H2AY_HUMAN
ID H2AY_HUMAN Reviewed; 372 AA.
AC O75367; O75377; Q503A8; Q7Z5E3; Q96D41; Q9H8P3; Q9UP96;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Core histone macro-H2A.1;
DE Short=Histone macroH2A1;
DE Short=mH2A1;
DE AltName: Full=Histone H2A.y;
DE Short=H2A/y;
DE AltName: Full=Medulloblastoma antigen MU-MB-50.205;
GN Name=MACROH2A1 {ECO:0000312|HGNC:HGNC:4740};
GN Synonyms=H2AFY {ECO:0000312|HGNC:HGNC:4740};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9714746; DOI=10.1016/s0167-4781(98)00098-0;
RA Lee Y., Hong M., Kim J.W., Hong Y.M., Choe Y.-K., Chang S.Y., Lee K.S.,
RA Choe I.S.;
RT "Isolation of cDNA clones encoding human histone macroH2A1 subtypes.";
RL Biochim. Biophys. Acta 1399:73-77(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-length
RT cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow, and Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-372 (ISOFORM 3).
RC TISSUE=Medulloblastoma;
RX PubMed=12800201; DOI=10.1002/ijc.11208;
RA Behrends U., Schneider I., Roessler S., Frauenknecht H., Golbeck A.,
RA Lechner B., Eigenstetter G., Zobywalski C., Mueller-Weihrich S.,
RA Graubner U., Schmid I., Sackerer D., Spaeth M., Goetz C., Prantl F.,
RA Asmuss H.-P., Bise K., Mautner J.;
RT "Novel tumor antigens identified by autologous antibody screening of
RT childhood medulloblastoma cDNA libraries.";
RL Int. J. Cancer 106:244-251(2003).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=9634239; DOI=10.1038/31275;
RA Costanzi C., Pehrson J.R.;
RT "Histone macroH2A1 is concentrated in the inactive X chromosome of female
RT mammals.";
RL Nature 393:599-601(1998).
RN [8]
RP FUNCTION.
RX PubMed=12718888; DOI=10.1016/s1097-2765(03)00100-x;
RA Angelov D., Molla A., Perche P.-Y., Hans F., Cote J., Khochbin S.,
RA Bouvet P., Dimitrov S.;
RT "The histone variant macroH2A interferes with transcription factor binding
RT and SWI/SNF nucleosome remodeling.";
RL Mol. Cell 11:1033-1041(2003).
RN [9]
RP UBIQUITINATION AT LYS-116 AND LYS-117, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16129414; DOI=10.1016/j.bbrc.2005.08.046;
RA Ogawa Y., Ono T., Wakata Y., Okawa K., Tagami H., Shibahara K.;
RT "Histone variant macroH2A1.2 is mono-ubiquitinated at its histone domain.";
RL Biochem. Biophys. Res. Commun. 336:204-209(2005).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15621527; DOI=10.1016/j.devcel.2004.10.019;
RA Zhang R., Poustovoitov M.V., Ye X., Santos H.A., Chen W., Daganzo S.M.,
RA Erzberger J.P., Serebriiskii I.G., Canutescu A.A., Dunbrack R.L.,
RA Pehrson J.R., Berger J.M., Kaufman P.D., Adams P.D.;
RT "Formation of MacroH2A-containing senescence-associated heterochromatin
RT foci and senescence driven by ASF1a and HIRA.";
RL Dev. Cell 8:19-30(2005).
RN [11]
RP FUNCTION, AND BINDING OF THE MACRO DOMAIN TO ADP-RIBOSE (ISOFORM 1).
RX PubMed=15902274; DOI=10.1038/sj.emboj.7600664;
RA Karras G.I., Kustatscher G., Buhecha H.R., Allen M.D., Pugieux C., Sait F.,
RA Bycroft M., Ladurner A.G.;
RT "The macro domain is an ADP-ribose binding module.";
RL EMBO J. 24:1911-1920(2005).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH CULLIN3 AND SPOP, UBIQUITINATION,
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15897469; DOI=10.1073/pnas.0408918102;
RA Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I.,
RA Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M.;
RT "Stable X chromosome inactivation involves the PRC1 Polycomb complex and
RT requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129 AND THR-178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP FUNCTION.
