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Protein

RE1-silencing transcription factor

Gene

REST

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression.6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri159 – 181C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri216 – 238C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 326C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri332 – 355C2H2-type 6PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri361 – 383C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri389 – 412C2H2-type 8PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri1060 – 1082C2H2-type 9PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

GO - Biological processi

  • cardiac muscle cell myoblast differentiation Source: UniProtKB
  • cellular response to drug Source: UniProtKB
  • cellular response to electrical stimulus Source: UniProtKB
  • cellular response to glucocorticoid stimulus Source: UniProtKB
  • hematopoietic progenitor cell differentiation Source: Ensembl
  • histone H4 deacetylation Source: UniProtKB
  • negative regulation by host of viral transcription Source: UniProtKB
  • negative regulation of aldosterone biosynthetic process Source: UniProtKB
  • negative regulation of amniotic stem cell differentiation Source: UniProtKB
  • negative regulation of calcium ion-dependent exocytosis Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cortisol biosynthetic process Source: UniProtKB
  • negative regulation of dense core granule biogenesis Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of insulin secretion Source: UniProtKB
  • negative regulation of mesenchymal stem cell differentiation Source: UniProtKB
  • negative regulation of neurogenesis Source: UniProtKB
  • negative regulation of neuron differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB

Keywordsi

Molecular functionRepressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214815 HDACs deacetylate histones
R-HSA-8943724 Regulation of PTEN gene transcription
SignaLinkiQ13127
SIGNORiQ13127

Names & Taxonomyi

Protein namesi
Recommended name:
RE1-silencing transcription factor
Alternative name(s):
Neural-restrictive silencer factor
X2 box repressor
Gene namesi
Name:REST
Synonyms:NRSF, XBR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000084093.15
HGNCiHGNC:9966 REST
MIMi600571 gene
neXtProtiNX_Q13127

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Wilms tumor 6 (WT6)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:616806
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076333160R → P in WT6; inhibits transcriptional repression activity. 1 Publication1
Natural variantiVAR_076334290N → Y in WT6; inhibits transcriptional repression activity. 1 Publication1
Natural variantiVAR_076335322H → R in WT6; inhibits transcriptional repression activity. 1 PublicationCorresponds to variant dbSNP:rs869025312EnsemblClinVar.1
Natural variantiVAR_076336412H → Q in WT6. 1 Publication1
Fibromatosis, gingival, 5 (GINGF5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:617626
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079529437 – 1097Missing in GINGF5. 1 PublicationAdd BLAST661

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91E → G: Does not change transcriptional repression activity. 1 Publication1
Mutagenesisi420M → T: Inhibits transcriptional repression activity. 1 Publication1
Mutagenesisi593S → N: Does not change transcriptional repression activity. 1 Publication1
Mutagenesisi642A → T: Does not change transcriptional repression activity. 1 Publication1
Mutagenesisi918H → Y: Does not change transcriptional repression activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5978
MalaCardsiREST
MIMi616806 phenotype
617626 phenotype
OpenTargetsiENSG00000084093
PharmGKBiPA34334

Polymorphism and mutation databases

BioMutaiREST
DMDMi296452989

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002695471 – 1097RE1-silencing transcription factorAdd BLAST1097

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei864PhosphoserineCombined sources1
Modified residuei971PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13127
MaxQBiQ13127
PaxDbiQ13127
PeptideAtlasiQ13127
PRIDEiQ13127

PTM databases

iPTMnetiQ13127
PhosphoSitePlusiQ13127

Expressioni

Tissue specificityi

Ubiquitous. Expressed at higher levels in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes and ovary.1 Publication

Gene expression databases

BgeeiENSG00000084093
CleanExiHS_REST
ExpressionAtlasiQ13127 baseline and differential
GenevisibleiQ13127 HS

Organism-specific databases

HPAiCAB068222
HPA006079

Interactioni

Subunit structurei

Interacts with SIN3A, SIN3B and RCOR1. Interacts with CDYL. Interacts with EHMT1 and EHMT2 only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. Interacts (via zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the interaction inhibits REST repressor activity (PubMed:21284946).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111910, 44 interactors
CORUMiQ13127
DIPiDIP-35264N
IntActiQ13127, 14 interactors
STRINGi9606.ENSP00000311816

Structurei

Secondary structure

11097
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi44 – 55Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CZYNMR-B43-57[»]
ProteinModelPortaliQ13127
SMRiQ13127
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13127

