ID   REST_MOUSE              Reviewed;        1082 AA.
AC   Q8VIG1; A0JNY8; Q155C6; Q3U0W0; Q4VAD6; Q9CW43;
DT   12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=RE1-silencing transcription factor;
DE   AltName: Full=Neural-restrictive silencer factor;
GN   Name=Rest; Synonyms=Nrsf;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=129;
RA   Kojima T., Naruse Y., Mori N.;
RT   "Alternative promoter and splicing generate multiple isoforms of the
RT   neural-restrictive silencer factor NRSF/REST,a general transcriptional
RT   repressor for multiple neuron specific genes.";
RL   Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Neuroblastoma;
RA   Puhl H.L. III, Ikeda S.R.;
RT   "Cloning of the REST4 splice variant of the mouse REST protein.";
RL   Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-853 (ISOFORM 1).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Liver, and Spleen;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   DEVELOPMENTAL STAGE.
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   [6]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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   [7]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=9771705; DOI=10.1038/2431;
RA   Chen Z.F., Paquette A.J., Anderson D.J.;
RT   "NRSF/REST is required in vivo for repression of multiple neuronal target
RT   genes during embryogenesis.";
RL   Nat. Genet. 20:136-142(1998).
RN   [8]
RP   ALTERNATIVE SPLICING (ISOFORMS 2 AND 3).
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 SUBUNIT.
RX   PubMed=10490617; DOI=10.1128/mcb.19.10.6788;
RA   Shimojo M., Paquette A.J., Anderson D.J., Hersh L.B.;
RT   "Protein kinase A regulates cholinergic gene expression in PC12 cells:
RT   REST4 silences the silencing activity of neuron-restrictive silencer
RT   factor/REST.";
RL   Mol. Cell. Biol. 19:6788-6795(1999).
RN   [10]
RP   FUNCTION, SUBUNIT (ISOFORM 2), GLYCOSYLATION, AND MUTAGENESIS OF
RP   1-MET--GLY-209 AND 243-TYR--HIS-265.
RX   PubMed=11039732; DOI=10.1016/s0169-328x(00)00129-7;
RA   Lee J.H., Shimojo M., Chai Y.G., Hersh L.B.;
RT   "Studies on the interaction of REST4 with the cholinergic repressor
RT   element-1/neuron restrictive silencer element.";
RL   Brain Res. Mol. Brain Res. 80:88-98(2000).
RN   [11]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=15907476; DOI=10.1016/j.cell.2005.03.013;
RA   Ballas N., Grunseich C., Lu D.D., Speh J.C., Mandel G.;
RT   "REST and its corepressors mediate plasticity of neuronal gene chromatin
RT   throughout neurogenesis.";
RL   Cell 121:645-657(2005).
RN   [12]
RP   INTERACTION WITH ZFP90, AND SUBCELLULAR LOCATION.
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   [13]
RP   FUNCTION.
RX   PubMed=21884984; DOI=10.1016/j.molcel.2011.08.014;
RA   Raj B., O'Hanlon D., Vessey J.P., Pan Q., Ray D., Buckley N.J.,
RA   Miller F.D., Blencowe B.J.;
RT   "Cross-regulation between an alternative splicing activator and a
RT   transcription repressor controls neurogenesis.";
RL   Mol. Cell 43:843-850(2011).
RN   [14]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
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   [15]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=25727884; DOI=10.1002/jcb.25148;
RA   Liu B., Cheng S., Xing W., Pourteymoor S., Mohan S.;
RT   "RE1-silencing transcription factor (Rest) is a novel regulator of
RT   osteoblast differentiation.";
RL   J. Cell. Biochem. 116:1932-1938(2015).
RN   [16]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=27819263; DOI=10.1038/ncomms13360;
RA   Mukherjee S., Brulet R., Zhang L., Hsieh J.;
RT   "REST regulation of gene networks in adult neural stem cells.";
RL   Nat. Commun. 7:13360-13360(2016).
RN   [17]
RP   FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY (ISOFORM 1
RP   AND 2), AND DEVELOPMENTAL STAGE.
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:29961578, PubMed:9771705). Restricts the
CC       expression of neuronal genes by associating with two distinct
CC       corepressors, SIN3A and RCOR1, which in turn recruit histone
CC       deacetylase to the promoters of REST-regulated genes (By similarity).
