H2AW_HUMAN
ID H2AW_HUMAN Reviewed; 372 AA.
AC Q9P0M6; Q5SQT2;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Core histone macro-H2A.2;
DE Short=Histone macroH2A2;
DE Short=mH2A2;
GN Name=MACROH2A2 {ECO:0000312|HGNC:HGNC:14453};
GN Synonyms=H2AFY2 {ECO:0000312|HGNC:HGNC:14453};
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], AND SUBCELLULAR LOCATION.
RX PubMed=11331621; DOI=10.1093/hmg/10.10.1101;
RA Chadwick B.P., Willard H.F.;
RT "Histone H2A variants and the inactive X chromosome: identification of a
RT second macroH2A variant.";
RL Hum. Mol. Genet. 10:1101-1113(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=11262398; DOI=10.1074/jbc.m010919200;
RA Costanzi C., Pehrson J.R.;
RT "MACROH2A2, a new member of the MACROH2A core histone family.";
RL J. Biol. Chem. 276:21776-21784(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 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 [7]
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 [8]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-239, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [9]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-239, AND IDENTIFICATION BY MASS
RP 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).
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. May be involved in
CC stable X chromosome inactivation. {ECO:0000269|PubMed:15621527}.
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.
CC -!- INTERACTION:
CC Q9P0M6; Q8N9E0: FAM133A; NbExp=3; IntAct=EBI-3922608, EBI-10268158;
CC Q9P0M6; U3KQK0: H2BC15; NbExp=3; IntAct=EBI-3922608, EBI-12142839;
CC Q9P0M6; PRO_0000037315 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-3922608, EBI-25487941;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11262398,
CC ECO:0000269|PubMed:11331621, ECO:0000269|PubMed:15621527}. Chromosome
CC {ECO:0000269|PubMed:11262398, ECO:0000269|PubMed:11331621,
CC ECO:0000269|PubMed:15621527}. Note=Enriched in inactive X chromosome
CC chromatin (PubMed:11331621, PubMed:11262398) and in senescence-
CC associated heterochromatin (PubMed:15621527).
CC {ECO:0000269|PubMed:11262398, ECO:0000269|PubMed:11331621,
CC ECO:0000269|PubMed:15621527}.
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; AF336304; AAK52471.1; -; mRNA.
DR EMBL; AF151534; AAF72101.1; -; mRNA.
DR EMBL; AK022776; BAB14239.1; -; mRNA.
DR EMBL; AL731540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016172; AAH16172.1; -; mRNA.
DR CCDS; CCDS7296.1; -.
DR RefSeq; NP_061119.1; NM_018649.2.
DR PDB; 2XD7; X-ray; 2.09 A; A/B/C/D=177-369.
DR PDB; 6FY5; X-ray; 1.65 A; A/B=178-372.
DR PDBsum; 2XD7; -.
DR PDBsum; 6FY5; -.
DR AlphaFoldDB; Q9P0M6; -.
DR SMR; Q9P0M6; -.
DR BioGRID; 120686; 178.
DR DIP; DIP-48563N; -.
DR IntAct; Q9P0M6; 108.
DR MINT; Q9P0M6; -.
DR STRING; 9606.ENSP00000362352; -.
DR iPTMnet; Q9P0M6; -.
DR PhosphoSitePlus; Q9P0M6; -.
DR BioMuta; H2AFY2; -.
DR DMDM; 12585260; -.
DR EPD; Q9P0M6; -.
DR jPOST; Q9P0M6; -.
DR MassIVE; Q9P0M6; -.
DR MaxQB; Q9P0M6; -.
DR PaxDb; Q9P0M6; -.
DR PeptideAtlas; Q9P0M6; -.
DR PRIDE; Q9P0M6; -.
DR ProteomicsDB; 83580; -.
DR Antibodypedia; 28963; 356 antibodies from 24 providers.
DR DNASU; 55506; -.