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni32 – 122Interaction with SIN3A1 PublicationAdd BLAST91
Regioni43 – 57Interaction with SIN3B1 PublicationAdd BLAST15
Regioni145 – 418Interaction with ZFP901 PublicationAdd BLAST274
Regioni1009 – 1087Interaction with RCOR1Add BLAST79

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi11 – 14Poly-Gly4
Compositional biasi400 – 603Lys-richAdd BLAST204
Compositional biasi595 – 815Pro-richAdd BLAST221

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri159 – 181C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri216 – 238C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 270C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri276 – 298C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri304 – 326C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri332 – 355C2H2-type 6PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri361 – 383C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri389 – 412C2H2-type 8PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri1060 – 1082C2H2-type 9PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00910000144144
HOVERGENiHBG093893
InParanoidiQ13127
KOiK09222
OMAiVQKEPVQ
OrthoDBiEOG091G01NI
PhylomeDBiQ13127
TreeFamiTF332861

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 9 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 1 hit
PS50157 ZINC_FINGER_C2H2_2, 6 hits

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q13127-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATQVMGQSS GGGGLFTSSG NIGMALPNDM YDLHDLSKAE LAAPQLIMLA
60 70 80 90 100
NVALTGEVNG SCCDYLVGEE RQMAELMPVG DNNFSDSEEG EGLEESADIK
110 120 130 140 150
GEPHGLENME LRSLELSVVE PQPVFEASGA PDIYSSNKDL PPETPGAEDK
160 170 180 190 200
GKSSKTKPFR CKPCQYEAES EEQFVHHIRV HSAKKFFVEE SAEKQAKARE
210 220 230 240 250
SGSSTAEEGD FSKGPIRCDR CGYNTNRYDH YTAHLKHHTR AGDNERVYKC
260 270 280 290 300
IICTYTTVSE YHWRKHLRNH FPRKVYTCGK CNYFSDRKNN YVQHVRTHTG
310 320 330 340 350
ERPYKCELCP YSSSQKTHLT RHMRTHSGEK PFKCDQCSYV ASNQHEVTRH
360 370 380 390 400
ARQVHNGPKP LNCPHCDYKT ADRSNFKKHV ELHVNPRQFN CPVCDYAASK
410 420 430 440 450
KCNLQYHFKS KHPTCPNKTM DVSKVKLKKT KKREADLPDN ITNEKTEIEQ
460 470 480 490 500
TKIKGDVAGK KNEKSVKAEK RDVSKEKKPS NNVSVIQVTT RTRKSVTEVK
510 520 530 540 550
EMDVHTGSNS EKFSKTKKSK RKLEVDSHSL HGPVNDEESS TKKKKKVESK
560 570 580 590 600
SKNNSQEVPK GDSKVEENKK QNTCMKKSTK KKTLKNKSSK KSSKPPQKEP
610 620 630 640 650
VEKGSAQMDP PQMGPAPTEA VQKGPVQVEP PPPMEHAQME GAQIRPAPDE
660 670 680 690 700
PVQMEVVQEG PAQKELLPPV EPAQMVGAQI VLAHMELPPP METAQTEVAQ
710 720 730 740 750
MGPAPMEPAQ MEVAQVESAP MQVVQKEPVQ MELSPPMEVV QKEPVQIELS
760 770 780 790 800
PPMEVVQKEP VKIELSPPIE VVQKEPVQME LSPPMGVVQK EPAQREPPPP
810 820 830 840 850
REPPLHMEPI SKKPPLRKDK KEKSNMQSER ARKEQVLIEV GLVPVKDSWL
860 870 880 890 900
LKESVSTEDL SPPSPPLPKE NLREEASGDQ KLLNTGEGNK EAPLQKVGAE
910 920 930 940 950
EADESLPGLA ANINESTHIS SSGQNLNTPE GETLNGKHQT DSIVCEMKMD
960 970 980 990 1000
TDQNTRENLT GINSTVEEPV SPMLPPSAVE EREAVSKTAL ASPPATMAAN
1010 1020 1030 1040 1050
ESQEIDEDEG IHSHEGSDLS DNMSEGSDDS GLHGARPVPQ ESSRKNAKEA
1060 1070 1080 1090
LAVKAAKGDF VCIFCDRSFR KGKDYSKHLN RHLVNVYYLE EAAQGQE
Length:1,097
Mass (Da):121,872
Last modified:May 18, 2010 - v3
Checksum:iEBC652EED19CA161
GO
Isoform 2 (identifier: Q13127-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     301-313: ERPYKCELCPYSS → KRSFLVHKFSSLF
     314-1097: Missing.