RX PubMed=16428466; DOI=10.1128/mcb.26.3.1156-1164.2006;
RA Doyen C.-M., An W., Angelov D., Bondarenko V., Mietton F., Studitsky V.M.,
RA Hamiche A., Roeder R.G., Bouvet P., Dimitrov S.;
RT "Mechanism of polymerase II transcription repression by the histone variant
RT macroH2A.";
RL Mol. Cell. Biol. 26:1156-1164(2006).
RN [15]
RP METHYLATION AT LYS-18 AND LYS-123, PHOSPHORYLATION AT THR-129, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16210244; DOI=10.1074/mcp.m500285-mcp200;
RA Chu F., Nusinow D.A., Chalkley R.J., Plath K., Panning B., Burlingame A.L.;
RT "Mapping post-translational modifications of the histone variant MacroH2A1
RT using tandem mass spectrometry.";
RL Mol. Cell. Proteomics 5:194-203(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170 AND THR-178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129; SER-170; SER-173 AND
RP THR-178, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129 AND THR-178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP LACK OF ADP-RIBOSE GLYCOHYDROLASE ACTIVITY.
RX PubMed=23474714; DOI=10.1038/nsmb.2521;
RA Rosenthal F., Feijs K.L., Frugier E., Bonalli M., Forst A.H., Imhof R.,
RA Winkler H.C., Fischer D., Caflisch A., Hassa P.O., Luescher B.,
RA Hottiger M.O.;
RT "Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases.";
RL Nat. Struct. Mol. Biol. 20:502-507(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129 AND SER-170, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP FUNCTION (ISOFORMS 1 AND 2), AND ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=23022728; DOI=10.1038/nsmb.2390;
RA Dardenne E., Pierredon S., Driouch K., Gratadou L., Lacroix-Triki M.,
RA Espinoza M.P., Zonta E., Germann S., Mortada H., Villemin J.P.,
RA Dutertre M., Lidereau R., Vagner S., Auboeuf D.;
RT "Splicing switch of an epigenetic regulator by RNA helicases promotes
RT tumor-cell invasiveness.";
RL Nat. Struct. Mol. Biol. 19:1139-1146(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129; SER-170; SER-173 AND
RP THR-178, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-123; LYS-167; LYS-189 AND
RP LYS-323, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-120 IN COMPLEX WITH THE
RP NUCLEOSOME CORE PARTICLE, 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).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 162-372 (ISOFORM 1), X-RAY
RP CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 161-372 (ISOFORM 2), AND BINDING TO
RP ADP-RIBOSE AND O-ACETYL-ADP-RIBOSE (ISOFORM 1).
RX PubMed=15965484; DOI=10.1038/nsmb956;
RA Kustatscher G., Hothorn M., Pugieux C., Scheffzek K., Ladurner A.G.;
RT "Splicing regulates NAD metabolite binding to histone macroH2A.";
RL Nat. Struct. Mol. Biol. 12:624-625(2005).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 172-186 IN COMPLEXES WITH SPOP,
RP SUBUNIT, AND UBIQUITINATION.
RX PubMed=19818708; DOI=10.1016/j.molcel.2009.09.022;
RA Zhuang M., Calabrese M.F., Liu J., Waddell M.B., Nourse A., Hammel M.,
RA Miller D.J., Walden H., Duda D.M., Seyedin S.N., Hoggard T., Harper J.W.,
RA White K.P., Schulman B.A.;
RT "Structures of SPOP-substrate complexes: insights into molecular
RT architectures of BTB-Cul3 ubiquitin ligases.";
RL Mol. Cell 36:39-50(2009).
