ID P66A_HUMAN Reviewed; 633 AA. AC Q86YP4; B5MC40; Q7L3J2; Q96F28; Q9NPU2; Q9NXS1; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 27-MAR-2024, entry version 187. DE RecName: Full=Transcriptional repressor p66-alpha; DE Short=Hp66alpha; DE AltName: Full=GATA zinc finger domain-containing protein 2A; GN Name=GATAD2A; 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] (ISOFORM 1), FUNCTION, INTERACTION WITH MBD2 AND RP MBD3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DOMAIN CR1. RX PubMed=12183469; DOI=10.1074/jbc.m207467200; RA Brackertz M., Boeke J., Zhang R., Renkawitz R.; RT "Two highly related p66 proteins comprise a new family of potent RT transcriptional repressors interacting with MBD2 and MBD3."; RL J. Biol. Chem. 277:40958-40966(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Ovary, and Skin; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 417-633 (ISOFORM 1). RC TISSUE=Colon; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 465-633 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100; SER-107 AND SER-114, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP FUNCTION, INTERACTION WITH MBD2 AND HISTONE TAILS, SUBCELLULAR LOCATION, RP MUTAGENESIS OF LYS-149, AND DOMAINS CR1 AND CR2. RX PubMed=16415179; DOI=10.1093/nar/gkj437; RA Brackertz M., Gong Z., Leers J., Renkawitz R.; RT "p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone RT interaction."; RL Nucleic Acids Res. 34:397-406(2006). RN [10] RP FUNCTION, IDENTIFICATION IN THE NURD COMPLEX, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=16428440; DOI=10.1128/mcb.26.3.843-851.2006; RA Le Guezennec X., Vermeulen M., Brinkman A.B., Hoeijmakers W.A., Cohen A., RA Lasonder E., Stunnenberg H.G.; RT "MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical RT and functional properties."; RL Mol. Cell. Biol. 26:843-851(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100 AND SER-107, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; RP SER-114; SER-546; SER-548 AND SER-598, AND IDENTIFICATION BY MASS RP 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 [14] 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; RP SER-114; THR-189 AND SER-340, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107; SER-546 RP AND SER-548, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107 AND RP SER-343, AND 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-20; THR-49; SER-100; SER-107; RP SER-114; SER-137; THR-189; SER-275; SER-340; SER-512; SER-546; SER-548; RP SER-556 AND SER-598, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-100; SER-107 AND RP THR-189, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-249; ARG-258; ARG-273; ARG-285 RP AND ARG-539, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [22] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-487 AND LYS-550, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-487 AND LYS-550, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-487, 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 [25] RP INTERACTION WITH ERCC6. RX PubMed=26030138; DOI=10.1371/journal.pone.0128558; RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G., RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.; RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin RT Dynamics."; RL PLoS ONE 10:E0128558-E0128558(2015). RN [26] RP SUBUNIT, INTERACTION WITH ZMYND8; MBD2 AND MBD3, IDENTIFICATION IN THE NURD RP COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=27732854; DOI=10.1016/j.celrep.2016.09.037; RA Spruijt C.G., Luijsterburg M.S., Menafra R., Lindeboom R.G., Jansen P.W., RA Edupuganti R.R., Baltissen M.P., Wiegant W.W., Voelker-Albert M.C., RA Matarese F., Mensinga A., Poser I., Vos H.R., Stunnenberg