H2AY_RAT
ID H2AY_RAT Reviewed; 371 AA.
AC Q02874; O09140; Q63325;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Core histone macro-H2A.1;
DE Short=Histone macroH2A1;
DE Short=mH2A1;
DE AltName: Full=H2A.y;
DE AltName: Full=H2A/y;
GN Name=Macroh2a1 {ECO:0000312|RGD:621462};
GN Synonyms=H2afy {ECO:0000312|RGD:621462};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND PARTIAL PROTEIN
RP SEQUENCE.
RC TISSUE=Liver;
RX PubMed=1529340; DOI=10.1126/science.1529340;
RA Pehrson J.R., Fried V.A.;
RT "MacroH2A, a core histone containing a large nonhistone region.";
RL Science 257:1398-1400(1992).
RN [2]
RP SEQUENCE REVISION (ISOFORM 1).
RA Pehrson J.R.;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=9138085;
RX DOI=10.1002/(sici)1097-4644(199704)65:1<107::aid-jcb11>3.0.co;2-h;
RA Pehrson J.R., Costanzi C., Dharia C.;
RT "Developmental and tissue expression patterns of histone macroH2A1
RT subtypes.";
RL J. Cell. Biochem. 65:107-113(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Brown Norway; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 181-371 (ISOFORM 1), AND FUNCTION.
RX PubMed=16107708; DOI=10.1128/mcb.25.17.7616-7624.2005;
RA Chakravarthy S., Gundimella S.K., Caron C., Perche P.-Y., Pehrson J.R.,
RA Khochbin S., Luger K.;
RT "Structural characterization of the histone variant macroH2A.";
RL Mol. Cell. Biol. 25:7616-7624(2005).
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes where it represses transcription. Nucleosomes
CC wrap and compact DNA into chromatin, limiting DNA accessibility to the
CC cellular machineries which require DNA as a template. Histones thereby
CC play a central role in transcription regulation, DNA repair, DNA
CC replication and chromosomal stability. DNA accessibility is regulated
CC via a complex set of post-translational modifications of histones, also
CC called histone code, and nucleosome remodeling. Involved in stable X
CC chromosome inactivation. Inhibits the binding of transcription factors
CC and interferes with the activity of remodeling SWI/SNF complexes.
CC Inhibits histone acetylation by EP300 and recruits class I HDACs, which
CC induces a hypoacetylated state of chromatin. In addition, isoform 1,
CC but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be
CC involved in ADP-ribose-mediated chromatin modulation.
CC {ECO:0000269|PubMed:16107708}.
CC -!- SUBUNIT: The nucleosome is a histone octamer containing two molecules
CC each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and
CC two H2A-H2B heterodimers. Interacts with SPOP. Part of a complex
CC consisting of MACROH2A1, CUL3 and SPOP. Interacts with HDAC1 and HDAC2
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {ECO:0000250}.
CC Note=Enriched in inactive X chromosome chromatin and in senescence-
CC associated heterochromatin. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=Q02874-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q02874-2; Sequence=VSP_002057;
CC -!- TISSUE SPECIFICITY: Isoform 1 is present only in liver and brain,
CC whereas isoform 2 is present in brain, thymus, testis, liver and kidney
CC (at protein level). {ECO:0000269|PubMed:9138085}.
CC -!- PTM: Monoubiquitinated at either Lys-116 or Lys-117. May also be
CC polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3
CC complex and does not promote proteasomal degradation. Instead, it is
CC required for enrichment in inactive X chromosome chromatin (By
CC similarity). {ECO:0000250}.
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DR EMBL; M99065; AAA41561.2; -; mRNA.
DR EMBL; M99066; AAA41560.1; -; mRNA.
DR EMBL; U79139; AAB38330.1; -; mRNA.
DR EMBL; BC089093; AAH89093.1; -; mRNA.
DR PIR; I59567; I59567.
DR PIR; I80811; I80811.
DR RefSeq; NP_058878.1; NM_017182.2. [Q02874-1]
DR RefSeq; XP_006253638.1; XM_006253576.3.
DR PDB; 1YD9; X-ray; 1.60 A; A/B/C/D=229-371.
DR PDBsum; 1YD9; -.
DR AlphaFoldDB; Q02874; -.
DR SMR; Q02874; -.
DR BioGRID; 248036; 2.
DR IntAct; Q02874; 1.
DR MINT; Q02874; -.
DR STRING; 10116.ENSRNOP00000049143; -.
DR iPTMnet; Q02874; -.
DR PhosphoSitePlus; Q02874; -.
DR jPOST; Q02874; -.
DR PaxDb; Q02874; -.
DR PRIDE; Q02874; -.
DR Ensembl; ENSRNOT00000051702; ENSRNOP00000049143; ENSRNOG00000011523. [Q02874-1]
DR GeneID; 29384; -.
DR KEGG; rno:29384; -.
DR UCSC; RGD:621462; rat. [Q02874-1]
DR CTD; 9555; -.