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes where it represses transcription
CC (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap
CC 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 (PubMed:15897469). Inhibits the binding of
CC transcription factors, including NF-kappa-B, and interferes with the
CC activity of remodeling SWI/SNF complexes (PubMed:12718888,
CC PubMed:16428466). Inhibits histone acetylation by EP300 and recruits
CC class I HDACs, which induces a hypoacetylated state of chromatin
CC (PubMed:16428466, PubMed:16107708). {ECO:0000269|PubMed:12718888,
CC ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469,
CC ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:16428466}.
CC -!- FUNCTION: [Isoform 1]: Binds ADP-ribose and O-acetyl-ADP-ribose, and
CC may be involved in ADP-ribose-mediated chromatin modulation
CC (PubMed:15902274). Increases the expression of genes involved in redox
CC metabolism, including SOD3 (PubMed:23022728).
CC {ECO:0000269|PubMed:15902274, ECO:0000269|PubMed:23022728}.
CC -!- FUNCTION: [Isoform 2]: Represses SOD3 gene expression.
CC {ECO:0000269|PubMed:23022728}.
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 (By
CC similarity). Interacts with SPOP. Part of a complex consisting of
CC MACROH2A1, CUL3 and SPOP. {ECO:0000250, ECO:0000269|PubMed:15897469,
CC ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:19818708}.
CC -!- INTERACTION:
CC O75367; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2868511, EBI-3867333;
CC O75367; P04626: ERBB2; NbExp=6; IntAct=EBI-2868511, EBI-641062;
CC O75367; A1L162: ERICH2; NbExp=6; IntAct=EBI-2868511, EBI-2682520;
CC O75367; Q8N9E0: FAM133A; NbExp=3; IntAct=EBI-2868511, EBI-10268158;
CC O75367; U3KQK0: H2BC15; NbExp=6; IntAct=EBI-2868511, EBI-12142839;
CC O75367; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2868511, EBI-10171774;
CC O75367; P61244: MAX; NbExp=2; IntAct=EBI-2868511, EBI-751711;
CC O75367; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-2868511, EBI-3920396;
CC O75367; Q8N9Q2: SREK1IP1; NbExp=3; IntAct=EBI-2868511, EBI-10268630;
CC O75367; Q12933: TRAF2; NbExp=3; IntAct=EBI-2868511, EBI-355744;
CC O75367; Q12899: TRIM26; NbExp=3; IntAct=EBI-2868511, EBI-2341136;
CC O75367; Q3SXR9: VCX2; NbExp=3; IntAct=EBI-2868511, EBI-11983741;
CC O75367; Q969S3: ZNF622; NbExp=3; IntAct=EBI-2868511, EBI-2687480;
CC O75367-2; P46100: ATRX; NbExp=2; IntAct=EBI-6249599, EBI-396461;
CC O75367-2; O95271: TNKS; NbExp=6; IntAct=EBI-6249599, EBI-1105254;
CC O75367-3; P04626: ERBB2; NbExp=3; IntAct=EBI-6250866, EBI-641062;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15621527,
CC ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9634239}. Chromosome
CC {ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469,
CC ECO:0000269|PubMed:9634239}. Note=Enriched in inactive X chromosome
CC chromatin and in senescence-associated heterochromatin.
CC {ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469,
CC ECO:0000269|PubMed:9634239}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=mH2A1.2 {ECO:0000303|PubMed:23022728};
CC IsoId=O75367-1; Sequence=Displayed;
CC Name=1; Synonyms=mH2A1.1 {ECO:0000303|PubMed:23022728};
CC IsoId=O75367-2; Sequence=VSP_002056;
CC Name=3;
CC IsoId=O75367-3; Sequence=VSP_038379;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9714746}.
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:0000269|PubMed:15897469, ECO:0000269|PubMed:16129414,
CC ECO:0000269|PubMed:19818708}.
CC -!- MISCELLANEOUS: [Isoform 2]: The preferential expression of isoform 2
CC over that of isoform 1 requires the presence of DDX5/DDX17.
