H2A2A_HUMAN
ID H2A2A_HUMAN Reviewed; 130 AA.
AC Q6FI13; B2R5F0; P20670;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Histone H2A type 2-A;
DE AltName: Full=H2A-clustered histone 18 {ECO:0000312|HGNC:HGNC:4736};
DE AltName: Full=H2A-clustered histone 19 {ECO:0000312|HGNC:HGNC:29668};
DE AltName: Full=Histone H2A.2;
DE AltName: Full=Histone H2A/o;
GN Name=H2AC18 {ECO:0000312|HGNC:HGNC:4736};
GN Synonyms=H2AFO, HIST2H2AA, HIST2H2AA3 {ECO:0000312|HGNC:HGNC:4736};
GN and
GN Name=H2AC19; Synonyms=HIST2H2AA4 {ECO:0000312|HGNC:HGNC:29668};
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].
RX PubMed=8179821; DOI=10.1089/dna.1994.13.161;
RA Mannironi C., Orr A., Hatch C., Pilch D., Ivanova V., Bonner W.;
RT "The relative expression of human histone H2A genes is similar in different
RT types of proliferating cells.";
RL DNA Cell Biol. 13:161-170(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12408966; DOI=10.1006/geno.2002.6850;
RA Marzluff W.F., Gongidi P., Woods K.R., Jin J., Maltais L.J.;
RT "The human and mouse replication-dependent histone genes.";
RL Genomics 80:487-498(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP PHOSPHORYLATION AT THR-121.
RX PubMed=15078818; DOI=10.1101/gad.1184604;
RA Aihara H., Nakagawa T., Yasui K., Ohta T., Hirose S., Dhomae N., Takio K.,
RA Kaneko M., Takeshima Y., Muramatsu M., Ito T.;
RT "Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in
RT the early Drosophila embryo.";
RL Genes Dev. 18:877-888(2004).
RN [9]
RP PHOSPHORYLATION AT SER-2, AND MUTAGENESIS OF SER-2.
RX PubMed=15010469; DOI=10.1074/jbc.m400099200;
RA Zhang Y., Griffin K., Mondal N., Parvin J.D.;
RT "Phosphorylation of histone H2A inhibits transcription on chromatin
RT templates.";
RL J. Biol. Chem. 279:21866-21872(2004).
RN [10]
RP UBIQUITINATION AT LYS-120.
RX PubMed=15386022; DOI=10.1038/nature02985;
RA Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S.,
RA Zhang Y.;
RT "Role of histone H2A ubiquitination in Polycomb silencing.";
RL Nature 431:873-878(2004).
RN [11]
RP ACETYLATION AT SER-2, CITRULLINATION AT ARG-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15823041; DOI=10.1021/bi047505c;
RA Hagiwara T., Hidaka Y., Yamada M.;
RT "Deimination of histone H2A and H4 at arginine 3 in HL-60 granulocytes.";
RL Biochemistry 44:5827-5834(2005).
RN [12]
RP UBIQUITINATION AT LYS-120.
RX PubMed=16359901; DOI=10.1016/j.molcel.2005.12.002;
RA Cao R., Tsukada Y., Zhang Y.;
RT "Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.";
RL Mol. Cell 20:845-854(2005).
RN [13]
RP UBIQUITINATION AT LYS-120.
RX PubMed=16702407; DOI=10.1101/gad.373706;
RA Bergink S., Salomons F.A., Hoogstraten D., Groothuis T.A.M., de Waard H.,
RA Wu J., Yuan L., Citterio E., Houtsmuller A.B., Neefjes J.,
RA Hoeijmakers J.H.J., Vermeulen W., Dantuma N.P.;
RT "DNA damage triggers nucleotide excision repair-dependent
RT monoubiquitylation of histone H2A.";
RL Genes Dev. 20:1343-1352(2006).
RN [14]
RP MASS SPECTROMETRY, ACETYLATION AT SER-2 AND LYS-6, AND UBIQUITINATION AT
RP LYS-120.
RX PubMed=16457589; DOI=10.1021/pr050269n;
RA Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L.;
RT "Precise characterization of human histones in the H2A gene family by top
RT down mass spectrometry.";
RL J. Proteome Res. 5:248-253(2006).
RN [15]
RP UBIQUITINATION.
RX PubMed=18001824; DOI=10.1016/j.cell.2007.09.040;
RA Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J.,
RA Lukas C., Lukas J.;
RT "RNF8 ubiquitylates histones at DNA double-strand breaks and promotes
RT assembly of repair proteins.";
RL Cell 131:887-900(2007).
RN [16]
RP UBIQUITINATION.
RX PubMed=18001825; DOI=10.1016/j.cell.2007.09.041;
RA Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J.;
RT "RNF8 transduces the DNA-damage signal via histone ubiquitylation and
RT checkpoint protein assembly.";
RL Cell 131:901-914(2007).
RN [17]
RP UBIQUITINATION.
RX PubMed=19203578; DOI=10.1016/j.cell.2008.12.042;
RA Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K.,
RA Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C.,
RA Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A.,
RA Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D.;
RT "The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling
RT cascade at sites of DNA damage.";
RL Cell 136:420-434(2009).
RN [18]
RP UBIQUITINATION.
RX PubMed=19203579; DOI=10.1016/j.cell.2008.12.041;
RA Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H.,
RA Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J.,
RA Lukas C.;
RT "RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to
RT allow accumulation of repair proteins.";
RL Cell 136:435-446(2009).
RN [19]
RP CROTONYLATION AT LYS-37; LYS-119; LYS-120 AND LYS-126.
RX PubMed=21925322; DOI=10.1016/j.cell.2011.08.008;
RA Tan M., Luo H., Lee S., Jin F., Yang J.S., Montellier E., Buchou T.,
RA Cheng Z., Rousseaux S., Rajagopal N., Lu Z., Ye Z., Zhu Q., Wysocka J.,
RA Ye Y., Khochbin S., Ren B., Zhao Y.;
RT "Identification of 67 histone marks and histone lysine crotonylation as a
RT new type of histone modification.";
RL Cell 146:1016-1028(2011).
RN [20]
RP UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
RX PubMed=22980979; DOI=10.1016/j.cell.2012.08.005;
RA Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E.,
RA Vermeulen W., Marteijn J.A., Sixma T.K.;
RT "RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling.";
RL Cell 150:1182-1195(2012).
RN [21]
RP UBIQUITINATION AT LYS-14 AND LYS-16 BY RNF168.
RX PubMed=22713238; DOI=10.4161/cc.20919;
RA Gatti M., Pinato S., Maspero E., Soffientini P., Polo S., Penengo L.;
RT "A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by
RT RNF168 ubiquitin ligase.";
RL Cell Cycle 11:2538-2544(2012).
RN [22]
RP SUCCINYLATION AT LYS-10 AND LYS-96.
RX PubMed=22389435; DOI=10.1074/mcp.m111.015875;
RA Xie Z., Dai J., Dai L., Tan M., Cheng Z., Wu Y., Boeke J.D., Zhao Y.;
RT "Lysine succinylation and lysine malonylation in histones.";
RL Mol. Cell. Proteomics 11:100-107(2012).
RN [23]
RP PHOSPHORYLATION AT THR-121.
RX PubMed=24140421; DOI=10.1016/j.molcel.2013.09.017;
RA Kim K., Kim J.M., Kim J.S., Choi J., Lee Y.S., Neamati N., Song J.S.,
RA Heo K., An W.;
RT "VprBP has intrinsic kinase activity targeting histone H2A and represses
RT gene transcription.";
RL Mol. Cell 52:459-467(2013).
RN [24]
RP HYDROXYBUTYRYLATION AT LYS-6; LYS-10; LYS-37; LYS-75; LYS-76; LYS-96 AND
RP LYS-119.
RX PubMed=24681537; DOI=10.1038/nchembio.1497;
RA Dai L., Peng C., Montellier E., Lu Z., Chen Y., Ishii H., Debernardi A.,
RA Buchou T., Rousseaux S., Jin F., Sabari B.R., Deng Z., Allis C.D., Ren B.,
RA Khochbin S., Zhao Y.;
RT "Lysine 2-hydroxyisobutyrylation is a widely distributed active histone
RT mark.";
RL Nat. Chem. Biol. 10:365-370(2014).
RN [25]
RP METHYLATION AT GLN-105.
RX PubMed=24352239; DOI=10.1038/nature12819;
RA Tessarz P., Santos-Rosa H., Robson S.C., Sylvestersen K.B., Nelson C.J.,
RA Nielsen M.L., Kouzarides T.;
RT "Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated
RT modification.";
RL Nature 505:564-568(2014).
