ID REST_HUMAN Reviewed; 1097 AA. AC Q13127; A2RUE0; B9EGJ0; Q12956; Q12957; Q13134; Q59ER1; Q8IWI3; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 28-JAN-2026, entry version 209. DE RecName: Full=RE1-silencing transcription factor; DE AltName: Full=Neural-restrictive silencer factor; DE AltName: Full=X2 box repressor; GN Name=REST; Synonyms=NRSF, XBR; 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), AND FUNCTION. RX PubMed=7697725; DOI=10.1016/0092-8674(95)90298-8; RA Chong J.A., Tapia-Ramirez J., Kim S., Toledo-Aral J.J., Zheng Y., RA Boutros M.C., Altshuller Y.M., Frohman M.A., Kraner S.D., Mandel G.; RT "REST: a mammalian silencer protein that restricts sodium channel gene RT expression to neurons."; RL Cell 80:949-957(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 1-599 RP (ISOFORM 1), AND FUNCTION. RX PubMed=7871435; DOI=10.1126/science.7871435; RA Schoenherr C.J., Anderson D.J.; RT "The neuron-restrictive silencer factor (NRSF): a coordinate repressor of RT multiple neuron-specific genes."; RL Science 267:1360-1363(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP VARIANT LEU-797. RX PubMed=8568247; RA Scholl T., Stevens M.B., Mahanta S., Strominger J.L.; RT "A zinc finger protein that represses transcription of the human MHC class RT II gene, DPA."; RL J. Immunol. 156:1448-1457(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). 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] (ISOFORM 1), AND VARIANT ILE-626. RC TISSUE=Testis, and 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 [8] RP ALTERNATIVE SPLICING (ISOFORMS 3 AND 4). RX PubMed=10521596; DOI=10.1016/s0169-328x(99)00196-5; RA Palm K., Metsis M., Timmusk T.; RT "Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR RT is frequent in neuroblastomas and conserved in human, mouse and rat."; RL Brain Res. Mol. Brain Res. 72:30-39(1999). RN [9] RP FUNCTION, AND INTERACTION WITH RCOR1. RX PubMed=10449787; DOI=10.1073/pnas.96.17.9873; RA Andres M.E., Burger C., Peral-Rubio M.J., Battaglioli E., Anderson M.E., RA Grimes J., Dallman J., Ballas N., Mandel G.; RT "CoREST: a functional corepressor required for regulation of neural- RT specific gene expression."; RL Proc. Natl. Acad. Sci. U.S.A. 96:9873-9878(1999). RN [10] RP FUNCTION, AND INTERACTION WITH RCOR1 AND SIN3A. RX PubMed=10734093; DOI=10.1074/jbc.275.13.9461; RA Grimes J.A., Nielsen S.J., Battaglioli E., Miska E.A., Speh J.C., RA Berry D.L., Atouf F., Holdener B.C., Mandel G., Kouzarides T.; RT "The co-repressor mSin3A is a functional component of the REST-CoREST RT repressor complex."; RL J. Biol. Chem. 275:9461-9467(2000). RN [11] RP FUNCTION. RX PubMed=11779185; DOI=10.1006/bbrc.2001.6194; RA Tabuchi A., Yamada T., Sasagawa S., Naruse Y., Mori N., Tsuda M.; RT "REST4-mediated modulation of REST/NRSF-silencing function during BDNF gene RT promoter activation."; RL Biochem. Biophys. Res. Commun. 290:415-420(2002). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION (ISOFORM 3). RX PubMed=11741002; DOI=10.1016/s0197-0186(01)00091-2; RA Magin A., Lietz M., Cibelli G., Thiel G.; RT "RE-1 silencing transcription factor-4 (REST4) is neither a transcriptional RT repressor nor a de-repressor."; RL Neurochem. Int. 40:195-202(2002). RN [13] RP FUNCTION. RX PubMed=12399542; DOI=10.1126/science.1076469; RA Lunyak V.V., Burgess R., Prefontaine G.G., Nelson C., Sze S.-H., RA Chenoweth J., Schwartz P., Pevzner P.A., Glass C., Mandel G., RA Rosenfeld M.G.; RT "Corepressor-dependent silencing of chromosomal regions encoding neuronal RT genes."; RL Science 298:1747-1752(2002). RN [14] RP ERRATUM OF PUBMED:12399542. RA Lunyak V.V., Burgess R., Prefontaine G.G., Nelson C., Sze S.-H., RA Chenoweth J., Schwartz P., Pevzner P.A., Glass C., Mandel G., RA Rosenfeld M.G.; RL Science 299:1663-1663(2003). RN [15] RP INTERACTION WITH PRICKLE1. RC TISSUE=Brain; RX PubMed=14645515; DOI=10.1128/mcb.23.24.9025-9031.2003; RA Shimojo M., Hersh L.B.; RT "REST/NRSF-interacting LIM domain protein, a putative nuclear translocation RT receptor."; RL Mol. Cell. Biol. 23:9025-9031(2003). RN [16] RP INTERACTION WITH PRICKLE1, SUBCELLULAR LOCATION (ISOFORMS 1; 2; 3 AND 4), RP AND MUTAGENESIS OF 512-LYS--LYS-522. RX PubMed=16442230; DOI=10.1016/j.neulet.2005.12.080; RA Shimojo M.; RT "Characterization of the nuclear targeting signal of REST/NRSF."; RL Neurosci. Lett. 398:161-166(2006). RN [17] RP FUNCTION, INTERACTION WITH CDYL; EHMT1 AND EHMT2, AND IDENTIFICATION IN A RP COMPLEX WITH CDYL; SETB1; EHMT1; EHMT2 AND WIZ. RX PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025; RA Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B., Macia