CC {ECO:0000269|PubMed:23022728}.
CC -!- MISCELLANEOUS: [Isoform 1]: Specifically binds ADP-ribose and O-acetyl-
CC ADP-ribose. Important residues for binding are Asp-203, Gly-224, Gly-
CC 314 and Phe-348. Preferentially expressed over isoform 2 in the absence
CC of DDX5/DDX17. {ECO:0000269|PubMed:15902274,
CC ECO:0000269|PubMed:23022728}.
CC -!- CAUTION: [Isoform 1]: In contrast to other Macro-domain containing
CC proteins, lacks ADP-ribose glycohydrolase activity.
CC {ECO:0000269|PubMed:23474714}.
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DR EMBL; AF041483; AAC33433.1; -; mRNA.
DR EMBL; AF044286; AAC33434.1; -; mRNA.
DR EMBL; AF054174; AAC39908.1; -; mRNA.
DR EMBL; AK023409; BAB14565.1; -; mRNA.
DR EMBL; AC026691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013331; AAH13331.1; -; mRNA.
DR EMBL; BC095406; AAH95406.1; -; mRNA.
DR EMBL; AY134746; AAN08620.1; -; mRNA.
DR CCDS; CCDS4183.1; -. [O75367-3]
DR CCDS; CCDS4184.1; -. [O75367-2]
DR CCDS; CCDS4185.1; -. [O75367-1]
DR RefSeq; NP_001035248.1; NM_001040158.1. [O75367-3]
DR RefSeq; NP_004884.1; NM_004893.2. [O75367-3]
DR RefSeq; NP_613075.1; NM_138609.2. [O75367-2]
DR RefSeq; NP_613258.2; NM_138610.2. [O75367-1]
DR RefSeq; XP_011542031.1; XM_011543729.2. [O75367-1]
DR RefSeq; XP_011542032.1; XM_011543730.2. [O75367-3]
DR PDB; 1U35; X-ray; 3.00 A; C/G=1-120.
DR PDB; 1ZR3; X-ray; 1.66 A; A/B/C/D=162-372.
DR PDB; 1ZR5; X-ray; 2.92 A; A/B=161-372.
DR PDB; 2F8N; X-ray; 2.90 A; G=1-120.
DR PDB; 2FXK; X-ray; 2.54 A; A/B=162-372.
DR PDB; 3HQH; X-ray; 2.30 A; M=167-181.
DR PDB; 3HSV; X-ray; 1.43 A; M=172-186.
DR PDB; 3IID; X-ray; 1.90 A; A=162-372.
DR PDB; 3IIF; X-ray; 2.10 A; A/B/C=162-372.
DR PDB; 3IVB; X-ray; 1.75 A; M=167-181.
DR PDB; 5IIT; X-ray; 2.13 A; A/B/C/D=181-369.
DR PDB; 5LNC; X-ray; 3.29 A; A/B=182-369.
DR PDB; 7D3Y; X-ray; 3.11 A; A/B=181-372.
DR PDBsum; 1U35; -.
DR PDBsum; 1ZR3; -.
DR PDBsum; 1ZR5; -.
DR PDBsum; 2F8N; -.
DR PDBsum; 2FXK; -.
DR PDBsum; 3HQH; -.
DR PDBsum; 3HSV; -.
DR PDBsum; 3IID; -.
DR PDBsum; 3IIF; -.
DR PDBsum; 3IVB; -.
DR PDBsum; 5IIT; -.
DR PDBsum; 5LNC; -.
DR PDBsum; 7D3Y; -.
DR AlphaFoldDB; O75367; -.
DR SMR; O75367; -.
DR BioGRID; 114927; 388.
DR CORUM; O75367; -.
DR DIP; DIP-44283N; -.
DR ELM; O75367; -.
DR IntAct; O75367; 77.
DR MINT; O75367; -.
DR STRING; 9606.ENSP00000423563; -.