CC       Mediates repression by recruiting the BHC complex at RE1/NRSE sites
CC       which acts by deacetylating and demethylating specific sites on
CC       histones, thereby acting as a chromatin modifier (By similarity).
CC       Transcriptional repression by REST-CDYL via the recruitment of histone
CC       methyltransferase EHMT2 may be important in transformation suppression
CC       (By similarity). Represses the expression of SRRM4 in non-neural cells
CC       to prevent the activation of neural-specific splicing events and to
CC       prevent production of REST isoform 2 (PubMed:21884984). Repressor
CC       activity may be inhibited by forming heterodimers with isoform 2,
CC       thereby preventing binding to NRSE or binding to corepressors and
CC       leading to derepression of target genes (PubMed:10490617,
CC       PubMed:11039732). Also maintains repression of neuronal genes in neural
CC       stem cells, and allows transcription and differentiation into neurons
CC       by dissociation from RE1/NRSE sites of target genes (PubMed:15907476).
CC       Thereby is involved in maintaining the quiescent state of adult neural
CC       stem cells and preventing premature differentiation into mature neurons
CC       (PubMed:27819263). Plays a role in the developmental switch in synaptic
CC       NMDA receptor composition during postnatal development, by repressing
CC       GRIN2B expression and thereby altering NMDA receptor properties from
CC       containing primarily GRIN2B to primarily GRIN2A subunits (By
CC       similarity). Acts as a regulator of osteoblast differentiation
CC       (PubMed:25727884). Key repressor of gene expression in hypoxia;
CC       represses genes in hypoxia by direct binding to an RE1/NRSE site on
CC       their promoter regions (By similarity). May also function in stress
CC       resistance in the brain during aging; possibly by regulating expression
CC       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). {ECO:0000250|UniProtKB:O54963,
CC       ECO:0000250|UniProtKB:Q13127, ECO:0000269|PubMed:10490617,
CC       ECO:0000269|PubMed:11039732, ECO:0000269|PubMed:15907476,
CC       ECO:0000269|PubMed:21884984, ECO:0000269|PubMed:24670762,
CC       ECO:0000269|PubMed:25727884, ECO:0000269|PubMed:27819263,
CC       ECO:0000269|PubMed:29961578, ECO:0000269|PubMed:9771705}.
CC   -!- FUNCTION: [Isoform 2]: Binds to the 3' region of the neuron-restrictive
CC       silencer element (NRSE), with lower affinity than isoform 1
CC       (PubMed:11039732). Exhibits weaker repressor activity compared to
CC       isoform 1 (By similarity). 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:11039732, PubMed:10490617). However, in another study, does not
CC       appear to be implicated in repressor activity of a NRSE motif-
CC       containing reporter construct nor in inhibitory activity on the isoform
CC       1 transcriptional repressor activity (By similarity). Post-
CC       transcriptional inactivation of REST by SRRM4-dependent alternative
CC       splicing into isoform 2 is required in mechanosensory hair cells in the
CC       inner ear for derepression of neuronal genes, maintenance of hair cells
CC       and hearing (PubMed:29961578). {ECO:0000250|UniProtKB:Q13127,
CC       ECO:0000269|PubMed:10490617, ECO:0000269|PubMed:11039732,
CC       ECO:0000269|PubMed:29961578}.
CC   -!- SUBUNIT: Isoform 1 and isoform 2 form heterodimers (PubMed:10490617).
CC       Isoform 2: Forms homodimers and homooligomers; binds to the neuron-
CC       restrictive silencer element (NRSE) as monomer (PubMed:11039732).
CC       Interacts with SIN3A, SIN3B and RCOR1 (By similarity). Interacts with
CC       CDYL (By similarity). Interacts with EHMT1 and EHMT2 only in the
CC       presence of CDYL (By similarity). Part of a complex containing at least
CC       CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). 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 (By similarity).
CC       Interacts with FBXW11 and BTRC (By similarity). Interacts with USP7 (By
CC       similarity). {ECO:0000250|UniProtKB:Q13127,
CC       ECO:0000269|PubMed:10490617, ECO:0000269|PubMed:11039732,
CC       ECO:0000269|PubMed:21284946}.
