Q7L7L0 (H2A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H2A type 3

Gene names

Name:

HIST3H2A

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	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.6 Ref.7 Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 (H2AK119Ub) 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 (H3K27me). H2AK119Ub 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. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 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. 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.16
Sequence similarities	Belongs to the histone H2A family.

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Ligand	DNA-binding
PTM	Acetylation Citrullination Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleosome assembly Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleosome Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 130	129	Histone H2A type 3		PRO_0000230201
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.9
	Modified residue	2	1	Phosphoserine; by RPS6KA5 Ref.7
	Modified residue	4	1	Citrulline; alternate
	Modified residue	37	1	N6-crotonyl-L-lysine Ref.16
	Modified residue	119	1	N6-crotonyl-L-lysine Ref.16
	Modified residue	120	1	N6-crotonyl-L-lysine; alternate Ref.16
	Modified residue	121	1	Phosphothreonine Ref.6
	Modified residue	126	1	N6-crotonyl-L-lysine Ref.16
	Cross-link	14		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.17 Ref.18
	Cross-link	16		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.17 Ref.18
	Cross-link	120		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.8 Ref.10 Ref.11
Experimental info
	Mutagenesis	2	1	S → A: Blocks the inhibition of transcription by RPS6KA5/MSK1. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q7L7L0 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: ECFC34D4B2CC89F0	FASTA	130	14,121
	10 20 30 40 50 60 MSGRGKQGGK ARAKAKSRSS 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 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].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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: Ovary.
[6]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-121.
[7]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-2, MUTAGENESIS OF SER-2.
[8]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[9]	"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] [Europe PMC] [Abstract] Cited for: ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, MASS SPECTROMETRY.
[10]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[11]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-120.
[12]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[14]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[15]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[16]	"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-37; LYS-119; LYS-120 AND LYS-126.
[17]	"RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling." Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E., Vermeulen W., Marteijn J.A., Sixma T.K. Cell 150:1182-1195(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
[18]	"A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase." Gatti M., Pinato S., Maspero E., Soffientini P., Polo S., Penengo L. Cell Cycle 11:2538-2544(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY131974 Genomic DNA. Translation: AAN59960.1. AK311930 mRNA. Translation: BAG34871.1. AL139288 Genomic DNA. Translation: CAI23331.1. CH471098 Genomic DNA. Translation: EAW69878.1. BC082269 mRNA. No translation available.
IPI	IPI00031562.
RefSeq	NP_254280.1. NM_033445.2.
UniGene	Hs.26331. Hs.741414.
3D structure databases
ProteinModelPortal	Q7L7L0.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48936N.
IntAct	Q7L7L0. 14 interactions.
MINT	MINT-1454952.
STRING	9606.ENSP00000355656.
PTM databases
PhosphoSite	Q7L7L0.
Polymorphism databases
DMDM	74749897.
Proteomic databases
PRIDE	Q7L7L0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366695; ENSP00000355656; ENSG00000181218.
GeneID	92815.
KEGG	hsa:92815.
UCSC	uc001hsy.3. human.
Organism-specific databases
CTD	92815.
GeneCards	GC01M228645.
HGNC	HGNC:20507. HIST3H2A.
MIM	615015. gene.
neXtProt	NX_Q7L7L0.
PharmGKB	PA134962147.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000234652.
HOVERGEN	HBG009342.
InParanoid	Q7L7L0.
KO	K11251.
OMA	LAIHNDE.
OrthoDB	EOG4TXBTD.
PhylomeDB	Q7L7L0.
Gene expression databases
Bgee	Q7L7L0.
CleanEx	HS_HIST3H2A.
Genevestigator	Q7L7L0.
GermOnline	ENSG00000181218. Homo sapiens.
Family and domain databases
Gene3D	1.10.20.10. 1 hit.
InterPro	IPR009072. Histone-fold. IPR007125. Histone_core_D. IPR002119. Histone_H2A. [Graphical view]
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
GenomeRNAi	92815.
NextBio	77892.
SOURCE	Search...

Entry information

Entry name

H2A3_HUMAN

Accession

Primary (citable) accession number: Q7L7L0
Secondary accession number(s): B2R4S4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 88 of the entry and version 3 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.