DR GlyGen; O75367; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; O75367; -.
DR PhosphoSitePlus; O75367; -.
DR SwissPalm; O75367; -.
DR BioMuta; H2AFY; -.
DR SWISS-2DPAGE; O75367; -.
DR CPTAC; CPTAC-383; -.
DR CPTAC; CPTAC-384; -.
DR EPD; O75367; -.
DR jPOST; O75367; -.
DR MassIVE; O75367; -.
DR MaxQB; O75367; -.
DR PaxDb; O75367; -.
DR PeptideAtlas; O75367; -.
DR PRIDE; O75367; -.
DR ProteomicsDB; 49934; -. [O75367-1]
DR ProteomicsDB; 49935; -. [O75367-2]
DR ProteomicsDB; 49936; -. [O75367-3]
DR TopDownProteomics; O75367-1; -. [O75367-1]
DR TopDownProteomics; O75367-2; -. [O75367-2]
DR Antibodypedia; 26391; 213 antibodies from 31 providers.
DR DNASU; 9555; -.
DR Ensembl; ENST00000304332.8; ENSP00000302572.4; ENSG00000113648.17. [O75367-3]
DR Ensembl; ENST00000312469.8; ENSP00000310169.4; ENSG00000113648.17. [O75367-2]
DR Ensembl; ENST00000510038.1; ENSP00000424971.1; ENSG00000113648.17. [O75367-1]
DR Ensembl; ENST00000511689.6; ENSP00000423563.1; ENSG00000113648.17. [O75367-1]
DR GeneID; 9555; -.
DR KEGG; hsa:9555; -.
DR MANE-Select; ENST00000511689.6; ENSP00000423563.1; NM_138610.3; NP_613258.2.
DR UCSC; uc003lam.2; human. [O75367-1]
DR CTD; 9555; -.
DR DisGeNET; 9555; -.
DR GeneCards; MACROH2A1; -.
DR HGNC; HGNC:4740; MACROH2A1.
DR HPA; ENSG00000113648; Low tissue specificity.
DR MalaCards; MACROH2A1; -.
DR MIM; 610054; gene.
DR neXtProt; NX_O75367; -.
DR OpenTargets; ENSG00000113648; -.
DR Orphanet; 1275; Brachydactyly-elbow wrist dysplasia syndrome.
DR VEuPathDB; HostDB:ENSG00000113648; -.
DR eggNOG; KOG1756; Eukaryota.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000159541; -.
DR HOGENOM; CLU_062828_0_0_1; -.
DR InParanoid; O75367; -.
DR OMA; GHNFPAK; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; O75367; -.
DR TreeFam; TF332276; -.
DR PathwayCommons; O75367; -.
DR SignaLink; O75367; -.
DR BioGRID-ORCS; 9555; 6 hits in 1081 CRISPR screens.
DR ChiTaRS; H2AFY; human.
DR EvolutionaryTrace; O75367; -.
DR GeneWiki; H2AFY; -.
DR GenomeRNAi; 9555; -.
DR Pharos; O75367; Tbio.
DR PRO; PR:O75367; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O75367; protein.
DR Bgee; ENSG00000113648; Expressed in epithelium of nasopharynx and 209 other tissues.
DR ExpressionAtlas; O75367; baseline and differential.
DR Genevisible; O75367; HS.
DR GO; GO:0001740; C:Barr body; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000786; C:nucleosome; NAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:BHF-UCL.
DR GO; GO:0001739; C:sex chromatin; TAS:BHF-UCL.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0031492; F:nucleosomal DNA binding; IDA:UniProtKB.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0000182; F:rDNA binding; IDA:UniProtKB.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0007549; P:dosage compensation; IDA:MGI.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; IMP:UniProtKB.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:1902750; P:negative regulation of cell cycle G2/M phase transition; IMP:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0061086; P:negative regulation of histone H3-K27 methylation; IMP:UniProtKB.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IMP:UniProtKB.
