CPLM-001160

Genbank Nucleotide ID

Core histone macro-H2A.1

Protein Synonyms/Alias

Histone macroH2A1; mH2A1; Histone H2A.y; H2A/y; Medulloblastoma antigen MU-MB-50.205

Homo sapiens (Human)

Position	Peptide	Type	References
18	TKTSRSAKAGVIFPV	acetylation	[1]
18	TKTSRSAKAGVIFPV	methylation	[2, 3]
18	TKTSRSAKAGVIFPV	ubiquitination	[4, 5]
116	IHPELLAKKRGSKGK	ubiquitination	[4, 5, 6, 7, 8, 9, 10, 11]
117	HPELLAKKRGSKGKL	ubiquitination	[5, 6, 7, 8, 9, 10, 11]
121	LAKKRGSKGKLEAII	ubiquitination	[5, 8, 11]
123	KKRGSKGKLEAIITP	methylation	[2]
123	KKRGSKGKLEAIITP	ubiquitination	[4, 5, 8, 9, 10, 11]
167	KKQGEVSKAASADST	ubiquitination	[4, 5, 12, 13, 14]
189	GFTVLSTKSLFLGQK	ubiquitination	[4, 5, 8, 10, 11, 12, 13, 14]
235	DLGNTLEKKGGKEFV	ubiquitination	[4]
239	TLEKKGGKEFVEAVL	methylation	[2]
250	EAVLELRKKNGPLEV	ubiquitination	[4]
251	AVLELRKKNGPLEVA	ubiquitination	[8, 11]
285	SPVWGADKCEELLEK	ubiquitination	[5]
292	KCEELLEKTVKNCLA	ubiquitination	[5, 6, 9, 10]
295	ELLEKTVKNCLALAD	ubiquitination	[5, 8, 9, 10, 11]
304	CLALADDKKLKSIAF	ubiquitination	[5]
305	LALADDKKLKSIAFP	ubiquitination	[5]
307	LADDKKLKSIAFPSI	ubiquitination	[5, 8, 11]
323	SGRNGFPKQTAAQLI	ubiquitination	[8, 10, 11]

[1] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[2] Mapping post-translational modifications of the histone variant MacroH2A1 using tandem mass spectrometry.
Chu F, Nusinow DA, Chalkley RJ, Plath K, Panning B, Burlingame AL.
Mol Cell Proteomics. 2006 Jan;5(1):194-203. [PMID: 16210244]
[3] Update on activities at the Universal Protein Resource (UniProt) in 2013.
e="String">UniProt Consortium.
Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. [PMID: 23161681]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[6] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[11] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[12] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[13] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[14] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

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.

DOMAIN 2 117 Histone H2A.
DOMAIN 184 370 Macro.
MOD_RES 18 18 N6-methyllysine.
MOD_RES 123 123 N6,N6-dimethyllysine (Probable).
MOD_RES 129 129 Phosphothreonine.
MOD_RES 170 170 Phosphoserine.
MOD_RES 173 173 Phosphoserine.
MOD_RES 178 178 Phosphothreonine.
CROSSLNK 116 116 Glycyl lysine isopeptide (Lys-Gly)
CROSSLNK 117 117 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Complete proteome; DNA-binding; Isopeptide bond; Methylation; Nucleosome core; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0001740; C:Barr body; IDA:MGI.
GO:0000793; C:condensed chromosome; IEA:Compara.
GO:0000786; C:nucleosome; NAS:UniProtKB.
GO:0003682; F:chromatin binding; IEA:Compara.
GO:0003677; F:DNA binding; NAS:UniProtKB.
GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
GO:0007549; P:dosage compensation; IDA:MGI.
GO:0006334; P:nucleosome assembly; NAS:UniProtKB.

IPR002589; A1pp.
IPR021171; Core_histone_macro-H2A.
IPR009072; Histone-fold.
IPR007125; Histone_core_D.
IPR002119; Histone_H2A.

PF00125; Histone
PF01661; Macro

SM00506; A1pp
SM00414; H2A

PR00620; HISTONEH2A.