Human Gene REST (uc031sfp.1) Description and Page Index
  Description: Homo sapiens RE1-silencing transcription factor (REST), transcript variant 2, mRNA.
RefSeq Summary (NM_005612): This gene was initially identified as a transcriptional repressor that represses neuronal genes in non-neuronal tissues. However, depending on the cellular context, this gene can act as either an oncogene or a tumor suppressor. The encoded protein is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element. The protein is also found in undifferentiated neuronal progenitor cells and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2018]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803614.130457.1, SRR1803615.176357.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000309042.12/ ENSP00000311816.7 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr4:57,775,727-57,802,010 Size: 26,284 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg19 chr4:57,776,805-57,798,318 Size: 21,514 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:57,775,727-57,802,010)mRNA (may differ from genome)Protein (948 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: REST_HUMAN
DESCRIPTION: RecName: Full=RE1-silencing transcription factor; AltName: Full=Neural-restrictive silencer factor; AltName: Full=X2 box repressor;
FUNCTION: Transcriptional repressor which 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, mSin3 and CoREST, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. 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.
SUBUNIT: Interacts with SIN3A, SIN3B and RCOR1.
INTERACTION: P51532:SMARCA4; NbExp=2; IntAct=EBI-926706, EBI-302489;
SUBCELLULAR LOCATION: Nucleus (Probable).
TISSUE SPECIFICITY: Ubiquitous. Expressed at higher levels in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes and ovary.
SIMILARITY: Contains 9 C2H2-type zinc fingers.
SEQUENCE CAUTION: Sequence=AAA98503.1; Type=Frameshift; Positions=188, 198, 202, 212, 1087; Sequence=AAC50114.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAC50115.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH38985.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=BAD92987.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): REST
CDC HuGE Published Literature: REST
Positive Disease Associations: Bleomycin , Body Height , cognitive ability , Macular Degeneration
Related Studies:
  1. Bleomycin
    Jian Gu et al. Human molecular genetics 2011, A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity., Human molecular genetics. [PubMed 21106707]
  2. Body Height
    Hana Lango Allen et al. Nature 2010, Hundreds of variants clustered in genomic loci and biological pathways affect human height., Nature. [PubMed 20881960]
  3. cognitive ability
    F Miyajima , et al. Genes, brain, and behavior 2008 7(7):714-9, Additive effect of BDNF and REST polymorphisms is associated with improved general cognitive ability., Genes, brain, and behavior 2008 7(7):714-9. [PubMed 18518926]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: REST
Diseases sorted by gene-association score: wilms tumor 6* (905), fibromatosis, gingival, 5* (900), wilms tumor susceptibility-5* (8), hereditary wilms' tumor (7), gingival fibromatosis (7), huntington disease (4), medulloblastoma (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.39 RPKM in Testis
Total median expression: 178.97 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -4.5036-0.125 Picture PostScript Text
3' UTR -915.653692-0.248 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00096 - Zinc finger, C2H2 type
PF13909 - C2H2-type zinc-finger domain

SCOP Domains:
57667 - C2H2 and C2HC zinc fingers

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2CZY
- NMR


ModBase Predicted Comparative 3D Structure on Q13127
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001046 core promoter sequence-specific DNA binding
GO:0001047 core promoter binding
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0015271 outward rectifier potassium channel activity
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0002244 hematopoietic progenitor cell differentiation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0008285 negative regulation of cell proliferation
GO:0010629 negative regulation of gene expression
GO:0032348 negative regulation of aldosterone biosynthetic process
GO:0035690 cellular response to drug
GO:0043065 positive regulation of apoptotic process
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043922 negative regulation by host of viral transcription
GO:0045665 negative regulation of neuron differentiation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0045955 negative regulation of calcium ion-dependent exocytosis
GO:0046676 negative regulation of insulin secretion
GO:0050768 negative regulation of neurogenesis
GO:0060379 cardiac muscle cell myoblast differentiation
GO:0070933 histone H4 deacetylation
GO:0071257 cellular response to electrical stimulus
GO:0071385 cellular response to glucocorticoid stimulus
GO:0071805 potassium ion transmembrane transport
GO:2000065 negative regulation of cortisol biosynthetic process
GO:2000706 negative regulation of dense core granule biogenesis
GO:2000740 negative regulation of mesenchymal stem cell differentiation
GO:2000798 negative regulation of amniotic stem cell differentiation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0017053 transcriptional repressor complex


