P08985 (H2AV_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H2A.v

Alternative name(s):
H2A.F/Z
Short name=H2A.Z

Gene names

Name:	His2Av
Synonyms:	H2AvD, His2AvD
ORF Names:	CG5499

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	141 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	Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. Acts as a Polycomb group (PcG) protein required to maintain the transcriptionally repressive state of homeotic genes of the animal throughout development. Required for histone H3 'Lys-9' methylation and histone H4 'Lys-12' acetylation, two modifications that are essential for heterochromatin formation. Also involved in DNA double strand break (DSB) repair. Essential for early development. Ref.8 Ref.9 Ref.11 Ref.13
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. H2A or its variant His2Av forms a heterodimer with H2B.
Subcellular location	Nucleus. Chromosome. Note: Widely distributed in the genome, irrespective of the transcriptional status or coding capacity of the sequence. Ref.10
Developmental stage	Expressed both maternally and zygotically. Expressed in embryos and adults (females only). Ref.8
Domain	The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
Post-translational modification	Phosphorylated. Phosphorylation of Ser-138 occurs in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents. Phosphorylation is dependent on the DNA damage checkpoint kinases ATR and ATM, spreads on either side of a detected DSB site and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Ref.11 Acetylated on Lys-5 by Tip60. Acetylation is enhanced by Ser-138 phosphorylation and promotes the exchange of the phosphorylated form with the unmodified form of H2AV. Ref.11 Monoubiquitination of Lys-121 by sce/dRING gives a specific tag for epigenetic transcriptional repression By similarity.
Sequence similarities	Belongs to the histone H2A family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosome Nucleosome core Nucleus
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW nucleosome assembly Inferred from electronic annotation. Source: InterPro protein localization to chromatin Inferred from direct assay PubMed 21444826. Source: FlyBase response to DNA damage stimulus Inferred from mutant phenotype PubMed 19543366. Source: FlyBase
Cellular_component	lipid particle Inferred from direct assay PubMed 16543254PubMed 16979555. Source: FlyBase nucleosome Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay Ref.10. Source: FlyBase polytene chromosome Inferred from direct assay Ref.10. Source: FlyBase
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 By similarity
	Chain	2 – 141	140	Histone H2A.v		PRO_0000055309
Regions
	Region	93 – 103	11	Essential for function in development
	Motif	138 – 139	2	[ST]-Q motif
Amino acid modifications
	Modified residue	5	1	N6-acetyllysine Ref.12
	Modified residue	138	1	Phosphoserine Ref.11
	Cross-link	121		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	25	1	G → D in strain: ZBMEL377.
	Natural variant	90	1	A → T in strain: ZBMEL131.
	Natural variant	95	1	E → K in strain: MEL16 and ZBMEL84. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P08985 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 0DA41C01F831A5B6	FASTA	141	14,981
	10 20 30 40 50 60 MAGGKAGKDS GKAKAKAVSR SARAGLQFPV GRIHRHLKSR TTSHGRVGAT AAVYSAAILE 70 80 90 100 110 120 YLTAEVLELA GNASKDLKVK RITPRHLQLA IRGDEELDSL IKATIAGGGV IPHIHKSLIG 130 140 KKEETVQDPQ RKGNVILSQA Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Drosophila has a single copy of the gene encoding a highly conserved histone H2A variant of the H2A.F/Z type." van Daal A., White E.M., Gorovsky M.A., Elgin S.C.R. Nucleic Acids Res. 16:7487-7497(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryo.
[2]	"Conservation of intron position indicates separation of major and variant H2As is an early event in the evolution of eukaryotes." van Daal A., White E.M., Elgin S.C.R., Gorovsky M.A. J. Mol. Evol. 30:449-455(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Canton-S.
[3]	"Widespread adaptive evolution of Drosophila genes with sex-biased expression." Proeschel M., Zhang Z., Parsch J. Genetics 174:893-900(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ZBMEL131, ZBMEL186, ZBMEL191, ZBMEL377, ZBMEL384, ZBMEL82, ZBMEL84 and ZBMEL95.