RN [26]
RP UBIQUITINATION AT LYS-120.
RX PubMed=25470042; DOI=10.1038/nature13955;
RA Bhatnagar S., Gazin C., Chamberlain L., Ou J., Zhu X., Tushir J.S.,
RA Virbasius C.M., Lin L., Zhu L.J., Wajapeyee N., Green M.R.;
RT "TRIM37 is a new histone H2A ubiquitin ligase and breast cancer
RT oncoprotein.";
RL Nature 516:116-120(2014).
RN [27]
RP DEUBIQUITINATION AT LYS-14 AND LYS-16 BY USP51.
RX PubMed=27083998; DOI=10.1101/gad.271841.115;
RA Wang Z., Zhang H., Liu J., Cheruiyot A., Lee J.H., Ordog T., Lou Z.,
RA You Z., Zhang Z.;
RT "USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response.";
RL Genes Dev. 30:946-959(2016).
RN [28]
RP HYDROXYBUTYRYLATION AT LYS-10; LYS-14; LYS-37; LYS-96 AND LYS-119.
RX PubMed=27105115; DOI=10.1016/j.molcel.2016.03.036;
RA Xie Z., Zhang D., Chung D., Tang Z., Huang H., Dai L., Qi S., Li J.,
RA Colak G., Chen Y., Xia C., Peng C., Ruan H., Kirkey M., Wang D.,
RA Jensen L.M., Kwon O.K., Lee S., Pletcher S.D., Tan M., Lombard D.B.,
RA White K.P., Zhao H., Li J., Roeder R.G., Yang X., Zhao Y.;
RT "Metabolic regulation of gene expression by histone lysine beta-
RT hydroxybutyrylation.";
RL Mol. Cell 62:194-206(2016).
RN [29]
RP GLUTARYLATION AT LYS-96; LYS-100; LYS-119; LYS-120 AND LYS-126.
RX PubMed=31542297; DOI=10.1016/j.molcel.2019.08.018;
RA Bao X., Liu Z., Zhang W., Gladysz K., Fung Y.M.E., Tian G., Xiong Y.,
RA Wong J.W.H., Yuen K.W.Y., Li X.D.;
RT "Glutarylation of histone H4 lysine 91 regulates chromatin dynamics.";
RL Mol. Cell 0:0-0(2019).
RN [30] {ECO:0007744|PDB:6Y5D}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS) IN COMPLEX WITH
RP NUCLEOSOME CORE AND CGAS.
RX PubMed=32911482; DOI=10.1038/s41586-020-2750-6;
RA Pathare G.R., Decout A., Glueck S., Cavadini S., Makasheva K., Hovius R.,
RA Kempf G., Weiss J., Kozicka Z., Guey B., Melenec P., Fierz B., Thomae N.H.,
RA Ablasser A.;
RT "Structural mechanism of cGAS inhibition by the nucleosome.";
RL Nature 587:668-672(2020).
CC -!- FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact
CC DNA into chromatin, limiting DNA accessibility to the cellular
CC machineries which require DNA as a template. Histones thereby play a
CC central role in transcription regulation, DNA repair, DNA replication
CC and chromosomal stability. DNA accessibility is regulated via a complex
CC set of post-translational modifications of histones, also called
CC histone code, and nucleosome remodeling.
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. The octamer wraps approximately 147 bp of
CC DNA.
CC -!- INTERACTION:
CC Q6FI13; U3KQK0: H2BC15; NbExp=3; IntAct=EBI-353620, EBI-12142839;
CC Q6FI13; Q12824: SMARCB1; NbExp=5; IntAct=EBI-353620, EBI-358419;
CC Q6FI13; Q9QR71: LANA1; Xeno; NbExp=3; IntAct=EBI-353620, EBI-15602554;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- PTM: Deiminated on Arg-4 in granulocytes upon calcium entry.
CC {ECO:0000269|PubMed:15823041}.
CC -!- PTM: Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and
CC RNF2/RING2 complex gives a specific tag for epigenetic transcriptional
CC repression and participates in X chromosome inactivation of female
CC mammals. It is involved in the initiation of both imprinted and random
CC X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome
CC chromatin. Ubiquitination of H2A functions downstream of methylation of
CC 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be
CC induced by ultraviolet and may be involved in DNA repair.
