REST a transcriptional repressor that binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. 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. Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events, including the alternative splicing of isoform 3 of REST. Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from NRSE sites of target genes. Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development. May function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response. Repressor of gene expression in the hippocampus after ischemia by directly binding to NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death. Induced during ageing in human cortical and hippocampal neurons, where it represses genes that promote cell death and induces the expression of stress response genes. Protects neurons from amyloid beta- and oxidative stress-induced toxicity. The deletion of REST in the mouse brain induces age-related neurodegeneration. 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. 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. Four isoforms of the human protein are produced by alternative splicing. Isoform 3 negatively regulates the repressor activity of isoform 1. Isoform 3 binds to the 3' region of NRSE with lower affinity than full-length isoform 1, exhibiting weaker repressor activity than isoform 1. Note: This description may include information from UniProtKB.
Protein type: C2H2-type zinc finger protein; Cell development/differentiation; DNA-binding; Transcription factor
Chromosomal Location of rat Ortholog: 14p11
Cellular Component:  chromatin; cytoplasm; cytosol; nucleoplasm; nucleus; protein-containing complex; transcription repressor complex
Molecular Function:  chromatin binding; DNA binding; DNA-binding transcription factor activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding; metal ion binding; protein binding; protein-containing complex binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; RNA polymerase II core promoter sequence-specific DNA binding; RNA polymerase II-specific DNA-binding transcription factor binding; sequence-specific DNA binding; transcription cis-regulatory region binding
Biological Process:  auditory receptor cell stereocilium organization; cardiac muscle cell myoblast differentiation; cellular response to electrical stimulus; cellular response to glucocorticoid stimulus; cellular response to xenobiotic stimulus; chromatin remodeling; detection of mechanical stimulus involved in sensory perception of sound; hematopoietic progenitor cell differentiation; modification of synaptic structure; negative regulation by host of viral transcription; negative regulation of aldosterone biosynthetic process; negative regulation of amniotic stem cell differentiation; negative regulation of calcium ion-dependent exocytosis; negative regulation of cell population proliferation; negative regulation of cortisol biosynthetic process; negative regulation of dense core granule biogenesis; negative regulation of DNA-templated transcription; negative regulation of gene expression; negative regulation of insulin secretion; negative regulation of mesenchymal stem cell differentiation; negative regulation of miRNA transcription; negative regulation of neurogenesis; negative regulation of neuron differentiation; negative regulation of transcription by RNA polymerase II; negative regulation of transcription regulatory region DNA binding; nervous system process; neuromuscular process controlling balance; neuron differentiation; neuronal stem cell population maintenance; positive regulation of apoptotic process; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of DNA-templated transcription; positive regulation of gene expression; positive regulation of neuron differentiation; positive regulation of programmed cell death; positive regulation of stem cell population maintenance; positive regulation of transcription by RNA polymerase II; regulation of alternative mRNA splicing, via spliceosome; regulation of DNA-templated transcription; regulation of gene expression; regulation of osteoblast differentiation; response to hypoxia; response to ischemia; somatic stem cell population maintenance
Reference #:  O54963 (UniProtKB)
Alt. Names/Synonyms: Neural-restrictive silencer factor; Nrsf; RE1-silencing transcription factor; Rest; zinc finger transcription factor REST protein
Gene Symbols: Rest
Molecular weight: 117,126 Da
Basal Isoelectric point: 5.97  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  Pfam  |  Phospho.ELM  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene