." Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C., Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A., Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D. Cell 136:420-434(2009) [PubMed: 19203578] [Abstract] Cited for: UBIQUITINATION.
[21]	"RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins." Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H., Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J., Lukas C. Cell 136:435-446(2009) [PubMed: 19203579] [Abstract] Cited for: UBIQUITINATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00089 Genomic DNA. Translation: CAA24951.1.
M60752 Genomic DNA. Translation: AAA63191.1.
Z83741 Genomic DNA. Translation: CAB06036.1.
AY131983 Genomic DNA. Translation: AAN59964.1.
AY131986 Genomic DNA. Translation: AAN59967.1.
AL031777 Genomic DNA. Translation: CAB39192.1.
BC093836 mRNA. Translation: AAH93836.1.
BC093862 mRNA. Translation: AAH93862.1.

IPI

IPI00026272.

PIR

HSHUA5. B26318.
G40335.

RefSeq

NP_003504.2. NM_003513.2.
NP_066390.1. NM_021052.2.

UniGene

Hs.121017.
Hs.248174.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CV5	X-ray	2.50	C/G	1-130	[»]
3A6N	X-ray	2.70	C/G	1-130	[»]
3AFA	X-ray	2.50	C/G	1-130	[»]
3AN2	X-ray	3.60	C/G	1-130	[»]
3AV1	X-ray	2.50	C/G	1-130	[»]
3AV2	X-ray	2.80	C/G	1-130	[»]
3AYW	X-ray	2.90	C/G	1-130	[»]
3AZE	X-ray	3.00	C/G	1-130	[»]
3AZF	X-ray	2.70	C/G	1-130	[»]
3AZG	X-ray	2.40	C/G	1-130	[»]
3AZH	X-ray	3.49	C/G	1-130	[»]
3AZI	X-ray	2.70	C/G	1-130	[»]
3AZJ	X-ray	2.89	C/G	1-130	[»]
3AZK	X-ray	3.20	C/G	1-130	[»]
3AZL	X-ray	2.70	C/G	1-130	[»]
3AZM	X-ray	2.89	C/G	1-130	[»]
3AZN	X-ray	3.00	C/G	1-130	[»]

ProteinModelPortal

P04908.

SMR

P04908. Positions 12-119.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04908. 10 interactions.

MINT

MINT-1139478.

STRING

P04908.

PTM databases

PhosphoSite

P04908.

Proteomic databases

PRIDE

P04908.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259791; ENSP00000259791; ENSG00000137259.
ENST00000303910; ENSP00000303373; ENSG00000168274.

GeneID

3012.
8335.

KEGG

hsa:3012.
hsa:8335.

Organism-specific databases

CTD

3012.
8335.

GeneCards

GC06M025976.
GC06P026221.

H-InvDB

HIX0032979.
HIX0032991.

HGNC

HGNC:4734. HIST1H2AB.
HGNC:4724. HIST1H2AE.

HPA

CAB011483.
CAB012242.

MIM

602786. gene.
602795. gene.

neXtProt

NX_P04908.

PharmGKB

PA29111.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15995.

HOGENOM

HBG610736.

HOVERGEN

HBG009342.

InParanoid

P04908.

OMA

KGPSQEL.

OrthoDB

EOG4TXBTD.

PhylomeDB

P04908.

Enzyme and pathway databases

Reactome

REACT_111183. Meiosis.
REACT_22172. Chromosome Maintenance.
REACT_75925. Amyloids.

Gene expression databases

ArrayExpress

P04908.

Bgee

P04908.

CleanEx

HS_HIST1H2AB.
HS_HIST1H2AE.

Genevestigator

P04908.

GermOnline

ENSG00000137259. Homo sapiens.
ENSG00000168274. Homo sapiens.

Family and domain databases

InterPro

IPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR002119. Histone_H2A.
[Graphical view]

Gene3D

G3DSA:1.10.20.10. Histone-fold. 1 hit.

KO

K11251.

Pfam

PF00125. Histone. 1 hit.
[Graphical view]

PRINTS

PR00620. HISTONEH2A.

SMART

SM00414. H2A. 1 hit.
[Graphical view]

SUPFAM

SSF47113. Histone-fold. 1 hit.

PROSITE

PS00046. HISTONE_H2A. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

11940.

SOURCE

Search...

Entry information

Entry name

H2A1B_HUMAN

Accession

Primary (citable) accession number: P04908
Secondary accession number(s): P28001, Q76P63

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
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.