[4]	"The influence of demography and weak selection on the McDonald-Kreitman test: an empirical study in Drosophila." Parsch J., Zhang Z., Baines J.F. Mol. Biol. Evol. 26:691-698(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-95. Strain: MEL01, MEL02, MEL11, MEL12, MEL13, MEL14, MEL15, MEL16, MEL17, MEL18, MEL19 and MEL20.
[5]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[6]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[7]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[8]	"A histone variant, H2AvD, is essential in Drosophila melanogaster." Van Daal A., Elgin S.C.R. Mol. Biol. Cell 3:593-602(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53, FUNCTION, DEVELOPMENTAL STAGE.
[9]	"Regions of variant histone His2AvD required for Drosophila development." Clarkson M.J., Wells J.R.E., Gibson F., Saint R., Tremethick D.J. Nature 399:694-697(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Histone H2A.Z is widely but nonrandomly distributed in chromosomes of Drosophila melanogaster." Leach T.J., Mazzeo M., Chotkowski H.L., Madigan J.P., Wotring M.G., Glaser R.L. J. Biol. Chem. 275:23267-23272(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"DNA double-strand break-induced phosphorylation of Drosophila histone variant H2Av helps prevent radiation-induced apoptosis." Madigan J.P., Chotkowski H.L., Glaser R.L. Nucleic Acids Res. 30:3698-3705(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-138.
[12]	"Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions." Kusch T., Florens L., Macdonald W.H., Swanson S.K., Glaser R.L., Yates J.R. III, Abmayr S.M., Washburn M.P., Workman J.L. Science 306:2084-2087(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-5.
[13]	"The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin." Swaminathan J., Baxter E.M., Corces V.G. Genes Dev. 19:65-76(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X07485 mRNA. Translation: CAA30370.1. X15549 Genomic DNA. Translation: CAA33555.1. AM294365 Genomic DNA. Translation: CAL26295.1. AM294366 Genomic DNA. Translation: CAL26296.1. AM294367 Genomic DNA. Translation: CAL26297.1. AM294368 Genomic DNA. Translation: CAL26298.1. AM294369 Genomic DNA. Translation: CAL26299.1. AM294370 Genomic DNA. Translation: CAL26300.1. AM294371 Genomic DNA. Translation: CAL26301.1. AM294372 Genomic DNA. Translation: CAL26302.1. FM245434 Genomic DNA. Translation: CAR93360.1. FM245435 Genomic DNA. Translation: CAR93361.1. FM245436 Genomic DNA. Translation: CAR93362.1. FM245437 Genomic DNA. Translation: CAR93363.1. FM245438 Genomic DNA. Translation: CAR93364.1. FM245439 Genomic DNA. Translation: CAR93365.1. FM245440 Genomic DNA. Translation: CAR93366.1. FM245441 Genomic DNA. Translation: CAR93367.1. FM245442 Genomic DNA. Translation: CAR93368.1. FM245443 Genomic DNA. Translation: CAR93369.1. FM245444 Genomic DNA. Translation: CAR93370.1. FM245445 Genomic DNA. Translation: CAR93371.1. AE014297 Genomic DNA. Translation: AAF56631.1. AY118910 mRNA. Translation: AAM50770.1. S42733 Genomic DNA. Translation: AAB22897.1.
PIR	S08118.
RefSeq	NP_001262997.1. NM_001276068.1. NP_524519.1. NM_079795.3.
UniGene	Dm.2346.
3D structure databases
ProteinModelPortal	P08985.
SMR	P08985. Positions 17-122.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-23205N.
MINT	MINT-1547881.
Proteomic databases
PaxDb	P08985.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0085062; FBpp0084434; FBgn0001197.
GeneID	43229.
KEGG	dme:Dmel_CG5499.
Organism-specific databases
CTD	43229.
FlyBase	FBgn0001197. His2Av.
Phylogenomic databases
eggNOG	COG5262.
GeneTree	ENSGT00690000101745.
InParanoid	P08985.
KO	K11251.
OMA	LQFPCGR.
OrthoDB	EOG4FJ6SB.
PhylomeDB	P08985.
Gene expression databases
Bgee	P08985.
GermOnline	CG5499. Drosophila melanogaster.
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
ChiTaRS	His2Av. drosophila.
GenomeRNAi	43229.
NextBio	832825.

Entry information

Entry name

H2AV_DROME

Accession

Primary (citable) accession number: P08985
Secondary accession number(s): A0ANX7 , A0ANX8, A0ANY0, A0ANY3, C0MJB2, C0MJB9, Q26252, Q540X2, Q9VBB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project