REST_MOUSE
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 03-AUG-2022, entry version 170.
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; 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};
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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; 5.
DR MINT; Q8VIG1; -.
DR STRING; 10090.ENSMUSP00000079231; -.
DR iPTMnet; Q8VIG1; -.
DR PhosphoSitePlus; Q8VIG1; -.
DR EPD; Q8VIG1; -.
DR jPOST; Q8VIG1; -.
DR MaxQB; Q8VIG1; -.
DR PaxDb; Q8VIG1; -.
DR PeptideAtlas; Q8VIG1; -.
DR PRIDE; Q8VIG1; -.
DR ProteomicsDB; 254914; -. [Q8VIG1-1]
DR ProteomicsDB; 254915; -. [Q8VIG1-2]
DR ProteomicsDB; 254916; -. [Q8VIG1-3]
DR Antibodypedia; 1755; 295 antibodies from 36 providers.
DR DNASU; 19712; -.
DR Ensembl; ENSMUST00000080359; ENSMUSP00000079231; ENSMUSG00000029249. [Q8VIG1-1]
DR Ensembl; ENSMUST00000113449; ENSMUSP00000109076; ENSMUSG00000029249. [Q8VIG1-1]
DR GeneID; 19712; -.
DR KEGG; mmu:19712; -.
DR UCSC; uc008xvz.2; mouse. [Q8VIG1-1]
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; NQRDAGI; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q8VIG1; -.
DR TreeFam; TF332861; -.
DR Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR BioGRID-ORCS; 19712; 7 hits in 75 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 256 other tissues.
DR Genevisible; Q8VIG1; MM.
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: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:0070933; P:histone H4 deacetylation; ISS:UniProtKB.
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: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:1903204; P:negative regulation of oxidative stress-induced neuron death; ISS: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:0045892; P:negative regulation of transcription, DNA-templated; IDA: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:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP: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; ISS: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; ISO:MGI.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP: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:1903203; P:regulation of oxidative stress-induced neuron death; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS: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 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 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