H.G., RA van Attikum H., Vermeulen M.; RT "ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP- RT Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage."; RL Cell Rep. 17:783-798(2016). RN [27] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-93; LYS-178; LYS-204; LYS-233; RP LYS-464; LYS-487; LYS-550; LYS-585 AND LYS-605, 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). RN [28] RP FUNCTION, IDENTIFICATION IN THE NURD COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=28977666; DOI=10.1093/nar/gkx711; RA Hoffmeister H., Fuchs A., Erdel F., Pinz S., Groebner-Ferreira R., RA Bruckmann A., Deutzmann R., Schwartz U., Maldonado R., Huber C., RA Dendorfer A.S., Rippe K., Laengst G.; RT "CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping RT functionality."; RL Nucleic Acids Res. 45:10534-10554(2017). RN [29] RP IDENTIFICATION IN THE NURD COMPLEX, INTERACTION WITH HDAC1; HDAC2; MTA2; RP MBD2; CHD4 AND CDK2AP1, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=33283408; DOI=10.1111/febs.15650; RA Spruijt C.G., Graewe C., Kleinendorst S.C., Baltissen M.P.A., Vermeulen M.; RT "Cross-linking mass spectrometry reveals the structural topology of RT peripheral NuRD subunits relative to the core complex."; RL FEBS J. 288:3231-3245(2021). RN [30] RP INTERACTION WITH ZMYND8. RX PubMed=35916866; DOI=10.1016/j.gim.2022.06.001; RA Dias K.R., Carlston C.M., Blok L.E.R., De Hayr L., Nawaz U., Evans C.A., RA Bayrak-Toydemir P., Htun S., Zhu Y., Ma A., Lynch S.A., Moorwood C., RA Stals K., Ellard S., Bainbridge M.N., Friedman J., Pappas J.G., Rabin R., RA Nowak C.B., Douglas J., Wilson T.E., Guillen Sacoto M.J., Mullegama S.V., RA Palculict T.B., Kirk E.P., Pinner J.R., Edwards M., Montanari F., RA Graziano C., Pippucci T., Dingmann B., Glass I., Mefford H.C., Shimoji T., RA Suzuki T., Yamakawa K., Streff H., Schaaf C.P., Slavotinek A.M., RA Voineagu I., Carey J.C., Buckley M.F., Schenck A., Harvey R.J., RA Roscioli T.; RT "De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental RT disorder with cardiac malformations."; RL Genet. Med. 24:1952-1966(2022). RN [31] RP STRUCTURE BY NMR OF 137-178 IN COMPLEX WITH MBD2, SUBUNIT, AND INTERACTION RP WITH MBD2. RX PubMed=21490301; DOI=10.1073/pnas.1015341108; RA Gnanapragasam M.N., Scarsdale J.N., Amaya M.L., Webb H.D., Desai M.A., RA Walavalkar N.M., Wang S.Z., Zu Zhu S., Ginder G.D., Williams D.C. Jr.; RT "p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical RT for globin gene silencing by the MBD2-NuRD complex."; RL Proc. Natl. Acad. Sci. U.S.A. 108:7487-7492(2011). CC -!- FUNCTION: Transcriptional repressor (PubMed:12183469, PubMed:16415179). CC Acts as a component of the histone deacetylase NuRD complex which CC participates in the remodeling of chromatin (PubMed:16428440, CC PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, CC PubMed:16415179). Efficient repression requires the presence of GATAD2B CC (PubMed:16415179). {ECO:0000269|PubMed:12183469, CC ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:16428440, CC ECO:0000269|PubMed:28977666}. CC -!- SUBUNIT: Homooligomer (PubMed:27732854). Component of the nucleosome CC remodeling and deacetylase (NuRD) repressor complex, composed of core CC proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and CC peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CC CHD3, CHD4 and CHD5 (PubMed:33283408, PubMed:28977666, PubMed:16428440, CC PubMed:27732854). The exact stoichiometry of the NuRD complex is CC unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, CC and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes CC (PubMed:33283408, PubMed:16428440, PubMed:28977666, PubMed:27732854). CC Component of the MeCP1 histone deacetylase complex (PubMed:21490301). CC Interacts with CDK2AP1 (PubMed:33283408). Interacts with CHD4 CC (PubMed:33283408). Interacts with ERCC6 (PubMed:26030138). Interacts CC with HDAC1 (PubMed:33283408). Interacts with HDAC2 (PubMed:33283408). CC Interacts with MBD2; this interaction is required for the enhancement CC of MBD2-mediated repression and for targeting to the chromatin CC (PubMed:12183469, PubMed:16415179, PubMed:21490301, PubMed:33283408, CC PubMed:27732854). Interacts with MBD3 (PubMed:12183469, CC PubMed:27732854). Interacts with MTA2 (PubMed:33283408). Interacts with CC ZMYND8 (PubMed:35916866, PubMed:27732854). Interacts with histone CC tails, including that of histones H2A, H2B, H3 and H4, the interaction CC is reduced by histone acetylation (PubMed:16415179). CC {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16415179, CC ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:21490301, CC ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:27732854, CC ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:33283408, CC ECO:0000269|PubMed:35916866}. CC -!- INTERACTION: CC Q86YP4; Q08379: GOLGA2; NbExp=3; IntAct=EBI-726224, EBI-618309; CC Q86YP4; Q14532: KRT32; NbExp=3; IntAct=EBI-726224, EBI-1044146; CC Q86YP4; O76011: KRT34; NbExp=3; IntAct=EBI-726224, EBI-1047093; CC Q86YP4; Q9UBB5: MBD2; NbExp=8; IntAct=EBI-726224, EBI-923391; CC Q86YP4; O95983-2: MBD3; NbExp=3; IntAct=EBI-726224, EBI-11978579; CC Q86YP4; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-726224, EBI-12516603; CC Q86YP4-3; Q6A162: KRT40; NbExp=3; IntAct=EBI-10261080, EBI-10171697; CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:12183469, CC ECO:0000269|PubMed:16415179}. Nucleus {ECO:0000269|PubMed:27732854, CC ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:33283408}. Chromosome CC {ECO:0000269|PubMed:27732854}. Note=Speckled nuclear localization CC requires both CR1 and CR2 regions (PubMed:16415179). Localizes to sites CC of DNA damage in a manner partially dependent on ZMYND8 CC (PubMed:27732854). {ECO:0000269|PubMed:16415179, CC ECO:0000269|PubMed:27732854}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q86YP4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86YP4-2; Sequence=VSP_010929; CC Name=3; CC IsoId=Q86YP4-3; Sequence=VSP_053410; CC -!- TISSUE SPECIFICITY: Ubiquitous, both in fetal and adult tissues. CC {ECO:0000269|PubMed:12183469}. CC -!- DOMAIN: Both CR1 and CR2 regions are required for speckled nuclear CC localization. {ECO:0000269|PubMed:16415179}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH11684.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA90939.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AY186731; AAO31797.1; -; mRNA. DR EMBL; AC003030; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092067; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471106; EAW84819.1; -; Genomic_DNA. DR EMBL; BC011684; AAH11684.1; ALT_INIT; mRNA. DR EMBL; BC012902; AAH12902.2; -; mRNA. DR EMBL; AK000092; BAA90939.1; ALT_INIT; mRNA. DR EMBL; AL390164; CAB99095.1; -; mRNA. DR CCDS; CCDS12402.2; -. [Q86YP4-1] DR CCDS; CCDS77270.1; -. [Q86YP4-3] DR PIR; T51878; T51878. DR RefSeq; NP_001287875.1; NM_001300946.1. [Q86YP4-3] DR RefSeq; NP_060130.3; NM_017660.3. [Q86YP4-1] DR RefSeq; XP_011526407.1; XM_011528105.1. DR PDB; 2L2L; NMR; -; A=137-178. DR PDBsum; 2L2L; -. DR AlphaFoldDB; Q86YP4; -. DR BMRB; Q86YP4; -. DR SMR; Q86YP4; -. DR BioGRID; 120172; 227. DR ComplexPortal; CPX-880; MBD2/NuRD nucleosome remodeling and deacetylase complex. DR ComplexPortal; CPX-922; MBD3/NuRD nucleosome remodeling and deacetylase complex. DR CORUM; Q86YP4; -. DR DIP; DIP-36053N; -. DR IntAct; Q86YP4; 68. DR MINT; Q86YP4; -. DR STRING; 9606.ENSP00000384899; -. DR