-  Descriptions from all associated GenBank mRNAs
  JX896984 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E5 (REST) mRNA, complete cds, alternatively spliced.
JX896985 - Homo sapiens RE1-silencing transcription factor variant E1a/E3/E5 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896983 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E3/E5 (REST) mRNA, complete cds, alternatively spliced.
JX896989 - Homo sapiens RE1-silencing transcription factor variant E1b/E2/E3/E5 (REST) mRNA, complete cds, alternatively spliced.
KC117265 - Homo sapiens RE1-silencing transcription factor variant E1b/E3/E5 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896990 - Homo sapiens RE1-silencing transcription factor variant E1c/E2/E3/E5 (REST) mRNA, complete cds, alternatively spliced.
BC038985 - Homo sapiens, Similar to RE1-silencing transcription factor, clone IMAGE:5785778, mRNA, partial cds.
U13879 - Human neuron-restrictive silencer factor mRNA, partial cds.
JX896991 - Homo sapiens RE1-silencing transcription factor variant E1a/E2a/E2k (REST) mRNA, complete cds, alternatively spliced.
JX896957 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E3/E4c (REST) mRNA, complete cds, alternatively spliced.
JX896958 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E3/N3c/E4 (REST) mRNA, complete cds, alternatively spliced.
JX896959 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E4 (REST) mRNA, partial cds, alternatively spliced.
JX896960 - Homo sapiens RE1-silencing transcription factor variant E1a/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896962 - Homo sapiens RE1-silencing transcription factor variant E1a/E3/N3c/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896963 - Homo sapiens RE1-silencing transcription factor variant E1a/N2a/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896964 - Homo sapiens RE1-silencing transcription factor variant E1a/N2b/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896965 - Homo sapiens RE1-silencing transcription factor variant E1a/E2b/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896961 - Homo sapiens RE1-silencing transcription factor variant E1a/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
KC117266 - Homo sapiens RE1-silencing transcription factor variant E1a/E2l/E2i/E3/E4j (REST) mRNA, complete cds, alternatively spliced.
JX896971 - Homo sapiens RE1-silencing transcription factor variant E1a/E2/E3/N3a/E4i (REST) mRNA, complete cds, alternatively spliced.
JX896972 - Homo sapiens RE1-silencing transcription factor variant E1a/E3/E4b/E4d non-coding RNA (REST), complete sequence, alternatively spliced.
JX896973 - Homo sapiens RE1-silencing transcription factor variant E1a/E3/E4i non-coding RNA (REST), complete sequence, alternatively spliced.
JX896974 - Homo sapiens RE1-silencing transcription factor variant E1a/E4i non-coding RNA (REST), complete sequence, alternatively spliced.
JX896975 - Homo sapiens RE1-silencing transcription factor variant E1a/E2b/E2i/E3/E4i non-coding RNA (REST), complete sequence, alternatively spliced.
JX896976 - Homo sapiens RE1-silencing transcription factor variant E1a/E2b/E4f/E4i non-coding RNA (REST), complete sequence, alternatively spliced.
JX896977 - Homo sapiens RE1-silencing transcription factor variant E1a/E2b/E4i non-coding RNA (REST), complete sequence, alternatively spliced.
JX896978 - Homo sapiens RE1-silencing transcription factor variant E1a/E2d/E4g (REST) mRNA, complete cds, alternatively spliced.
JX896979 - Homo sapiens RE1-silencing transcription factor variant E1a/E2e/E4h (REST) mRNA, complete cds, alternatively spliced.