DR GO; GO:1904815; P:negative regulation of protein localization to chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:1902883; P:negative regulation of response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:1901837; P:negative regulation of transcription of nucleolar large rRNA by RNA polymerase I; IMP:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; NAS:UniProtKB.
DR GO; GO:1903226; P:positive regulation of endodermal cell differentiation; IMP:UniProtKB.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0034184; P:positive regulation of maintenance of mitotic sister chromatid cohesion; IDA:BHF-UCL.
DR GO; GO:1902884; P:positive regulation of response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:1902882; P:regulation of response to oxidative stress; IMP:UniProtKB.
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; DNA-binding; Isopeptide bond; Methylation; Nucleosome core;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..372
FT /note="Core histone macro-H2A.1"
FT /id="PRO_0000055318"
FT DOMAIN 2..117
FT /note="Histone H2A"
FT DOMAIN 184..370
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT REGION 128..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..160
FT /note="Basic 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:0000269|PubMed:16210244"
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:0000305|PubMed:16210244"
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:0000269|PubMed:16210244,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17924679,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 178
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT CROSSLNK 116
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:16129414"
FT CROSSLNK 117
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16129414"
FT CROSSLNK 123
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 189
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 323
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 159
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12800201,
FT ECO:0000303|PubMed:9653160"
FT /id="VSP_038379"
FT VAR_SEQ 198..229
FT /note="NLIHSEISNLAGFEVEAIINPTNADIDLKDDL -> QVVQADIASIDSDAVV
FT HPTNTDFYIGGEV (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:9714746"
FT /id="VSP_002056"
FT CONFLICT 186
FT /note="L -> F (in Ref. 3; BAB14565)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="F -> S (in Ref. 3; BAB14565)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="L -> P (in Ref. 1; AAC33433)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="E -> G (in Ref. 5; AAH95406)"
FT /evidence="ECO:0000305"
FT HELIX 15..19
FT /evidence="ECO:0007829|PDB:2F8N"
FT HELIX 25..35
FT /evidence="ECO:0007829|PDB:2F8N"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:2F8N"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1U35"
FT HELIX 44..70
FT /evidence="ECO:0007829|PDB:2F8N"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2F8N"
FT HELIX 78..86
FT /evidence="ECO:0007829|PDB:2F8N"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:2F8N"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:2F8N"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2F8N"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:2F8N"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:3IVB"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:1ZR3"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:1ZR5"
FT STRAND 213..219
FT /evidence="ECO:0007829|PDB:1ZR3"
FT HELIX 227..252
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 268..277
FT /evidence="ECO:0007829|PDB:1ZR3"
FT HELIX 286..303
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:2FXK"
FT HELIX 323..340
FT /evidence="ECO:0007829|PDB:1ZR3"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:1ZR5"
FT STRAND 348..355
FT /evidence="ECO:0007829|PDB:1ZR3"
FT HELIX 356..367
FT /evidence="ECO:0007829|PDB:1ZR3"
SQ SEQUENCE 372 AA; 39617 MW; 37DED989EF7E69DC CRC64;
MSSRGGKKKS TKTSRSAKAG VIFPVGRMLR YIKKGHPKYR IGVGAPVYMA AVLEYLTAEI
LELAGNAARD NKKGRVTPRH ILLAVANDEE LNQLLKGVTI ASGGVLPNIH PELLAKKRGS
KGKLEAIITP PPAKKAKSPS QKKPVSKKAG GKKGARKSKK KQGEVSKAAS ADSTTEGTPA
DGFTVLSTKS LFLGQKLNLI HSEISNLAGF EVEAIINPTN ADIDLKDDLG NTLEKKGGKE
FVEAVLELRK KNGPLEVAGA AVSAGHGLPA KFVIHCNSPV WGADKCEELL EKTVKNCLAL
ADDKKLKSIA FPSIGSGRNG FPKQTAAQLI LKAISSYFVS TMSSSIKTVY FVLFDSESIG
IYVQEMAKLD AN
