REST
entrez
5978
canonical
uniprot
Q13127
canonical
ensembl
ENSG00000084093
resolver
ensp
ENSP00000311816
resolver
ensp
ENSP00000492006
resolver
ensp
ENSP00000502313
resolver
ensp
ENSP00000601587
resolver
ensp
ENSP00000616754
resolver
enst
ENST00000638187
resolver
enst
ENST00000946695
resolver
genesymbol
REST
resolver
genesymbol_syn
NRSF
resolver
genesymbol_syn
XBR
resolver
hgnc
HGNC:9966
resolver
uniprot
A0A1W2PQA1
resolver
uniprot
A2RUE0
resolver
uniprot
B9EGJ0
resolver
uniprot
Q12956
resolver
uniprot
Q12957
resolver
uniprot
Q13134
resolver
uniprot
Q59ER1
resolver
uniprot
Q8IWI3
resolver
uniprot_entry
A0A1W2PQA1_HUMAN
resolver
uniprot_entry
REST_HUMAN
resolver
uniprot_sec
A2RUE0
resolver
uniprot_sec
B9EGJ0
resolver
uniprot_sec
Q12956
resolver
uniprot_sec
Q12957
resolver
uniprot_sec
Q13134
resolver
uniprot_sec
Q59ER1
resolver
uniprot_sec
Q8IWI3
resolver
amino_acid_sequence
MATQVMGQSSGGGGLFTSSGNIGMALPNDMYDLHDLSKAELAAPQLIMLANVALTGEVNGSCCDYLVGEERQMAELMPVGDNNFSDSEEGEGLEESADIKGEPHGLENMELRSLELSVVEPQPVFEASGAPDIYSSNKDLPPETPGAEDKGKSSKTKPFRCKPCQYEAESEEQFVHHIRVHSAKKFFVEESAEKQAKARESGSSTAEEGDFSKGPIRCDRCGYNTNRYDHYTAHLKHHTRAGDNERVYKCIICTYTTVSEYHWRKHLRNHFPRKVYTCGKCNYFSDRKNNYVQHVRTHTGERPYKCELCPYSSSQKTHLTRHMRTHSGEKPFKCDQCSYVASNQHEVTRHARQVHNGPKPLNCPHCDYKTADRSNFKKHVELHVNPRQFNCPVCDYAASKKCNLQYHFKSKHPTCPNKTMDVSKVKLKKTKKREADLPDNITNEKTEIEQTKIKGDVAGKKNEKSVKAEKRDVSKEKKPSNNVSVIQVTTRTRKSVTEVKEMDVHTGSNSEKFSKTKKSKRKLEVDSHSLHGPVNDEESSTKKKKKVESKSKNNSQEVPKGDSKVEENKKQNTCMKKSTKKKTLKNKSSKKSSKPPQKEPVEKGSAQMDPPQMGPAPTEAVQKGPVQVEPPPPMEHAQMEGAQIRPAPDEPVQMEVVQEGPAQKELLPPVEPAQMVGAQIVLAHMELPPPMETAQTEVAQMGPAPMEPAQMEVAQVESAPMQVVQKEPVQMELSPPMEVVQKEPVQIELSPPMEVVQKEPVKIELSPPIEVVQKEPVQMELSPPMGVVQKEPAQREPPPPREPPLHMEPISKKPPLRKDKKEKSNMQSERARKEQVLIEVGLVPVKDSWLLKESVSTEDLSPPSPPLPKENLREEASGDQKLLNTGEGNKEAPLQKVGAEEADESLPGLAANINESTHISSSGQNLNTPEGETLNGKHQTDSIVCEMKMDTDQNTRENLTGINSTVEEPVSPMLPPSAVEEREAVSKTALASPPATMAANESQEIDEDEGIHSHEGSDLSDNMSEGSDDSGLHGARPVPQESSRKNAKEALAVKAAKGDFVCIFCDRSFRKGKDYSKHLNRHLVNVYYLEEAAQGQE
uniprot
proteins
disease_involvement
DISEASE: Wilms tumor 6 (WT6) [MIM:616806]: A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells. {ECO:0000269|PubMed:26551668}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Fibromatosis, gingival, 5 (GINGF5) [MIM:617626]: An autosomal dominant form of hereditary gingival fibromatosis, a rare condition characterized by a slow, progressive overgrowth of the gingiva. The excess gingival tissue can cover part of or the entire crown, and can result in diastemas, teeth displacement, or retention of primary or impacted teeth. {ECO:0000269|PubMed:28686854}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=An intronic variant that affects alternative splicing of REST into isoform 3 and inactivation of REST repressor activity is associated with progressive hearing loss and deafness. {ECO:0000269|PubMed:29961578}.; DISEASE: Deafness, autosomal dominant, 27 (DFNA27) [MIM:612431]: A form of non-syndromic deafness characterized by postlingual, progressive, moderate to profound sensorineural hearing loss. {ECO:0000269|PubMed:29961578}. Note=The disease may be caused by variants affecting the gene represented in this entry. An intronic variant that affects alternative splicing of REST and inactivation of REST repressor activity fully segregates with deafness in a 3-generation family. {ECO:0000269|PubMed:29961578}.
