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 24-JAN-2024, entry version 201.
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:12399542, PubMed:26551668, PubMed:7697725,
CC PubMed:7871435, PubMed:8568247, PubMed:11741002, PubMed:11779185).
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_001193508.1. [Q13127-1]
DR RefSeq; NP_005603.3; NM_005612.4. [Q13127-1]
DR RefSeq; XP_011532703.1; XM_011534401.2.
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; 262.
DR CORUM; Q13127; -.
DR DIP; DIP-35264N; -.
DR IntAct; Q13127; 19.
DR MINT; Q13127; -.
DR STRING; 9606.ENSP00000311816; -.
DR GlyGen; Q13127; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13127; -.
DR PhosphoSitePlus; Q13127; -.
DR BioMuta; REST; -.
DR DMDM; 296452989; -.
DR EPD; Q13127; -.
DR jPOST; Q13127; -.
DR MassIVE; Q13127; -.
DR MaxQB; 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; 342 antibodies from 36 providers.
DR DNASU; 5978; -.
DR Ensembl; ENST00000309042.12; ENSP00000311816.7; ENSG00000084093.19. [Q13127-1]
DR Ensembl; ENST00000675105.1; ENSP00000502313.1; ENSG00000084093.19. [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 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 neXtProt; NX_Q13127; -.
DR OpenTargets; ENSG00000084093; -.
DR Orphanet; 2024; Hereditary gingival fibromatosis.
DR Orphanet; 654; Nephroblastoma.
DR PharmGKB; PA34334; -.
DR VEuPathDB; HostDB:ENSG00000084093; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000155341; -.
DR HOGENOM; CLU_009801_2_0_1; -.
DR InParanoid; Q13127; -.
DR OMA; NDCDPNK; -.
DR OrthoDB; 4169790at2759; -.
DR PhylomeDB; Q13127; -.
DR TreeFam; TF332861; -.
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 BioGRID-ORCS; 5978; 49 hits in 1187 CRISPR screens.
DR ChiTaRS; REST; human.
DR EvolutionaryTrace; Q13127; -.
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 Genevisible; Q13127; HS.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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:0071466; P:cellular response to xenobiotic stimulus; IMP:UniProtKB.
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:0099563; P:modification of synaptic structure; ISS:UniProtKB.
DR GO; GO:0043922; P:negative regulation by host of viral transcription; IDA: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:0008285; P:negative regulation of cell population proliferation; IMP: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; IMP: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:2000678; P:negative regulation of transcription regulatory region DNA binding; ISS: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:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP: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 Gene3D; 3.30.160.60; Classic Zinc Finger; 5.
DR IDEAL; IID00169; -.
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 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 Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; 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 143..159
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..478
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 479..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..591
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..836
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 910..938
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1005..1021
FT /note="Basic and acidic 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
//