DR RGD; 621462; Macroh2a1.
DR eggNOG; KOG1756; Eukaryota.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000159541; -.
DR HOGENOM; CLU_062828_0_0_1; -.
DR InParanoid; Q02874; -.
DR OMA; GHNFPAK; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; Q02874; -.
DR EvolutionaryTrace; Q02874; -.
DR PRO; PR:Q02874; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000011523; Expressed in thymus and 20 other tissues.
DR ExpressionAtlas; Q02874; baseline and differential.
DR Genevisible; Q02874; RN.
DR GO; GO:0001740; C:Barr body; ISO:RGD.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0000793; C:condensed chromosome; ISO:RGD.
DR GO; GO:0000228; C:nuclear chromosome; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0000786; C:nucleosome; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005721; C:pericentric heterochromatin; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0031492; F:nucleosomal DNA binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISO:RGD.
DR GO; GO:0000182; F:rDNA binding; ISO:RGD.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0007549; P:dosage compensation; ISO:RGD.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISO:RGD.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; ISO:RGD.
DR GO; GO:1902750; P:negative regulation of cell cycle G2/M phase transition; ISO:RGD.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISO:RGD.
DR GO; GO:0061086; P:negative regulation of histone H3-K27 methylation; ISO:RGD.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; ISO:RGD.
DR GO; GO:0033128; P:negative regulation of histone phosphorylation; ISO:RGD.
DR GO; GO:1904815; P:negative regulation of protein localization to chromosome, telomeric region; ISO:RGD.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:1902883; P:negative regulation of response to oxidative stress; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1901837; P:negative regulation of transcription of nucleolar large rRNA by RNA polymerase I; ISO:RGD.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR GO; GO:1903226; P:positive regulation of endodermal cell differentiation; ISO:RGD.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:RGD.
DR GO; GO:0034184; P:positive regulation of maintenance of mitotic sister chromatid cohesion; ISO:RGD.
DR GO; GO:1902884; P:positive regulation of response to oxidative stress; ISO:RGD.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISO:RGD.
DR GO; GO:1902882; P:regulation of response to oxidative stress; ISO:RGD.
DR CDD; cd00074; H2A; 1.
DR CDD; cd02904; Macro_H2A-like; 1.
DR Gene3D; 1.10.20.10; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR InterPro; IPR021171; Core_histone_macro-H2A.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR002119; Histone_H2A.
DR InterPro; IPR007125; Histone_H2A/H2B/H3.
DR InterPro; IPR032454; Histone_H2A_C.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR035796; Macro_H2A.
DR PANTHER; PTHR23430; PTHR23430; 1.
DR Pfam; PF00125; Histone; 1.
DR Pfam; PF16211; Histone_H2A_C; 1.
DR Pfam; PF01661; Macro; 1.
DR PIRSF; PIRSF037942; Core_histone_macro-H2A; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00506; A1pp; 1.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR PROSITE; PS51154; MACRO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator;
KW Chromosome; Direct protein sequencing; DNA-binding; Isopeptide bond;
KW Methylation; Nucleosome core; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..371
FT /note="Core histone macro-H2A.1"
FT /id="PRO_0000055319"
FT DOMAIN 2..117
FT /note="Histone H2A"
FT DOMAIN 183..369
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT REGION 128..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..155
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 7
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 9
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 18
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT MOD_RES 116
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9QZQ8"
FT MOD_RES 123
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT MOD_RES 123
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9QZQ8"
FT MOD_RES 129
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 116
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 117
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 123
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 166
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 188
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75367"
FT VAR_SEQ 197..228
FT /note="NLIHSEISNLAGFEVEAIINPTNADIDLKDDL -> QVVQADIASIDSDAVV
FT HPTNADFYIGGEV (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:1529340"
FT /id="VSP_002057"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:1YD9"
FT HELIX 227..251
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 267..275
FT /evidence="ECO:0007829|PDB:1YD9"
FT HELIX 285..302
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:1YD9"
FT HELIX 322..337
FT /evidence="ECO:0007829|PDB:1YD9"
FT STRAND 347..351
FT /evidence="ECO:0007829|PDB:1YD9"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:1YD9"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:1YD9"
SQ SEQUENCE 371 AA; 39504 MW; 697D4EF813AAAC6D CRC64;
MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA AVLEYLTAEI
LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI ASGGVLPNIH PELLAKKRGS
KGKLEAIITP PPAKKAKSPS QKKPVAKKTG GKKGARKSKK QGEVSKAASA DSTTEGAPTD
GFTVLSTKSL FLGQKLNLIH SEISNLAGFE VEAIINPTNA DIDLKDDLGS TLEKKGGKEF
VEAVLELRKK NGPLEVAGAA VSAGHGLPAK FVIHCNSPVW GADKCEELLE KTVKNCLALA
DDRKLKSIAF PSIGSGRNGF PKQTAAQLIL KAISSYFVST MSSSIKTVYF VLFDSESIGI
YVQEMAKLDA N