CC   -!- INTERACTION:
CC       Q8VIG1; Q3U5C7: Prickle1; NbExp=2; IntAct=EBI-2312802, EBI-27099745;
CC       Q8VIG1; Q96MT3: PRICKLE1; Xeno; NbExp=4; IntAct=EBI-2312802, EBI-2348662;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15907476,
CC       ECO:0000269|PubMed:21284946, ECO:0000269|PubMed:24670762}. Cytoplasm
CC       {ECO:0000269|PubMed:24670762}. Note=Colocalizes with ZFP90 in the
CC       nucleus (PubMed:21284946). In response to hypoxia, there is a more
CC       pronounced increase in levels in the nucleus as compared to the
CC       cytoplasm (By similarity). In aging neurons, increased levels in the
CC       nucleus as compared to the cytoplasm (By similarity).
CC       {ECO:0000250|UniProtKB:Q13127, ECO:0000269|PubMed:21284946}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC       {ECO:0000250|UniProtKB:Q13127}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8VIG1-1; Sequence=Displayed;
CC       Name=2; Synonyms=N16, REST4;
CC         IsoId=Q8VIG1-2; Sequence=VSP_022069, VSP_022071;
CC       Name=3; Synonyms=N28;
CC         IsoId=Q8VIG1-3; Sequence=VSP_022070, VSP_022072;
CC   -!- TISSUE SPECIFICITY: Expressed in the hippocampus, including quiescent
CC       neuronal progenitor (QNP) cells, transient-amplifying progenitor (TAP)
CC       cells, neuroblasts and mature neurons (at protein level)
CC       (PubMed:27819263). Expressed in embryonic stem cells (at protein level)
CC       (PubMed:15907476). Expressed in many non-neuronal tissues including the
CC       heart and liver (PubMed:7871435). Abundantly expressed in osteoblastic
CC       lineage cells (PubMed:25727884). Expressed in the spleen, kidney, blood
CC       cells, cortex, neocortex and in the utricle, saccule and organ of Corti
CC       of the inner ear (PubMed:29961578). Isoform 2: Expressed in the cortex,
CC       neocortex and in the utricle, saccule and organ of Corti of the inner
CC       ear (PubMed:29961578). {ECO:0000269|PubMed:15907476,
CC       ECO:0000269|PubMed:25727884, ECO:0000269|PubMed:27819263,
CC       ECO:0000269|PubMed:29961578, ECO:0000269|PubMed:7871435}.
CC   -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in 8.5 dpc and 9.5 dpc
CC       embryos (PubMed:9771705). During embryogenesis, expressed at high
CC       levels in non-neuronal and differentiated peripheral nervous tissues,
CC       but is not expressed in differentiating neurons in the CNS
CC       (PubMed:7697725, PubMed:7871435). Expressed in the neocortex at
CC       embryonic stage 14.5 dpc and 16 dpc and in the utricle at 15.5 dpc
CC       (PubMed:29961578). Isoform 2: Expressed in the neocortex at embryonic
CC       stage 14.5 dpc and 16 dpc and in the utricle and saccule at 16 dpc
CC       (PubMed:29961578). {ECO:0000269|PubMed:29961578,
CC       ECO:0000269|PubMed:7697725, ECO:0000269|PubMed:7871435,
CC       ECO:0000269|PubMed:9771705}.
CC   -!- INDUCTION: Down-regulated in differentiating neurons and mature
CC       neurons. {ECO:0000269|PubMed:15907476}.
CC   -!- DOMAIN: The C2H2-type zinc finger 5 is required for nuclear
CC       localization. {ECO:0000250|UniProtKB:Q13127}.
CC   -!- PTM: O-glycosylated. {ECO:0000269|PubMed:11039732}.
CC   -!- PTM: Phosphorylated; phosphorylation is required for ubiquitination.
CC       {ECO:0000250|UniProtKB:Q13127}.
CC   -!- PTM: Ubiquitinated; ubiquitination is mediated by BTRC and leads to
CC       proteasomal degradation in G2 phase (By similarity). Ubiquitination
CC       increases during neuronal differentiation (By similarity).
CC       Deubiquitinated by USP7; leading to its stabilization and promoting the
CC       maintenance of neural progenitor cells (By similarity).
CC       {ECO:0000250|UniProtKB:Q13127}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality by embryonic day 11.5 dpc
CC       (PubMed:9771705). At 9.25 dpc, disorganization of the head mesenchyme
CC       in the midbrain region with separation of myotomal cells from the
CC       dermomyotome and widespread apoptotic cell death (PubMed:9771705).