DR Ensembl; ENST00000373255.9; ENSP00000362352.3; ENSG00000099284.15.
DR Ensembl; ENST00000679349.1; ENSP00000503835.1; ENSG00000099284.15.
DR GeneID; 55506; -.
DR KEGG; hsa:55506; -.
DR MANE-Select; ENST00000373255.9; ENSP00000362352.3; NM_018649.3; NP_061119.1.
DR UCSC; uc001jqm.4; human.
DR CTD; 55506; -.
DR DisGeNET; 55506; -.
DR GeneCards; MACROH2A2; -.
DR HGNC; HGNC:14453; MACROH2A2.
DR HPA; ENSG00000099284; Low tissue specificity.
DR MIM; 616141; gene.
DR neXtProt; NX_Q9P0M6; -.
DR OpenTargets; ENSG00000099284; -.
DR VEuPathDB; HostDB:ENSG00000099284; -.
DR eggNOG; KOG1756; Eukaryota.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000158120; -.
DR InParanoid; Q9P0M6; -.
DR OMA; FPKQMAA; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; Q9P0M6; -.
DR TreeFam; TF332276; -.
DR PathwayCommons; Q9P0M6; -.
DR SignaLink; Q9P0M6; -.
DR BioGRID-ORCS; 55506; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; H2AFY2; human.
DR EvolutionaryTrace; Q9P0M6; -.
DR GeneWiki; H2AFY2; -.
DR GenomeRNAi; 55506; -.
DR Pharos; Q9P0M6; Tbio.
DR PRO; PR:Q9P0M6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9P0M6; protein.
DR Bgee; ENSG00000099284; Expressed in cortical plate and 195 other tissues.
DR ExpressionAtlas; Q9P0M6; baseline and differential.
DR Genevisible; Q9P0M6; HS.
DR GO; GO:0001740; C:Barr body; IDA:MGI.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
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:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0007549; P:dosage compensation; IDA:MGI.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; 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; IGI:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; 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; Chromatin regulator; Chromosome; DNA-binding;
KW Isopeptide bond; Nucleosome core; Nucleus; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..372
FT /note="Core histone macro-H2A.2"
FT /id="PRO_0000055320"
FT DOMAIN 2..117
FT /note="Histone H2A"
FT DOMAIN 184..370
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT REGION 115..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..139
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..157
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 CROSSLNK 239
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT STRAND 183..191
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:6FY5"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 213..219
FT /evidence="ECO:0007829|PDB:6FY5"
FT HELIX 227..252
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 266..277
FT /evidence="ECO:0007829|PDB:6FY5"
FT HELIX 286..302
FT /evidence="ECO:0007829|PDB:6FY5"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:6FY5"
FT HELIX 323..339
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:6FY5"
FT HELIX 356..366
FT /evidence="ECO:0007829|PDB:6FY5"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:6FY5"
SQ SEQUENCE 372 AA; 40058 MW; C4B35CD156031AF1 CRC64;
MSGRSGKKKM SKLSRSARAG VIFPVGRLMR YLKKGTFKYR ISVGAPVYMA AVIEYLAAEI
LELAGNAARD NKKARIAPRH ILLAVANDEE LNQLLKGVTI ASGGVLPRIH PELLAKKRGT
KGKSETILSP PPEKRGRKAT SGKKGGKKSK AAKPRTSKKS KPKDSDKEGT SNSTSEDGPG
DGFTILSSKS LVLGQKLSLT QSDISHIGSM RVEGIVHPTT AEIDLKEDIG KALEKAGGKE
FLETVKELRK SQGPLEVAEA AVSQSSGLAA KFVIHCHIPQ WGSDKCEEQL EETIKNCLSA
AEDKKLKSVA FPPFPSGRNC FPKQTAAQVT LKAISAHFDD SSASSLKNVY FLLFDSESIG
IYVQEMAKLD AK