CC Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote
CC transformation of cells in a number of breast cancers
CC (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is
CC ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2
CC ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the
CC recruitment of repair proteins to sites of DNA damage. Ubiquitination
CC at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response
CC to DNA damage is initiated by RNF168 that mediates monoubiquitination
CC at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to
CC monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains
CC in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and
CC H2AK15Ub, respectively) after damaged DNA is repaired
CC (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-
CC linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.
CC {ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:16359901,
CC ECO:0000269|PubMed:16457589, ECO:0000269|PubMed:16702407,
CC ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825,
CC ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579,
CC ECO:0000269|PubMed:22713238, ECO:0000269|PubMed:22980979,
CC ECO:0000269|PubMed:24352239, ECO:0000269|PubMed:25470042,
CC ECO:0000269|PubMed:27083998}.
CC -!- PTM: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis.
CC Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses
CC transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by
CC RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is
CC present in the regulatory region of many tumor suppresor genes and
CC down-regulates their transcription. {ECO:0000269|PubMed:15010469,
CC ECO:0000269|PubMed:15078818, ECO:0000269|PubMed:15823041,
CC ECO:0000269|PubMed:16457589, ECO:0000269|PubMed:24140421}.
CC -!- PTM: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is
CC specifically dedicated to polymerase I. It is present at 35S ribosomal
CC DNA locus and impairs binding of the FACT complex (PubMed:24352239).
CC {ECO:0000269|PubMed:24352239}.
CC -!- PTM: Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may
CC play a crucial role in the germ-cell lineage.
CC {ECO:0000250|UniProtKB:P22752}.
CC -!- PTM: Crotonylation (Kcr) is specifically present in male germ cells and
CC marks testis-specific genes in post-meiotic cells, including X-linked
CC genes that escape sex chromosome inactivation in haploid cells.
CC Crotonylation marks active promoters and enhancers and confers
CC resistance to transcriptional repressors. It is also associated with
CC post-meiotically activated genes on autosomes.
CC {ECO:0000269|PubMed:21925322}.
CC -!- PTM: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA
CC directly derived from endogenous or exogenous lactate, leading to
CC stimulates gene transcription. {ECO:0000250|UniProtKB:P0C0S5}.
CC -!- MASS SPECTROMETRY: Mass=13997.9; Method=Electrospray; Note=Monoisotopic
CC with N-acetylserine.; Evidence={ECO:0000269|PubMed:16457589};
CC -!- SIMILARITY: Belongs to the histone H2A family. {ECO:0000305}.
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DR EMBL; L19779; AAC24465.1; -; mRNA.
DR EMBL; AY131971; AAN59957.1; -; Genomic_DNA.
DR EMBL; AK312163; BAG35097.1; -; mRNA.
DR EMBL; CR536525; CAG38762.1; -; mRNA.
DR EMBL; CR541872; CAG46670.1; -; mRNA.
DR EMBL; AL591493; CAI12562.1; -; Genomic_DNA.
DR EMBL; AL591493; CAI12565.1; -; Genomic_DNA.
DR EMBL; CH878687; EAW50859.1; -; Genomic_DNA.
DR EMBL; BC096705; AAH96705.1; -; mRNA.
DR EMBL; BC096739; AAH96739.1; -; mRNA.
DR EMBL; BC098171; AAH98171.1; -; mRNA.
DR CCDS; CCDS30849.1; -.
DR CCDS; CCDS934.1; -.
DR PIR; S06742; S06742.
DR RefSeq; NP_001035807.1; NM_001040874.1.
DR RefSeq; NP_003507.1; NM_003516.2.
DR PDB; 6SE6; EM; 3.50 A; C/G=1-130.
DR PDB; 6SEE; EM; 4.20 A; C/G=1-130.
DR PDB; 6SEF; EM; 3.70 A; C/G=1-130.
DR PDB; 6SEG; EM; 3.10 A; C/G=1-130.
DR PDB; 6Y5D; EM; 4.10 A; C/G/O/S=1-130.
DR PDB; 7JZV; EM; 3.90 A; N/n=2-130.
DR PDBsum; 6SE6; -.
DR PDBsum; 6SEE; -.
DR PDBsum; 6SEF; -.
DR PDBsum; 6SEG; -.
