ID H2AY_RAT Reviewed; 368 AA. AC Q02874; O09140; Q63325; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 12-OCT-2022, sequence version 5. DT 24-JAN-2024, entry version 187. 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 (PubMed:16107708). CC Histones thereby play a central role in transcription regulation, DNA CC repair, DNA replication and chromosomal stability (PubMed:16107708). CC DNA accessibility is regulated via a complex set of post-translational CC modifications of histones, also called histone code, and nucleosome CC remodeling (PubMed:16107708). Involved in stable X chromosome CC inactivation. Inhibits the binding of transcription factors, including CC NF-kappa-B, and interferes with the activity of remodeling SWI/SNF CC complexes (By similarity). Inhibits histone acetylation by EP300 and CC recruits class I HDACs, which induces a hypoacetylated state of CC chromatin (By similarity). {ECO:0000250|UniProtKB:O75367, CC ECO:0000250|UniProtKB:Q9QZQ8, ECO:0000269|PubMed:16107708}. CC -!- FUNCTION: [Isoform 1]: Isoform that specifically binds poly-ADP-ribose CC and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism. Able CC to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap CC them. This prevents PARP1 from further addition of ADP-ribose and thus CC limits the consumption of nuclear NAD(+), allowing the cell to maintain CC proper NAD(+) levels in both the nucleus and the mitochondria to CC promote proper mitochondrial respiration. Increases the expression of CC genes involved in redox metabolism, including SOD3. CC {ECO:0000250|UniProtKB:Q9QZQ8}. CC -!- FUNCTION: [Isoform 2]: In contrast to isoform 1, does not bind poly- CC ADP-ribose. Represses SOD3 gene expression. CC {ECO:0000250|UniProtKB:Q9QZQ8}. 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 HDAC1 and HDAC2. Interacts CC with SPOP. Part of a complex consisting of MACROH2A1, CUL3 and SPOP. CC {ECO:0000250|UniProtKB:O75367}. CC -!- SUBUNIT: [Isoform 1]: Interacts with PARP1. CC {ECO:0000250|UniProtKB:Q9QZQ8}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O75367}. CC Chromosome {ECO:0000250|UniProtKB:O75367}. Note=Enriched in inactive X CC chromosome chromatin and in senescence-associated heterochromatin. CC Recruited to DNA damage sites in an APLF-dependent manner. CC {ECO:0000250|UniProtKB:O75367}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=mH2A1.1; CC IsoId=Q02874-2; Sequence=Displayed; CC Name=2; Synonyms=mH2A1.2; CC IsoId=Q02874-1; Sequence=VSP_061612; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Present only in liver and brain (at CC protein level). {ECO:0000269|PubMed:9138085}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Present in brain, thymus, testis, CC liver and kidney (at protein level). {ECO:0000269|PubMed:9138085}. CC -!- DOMAIN: [Isoform 1]: The macro domain specifically binds poly-ADP- CC ribose. {ECO:0000250|UniProtKB:O75367}. 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. CC {ECO:0000250|UniProtKB:O75367}. CC -!- SIMILARITY: Belongs to the histone H2A family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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=226-368. 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; 10116-ENSRNOP00000049143; -. DR Ensembl; ENSRNOT00000051702.7; ENSRNOP00000049143.4; ENSRNOG00000011523.9. [Q02874-1] DR GeneID; 29384; -. DR KEGG; rno:29384; -. DR UCSC; RGD:621462; rat. [Q02874-2] DR AGR; RGD:621462; -. 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; 235643at2759; -. DR PhylomeDB; Q02874; -. DR EvolutionaryTrace; Q02874; -. DR PRO; PR:Q02874; -. DR Proteomes; UP000002494; Chromosome 17. DR Bgee; ENSRNOG00000011523; Expressed in thymus and 20 other cell types or tissues. DR ExpressionAtlas; Q02874; baseline and differential. 