Q9QZQ8 (H2AY_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Core histone macro-H2A.1
Short name=Histone macroH2A1
Short name=mH2A1

Alternative name(s):
H2A.y
H2A/y

Gene names

Name:

H2afy

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	372 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. Involved in stable X chromosome inactivation. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation. Ref.7
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. Interacts with SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Interacts with HDAC1 and HDAC2 By similarity. Ref.2 Ref.7
Subcellular location	Nucleus. Chromosome. Note: Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin. In quiescent lymphocytes, associated with centromeric constitutive heterochromatin. Ref.4 Ref.6
Tissue specificity	Ubiquitously expressed, with high levels in testis. Present in liver, kidney and adrenal gland (at protein level). In the liver, present in hepatocytes and at a lesser extent in cells of the bile ducts. In the kidney, present in proximal and distal convoluted tubules and in straight proximal tubules. In the adrenal gland, present in inner cells of the cortex and medulla. Ref.1 Ref.5
Post-translational modification	Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin By similarity.
Sequence similarities	Contains 1 histone H2A domain. Contains 1 Macro domain.

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Chromatin regulator
PTM	Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW dosage compensation Inferred from sequence orthology PubMed 15053874. Source: MGI nucleosome assembly Inferred from electronic annotation. Source: InterPro
Cellular_component	Barr body Inferred from sequence orthology PubMed 11331621. Source: MGI centrosome Traceable author statement PubMed 12082075. Source: MGI condensed chromosome Inferred from direct assay PubMed 12082075. Source: MGI nucleosome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin binding Inferred from direct assay PubMed 12082075. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q9QZQ8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Major form.

Isoform 1 (identifier: Q9QZQ8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     198-217: NLIHSEISNLAGFEVEAIIN → QVVQADIASIDSDAVVH
     221-229: ADIDLKDDL → TDFYTGGEV

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 372	372	Core histone macro-H2A.1		PRO_0000227904
Regions
	Domain	2 – 117	116	Histone H2A
	Domain	184 – 370	187	Macro
	Compositional bias	116 – 161	46	Lys-rich
Amino acid modifications
	Modified residue	18	1	N6-methyllysine By similarity
	Modified residue	129	1	Phosphothreonine Ref.8
	Modified residue	170	1	Phosphoserine By similarity
	Modified residue	173	1	Phosphoserine By similarity
	Modified residue	178	1	Phosphothreonine By similarity
	Cross-link	116		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
	Cross-link	117		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Natural variations
	Alternative sequence	198 – 217	20	NLIHS…EAIIN → QVVQADIASIDSDAVVH in isoform 1.		VSP_017596
	Alternative sequence	221 – 229	9	ADIDLKDDL → TDFYTGGEV in isoform 1.		VSP_017597