E., RA Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J., Shi Y.; RT "CDYL bridges REST and histone methyltransferases for gene repression and RT suppression of cellular transformation."; RL Mol. Cell 32:718-726(2008). RN [18] RP INTERACTION WITH FBXW11 AND BTRC, DEVELOPMENTAL STAGE, PHOSPHORYLATION, RP UBIQUITINATION BY BTRC, AND MUTAGENESIS OF 1009-GLU--SER-1013. RX PubMed=18354482; DOI=10.1038/nature06641; RA Guardavaccaro D., Frescas D., Dorrello N.V., Peschiaroli A., Multani A.S., RA Cardozo T., Lasorella A., Iavarone A., Chang S., Hernando E., Pagano M.; RT "Control of chromosome stability by the beta-TrCP-REST-Mad2 axis."; RL Nature 452:365-369(2008). RN [19] 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-864, AND IDENTIFICATION BY RP 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 INTERACTION WITH ZFP90. RX PubMed=21284946; DOI=10.1016/j.yjmcc.2011.01.017; RA Hata L., Murakami M., Kuwahara K., Nakagawa Y., Kinoshita H., Usami S., RA Yasuno S., Fujiwara M., Kuwabara Y., Minami T., Yamada Y., Yamada C., RA Nakao K., Ueshima K., Nishikimi T., Nakao K.; RT "Zinc-finger protein 90 negatively regulates neuron-restrictive silencer RT factor-mediated transcriptional repression of fetal cardiac genes."; RL J. Mol. Cell. Cardiol. 50:972-981(2011). RN [22] RP FUNCTION, INTERACTION WITH USP7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP INDUCTION, UBIQUITINATION BY BTRC, DEUBIQUITINATION BY USP7, AND RP MUTAGENESIS OF SER-313 AND SER-1042. RX PubMed=21258371; DOI=10.1038/ncb2153; RA Huang Z., Wu Q., Guryanova O.A., Cheng L., Shou W., Rich J.N., Bao S.; RT "Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural RT progenitor cells."; RL Nat. Cell Biol. 13:142-152(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-864, AND IDENTIFICATION BY RP 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 [24] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP AND INDUCTION BY WNT SIGNALING; AGING AND OXIDATIVE STRESS. RX PubMed=24670762; DOI=10.1038/nature13163; RA Lu T., Aron L., Zullo J., Pan Y., Kim H., Chen Y., Yang T.H., Kim H.M., RA Drake D., Liu X.S., Bennett D.A., Colaiacovo M.P., Yankner B.A.; RT "REST and stress resistance in ageing and Alzheimer's disease."; RL Nature 507:448-454(2014). RN [25] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=26053433; DOI=10.1038/srep11207; RA Lee N.S., Evgrafov O.V., Souaiaia T., Bonyad A., Herstein J., Lee J.Y., RA Kim J., Ning Y., Sixto M., Weitz A.C., Lenz H.J., Wang K., Knowles J.A., RA Press M.F., Salvaterra P.M., Shung K.K., Chow R.H.; RT "Non-coding RNAs derived from an alternatively spliced REST transcript RT (REST-003) regulate breast cancer invasiveness."; RL Sci. Rep. 5:11207-11207(2015). RN [26] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27531581; DOI=10.1038/srep31355; RA Cavadas M.A., Mesnieres M., Crifo B., Manresa M.C., Selfridge A.C., RA Keogh C.E., Fabian Z., Scholz C.C., Nolan K.A., Rocha L.M., Tambuwala M.M., RA Brown S., Wdowicz A., Corbett D., Murphy K.J., Godson C., Cummins E.P., RA Taylor C.T., Cheong A.; RT "REST is a hypoxia-responsive transcriptional repressor."; RL Sci. Rep. 6:31355-31355(2016). RN [27] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=30684677; DOI=10.1016/j.neulet.2019.01.042; RA Kawamura M., Sato S., Matsumoto G., Fukuda T., Shiba-Fukushima K., Noda S., RA Takanashi M., Mori N., Hattori N.; RT "Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's RT disease patients."; RL Neurosci. Lett. 699:59-63(2019). RN [28] RP STRUCTURE BY NMR OF 43-57 IN COMPLEX WITH SIN3B, AND INTERACTION WITH RP SIN3B. RX PubMed=16288918; DOI=10.1016/j.jmb.2005.10.008; RA Nomura M., Uda-Tochio H., Murai K., Mori N., Nishimura Y.; RT "The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 RT corepressor by using its distinct short hydrophobic helix."; RL J. Mol. Biol. 354:903-915(2005). RN [29] RP INVOLVEMENT IN WT6, VARIANTS WT6 PRO-160; TYR-290; ARG-322 AND GLN-412, RP CHARACTERIZATION OF VARIANT PRO-160; TYR-290 AND ARG-322, FUNCTION, AND RP MUTAGENESIS OF GLU-91; MET-420; SER-593; ALA-642 AND HIS-918. RX PubMed=26551668; DOI=10.1038/ng.3440; RA Mahamdallie S.S., Hanks S., Karlin K.L., Zachariou A., Perdeaux E.R., RA Ruark E., Shaw C.A., Renwick A., Ramsay E., Yost S., Elliott A., Birch J., RA Capra M., Gray J., Hale J., Kingston J., Levitt G., McLean T., Sheridan E., RA Renwick A., Seal S., Stiller C., Sebire N., Westbrook T.F., Rahman N.; RT "Mutations in the transcriptional repressor REST predispose to Wilms RT tumor."; RL Nat. Genet. 