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REST_HUMAN
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   03-AUG-2022, entry version 193.
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="http://atlasgeneticsoncology.org/Genes/RESTID44266ch4q12.html";
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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; 261.
DR   CORUM; Q13127; -.
DR   DIP; DIP-35264N; -.
DR   IntAct; Q13127; 17.
DR   MINT; Q13127; -.
DR   STRING; 9606.ENSP00000311816; -.
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; Q13127; -.
DR   PeptideAtlas; Q13127; -.
DR   PRIDE; Q13127; -.
DR   ProteomicsDB; 59175; -. [Q13127-1]
DR   ProteomicsDB; 59176; -. [Q13127-2]
DR   ProteomicsDB; 59177; -. [Q13127-3]
DR   ProteomicsDB; 59178; -. [Q13127-4]
DR   Antibodypedia; 1755; 295 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   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   OrthoDB; 1318335at2759; -.
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   SignaLink; Q13127; -.
DR   SIGNOR; Q13127; -.
DR   BioGRID-ORCS; 5978; 42 hits in 1108 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 mucosa of paranasal sinus and 207 other 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: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:0070933; P:histone H4 deacetylation; IDA:UniProtKB.
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: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:1903204; P:negative regulation of oxidative stress-induced neuron death; IMP: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:0045892; P:negative regulation of transcription, DNA-templated; IDA: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:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR   GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron 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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR   GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB.
DR   GO; GO:1903203; P:regulation of oxidative stress-induced neuron death; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA: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   IDEAL; IID00169; -.
DR   InterPro; IPR027757; REST.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR24403:SF64; PTHR24403:SF64; 1.
DR   SMART; SM00355; ZnF_C2H2; 9.
DR   SUPFAM; SSF57667; SSF57667; 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
 
 
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