DR PDBsum; 6Y5D; -.
DR PDBsum; 7JZV; -.
DR AlphaFoldDB; Q6FI13; -.
DR SMR; Q6FI13; -.
DR BioGRID; 113933; 50.
DR BioGRID; 593221; 77.
DR CORUM; Q6FI13; -.
DR DIP; DIP-33167N; -.
DR IntAct; Q6FI13; 35.
DR MINT; Q6FI13; -.
DR STRING; 9606.ENSP00000358155; -.
DR iPTMnet; Q6FI13; -.
DR PhosphoSitePlus; Q6FI13; -.
DR SwissPalm; Q6FI13; -.
DR BioMuta; HIST2H2AA4; -.
DR DMDM; 74757558; -.
DR EPD; Q6FI13; -.
DR jPOST; Q6FI13; -.
DR MassIVE; Q6FI13; -.
DR MaxQB; Q6FI13; -.
DR PaxDb; Q6FI13; -.
DR PeptideAtlas; Q6FI13; -.
DR PRIDE; Q6FI13; -.
DR TopDownProteomics; Q6FI13; -.
DR Antibodypedia; 73310; 87 antibodies from 15 providers.
DR Antibodypedia; 75563; 65 antibodies from 11 providers.
DR DNASU; 8337; -.
DR Ensembl; ENST00000369159.3; ENSP00000358155.2; ENSG00000288825.1.
DR Ensembl; ENST00000607355.3; ENSP00000475814.1; ENSG00000288859.1.
DR GeneID; 723790; -.
DR GeneID; 8337; -.
DR KEGG; hsa:723790; -.
DR KEGG; hsa:8337; -.
DR MANE-Select; ENST00000369159.3; ENSP00000358155.2; NM_003516.3; NP_003507.1.
DR MANE-Select; ENST00000607355.3; ENSP00000475814.1; NM_001040874.1; NP_001035807.1.
DR UCSC; uc001esw.4; human.
DR CTD; 723790; -.
DR CTD; 8337; -.
DR DisGeNET; 723790; -.
DR DisGeNET; 8337; -.
DR GeneCards; H2AC18; -.
DR GeneCards; H2AC19; -.
DR HGNC; HGNC:4736; H2AC18.
DR HGNC; HGNC:29668; H2AC19.
DR HPA; ENSG00000203812; Low tissue specificity.
DR HPA; ENSG00000272196; Low tissue specificity.
DR MIM; 142720; gene.
DR neXtProt; NX_Q6FI13; -.
DR PharmGKB; PA29113; -.
DR VEuPathDB; HostDB:ENSG00000203812; -.
DR VEuPathDB; HostDB:ENSG00000272196; -.
DR eggNOG; KOG1756; Eukaryota.
DR GeneTree; ENSGT00940000156302; -.
DR HOGENOM; CLU_062828_3_1_1; -.
DR InParanoid; Q6FI13; -.
DR OMA; HAYLYSA; -.
DR OrthoDB; 1504122at2759; -.
DR PhylomeDB; Q6FI13; -.
DR TreeFam; TF300137; -.
DR PathwayCommons; Q6FI13; -.
DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-HSA-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-HSA-110331; Cleavage of the damaged purine.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-171306; Packaging Of Telomere Ends.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA.
DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR Reactome; R-HSA-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-HSA-427389; ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-HSA-5334118; DNA methylation.
DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR Reactome; R-HSA-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-HSA-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-HSA-73728; RNA Polymerase I Promoter Opening.
DR Reactome; R-HSA-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR Reactome; R-HSA-9670095; Inhibition of DNA recombination at telomere.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; Q6FI13; -.
DR SIGNOR; Q6FI13; -.
DR BioGRID-ORCS; 723790; 76 hits in 604 CRISPR screens.
DR BioGRID-ORCS; 8337; 198 hits in 943 CRISPR screens.
DR ChiTaRS; HIST2H2AA3; human.
DR ChiTaRS; HIST2H2AA4; human.
DR GeneWiki; HIST2H2AA3; -.
DR Pharos; Q6FI13; Tbio.
DR PRO; PR:Q6FI13; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6FI13; protein.
DR Bgee; ENSG00000203812; Expressed in bone marrow cell and 93 other tissues.
DR Genevisible; Q6FI13; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; 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:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR CDD; cd00074; H2A; 1.