47:1471-1474(2015). RN [30] RP INVOLVEMENT IN GINGF5, AND VARIANT GINGF5 437-LEU--GLU-1097 DEL. RX PubMed=28686854; DOI=10.1016/j.ajhg.2017.06.006; RG Baylor-Hopkins Center for Mendelian Genomics; RA Bayram Y., White J.J., Elcioglu N., Cho M.T., Zadeh N., Gedikbasi A., RA Palanduz S., Ozturk S., Cefle K., Kasapcopur O., Coban Akdemir Z., RA Pehlivan D., Begtrup A., Carvalho C.M.B., Paine I.S., Mentes A., RA Bektas-Kayhan K., Karaca E., Jhangiani S.N., Muzny D.M., Gibbs R.A., RA Lupski J.R.; RT "REST final-exon-truncating mutations cause hereditary gingival RT fibromatosis."; RL Am. J. Hum. Genet. 101:149-156(2017). RN [31] RP INVOLVEMENT IN DFNA27, AND ALTERNATIVE SPLICING (ISOFORM 3). RX PubMed=29961578; DOI=10.1016/j.cell.2018.06.004; RA Nakano Y., Kelly M.C., Rehman A.U., Boger E.T., Morell R.J., Kelley M.W., RA Friedman T.B., Banfi B.; RT "Defects in the Alternative Splicing-Dependent Regulation of REST Cause RT Deafness."; RL Cell 174:536-548.E21(2018). CC -!- FUNCTION: Transcriptional repressor which binds neuron-restrictive CC silencer element (NRSE) and represses neuronal gene transcription in CC non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, CC PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). CC Restricts the expression of neuronal genes by associating with two CC distinct corepressors, SIN3A and RCOR1, which in turn recruit histone CC deacetylase to the promoters of REST-regulated genes (PubMed:10449787, CC PubMed:10734093). Mediates repression by recruiting the BHC complex at CC RE1/NRSE sites which acts by deacetylating and demethylating specific CC sites on histones, thereby acting as a chromatin modifier (By CC similarity). Transcriptional repression by REST-CDYL via the CC recruitment of histone methyltransferase EHMT2 may be important in CC transformation suppression (PubMed:19061646). Represses the expression CC of SRRM4 in non-neural cells to prevent the activation of neural- CC specific splicing events and to prevent production of REST isoform 3 CC (By similarity). Repressor activity may be inhibited by forming CC heterodimers with isoform 3, thereby preventing binding to NRSE or CC binding to corepressors and leading to derepression of target genes CC (PubMed:11779185). Also maintains repression of neuronal genes in CC neural stem cells, and allows transcription and differentiation into CC neurons by dissociation from RE1/NRSE sites of target genes (By CC similarity). Thereby is involved in maintaining the quiescent state of CC adult neural stem cells and preventing premature differentiation into CC mature neurons (PubMed:21258371). Plays a role in the developmental CC switch in synaptic NMDA receptor composition during postnatal CC development, by repressing GRIN2B expression and thereby altering NMDA CC receptor properties from containing primarily GRIN2B to primarily CC GRIN2A subunits (By similarity). Acts as a regulator of osteoblast CC differentiation (By similarity). Key repressor of gene expression in CC hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE CC site on their promoter regions (PubMed:27531581). May also function in CC stress resistance in the brain during aging; possibly by regulating CC expression of genes involved in cell death and in the stress response CC (PubMed:24670762). Repressor of gene expression in the hippocampus CC after ischemia by directly binding to RE1/NRSE sites and recruiting CC SIN3A and RCOR1 to promoters of target genes, thereby promoting changes CC in chromatin modifications and ischemia-induced cell death (By CC similarity). After ischemia, might play a role in repression of miR-132 CC expression in hippocampal neurons, thereby leading to neuronal cell CC death (By similarity). Negatively regulates the expression of SRRM3 in CC breast cancer cell lines (PubMed:26053433). CC {ECO:0000250|UniProtKB:O54963, ECO:0000250|UniProtKB:Q8VIG1, CC ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, CC ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185, CC ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:19061646, CC ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, CC ECO:0000269|PubMed:26053433, ECO:0000269|PubMed:26551668, CC ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:7697725, CC ECO:0000269|PubMed:7871435, ECO:0000269|PubMed:8568247}. CC -!