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; ISS:UniProtKB. DR GO; GO:0005721; C:pericentric heterochromatin; ISO:RGD. DR GO; GO:0090734; C:site of DNA damage; ISO:RGD. DR GO; GO:0072570; F:ADP-D-ribose binding; ISS:UniProtKB. DR GO; GO:0160002; F:ADP-D-ribose modification-dependent protein binding; ISS:UniProtKB. 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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD. DR GO; GO:0030527; F:structural constituent of chromatin; ISO:RGD. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD. DR GO; GO:0006281; P:DNA repair; ISO:RGD. DR GO; GO:0040029; P:epigenetic regulation of gene expression; 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:1904815; P:negative regulation of protein localization to chromosome, telomeric region; 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:0019216; P:regulation of lipid metabolic process; ISO:RGD. DR GO; GO:1902688; P:regulation of NAD metabolic process; ISS:UniProtKB. DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISO:RGD. DR GO; GO:1902882; P:regulation of response to oxidative stress; ISO:RGD. DR GO; GO:0007549; P:sex-chromosome dosage compensation; ISO:RGD. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; ISO:RGD. DR CDD; cd00074; H2A; 1. DR CDD; cd02904; Macro_H2A-like; 1. DR Gene3D; 1.10.20.10; Histone, subunit A; 1. DR Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 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:SF20; CORE HISTONE MACRO-H2A.1; 1. DR PANTHER; PTHR23430; HISTONE H2A; 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; Histone-fold; 1. DR SUPFAM; SSF52949; Macro domain-like; 1. DR PROSITE; PS51154; MACRO; 1. DR Genevisible; Q02874; RN. 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..368 FT /note="Core histone macro-H2A.1" FT /id="PRO_0000055319" FT DOMAIN 2..117 FT /note="Histone H2A" FT DOMAIN 183..366 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 BINDING 202 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 203 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 225 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 274 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 311 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 312 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 313 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" FT BINDING 315 FT /ligand="a glycoprotein" FT /ligand_id="ChEBI:CHEBI:17089" FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group" FT /ligand_part_id="ChEBI:CHEBI:157741" FT /evidence="ECO:0000250|UniProtKB:A0A0D2UG83" 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 319 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O75367" FT VAR_SEQ 197..225 FT /note="QVVQADIASIDSDAVVHPTNADFYIGGEV -> NLIHSEISNLAGFEVEAII FT NPTNADIDLKDDL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1529340" FT /id="VSP_061612" FT STRAND 184..189 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 195..199 FT /evidence="ECO:0007829|PDB:1YD9" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 209..214 FT /evidence="ECO:0007829|PDB:1YD9" FT HELIX 224..248 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 256..260 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 264..272 FT /evidence="ECO:0007829|PDB:1YD9" FT HELIX 282..299 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:1YD9" FT HELIX 319..334 FT /evidence="ECO:0007829|PDB:1YD9" FT STRAND 344..348 FT /evidence="ECO:0007829|PDB:1YD9" FT HELIX 352..362 FT /evidence="ECO:0007829|PDB:1YD9" FT TURN 363..366 FT /evidence="ECO:0007829|PDB:1YD9" SQ SEQUENCE 368 AA; 39040 MW; 59ACA1B086CF5C69 CRC64; MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA AVLEYLTAEI LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI ASGGVLPNIH PELLAKKRGS KGKLEAIITP PPAKKAKSPS QKKPVAKKTG GKKGARKSKK QGEVSKAASA DSTTEGAPTD GFTVLSTKSL FLGQKLQVVQ ADIASIDSDA VVHPTNADFY IGGEVGSTLE KKGGKEFVEA VLELRKKNGP LEVAGAAVSA GHGLPAKFVI HCNSPVWGAD KCEELLEKTV KNCLALADDR KLKSIAFPSI GSGRNGFPKQ TAAQLILKAI SSYFVSTMSS SIKTVYFVLF DSESIGIYVQ EMAKLDAN //