JX896980 - Homo sapiens RE1-silencing transcription factor variant E1a/E2f/E4e (REST) mRNA, complete cds, alternatively spliced.
KF429249 - Homo sapiens REST/EAPP fusion protein mRNA, complete cds.
BC132859 - Homo sapiens RE1-silencing transcription factor, mRNA (cDNA clone MGC:164490 IMAGE:40146881), complete cds.
BC136491 - Homo sapiens RE1-silencing transcription factor, mRNA (cDNA clone MGC:168103 IMAGE:9020480), complete cds.
AB209750 - Homo sapiens mRNA for RE1-silencing transcription factor variant protein.
BC017822 - Homo sapiens RE1-silencing transcription factor, mRNA (cDNA clone IMAGE:4690075), partial cds.
JX896992 - Homo sapiens RE1-silencing transcription factor variant E1b/E2a/E2k (REST) mRNA, complete cds, alternatively spliced.
JX896966 - Homo sapiens RE1-silencing transcription factor variant E1b/E2/E3/N3c/E4 (REST) mRNA, complete cds, alternatively spliced.
JX896968 - Homo sapiens RE1-silencing transcription factor variant E1b/E2c/E2j/E3/E4 (REST) mRNA, partial cds, alternatively spliced.
JX896969 - Homo sapiens RE1-silencing transcription factor variant E1b/N1/E2b/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
KC117263 - Homo sapiens RE1-silencing transcription factor variant E1b/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JX896981 - Homo sapiens RE1-silencing transcription factor variant E1b/E2/E3/N3b/E4i (REST) mRNA, complete cds, alternatively spliced.
JX896982 - Homo sapiens RE1-silencing transcription factor variant E1b/E2e/E4h (REST) mRNA, complete cds, alternatively spliced.
JX896993 - Homo sapiens RE1-silencing transcription factor variant E1c/E2a/E2k (REST) mRNA, complete cds, alternatively spliced.
JX896970 - Homo sapiens RE1-silencing transcription factor variant E1c/E2g/E3/E4 (REST) mRNA, partial cds, alternatively spliced.
KC117264 - Homo sapiens RE1-silencing transcription factor variant E1c/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
U13877 - Human neural-restrictive silencer factor, splice variant mRNA, partial cds.
U22314 - Human REST protein mRNA, complete cds.
AB385046 - Synthetic construct DNA, clone: pF1KB5115, Homo sapiens REST gene for RE1-silencing transcription factor, complete cds, without stop codon, in Flexi system.
JX896967 - Homo sapiens RE1-silencing transcription factor variant E1b/E2b/E2h/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
AF228045 - Homo sapiens truncated neuron restrictive silencer factor isoform (REST) mRNA, partial cds.
KC117262 - Homo sapiens RE1-silencing transcription factor variant E1b/E2b/E3/E4 non-coding RNA (REST), complete sequence, alternatively spliced.
JD042692 - Sequence 23716 from Patent EP1572962.
DL490548 - Novel nucleic acids.
U22680 - Human X2 box repressor mRNA, complete cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05016 - Huntington's disease

Reactome (by CSHL, EBI, and GO)

Protein Q13127 (Reactome details) participates in the following event(s):

R-HSA-3769447 HDAC1/2 containing-complexes deacetylate histones
R-HSA-6807077 NR2E1 associated with transcription repressors binds PTEN promoter
R-HSA-3214815 HDACs deacetylate histones
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-6807070 PTEN Regulation
R-HSA-4839726 Chromatin organization
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A2RUE0, B9EGJ0, JX896970, NM_005612, NP_005603, NRSF, Q12956, Q12957, Q13127, Q13134, Q59ER1, Q8IWI3, REST_HUMAN, uc003hch.3, XBR
UCSC ID: uc031sfp.1
RefSeq Accession: NM_005612
Protein: Q13127 (aka REST_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: JX896970.1
exon count: 4CDS single in 3' UTR: no RNA size: 609
ORF size: 2847CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5843.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.