- FUNCTION: [Isoform 3]: Binds to the 3' region of the neuron-restrictive CC silencer element (NRSE), with lower affinity than full-length REST CC isoform 1 (By similarity). Exhibits weaker repressor activity compared CC to isoform 1 (PubMed:11779185). May negatively regulate the repressor CC activity of isoform 1 by binding to isoform 1, thereby preventing its CC binding to NRSE and leading to derepression of target genes CC (PubMed:11779185). However, in another study, does not appear to be CC implicated in repressor activity of a NRSE motif-containing reporter CC construct nor in inhibitory activity on the isoform 1 transcriptional CC repressor activity (PubMed:11741002). Post-transcriptional inactivation CC of REST by SRRM4-dependent alternative splicing into isoform 3 is CC required in mechanosensory hair cells in the inner ear for derepression CC of neuronal genes and hearing (By similarity). CC {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002, CC ECO:0000269|PubMed:11779185}. CC -!- SUBUNIT: Isoform 1 and isoform 3 form heterodimers (By similarity). CC Isoform 3: Forms homodimers and homooligomers; binds to the neuron- CC restrictive silencer element (NRSE) as monomer (By similarity). CC Interacts with SIN3A, SIN3B and RCOR1 (PubMed:10449787, CC PubMed:10734093, PubMed:16288918). Interacts with CDYL CC (PubMed:19061646). Interacts with EHMT1 and EHMT2 only in the presence CC of CDYL (PubMed:19061646). Part of a complex containing at least CDYL, CC REST, WIZ, SETB1, EHMT1 and EHMT2 (PubMed:19061646). Interacts (via CC zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the CC interaction inhibits REST repressor activity (PubMed:21284946). CC Interacts (via C2H2-type zinc finger 5) with PRICKLE1 (PubMed:14645515, CC PubMed:16442230). Interacts with FBXW11 and BTRC (PubMed:18354482). CC Interacts with USP7 (PubMed:21258371). {ECO:0000250|UniProtKB:Q8VIG1, CC ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, CC ECO:0000269|PubMed:14645515, ECO:0000269|PubMed:16288918, CC ECO:0000269|PubMed:16442230, ECO:0000269|PubMed:18354482, CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21258371, CC ECO:0000269|PubMed:21284946}. CC -!- INTERACTION: CC Q13127; Q9Y297: BTRC; NbExp=10; IntAct=EBI-926706, EBI-307461; CC Q13127; Q9UKB1: FBXW11; NbExp=3; IntAct=EBI-926706, EBI-355189; CC Q13127; P07900: HSP90AA1; NbExp=4; IntAct=EBI-926706, EBI-296047; CC Q13127; P41229: KDM5C; NbExp=3; IntAct=EBI-926706, EBI-1246541; CC Q13127; P51532: SMARCA4; NbExp=2; IntAct=EBI-926706, EBI-302489; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16442230, CC ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, CC ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:30684677}. Cytoplasm CC {ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:27531581, CC ECO:0000269|PubMed:30684677}. Note=Colocalizes with ZFP90 in the CC nucleus (By similarity). In response to hypoxia, there is a more CC pronounced increase in levels in the nucleus as compared to the CC cytoplasm (PubMed:27531581). In aging neurons, increased levels in the CC nucleus as compared to the cytoplasm (PubMed:24670762, CC PubMed:30684677). {ECO:0000250|UniProtKB:Q8VIG1, CC ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:27531581, CC ECO:0000269|PubMed:30684677}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:16442230}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus CC {ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:16442230}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm CC {ECO:0000269|PubMed:16442230}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=REST1 {ECO:0000303|PubMed:16442230}; CC IsoId=Q13127-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13127-2; Sequence=VSP_022064, VSP_022065; CC Name=3; Synonyms=N4, REST4 {ECO:0000303|PubMed:11779185}; CC IsoId=Q13127-3; Sequence=VSP_022066, VSP_022068; CC Name=4; CC IsoId=Q13127-4; Sequence=VSP_022067; CC -!- TISSUE SPECIFICITY: Expressed in neurons of the prefrontal cortex, in CC hippocampal pyramidal neurons, dentate gyrus granule neurons and CC cerebellar Purkinje and granule neurons (at protein level) CC (PubMed:24670762). Expressed in dopaminergic neurons of the substantia CC nigra (at protein level) (PubMed:30684677). Expressed in neural CC progenitor cells (at protein level) (PubMed:21258371). In patients CC suffering from Alzheimer disease, frontotemporal dementia or dementia CC with Lewy bodies, decreased nuclear levels have been observed in CC neurons of the prefrontal cortex and the hippocampus, but not in CC neurons of the dentate gyrus and cerebellum (at protein level) CC (PubMed:24670762). In patients with Parkinson disease or dementia with CC Lewy bodies, decreased nuclear levels have been observed in CC dopaminergic neurons and in cortical neurons and localization to Lewy CC bodies and pale bodies was detected (at protein level) CC (PubMed:30684677). Expressed at higher levels in weakly invasive breast CC cancer cell lines and at lower levels in highly invasive breast cancer CC lines (at protein level) (PubMed:26053433). Ubiquitous CC (PubMed:8568247). Expressed at higher levels in the tissues of the CC lymphocytic compartment, including spleen, thymus, peripheral blood CC lymphocytes and ovary (PubMed:8568247). {ECO:0000269|PubMed:21258371, CC ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:26053433, CC ECO:0000269|PubMed:30684677, ECO:0000269|PubMed:8568247}. CC -!