GlyCosmos; Q86YP4; 17 sites, 2 glycans. DR GlyGen; Q86YP4; 34 sites, 2 O-linked glycans (34 sites). DR iPTMnet; Q86YP4; -. DR MetOSite; Q86YP4; -. DR PhosphoSitePlus; Q86YP4; -. DR BioMuta; GATAD2A; -. DR DMDM; 50401012; -. DR EPD; Q86YP4; -. DR jPOST; Q86YP4; -. DR MassIVE; Q86YP4; -. DR MaxQB; Q86YP4; -. DR PaxDb; 9606-ENSP00000353463; -. DR PeptideAtlas; Q86YP4; -. DR ProteomicsDB; 5986; -. DR ProteomicsDB; 70446; -. [Q86YP4-1] DR ProteomicsDB; 70447; -. [Q86YP4-2] DR Pumba; Q86YP4; -. DR Antibodypedia; 1819; 270 antibodies from 28 providers. DR DNASU; 54815; -. DR Ensembl; ENST00000358713.7; ENSP00000351552.3; ENSG00000167491.18. [Q86YP4-1] DR Ensembl; ENST00000360315.7; ENSP00000353463.3; ENSG00000167491.18. [Q86YP4-1] DR Ensembl; ENST00000404158.5; ENSP00000384899.2; ENSG00000167491.18. [Q86YP4-3] DR Ensembl; ENST00000683918.1; ENSP00000508398.1; ENSG00000167491.18. [Q86YP4-3] DR GeneID; 54815; -. DR KEGG; hsa:54815; -. DR MANE-Select; ENST00000683918.1; ENSP00000508398.1; NM_001384528.1; NP_001371457.1. [Q86YP4-3] DR UCSC; uc010xqt.3; human. [Q86YP4-1] DR AGR; HGNC:29989; -. DR CTD; 54815; -. DR DisGeNET; 54815; -. DR GeneCards; GATAD2A; -. DR HGNC; HGNC:29989; GATAD2A. DR HPA; ENSG00000167491; Low tissue specificity. DR MIM; 614997; gene. DR neXtProt; NX_Q86YP4; -. DR OpenTargets; ENSG00000167491; -. DR PharmGKB; PA142671746; -. DR VEuPathDB; HostDB:ENSG00000167491; -. DR eggNOG; KOG3740; Eukaryota. DR GeneTree; ENSGT00390000004097; -. DR HOGENOM; CLU_014315_1_0_1; -. DR InParanoid; Q86YP4; -. DR OMA; LEMHGRA; -. DR PhylomeDB; Q86YP4; -. DR TreeFam; TF321369; -. DR PathwayCommons; Q86YP4; -. DR Reactome; R-HSA-3214815; HDACs deacetylate histones. DR Reactome; R-HSA-427389; ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression. DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation. DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation. DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SignaLink; Q86YP4; -. DR SIGNOR; Q86YP4; -. DR BioGRID-ORCS; 54815; 144 hits in 1166 CRISPR screens. DR ChiTaRS; GATAD2A; human. DR GenomeRNAi; 54815; -. DR Pharos; Q86YP4; Tbio. DR PRO; PR:Q86YP4; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q86YP4; Protein. DR Bgee; ENSG00000167491; Expressed in buccal mucosa cell and 194 other cell types or tissues. DR ExpressionAtlas; Q86YP4; baseline and differential. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016581; C:NuRD complex; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0006338; P:chromatin remodeling; IDA:ComplexPortal. DR GO; GO:0006306; P:DNA methylation; TAS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS:ComplexPortal. DR GO; GO:0042659; P:regulation of cell fate specification; NAS:ComplexPortal. DR GO; GO:2000736; P:regulation of stem cell differentiation; NAS:ComplexPortal. DR Gene3D; 6.10.250.1650; -; 1. DR IDEAL; IID00731; -. DR InterPro; IPR040386; P66. DR InterPro; IPR032346; P66_CC. DR InterPro; IPR000679; Znf_GATA. DR PANTHER; PTHR13455:SF3; TRANSCRIPTIONAL REPRESSOR P66-ALPHA; 1. DR PANTHER; PTHR13455; TRANSCRIPTIONAL REPRESSOR P66-RELATED; 1. DR Pfam; PF00320; GATA; 1. DR Pfam; PF16563; P66_CC; 1. DR PROSITE; PS00344; GATA_ZN_FINGER_1; 1. DR PROSITE; PS50114; GATA_ZN_FINGER_2; 1. DR Genevisible; Q86YP4; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosome; Coiled coil; KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Repressor; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..633 FT /note="Transcriptional repressor p66-alpha" FT /id="PRO_0000083500" FT ZN_FING 411..464 FT /note="GATA-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00094" FT REGION 1..59 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 73..119 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 