Show »
Length:313
Mass (Da):35,048
Checksum:i3B0F550EBD70F79D
GO
Isoform 3 (identifier: Q13127-3) [UniParc]FASTAAdd to basket
Also known as: N4

The sequence of this isoform differs from the canonical sequence as follows:
     329-329: E → W
     330-1097: Missing.

Show »
Length:329
Mass (Da):36,972
Checksum:iAD25D9BAC94FCAF7
GO
Isoform 4 (identifier: Q13127-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-326: Missing.

Show »
Length:1,074
Mass (Da):119,083
Checksum:i7D5F7CBD2C74EC0A
GO

Sequence cautioni

The sequence AAA98503 differs from that shown. Reason: Frameshift at positions 188, 198, 202, 212 and 1087.Curated
The sequence AAC50114 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAC50115 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH38985 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAD92987 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti295V → L in AAC50114 (PubMed:7871435).Curated1
Sequence conflicti596 – 599PQKE → SRNS in AAC50115 (PubMed:7871435).Curated4
Sequence conflicti630P → L in AAB17211 (PubMed:7697725).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076333160R → P in WT6; inhibits transcriptional repression activity. 1 Publication1
Natural variantiVAR_076334290N → Y in WT6; inhibits transcriptional repression activity. 1 Publication1
Natural variantiVAR_076335322H → R in WT6; inhibits transcriptional repression activity. 1 PublicationCorresponds to variant dbSNP:rs869025312EnsemblClinVar.1
Natural variantiVAR_076336412H → Q in WT6. 1 Publication1
Natural variantiVAR_079529437 – 1097Missing in GINGF5. 1 PublicationAdd BLAST661
Natural variantiVAR_029795626V → I1 PublicationCorresponds to variant dbSNP:rs2228991Ensembl.1
Natural variantiVAR_029796692E → D. Corresponds to variant dbSNP:rs2227902Ensembl.1
Natural variantiVAR_029797762K → Q. Corresponds to variant dbSNP:rs2227903Ensembl.1
Natural variantiVAR_029798797P → L1 PublicationCorresponds to variant dbSNP:rs3796529Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022064301 – 313ERPYK…CPYSS → KRSFLVHKFSSLF in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_022067304 – 326Missing in isoform 4. CuratedAdd BLAST23
Alternative sequenceiVSP_022065314 – 1097Missing in isoform 2. 1 PublicationAdd BLAST784
Alternative sequenceiVSP_022066329E → W in isoform 3. Curated1
Alternative sequenceiVSP_022068330 – 1097Missing in isoform 3. CuratedAdd BLAST768

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22314 mRNA Translation: AAB17211.1
U13877 mRNA Translation: AAC50114.1 Different initiation.
U13879 mRNA Translation: AAC50115.1 Different initiation.
U22680 mRNA Translation: AAA98503.1 Frameshift.
AB209750 mRNA Translation: BAD92987.1 Different initiation.
AC069307 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX05517.1
BC038985 mRNA Translation: AAH38985.1 Sequence problems.
BC132859 mRNA Translation: AAI32860.1
BC136491 mRNA Translation: AAI36492.1
CCDSiCCDS3509.1 [Q13127-1]
PIRiA56138
I38754
I38755
RefSeqiNP_001180437.1, NM_001193508.1 [Q13127-1]
NP_005603.3, NM_005612.4 [Q13127-1]
XP_011532703.1, XM_011534401.2 [Q13127-1]
UniGeneiHs.307836

Genome annotation databases

EnsembliENST00000309042; ENSP00000311816; ENSG00000084093 [Q13127-1]
ENST00000619101; ENSP00000484836; ENSG00000084093 [Q13127-1]
GeneIDi5978
KEGGihsa:5978
UCSCiuc003hch.4 human [Q13127-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiREST_HUMAN
AccessioniPrimary (citable) accession number: Q13127
Secondary accession number(s): A2RUE0
, B9EGJ0, Q12956, Q12957, Q13134, Q59ER1, Q8IWI3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: May 18, 2010
Last modified: May 23, 2018
This is version 164 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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