DR Gene3D; 1.10.20.10; -; 1.
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; IPR032458; Histone_H2A_CS.
DR PANTHER; PTHR23430; PTHR23430; 1.
DR Pfam; PF00125; Histone; 1.
DR Pfam; PF16211; Histone_H2A_C; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00046; HISTONE_H2A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Citrullination; DNA-binding;
KW Hydroxylation; Isopeptide bond; Methylation; Nucleosome core; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15823041,
FT ECO:0000269|PubMed:16457589"
FT CHAIN 2..130
FT /note="Histone H2A type 2-A"
FT /id="PRO_0000055232"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:15823041,
FT ECO:0000269|PubMed:16457589"
FT MOD_RES 2
FT /note="Phosphoserine; by RPS6KA5"
FT /evidence="ECO:0000269|PubMed:15010469"
FT MOD_RES 4
FT /note="Citrulline; alternate"
FT /evidence="ECO:0000269|PubMed:15823041"
FT MOD_RES 4
FT /note="Symmetric dimethylarginine; by PRMT5; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q6GSS7"
FT MOD_RES 6
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 6
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:16457589"
FT MOD_RES 10
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 10
FT /note="N6-(beta-hydroxybutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:27105115"
FT MOD_RES 10
FT /note="N6-lactoyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0C0S5"
FT MOD_RES 10
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:22389435"
FT MOD_RES 14
FT /note="N6-(beta-hydroxybutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:27105115"
FT MOD_RES 37
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 37
FT /note="N6-(beta-hydroxybutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:27105115"
FT MOD_RES 37
FT /note="N6-crotonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21925322"
FT MOD_RES 75
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 76
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 96
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 96
FT /note="N6-(beta-hydroxybutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:27105115"
FT MOD_RES 96
FT /note="N6-glutaryllysine; alternate"
FT /evidence="ECO:0000269|PubMed:31542297"
FT MOD_RES 96
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:22389435"
FT MOD_RES 100
FT /note="N6-glutaryllysine"
FT /evidence="ECO:0000269|PubMed:31542297"
FT MOD_RES 105
FT /note="N5-methylglutamine"
FT /evidence="ECO:0000269|PubMed:24352239"
FT MOD_RES 119
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:24681537"
FT MOD_RES 119
FT /note="N6-(beta-hydroxybutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:27105115"
FT MOD_RES 119
FT /note="N6-crotonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21925322"
FT MOD_RES 119
FT /note="N6-glutaryllysine; alternate"
FT /evidence="ECO:0000269|PubMed:31542297"
FT MOD_RES 120
FT /note="N6-crotonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21925322"
FT MOD_RES 120
FT /note="N6-glutaryllysine; alternate"
FT /evidence="ECO:0000269|PubMed:31542297"
FT MOD_RES 121
FT /note="Phosphothreonine; by DCAF1"
FT /evidence="ECO:0000269|PubMed:15078818,
FT ECO:0000269|PubMed:24140421"
FT MOD_RES 126
FT /note="N6-crotonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21925322"
FT MOD_RES 126
FT /note="N6-glutaryllysine; alternate"
FT /evidence="ECO:0000269|PubMed:31542297"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:22713238,
FT ECO:0000269|PubMed:22980979"
FT CROSSLNK 16
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22713238,
FT ECO:0000269|PubMed:22980979"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:15386022,
FT ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16457589,
FT ECO:0000269|PubMed:16702407, ECO:0000269|PubMed:25470042"
FT MUTAGEN 2
FT /note="S->A: Blocks the inhibition of transcription by
FT RPS6KA5/MSK1."
FT /evidence="ECO:0000269|PubMed:15010469"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:6SEG"
FT HELIX 29..36
FT /evidence="ECO:0007829|PDB:6SEG"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:6SEG"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:6SEG"
FT HELIX 47..73
FT /evidence="ECO:0007829|PDB:6SEG"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:6SEG"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:6SEG"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:6SEG"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:6SEG"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6SEG"
SQ SEQUENCE 130 AA; 14095 MW; 53AEDC6CE3FE8317 CRC64;
MSGRGKQGGK ARAKAKSRSS RAGLQFPVGR VHRLLRKGNY AERVGAGAPV YMAAVLEYLT
AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLGK VTIAQGGVLP NIQAVLLPKK
TESHHKAKGK