- DEVELOPMENTAL STAGE: Expression is cell cycle-dependent with decreased CC levels in G2 phase; mediated by proteasomal degradation (at protein CC level) (PubMed:18354482). In aged individuals, increased expression in CC hippocampal CA1, CA3 and CA4 pyramidal neurons and in dentate granule CC cell neurons, but not in the cerebellum (PubMed:24670762). CC {ECO:0000269|PubMed:18354482, ECO:0000269|PubMed:24670762}. CC -!- INDUCTION: Up-regulated by Wnt signaling (PubMed:24670762). Up- CC regulated in the brain of aging individuals but not in Alzheimer CC disease patients (PubMed:24670762). Up-regulated by oxidative stress CC (PubMed:24670762). Down-regulated during neural progenitor cell CC differentiation (PubMed:21258371). {ECO:0000269|PubMed:21258371, CC ECO:0000269|PubMed:24670762}. CC -!- DOMAIN: The C2H2-type zinc finger 5 is required for nuclear CC localization. {ECO:0000269|PubMed:16442230}. CC -!- PTM: O-glycosylated. {ECO:0000250|UniProtKB:Q8VIG1}. CC -!- PTM: Phosphorylated; phosphorylation is required for ubiquitination. CC {ECO:0000269|PubMed:18354482}. CC -!- PTM: Ubiquitinated; ubiquitination is mediated by BTRC and leads to CC proteasomal degradation in G2 phase (PubMed:18354482, PubMed:21258371). CC Ubiquitination increases during neuronal differentiation CC (PubMed:21258371). Deubiquitinated by USP7; leading to its CC stabilization and promoting the maintenance of neural progenitor cells CC (PubMed:21258371). {ECO:0000269|PubMed:18354482, CC ECO:0000269|PubMed:21258371}. CC -!- DISEASE: Wilms tumor 6 (WT6) [MIM:616806]: A pediatric malignancy of CC kidney, and the most common childhood abdominal malignancy. It is CC caused by the uncontrolled multiplication of renal stem, stromal, and CC epithelial cells. {ECO:0000269|PubMed:26551668}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Fibromatosis, gingival, 5 (GINGF5) [MIM:617626]: An autosomal CC dominant form of hereditary gingival fibromatosis, a rare condition CC characterized by a slow, progressive overgrowth of the gingiva. The CC excess gingival tissue can cover part of or the entire crown, and can CC result in diastemas, teeth displacement, or retention of primary or CC impacted teeth. {ECO:0000269|PubMed:28686854}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Note=An intronic variant that affects alternative splicing of CC REST into isoform 3 and inactivation of REST repressor activity is CC associated with progressive hearing loss and deafness. CC {ECO:0000269|PubMed:29961578}. CC -!- DISEASE: Deafness, autosomal dominant, 27 (DFNA27) [MIM:612431]: A form CC of non-syndromic deafness characterized by postlingual, progressive, CC moderate to profound sensorineural hearing loss. CC {ECO:0000269|PubMed:29961578}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. An intronic CC variant that affects alternative splicing of REST and inactivation of CC REST repressor activity fully segregates with deafness in a 3- CC generation family. {ECO:0000269|PubMed:29961578}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by SRRM4-dependent alternative CC splicing in neurons and inner ear hair cells (By similarity). Lacks the CC four C-terminal zinc fingers and the RCOR1 corepressor interaction site CC found in full length REST isoform 1, which are required for full DNA- CC binding and repressive activity (PubMed:11741002). CC {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002}. CC -!- CAUTION: [Isoform 3]: Controversial data exists concerning the CC repressor activity of isoform 3. A study showed that isoform 3 exhibits CC weak repressor activity of a NRSE motif-containing reporter construct CC (PubMed:11779185). Another report, however, does not observe any CC isoform 3 transcriptional repressor activity of a NRSE motif-containing CC reporter construct (PubMed:11741002). Controversial data also exists CC regarding the function of isoform 3 on the negative regulation of CC isoform 1. It was shown that isoform 3 negatively regulates the CC repressor activity of isoform 1 by binding to isoform 1, thereby CC preventing its binding to NRSE and leading to derepression of target CC genes (PubMed:11779185). Another study, however, did not observe any CC inhibitory activity of isoform 3 on the isoform 1 transcriptional CC repressor activity (PubMed:11741002). {ECO:0000269|PubMed:11741002, CC ECO:0000269|PubMed:11779185}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA98503.