DegronMD - Q13127(REST)

FUNCTION: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247, PubMed:11741002, PubMed:11779185). 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}. View more >>

GO - Biological processes (BP): auditory receptor cell stereocilium organization [GO:0060088]; cardiac muscle cell myoblast differentiation [GO:0060379]; cellular response to electrical stimulus [GO:0071257]; cellular response to glucocorticoid stimulus [GO:0071385]; cellular response to xenobiotic stimulus [GO:0071466]; detection of mechanical stimulus involved in sensory perception of sound [GO:0050910]; hematopoietic progenitor cell differentiation [GO:0002244]; histone H4 deacetylation [GO:0070933]; modification of synaptic structure [GO:0099563]; negative regulation by host of viral transcription [GO:0043922]; negative regulation of aldosterone biosynthetic process [GO:0032348]; negative regulation of amniotic stem cell differentiation [GO:2000798]; negative regulation of calcium ion-dependent exocytosis [GO:0045955]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cortisol biosynthetic process [GO:2000065]; negative regulation of dense core granule biogenesis [GO:2000706]; negative regulation of gene expression [GO:0010629]; negative regulation of insulin secretion [GO:0046676]; negative regulation of mesenchymal stem cell differentiation [GO:2000740]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of neurogenesis [GO:0050768]; negative regulation of neuron differentiation [GO:0045665]; negative regulation of oxidative stress-induced neuron death [GO:1903204]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of transcription regulatory region DNA binding [GO:2000678]; neuromuscular process controlling balance [GO:0050885]; neuronal stem cell population maintenance [GO:0097150]; positive regulation of apoptotic process [GO:0043065]; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280]; positive regulation of gene expression [GO:0010628]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of oxidative stress-induced neuron death [GO:1903223]; positive regulation of stem cell population maintenance [GO:1902459]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of alternative mRNA splicing, via spliceosome [GO:0000381]; regulation of gene expression [GO:0010468]; regulation of osteoblast differentiation [GO:0045667]; regulation of oxidative stress-induced neuron death [GO:1903203]; regulation of transcription, DNA-templated [GO:0006355]; response to hypoxia [GO:0001666]; response to ischemia [GO:0002931]; somatic stem cell population maintenance [GO:0035019] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K155N	TCGA-06-5416	GBM	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation substituting flanking lysine	0.25
p.K155N	DO10880	GBM	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation substituting flanking lysine	0.25
p.T928M	TCGA-27-2519	GBM	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7423
p.T928M	DO233156	GACA	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7423
p.T928M	DO12790	GBM	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7423
p.E932K	TCGA-56-8309	LUSC	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7022
p.E932K	DO219141	LUSC	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7022
p.E932K	DO27885	ORCA	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.7022
p.A147T	TCGA-A5-A0G1	UCEC	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.6028
p.A147T	DO42472	UCEC	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.6028
p.D139N	TCGA-A5-A0G2	UCEC	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.2778
p.D139N	DO41235	UCEC	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.2778
p.N935H	TCGA-AP-A1E0	UCEC	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.25
p.N935H	DO43154	UCEC	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.25
p.D149G	TCGA-CG-5721	STAD	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.3056
p.D149G	DO38192	STAD	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.3056
p.S920L	TCGA-D3-A1Q6	SKCM	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1667
p.S920L	DO37450	SKCM	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1667
p.S920L	SIDM00383	Gastric Carcinoma	GDSC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1667
p.S920L	ACH-002198	Gastric Cancer	CCLE	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1667
p.S920L	SCH	stomach	COSMIC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1667
p.P929S	TCGA-DA-A95X	SKCM	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.6752
p.P929S	DO219480	SKCM	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation altering degron motif	0.6752
p.N871K	TCGA-DU-6392	LGG	TCGA	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation altering degron motif	0.6918
p.N871K	DO22237	LGG	ICGC	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation altering degron motif	0.6918
p.S916T	TCGA-E9-A1R7	BRCA	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.0556
p.S916T	DO1978	BRCA	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.0556
p.P141S	TCGA-EE-A2MJ	SKCM	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.6752
p.P141S	DO38099	SKCM	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.6752
p.K152T	TCGA-EO-A3AY	UCEC	TCGA	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation substituting flanking lysine	0.3333
p.K152T	DO43202	UCEC	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation substituting flanking lysine	0.3333
p.L934F	TCGA-P4-A5E7	KIRP	TCGA	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.2778
p.L934F	DO48479	KIRP	ICGC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.2778
p.D859V	DO228080	EOPC	ICGC	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation rewiring degron network	0.0833
p.E858A	DO233871	GACA	ICGC	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation rewiring degron network	0.0556
p.G151D	DO229018	LICA	ICGC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.25
p.K881I	DO231786	LINC	ICGC	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation substituting flanking lysine	0.1944
p.P141R	SIDM00944	Colorectal Carcinoma	GDSC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.7512
p.P141R	CL-11	large intestine	COSMIC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation altering degron motif	0.7512
p.T940S	SIDM00678	Bladder Carcinoma	GDSC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1111
p.T940S	ACH-000724	Bladder Cancer	CCLE	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1111
p.T940S	HT-1376	urinary tract	COSMIC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.1111
p.D941H	SIDM00146	Breast Carcinoma	GDSC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.0833
p.D941H	ACH-000768	Breast Cancer	CCLE	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.0833
p.D941H	MDA-MB-231	breast	COSMIC	LNTPEGE	DEG_SCF_FBW7_2	926:932	Mutation rewiring degron network	0.0833
p.D132H	SIDM00420	Bladder Carcinoma	GDSC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.0833
p.D132H	ACH-000566	Bladder Cancer	CCLE	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.0833
p.D132H	SW1710	urinary tract	COSMIC	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.0833
p.L882I	SIDM01574	Plasma Cell Myeloma	GDSC	PKENL	DEG_APCC_KENBOX_2	868:872	Mutation rewiring degron network	0.0556
p.S154L	ACH-000999	Colon/Colorectal Cancer	CCLE	PPETPGAE	DEG_SCF_FBW7_2	141:148	Mutation rewiring degron network	0.1667

Kaplan plot for REST in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

REST

UniProt ID: Q13127

Entrez ID: 5978

Protein name: RE1-silencing transcription factor (Neural-restrictive silencer factor) (X2 box repressor)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for REST in