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 076CF76A34FACAA0	FASTA	372	39,735
	10 20 30 40 50 60 MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA AVLEYLTAEI 70 80 90 100 110 120 LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI ASGGVLPNIH PELLAKKRGS 130 140 150 160 170 180 KGKLEAIITP PPAKKAKSPS QKKPVAKKTG GKKGARKSKK KQGEVSKAAS ADSTTEGTPT 190 200 210 220 230 240 DGFTVLSTKS LFLGQKLNLI HSEISNLAGF EVEAIINPTN ADIDLKDDLG NTLEKKGGKE 250 260 270 280 290 300 FVEAVLELRK KNGPLEVAGA AISAGHGLPA KFVIHCNSPV WGADKCEELL EKTVKNCLAL 310 320 330 340 350 360 ADDRKLKSIA FPSIGSGRNG FPKQTAAQLI LKAISSYFVS TMSSSIKTVY FMLFDSESIG 370 IYVQEMAKLD AN
	Isoform 1 [UniParc]. Checksum: 33F123DE5C9C46EC	FASTA	369	39,290
	10 20 30 40 50 60 MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA AVLEYLTAEI 70 80 90 100 110 120 LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI ASGGVLPNIH PELLAKKRGS 130 140 150 160 170 180 KGKLEAIITP PPAKKAKSPS QKKPVAKKTG GKKGARKSKK KQGEVSKAAS ADSTTEGTPT 190 200 210 220 230 240 DGFTVLSTKS LFLGQKLQVV QADIASIDSD AVVHPTNTDF YTGGEVGNTL EKKGGKEFVE 250 260 270 280 290 300 AVLELRKKNG PLEVAGAAIS AGHGLPAKFV IHCNSPVWGA DKCEELLEKT VKNCLALADD 310 320 330 340 350 360 RKLKSIAFPS IGSGRNGFPK QTAAQLILKA ISSYFVSTMS SSIKTVYFML FDSESIGIYV QEMAKLDAN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing." Rasmussen T.P., Huang T., Mastrangelo M.-A., Loring J., Panning B., Jaenisch R. Nucleic Acids Res. 27:3685-3689(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 197-229 (ISOFORM 1), TISSUE SPECIFICITY. Strain: 129/SvEvTacfBr.
[2]	"MacroH2A1.2 binds the nuclear protein Spop." Takahashi I., Kameoka Y., Hashimoto K. Biochim. Biophys. Acta 1591:63-68(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH SPOP. Tissue: Brain.
[3]	"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] (ISOFORM 1). Strain: FVB/N. Tissue: Mammary gland.
[4]	"Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals." Costanzi C., Pehrson J.R. Nature 393:599-601(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"MACROH2A2, a new member of the MACROH2A core histone family." Costanzi C., Pehrson J.R. J. Biol. Chem. 276:21776-21784(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence." Grigoryev S.A., Nikitina T., Pehrson J.R., Singh P.B., Woodcock C.L. J. Cell Sci. 117:6153-6162(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"Structural characterization of the histone variant macroH2A." Chakravarthy S., Gundimella S.K., Caron C., Perche P.-Y., Pehrson J.R., Khochbin S., Luger K. Mol. Cell. Biol. 25:7616-7624(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC1 AND HDAC2, FUNCTION.
[8]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF171080 mRNA. Translation: AAD53745.1. AF171081 mRNA. Translation: AAD53746.1. AB071988 mRNA. Translation: BAB68541.1. BC006955 mRNA. Translation: AAH06955.1.
IPI	IPI00137852. IPI00378480.
RefSeq	NP_001152985.1. NM_001159513.1. NP_001152986.1. NM_001159514.1. NP_001152987.1. NM_001159515.1. NP_036145.1. NM_012015.2.
UniGene	Mm.283802. Mm.478369. Mm.490262.
3D structure databases
ProteinModelPortal	Q9QZQ8.
SMR	Q9QZQ8. Positions 10-117, 181-369.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9QZQ8. 1 interaction.
PTM databases
PhosphoSite	Q9QZQ8.
Proteomic databases
PaxDb	Q9QZQ8.
PRIDE	Q9QZQ8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000016081; ENSMUSP00000016081; ENSMUSG00000015937. ENSMUST00000045788; ENSMUSP00000038221; ENSMUSG00000015937.
GeneID	26914.
KEGG	mmu:26914.
UCSC	uc007qsf.2. mouse. uc007qsg.2. mouse.
Organism-specific databases
CTD	9555.
MGI	MGI:1349392. H2afy.
Phylogenomic databases
eggNOG	COG2110.
GeneTree	ENSGT00690000101745.
HOGENOM	HOG000234653.
HOVERGEN	HBG009342.
InParanoid	Q9QZQ8.
KO	K11251.
OMA	KAISNYF.
OrthoDB	EOG4XH00N.
Enzyme and pathway databases
Reactome	REACT_118161. Cell Cycle. REACT_120463. Meiosis. REACT_27235. Meiotic Recombination (mouse). REACT_75800. Meiotic Synapsis (mouse).
Gene expression databases
ArrayExpress	Q9QZQ8.
Bgee	Q9QZQ8.
CleanEx	MM_H2AFY.
Genevestigator	Q9QZQ8.
GermOnline	ENSMUSG00000015937. Mus musculus.
Family and domain databases
Gene3D	1.10.20.10. 1 hit.
InterPro	IPR002589. A1pp. IPR021171. Core_histone_macro-H2A. IPR009072. Histone-fold. IPR007125. Histone_core_D. IPR002119. Histone_H2A. [Graphical view]
Pfam	PF00125. Histone. 1 hit. PF01661. Macro. 1 hit. [Graphical view]
PIRSF	PIRSF037942. Core_histone_macro-H2A. 1 hit.
PRINTS	PR00620. HISTONEH2A.
SMART	SM00506. A1pp. 1 hit. SM00414. H2A. 1 hit. [Graphical view]
SUPFAM	SSF47113. Histone-fold. 1 hit.
PROSITE	PS51154. MACRO. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	H2AFY. mouse.
NextBio	304793.
SOURCE	Search...

Entry information

Entry name

H2AY_MOUSE

Accession

Primary (citable) accession number: Q9QZQ8
Secondary accession number(s): Q91VZ2, Q9QZQ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program