uniprot
proteins
function
FUNCTION: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (PubMed:10449787, PubMed:10734093). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3 (By similarity). Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:11779185). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (PubMed:27531581). May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response (PubMed:24670762). Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity). Negatively regulates the expression of SRRM3 in breast cancer cell lines (PubMed:26053433). {ECO:0000250|UniProtKB:O54963, ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:26053433, ECO:0000269|PubMed:26551668, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:7697725, ECO:0000269|PubMed:7871435, ECO:0000269|PubMed:8568247}.; FUNCTION: [Isoform 3]: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity). {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185}.
uniprot
proteins
mass_dalton
121872
uniprot
proteins
mutagenesis
MUTAGEN 91; /note="E->G: Does not change transcriptional repression activity."; /evidence="ECO:0000269|PubMed:26551668"; MUTAGEN 313; /note="S->A: Lack of deubiquitination by USP7."; /evidence="ECO:0000269|PubMed:21258371"; MUTAGEN 420; /note="M->T: Inhibits transcriptional repression activity."; /evidence="ECO:0000269|PubMed:26551668"; MUTAGEN 512..522; /note="KFSKTKKSKRK->AFSKTADSMDA: No effect on nuclear localization."; /evidence="ECO:0000269|PubMed:16442230"; MUTAGEN 512..522; /note="KFSKTKKSKRK->GS: Reduced nuclear localization."; /evidence="ECO:0000269|PubMed:16442230"; MUTAGEN 512..522; /note="Missing: No effect on nuclear localization."; /evidence="ECO:0000269|PubMed:16442230"; MUTAGEN 593; /note="S->N: Does not change transcriptional repression activity."; /evidence="ECO:0000269|PubMed:26551668"; MUTAGEN 642; /note="A->T: Does not change transcriptional repression activity."; /evidence="ECO:0000269|PubMed:26551668"; MUTAGEN 918; /note="H->Y: Does not change transcriptional repression activity."; /evidence="ECO:0000269|PubMed:26551668"; MUTAGEN 1009..1013; /note="EGIHS->AGIHA: Loss of interaction with BTRC. Reduced ubiquitination. Decreased proteasomal degradation in G2. Decreased average time from nuclear envelope breakdown to anaphase onset. Increased number of lagging chromosomes and chromosome bridges in anaphase and prematurely separated sister chromatids. Reduced MAD2 levels."; /evidence="ECO:0000269|PubMed:18354482"; MUTAGEN 1009; /note="E->A: Loss of interaction with BTRC."; /evidence="ECO:0000269|PubMed:18354482"; MUTAGEN 1013; /note="S->A: Loss of interaction with BTRC."; /evidence="ECO:0000269|PubMed:18354482"; MUTAGEN 1042; /note="S->A: No impact on deubiquitination by USP7."; /evidence="ECO:0000269|PubMed:21258371
uniprot
proteins
post_translational_modification
PTM: O-glycosylated. {ECO:0000250|UniProtKB:Q8VIG1}.; PTM: Phosphorylated; phosphorylation is required for ubiquitination. {ECO:0000269|PubMed:18354482}.; PTM: Ubiquitinated; ubiquitination is mediated by BTRC and leads to proteasomal degradation in G2 phase (PubMed:18354482, PubMed:21258371). Ubiquitination increases during neuronal differentiation (PubMed:21258371). Deubiquitinated by USP7; leading to its stabilization and promoting the maintenance of neural progenitor cells (PubMed:21258371). {ECO:0000269|PubMed:18354482, ECO:0000269|PubMed:21258371}.
uniprot
proteins
pubmed
10449787
uniprot
proteins
pubmed
10521596
uniprot
proteins
pubmed
10734093
uniprot
proteins
pubmed
11741002
uniprot
proteins
pubmed
11779185
uniprot
proteins
pubmed
12399542
uniprot
proteins
pubmed
14645515
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16288918
uniprot
proteins
pubmed
16442230
uniprot
proteins
pubmed
18354482
uniprot
proteins
pubmed
19061646
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21258371
uniprot
proteins
pubmed
21284946
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24670762
uniprot
proteins
pubmed
26053433
uniprot
proteins
pubmed
26551668
uniprot
proteins
pubmed
27531581
uniprot
proteins
pubmed
28686854
uniprot
proteins
pubmed
29961578
uniprot
proteins
pubmed
30684677
uniprot
proteins
pubmed
7697725
uniprot
proteins
pubmed
7871435
uniprot
proteins
pubmed
8568247
uniprot
proteins
sequence_length
1097
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16442230, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:30684677}. Cytoplasm {ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:30684677}. Note=Colocalizes with ZFP90 in the nucleus (By similarity). In response to hypoxia, there is a more pronounced increase in levels in the nucleus as compared to the cytoplasm (PubMed:27531581). In aging neurons, increased levels in the nucleus as compared to the cytoplasm (PubMed:24670762, PubMed:30684677). {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:30684677}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:16442230}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus {ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:16442230}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000269|PubMed:16442230}.
uniprot
proteins