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAC50114.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAC50115.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH38985.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAD92987.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44266/REST"; 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; U22314; AAB17211.1; -; mRNA. DR EMBL; U13877; AAC50114.1; ALT_INIT; mRNA. DR EMBL; U13879; AAC50115.1; ALT_INIT; mRNA. DR EMBL; U22680; AAA98503.1; ALT_FRAME; mRNA. DR EMBL; AB209750; BAD92987.1; ALT_INIT; mRNA. DR EMBL; AC069307; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471057; EAX05517.1; -; Genomic_DNA. DR EMBL; BC038985; AAH38985.1; ALT_SEQ; mRNA. DR EMBL; BC132859; AAI32860.1; -; mRNA. DR EMBL; BC136491; AAI36492.1; -; mRNA. DR CCDS; CCDS3509.1; -. [Q13127-1] DR PIR; A56138; A56138. DR PIR; I38754; I38754. DR PIR; I38755; I38755. DR RefSeq; NP_001180437.1; NM_001193508.2. [Q13127-1] DR RefSeq; NP_001350382.1; NM_001363453.3. [Q13127-1] DR RefSeq; NP_005603.3; NM_005612.4. [Q13127-1] DR PDB; 2CZY; NMR; -; B=43-57. DR PDB; 6DU2; X-ray; 2.50 A; C/D=858-869. DR PDB; 6DU3; X-ray; 2.58 A; C/D=858-869. DR PDBsum; 2CZY; -. DR PDBsum; 6DU2; -. DR PDBsum; 6DU3; -. DR AlphaFoldDB; Q13127; -. DR BMRB; Q13127; -. DR SMR; Q13127; -. DR BioGRID; 111910; 267. DR CORUM; Q13127; -. DR DIP; DIP-35264N; -. DR FunCoup; Q13127; 4087. DR IntAct; Q13127; 20. DR MINT; Q13127; -. DR STRING; 9606.ENSP00000311816; -. DR GlyGen; Q13127; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q13127; -. DR PhosphoSitePlus; Q13127; -. DR BioMuta; REST; -. DR DMDM; 296452989; -. DR jPOST; Q13127; -. DR MassIVE; Q13127; -. DR PaxDb; 9606-ENSP00000311816; -. DR PeptideAtlas; Q13127; -. DR ProteomicsDB; 59175; -. [Q13127-1] DR ProteomicsDB; 59176; -. [Q13127-2] DR ProteomicsDB; 59177; -. [Q13127-3] DR ProteomicsDB; 59178; -. [Q13127-4] DR Pumba; Q13127; -. DR Antibodypedia; 1755; 291 antibodies from 38 providers. DR DNASU; 5978; -. DR Ensembl; ENST00000309042.12; ENSP00000311816.7; ENSG00000084093.20. [Q13127-1] DR Ensembl; ENST00000675105.1; ENSP00000502313.1; ENSG00000084093.20. [Q13127-1] DR GeneID; 5978; -. DR KEGG; hsa:5978; -. DR MANE-Select; ENST00000309042.12; ENSP00000311816.7; NM_005612.5; NP_005603.3. DR UCSC; uc003hch.4; human. [Q13127-1] DR AGR; HGNC:9966; -. DR ClinPGx; PA34334; -. DR CTD; 5978; -. DR DisGeNET; 5978; -. DR GeneCards; REST; -. DR HGNC; HGNC:9966; REST. DR HPA; ENSG00000084093; Low tissue specificity. DR MalaCards; REST; -. DR MIM; 600571; gene. DR MIM; 612431; phenotype. DR MIM; 616806; phenotype. DR MIM; 617626; phenotype. DR OpenTargets; ENSG00000084093; -. DR Orphanet; 2024; Hereditary gingival fibromatosis. DR Orphanet; 654; Nephroblastoma. DR VEuPathDB; HostDB:ENSG00000084093; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000155341; -. DR HOGENOM; CLU_009801_2_0_1; -. DR InParanoid; Q13127; -. DR OrthoDB; 427030at2759; -. DR PAN-GO; Q13127; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q13127; -. DR PathwayCommons; Q13127; -. DR Reactome; R-HSA-3214815; HDACs deacetylate histones. DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription. DR Reactome; R-HSA-9031628; NGF-stimulated transcription. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9768777; Regulation of NPAS4 gene transcription. DR SignaLink; Q13127; -. DR SIGNOR; Q13127; -. DR Agora; ENSG00000084093; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 5978; 49 hits in 1187 CRISPR screens. DR ChiTaRS; REST; human. DR GeneWiki; RE1-silencing_transcription_factor; -. DR GenomeRNAi; 5978; -. DR Pharos; Q13127; Tbio. DR PRO; PR:Q13127; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q13127; protein. DR Bgee; ENSG00000084093; Expressed in primordial germ cell in gonad and 209 other cell types or tissues. DR ExpressionAtlas; Q13127; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; ISS:UniProtKB. DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; ISS:UniProtKB. DR GO; GO:0071257; P:cellular response to electrical stimulus; IMP:UniProtKB. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB. DR GO; GO:0033554; P:cellular response to stress; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB. DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:UniProtKB. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0043922; P:host-mediated suppression of viral transcription; IDA:UniProtKB. DR GO; GO:0099563; P:modification of synaptic structure; ISS:UniProtKB. DR GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; IMP:UniProtKB. DR GO; GO:2000798; P:negative regulation of amniotic stem cell differentiation; IMP:UniProtKB. DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; ISS:UniProtKB. DR GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; IMP:UniProtKB. DR GO; GO:2000706; P:negative regulation of dense core granule biogenesis; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB. DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:UniProtKB. DR GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; IMP:UniProtKB. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:BHF-UCL. DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0050877; P:nervous system process; IMP:UniProtKB. DR GO; GO:0050885; P:neuromuscular process controlling balance; ISS:UniProtKB. DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0043068; P:positive regulation of programmed cell death; ISS:UniProtKB. DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB. DR GO; GO:0035019; P:somatic stem cell population maintenance; ISS:UniProtKB. DR FunFam; 3.30.160.60:FF:002187; RE1-silencing transcription factor; 1. DR FunFam; 3.30.160.60:FF:000448; RE1-silencing transcription factor A; 1. DR FunFam; 3.30.160.60:FF:000662; RE1-silencing transcription factor A; 1. DR FunFam; 3.30.160.60:FF:000805; RE1-silencing transcription factor B; 1. DR FunFam; 3.30.160.60:FF:000952; RE1-silencing transcription factor B; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 5. DR IDEAL; IID00169; -. DR InterPro; IPR057281; Zfn-C2H2_REST. DR InterPro; IPR050688; Zinc_finger/UBP_domain. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR24403:SF102; RE1-SILENCING TRANSCRIPTION FACTOR; 1. DR PANTHER; PTHR24403; ZINC FINGER PROTEIN; 1. DR Pfam; PF00096; zf-C2H2; 1. DR Pfam; PF24540; zf-C2H2_REST; 1. DR SMART; SM00355; ZnF_C2H2; 9. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Deafness; Disease variant; KW Metal-binding; Non-syndromic deafness; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1..1097 FT /note="RE1-silencing transcription factor" FT /id="PRO_0000269547" FT ZN_FING 159..181 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 216..238 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 248..270 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 276..298 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 304..326 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 332..355 FT /note="C2H2-type 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 361..383 FT /note="C2H2-type 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 389..412 FT /note="C2H2-type 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 1060..1082 FT /note="C2H2-type 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 32..122 FT /note="Interaction with SIN3A" FT /evidence="ECO:0000269|PubMed:10734093" FT REGION 43..57 FT /note="Interaction with SIN3B" FT /evidence="ECO:0000269|PubMed:16288918" FT REGION 83..103 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 127..159 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 145..418 FT /note="Interaction with ZFP90" FT /evidence="ECO:0000269|PubMed:21284946" FT REGION 201..212 FT /note="Required for binding to the neuron-restrictive FT silencer element" FT /evidence="ECO:0000250|UniProtKB:Q8VIG1" FT REGION 452..642 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 774..837 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 853..938 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 961..1049 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1009..1087 FT /note="Interaction with RCOR1" FT /evidence="ECO:0000269|PubMed:10449787" FT COMPBIAS 86..96 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 452..479 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 480..490 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 495..504 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 559..570 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 577..593 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 803..836 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 913..930 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 864 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 971 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O54963" FT VAR_SEQ 301..313 FT /note="ERPYKCELCPYSS -> KRSFLVHKFSSLF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7871435" FT /id="VSP_022064" FT VAR_SEQ 304..326 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_022067" FT VAR_SEQ 314..1097 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7871435" FT /id="VSP_022065" FT VAR_SEQ 329 FT /note="E -> W (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_022066" FT VAR_SEQ 330..1097 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_022068" FT VARIANT 160 FT /note="R -> P (in WT6; inhibits transcriptional repression FT activity)" FT /evidence="ECO:0000269|PubMed:26551668" FT /id="VAR_076333" FT VARIANT 290 FT /note="N -> Y (in WT6; inhibits transcriptional repression FT activity)" FT /evidence="ECO:0000269|PubMed:26551668" FT /id="VAR_076334" FT VARIANT 322 FT /note="H -> R (in WT6; inhibits transcriptional repression FT activity; dbSNP:rs869025312)" FT /evidence="ECO:0000269|PubMed:26551668" FT /id="VAR_076335" FT VARIANT 412 FT /note="H -> Q (in WT6)" FT /evidence="ECO:0000269|PubMed:26551668" FT /id="VAR_076336" FT VARIANT 437..1097 FT /note="Missing (in GINGF5)" FT /evidence="ECO:0000269|PubMed:28686854" FT /id="VAR_079529" FT VARIANT 626 FT /note="V -> I (in dbSNP:rs2228991)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_029795" FT VARIANT 692 FT /note="E -> D (in dbSNP:rs2227902)" FT /id="VAR_029796" FT VARIANT 762 FT /note="K -> Q (in dbSNP:rs2227903)" FT /id="VAR_029797" FT VARIANT 797 FT /note="P -> L (in dbSNP:rs3796529)" FT /evidence="ECO:0000269|PubMed:8568247" FT /id="VAR_029798" FT MUTAGEN 91 FT /note="E->G: Does not change transcriptional repression FT activity." FT /evidence="ECO:0000269|PubMed:26551668" FT MUTAGEN 313 FT /note="S->A: Lack of deubiquitination by USP7." FT /evidence="ECO:0000269|PubMed:21258371" FT MUTAGEN 420 FT /note="M->T: Inhibits transcriptional repression activity." FT /evidence="ECO:0000269|PubMed:26551668" FT MUTAGEN 512..522 FT /note="KFSKTKKSKRK->AFSKTADSMDA: No effect on nuclear FT localization." FT /evidence="ECO:0000269|PubMed:16442230" FT MUTAGEN 512..522 FT /note="KFSKTKKSKRK->GS: Reduced nuclear localization." FT /evidence="ECO:0000269|PubMed:16442230" FT MUTAGEN 512..522 FT /note="Missing: No effect on nuclear localization." FT /evidence="ECO:0000269|PubMed:16442230" FT MUTAGEN 593 FT /note="S->N: Does not change transcriptional repression FT activity." FT /evidence="ECO:0000269|PubMed:26551668" FT MUTAGEN 642 FT /note="A->T: Does not change transcriptional repression FT activity." FT /evidence="ECO:0000269|PubMed:26551668" FT MUTAGEN 918 FT /note="H->Y: Does not change transcriptional repression FT activity." FT /evidence="ECO:0000269|PubMed:26551668" FT MUTAGEN 1009..1013 FT /note="EGIHS->AGIHA: Loss of interaction with BTRC. Reduced FT ubiquitination. Decreased proteasomal degradation in G2. FT Decreased average time from nuclear envelope breakdown to FT anaphase onset. Increased number of lagging chromosomes and FT chromosome bridges in anaphase and prematurely separated FT sister chromatids. Reduced MAD2 levels." FT /evidence="ECO:0000269|PubMed:18354482" FT MUTAGEN 1009 FT /note="E->A: Loss of interaction with BTRC." FT /evidence="ECO:0000269|PubMed:18354482" FT MUTAGEN 1013 FT /note="S->A: Loss of interaction with BTRC." FT /evidence="ECO:0000269|PubMed:18354482" FT MUTAGEN 1042 FT /note="S->A: No impact on deubiquitination by USP7." FT /evidence="ECO:0000269|PubMed:21258371" FT CONFLICT 295 FT /note="V -> L (in Ref. 2; AAC50114)" FT /evidence="ECO:0000305" FT CONFLICT 596..599 FT /note="PQKE -> SRNS (in Ref. 2; AAC50115)" FT /evidence="ECO:0000305" FT CONFLICT 630 FT /note="P -> L (in Ref. 1; AAB17211)" FT /evidence="ECO:0000305" FT HELIX 44..55 FT /evidence="ECO:0007829|PDB:2CZY" SQ SEQUENCE 1097 AA; 121872 MW; EBC652EED19CA161 CRC64; MATQVMGQSS GGGGLFTSSG NIGMALPNDM YDLHDLSKAE LAAPQLIMLA NVALTGEVNG SCCDYLVGEE RQMAELMPVG DNNFSDSEEG EGLEESADIK GEPHGLENME LRSLELSVVE PQPVFEASGA PDIYSSNKDL PPETPGAEDK GKSSKTKPFR CKPCQYEAES EEQFVHHIRV HSAKKFFVEE SAEKQAKARE SGSSTAEEGD FSKGPIRCDR CGYNTNRYDH YTAHLKHHTR AGDNERVYKC IICTYTTVSE YHWRKHLRNH FPRKVYTCGK CNYFSDRKNN YVQHVRTHTG ERPYKCELCP YSSSQKTHLT RHMRTHSGEK PFKCDQCSYV ASNQHEVTRH ARQVHNGPKP LNCPHCDYKT ADRSNFKKHV ELHVNPRQFN CPVCDYAASK KCNLQYHFKS KHPTCPNKTM DVSKVKLKKT KKREADLPDN ITNEKTEIEQ TKIKGDVAGK KNEKSVKAEK RDVSKEKKPS NNVSVIQVTT RTRKSVTEVK EMDVHTGSNS EKFSKTKKSK RKLEVDSHSL HGPVNDEESS TKKKKKVESK SKNNSQEVPK GDSKVEENKK QNTCMKKSTK KKTLKNKSSK KSSKPPQKEP VEKGSAQMDP PQMGPAPTEA VQKGPVQVEP PPPMEHAQME GAQIRPAPDE PVQMEVVQEG PAQKELLPPV EPAQMVGAQI VLAHMELPPP METAQTEVAQ MGPAPMEPAQ MEVAQVESAP MQVVQKEPVQ MELSPPMEVV QKEPVQIELS PPMEVVQKEP VKIELSPPIE VVQKEPVQME LSPPMGVVQK EPAQREPPPP REPPLHMEPI SKKPPLRKDK KEKSNMQSER ARKEQVLIEV GLVPVKDSWL LKESVSTEDL SPPSPPLPKE NLREEASGDQ KLLNTGEGNK EAPLQKVGAE EADESLPGLA ANINESTHIS SSGQNLNTPE GETLNGKHQT DSIVCEMKMD TDQNTRENLT GINSTVEEPV SPMLPPSAVE EREAVSKTAL ASPPATMAAN ESQEIDEDEG IHSHEGSDLS DNMSEGSDDS GLHGARPVPQ ESSRKNAKEA LAVKAAKGDF VCIFCDRSFR KGKDYSKHLN RHLVNVYYLE EAAQGQE //