CC       Forebrain malformation and widening of the mesencephalic flexure at 9.5
CC       dpc and 10.5 dpc, and growth retardation by 10.5 dpc (PubMed:9771705).
CC       Conditional knockout in the nervous system results in a progressive
CC       age-related neurodegenerative phenotype (PubMed:24670762). At the age
CC       of 1 month, no change of neuronal numbers in the cortex and
CC       hippocampus, but at the age of 8 months, neuronal degeneration and
CC       apoptosis, accompanied by significant neuronal loss in the cerebral
CC       cortex and hippocampus, and pronounced gliosis (PubMed:24670762). In
CC       primary 16 dpc cortical neurons, increased degeneration and cell death
CC       upon oxidative stress or exposure to oligomeric amyloid-beta 42
CC       (PubMed:24670762). Conditional knockout in QNP cells leads to a higher
CC       number of proliferating QNP cells, an increased transition to TAP cells
CC       and increased differentiation into mature neurons (PubMed:27819263).
CC       Conditional knockdout in proliferating cells leads to a decreased
CC       number of proliferating TAP cells and an increase in immature and
CC       mature neurons (PubMed:27819263). {ECO:0000269|PubMed:24670762,
CC       ECO:0000269|PubMed:27819263, ECO:0000269|PubMed:9771705}.
CC   -!- MISCELLANEOUS: [Isoform 2]: Produced by SRRM4-dependent alternative
CC       splicing in neurons and inner ear hair cells (PubMed:11039732,
CC       PubMed:29961578). Lacks the four C-terminal zinc fingers and the RCOR1
CC       corepressor interaction site found in full length REST isoform 1, which
CC       are required for full DNA-binding and repressive activity
CC       (PubMed:11039732, PubMed:29961578). {ECO:0000269|PubMed:11039732,
CC       ECO:0000269|PubMed:29961578}.
CC   -!- CAUTION: [Isoform 2]: Controversial data exists concerning the
CC       repressor activity of isoform 2. A study in human showed that human
CC       isoform 3 exhibits weak repressor activity of a NRSE motif-containing
CC       reporter construct (By similarity). Another report, however, does not
CC       observe any isoform 3 transcriptional repressor activity of a NRSE
CC       motif-containing reporter construct (By similarity). Controversial data
CC       also exists regarding the function of isoform 2 on the negative
CC       regulation of full-length REST. It was shown that isoform 2 negatively
CC       regulates the repressor activity of isoform 1 by binding to isoform 1,
CC       thereby preventing its binding to NRSE and leading to derepression of
CC       target genes (PubMed:10490617, PubMed:11039732). Another study in
CC       human, however, did not observe any inhibitory activity of human
CC       isoform 3 on the isoform 1 repressor activity (By similarity).
CC       {ECO:0000250|UniProtKB:Q13127, ECO:0000269|PubMed:10490617,
CC       ECO:0000269|PubMed:11039732}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH96434.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB024496; BAB82460.1; -; mRNA.
DR   EMBL; DQ644039; ABG35129.1; -; mRNA.
DR   EMBL; BC127065; AAI27066.1; -; mRNA.
DR   EMBL; BC096434; AAH96434.1; ALT_SEQ; mRNA.
DR   EMBL; AK004945; BAB23689.3; -; mRNA.
DR   EMBL; AK156514; BAE33741.1; -; mRNA.
DR   CCDS; CCDS19372.1; -. [Q8VIG1-1]
DR   RefSeq; NP_035393.2; NM_011263.2. [Q8VIG1-1]
DR   RefSeq; XP_006534905.1; XM_006534842.3. [Q8VIG1-1]
DR   AlphaFoldDB; Q8VIG1; -.
DR   BMRB; Q8VIG1; -.
DR   SMR; Q8VIG1; -.
DR   BioGRID; 202864; 9.
DR   IntAct; Q8VIG1; 7.
DR   MINT; Q8VIG1; -.
DR   STRING; 10090.ENSMUSP00000079231; -.
DR   GlyGen; Q8VIG1; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8VIG1; -.
DR   PhosphoSitePlus; Q8VIG1; -.
DR   EPD; Q8VIG1; -.
DR   jPOST; Q8VIG1; -.
DR   MaxQB; Q8VIG1; -.
DR   PaxDb; 10090-ENSMUSP00000079231; -.