144..178 FT /note="CR1; interaction with HDAC1, HDAC2, MBD2 and MTA2" FT /evidence="ECO:0000269|PubMed:12183469, FT ECO:0000269|PubMed:33283408" FT REGION 172..238 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 181..295 FT /note="Interaction with ZMYND8" FT /evidence="ECO:0000269|PubMed:27732854" FT REGION 340..480 FT /note="CR2; histone tail-binding and interaction with CHD4 FT and CDK2AP1" FT /evidence="ECO:0000269|PubMed:16415179, FT ECO:0000269|PubMed:33283408" FT REGION 561..585 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 139..174 FT /evidence="ECO:0000255" FT COMPBIAS 1..34 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 172..215 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 20 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 49 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 107 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 113 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CHY6" FT MOD_RES 114 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 189 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 225 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8CHY6" FT MOD_RES 249 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 258 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 273 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 285 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 340 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 539 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 539 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 546 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 548 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 556 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 598 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 93 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 178 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 204 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 233 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 464 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 487 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 550 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 585 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 605 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 401 FT /note="Q -> QA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_053410" FT VAR_SEQ 500..524 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_010929" FT VARIANT 17 FT /note="R -> Q (in dbSNP:rs10426883)" FT /id="VAR_059308" FT VARIANT 296 FT /note="N -> S (in dbSNP:rs2288851)" FT /id="VAR_059309" FT MUTAGEN 149 FT /note="K->R: Disruption of MBD2-binding, loss of FT enhancement of MBD2-mediated repression and loss of FT speckled nuclear localization." FT /evidence="ECO:0000269|PubMed:16415179" FT CONFLICT 432 FT /note="K -> E (in Ref. 5; BAA90939)" FT /evidence="ECO:0000305" FT HELIX 138..168 FT /evidence="ECO:0007829|PDB:2L2L" SQ SEQUENCE 633 AA; 68063 MW; 64F0066B4BEFCB39 CRC64; MTEEACRTRS QKRALERDPT EDDVESKKIK MERGLLASDL NTDGDMRVTP EPGAGPTQGL LRATEATAMA MGRGEGLVGD GPVDMRTSHS DMKSERRPPS PDVIVLSDNE QPSSPRVNGL TTVALKETST EALMKSSPEE RERMIKQLKE ELRLEEAKLV LLKKLRQSQI QKEATAQKPT GSVGSTVTTP PPLVRGTQNI PAGKPSLQTS SARMPGSVIP PPLVRGGQQA SSKLGPQASS QVVMPPLVRG AQQIHSIRQH SSTGPPPLLL APRASVPSVQ IQGQRIIQQG LIRVANVPNT SLLVNIPQPT PASLKGTTAT SAQANSTPTS VASVVTSAES PASRQAAAKL ALRKQLEKTL LEIPPPKPPA PEMNFLPSAA NNEFIYLVGL EEVVQNLLET QGRMSAATVL SREPYMCAQC KTDFTCRWRE EKSGAIMCEN CMTTNQKKAL KVEHTSRLKA AFVKALQQEQ EIEQRLLQQG TAPAQAKAEP TAAPHPVLKQ VIKPRRKLAF RSGEARDWSN GAVLQASSQL SRGSATTPRG VLHTFSPSPK LQNSASATAL VSRTGRHSER TVSAGKGSAT SNWKKTPLST GGTLAFVSPS LAVHKSSSAV DRQREYLLDM IPPRSIPQSA TWK //