DR   PeptideAtlas; Q8VIG1; -.
DR   ProteomicsDB; 254914; -. [Q8VIG1-1]
DR   ProteomicsDB; 254915; -. [Q8VIG1-2]
DR   ProteomicsDB; 254916; -. [Q8VIG1-3]
DR   Pumba; Q8VIG1; -.
DR   Antibodypedia; 1755; 342 antibodies from 36 providers.
DR   DNASU; 19712; -.
DR   Ensembl; ENSMUST00000080359.12; ENSMUSP00000079231.6; ENSMUSG00000029249.16. [Q8VIG1-1]
DR   Ensembl; ENSMUST00000113449.2; ENSMUSP00000109076.2; ENSMUSG00000029249.16. [Q8VIG1-1]
DR   GeneID; 19712; -.
DR   KEGG; mmu:19712; -.
DR   UCSC; uc008xvz.2; mouse. [Q8VIG1-1]
DR   AGR; MGI:104897; -.
DR   CTD; 5978; -.
DR   MGI; MGI:104897; Rest.
DR   VEuPathDB; HostDB:ENSMUSG00000029249; -.
DR   eggNOG; KOG1721; Eukaryota.
DR   GeneTree; ENSGT00940000155341; -.
DR   HOGENOM; CLU_009801_2_0_1; -.
DR   InParanoid; Q8VIG1; -.
DR   OMA; NDCDPNK; -.
DR   OrthoDB; 4169790at2759; -.
DR   PhylomeDB; Q8VIG1; -.
DR   TreeFam; TF332861; -.
DR   Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR   BioGRID-ORCS; 19712; 7 hits in 81 CRISPR screens.
DR   ChiTaRS; Rest; mouse.
DR   PRO; PR:Q8VIG1; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q8VIG1; Protein.
DR   Bgee; ENSMUSG00000029249; Expressed in external carotid artery and 260 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISS: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; IPI:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR   GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:UniProtKB.
DR   GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IDA:UniProtKB.
DR   GO; GO:0071257; P:cellular response to electrical stimulus; ISS:UniProtKB.
DR   GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISS:UniProtKB.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS: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; IMP:UniProtKB.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR   GO; GO:0099563; P:modification of synaptic structure; ISS:UniProtKB.
DR   GO; GO:0043922; P:negative regulation by host of viral transcription; ISS:UniProtKB.
DR   GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; ISS:UniProtKB.
DR   GO; GO:2000798; P:negative regulation of amniotic stem cell differentiation; ISS: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; ISS:UniProtKB.
DR   GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; ISS: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; IDA:UniProtKB.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR   GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; ISO:MGI.
DR   GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:MGI.
DR   GO; GO:0050768; P:negative regulation of neurogenesis; IGI:MGI.
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; ISS:UniProtKB.
DR   GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IDA:UniProtKB.
DR   GO; GO:0050877; P:nervous system process; ISS:UniProtKB.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; IMP:UniProtKB.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0045666; P:positive regulation of neuron differentiation; IMP: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; ISS: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; IMP:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR   GO; GO:0045667; P:regulation of osteoblast differentiation; IMP:UniProtKB.
DR   GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR   GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IMP:UniProtKB.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 5.
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; 2.
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.
DR   Genevisible; Q8VIG1; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Metal-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Repeat; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..1082
FT                   /note="RE1-silencing transcription factor"
FT                   /id="PRO_0000269548"
FT   ZN_FING         154..176
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         211..235
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         243..265
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         271..293
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         299..321
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         327..350
FT                   /note="C2H2-type 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         356..378
FT                   /note="C2H2-type 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         384..407
FT                   /note="C2H2-type 8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         1036..1058
FT                   /note="C2H2-type 9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          32..117
FT                   /note="Interaction with SIN3A"
FT                   /evidence="ECO:0000250|UniProtKB:Q13127"
FT   REGION          43..57
FT                   /note="Interaction with SIN3B"
FT                   /evidence="ECO:0000250|UniProtKB:Q13127"
FT   REGION          140..413
FT                   /note="Interaction with ZFP90"
FT                   /evidence="ECO:0000250|UniProtKB:Q13127"
FT   REGION          196..207
FT                   /note="Required for binding to the neuron-restrictive
FT                   silencer element"
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   REGION          408..809
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          831..1027
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          985..1063
FT                   /note="Interaction with RCOR1"
FT                   /evidence="ECO:0000250|UniProtKB:Q13127"
FT   COMPBIAS        417..434
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        443..474
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        476..492
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        526..546
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        578..596
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        629..643
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        664..747
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        792..809
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        899..932
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        983..997
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         950
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O54963"
FT   VAR_SEQ         323..328
FT                   /note="GEKPFK -> ECDLAG (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_022069"
FT   VAR_SEQ         324..332
FT                   /note="EKPFKCDQC -> CDLVGYVFR (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_022070"
FT   VAR_SEQ         329..1082
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_022071"
FT   VAR_SEQ         333..1082
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_022072"
FT   MUTAGEN         1..209
FT                   /note="Missing: Abolished binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         1..194
FT                   /note="Missing: Decreased binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         1..176
FT                   /note="Missing: Decreased binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         1..152
FT                   /note="Missing: Decreased binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         1..86
FT                   /note="Missing: Increased binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         196..207
FT                   /note="Missing: Abolished binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   MUTAGEN         243..265
FT                   /note="Missing: Abolished binding to neuron-restrictive
FT                   silencer element."
FT                   /evidence="ECO:0000269|PubMed:11039732"
FT   CONFLICT        414
FT                   /note="T -> R (in Ref. 1; BAB82460)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        485
FT                   /note="T -> S (in Ref. 1; BAB82460)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        556
FT                   /note="G -> S (in Ref. 1; BAB82460)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        584
FT                   /note="K -> N (in Ref. 1; BAB82460)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1082 AA;  117784 MW;  0D3616BC0820BC2F CRC64;
     MATQVMGQSS GGGSLFNNSA NMGMALTNDM YDLHELSKAE LAAPQLIMLA NVALTGEASG
     SCCDYLVGEE RQMAELMPVG DNHFSESEGE GLEESADLKG LENMELGSLE LSAVEPQPVF
     EASAAPEIYS ANKDPAPETP VAEDKCRSSK AKPFRCKPCQ YEAESEEQFV HHIRIHSAKK
     FFVEESAEKQ AKAWESGSSP AEEGEFSKGP IRCDRCGYNT NRYDHYMAHL KHHLRAGENE
     RIYKCIICTY TTVSEYHWRK HLRNHFPRKV YTCSKCNYFS DRKNNYVQHV RTHTGERPYK
     CELCPYSSSQ KTHLTRHMRT HSGEKPFKCD QCNYVASNQH EVTRHARQVH NGPKPLNCPH
     CDYKTADRSN FKKHVELHVN PRQFNCPVCD YAASKKCNLQ YHFKSKHPTC PSKTMDVSKV
     KLKKTKKREA DLLNNAVSNE KMENEQTKTK GDVSGKKNEK PVKAVGKDAS KEKKPGSSVS
     VVQVTTRTRK SAVAAETKAA EVKHTDGQTG NNPEKPCKAK KNKRKKDAEA HPSEEPVNEG
     PVTKKKKKSE CKSKIGTNVP KGGGRAEERP GVKKQSASLK KGTKKTPPKT KTSKKGGKLA
     PKGMGQTEPS SGALAQVGVS PDPALIQAEV TGSGSSQTEL PSPMDIAKSE PAQMEVSLTG
     PPPVEPAQME PSPAKPPQVE APTYPQPPQR GPAPPTGPAP PTGPAPPTEP APPTGLAEME
     PSPTEPSQKE PPPSMEPPCP EELPQAEPPP MEDCQKELPS PVEPAQIEVA QTAPTQVQEE
     PPPVSEPPRV KPTKRSSLRK DRAEKELSLL SEMARQEQVL MGVGLVPVRD SKLLKGNKSA
     QDPPAPPSPS PKGNSREETP KDQEMVSDGE GTIVFPLKKG GPEEAGESPA ELAALKESAR
     VSSSEQNSAM PEGGASHSKC QTGSSGLCDV DTEQKTDTVP MKDSAAEPVS PPTPTVDRDA
     GSPAVVASPP ITLAENESQE IDEDEGIHSH DGSDLSDNMS EGSDDSGLHG ARPTPPEATS
     KNGKAGLAGK VTEGEFVCIF CDRSFRKEKD YSKHLNRHLV NVYFLEEAAE EQEEQEEREE
     QE
//