Q9UKL0 (RCOR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
REST corepressor 1

Alternative name(s):
Protein CoREST

Gene names

Name:	RCOR1
Synonyms:	KIAA0071, RCOR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	482 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Ref.5 Ref.7 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14
Subunit structure	Interacts directly with GFI1 and GFI1B in a RCOR/GFI/KDM1A/HDAC complex By similarity. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with REST. Interacts with the SMARCE1/BAF57, suggesting that the BHC complex may recruit the ATP-dependent chromatin-remodeling SWI-SNF complex. Interacts with herpes virus HSV-1 ICP0 protein; the interaction leads to the disruption of the BHC complex, thereby preventing the BHC complex from repressing transcription of viral genes. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15
Subcellular location	Nucleus. Note: Upon infection by HSV-1, it is partially translocated into the cytoplasm in an HSV-1-dependent manner. Ref.4 Ref.15
Tissue specificity	Ubiquitously expressed. Ref.1
Domain	The SANT domains may bridge the nucleosomal substrates and the demethylase KDM1A. Ref.13
Post-translational modification	Phosphorylated by HSV-1 protein kinases in case of infection. Ref.15
Sequence similarities	Belongs to the CoREST family. Contains 1 ELM2 domain. Contains 2 SANT domains.
Sequence caution	The sequence AAH64495.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Domain	Coiled coil Repeat
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome erythrocyte differentiation Inferred from electronic annotation. Source: Compara histone H4 deacetylation Inferred from direct assay PubMed 17555596. Source: UniProtKB positive regulation of megakaryocyte differentiation Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	transcriptional repressor complex Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay Ref.1. Source: UniProtKB chromatin binding Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from direct assay PubMed 17555596. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KDM1A	O60341	2	EBI-926563,EBI-710124
SMARCE1	Q969G3-1	2	EBI-926563,EBI-455091
SMARCE1	Q969G3-2	4	EBI-926563,EBI-455096

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 482

482

REST corepressor 1

PRO_0000226773

Regions

Domain

100 – 186

87

ELM2

Domain

187 – 238

52

SANT 1

Domain

378 – 429

52

SANT 2

Region

75 – 254

180

Interaction with HDAC1

Region

293 – 381

89

Interaction with KDM1A

Coiled coil

241 – 270

30

Potential

Coiled coil

331 – 366

36

Potential

Compositional bias

18 – 74

57

Ala-rich

Amino acid modifications

Modified residue

124

1

Phosphoserine Ref.17 Ref.18 Ref.19

Modified residue

257

1

Phosphoserine Ref.16 Ref.18 Ref.19 Ref.21

Modified residue

457

1

Phosphoserine Ref.21

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

482

Helix Strand Turn

Details...

Helix

318 – 324

7

Beta strand

326 – 329

4

Helix

330 – 362

33

Turn

364 – 367

4

Helix

368 – 370

3

Helix

385 – 398

14

Helix

402 – 409

8

Beta strand

410 – 412

3

Helix

414 – 423

10

Turn

424 – 429

6

Helix

430 – 438

9

Sequences

	Sequence		Length	Mass (Da)
	Q9UKL0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 17541695A56CFFD3	FASTA	482	53,028
	10 20 30 40 50 60 MVEKGPEVSG KRRGRNNAAA SASAAAASAA ASAACASPAA TAASGAAASS ASAAAASAAA 70 80 90 100 110 120 APNNGQNKSL AAAAPNGNSS SNSWEEGSSG SSSDEEHGGG GMRVGPQYQA VVPDFDPAKL 130 140 150 160 170 180 ARRSQERDNL GMLVWSPNQN LSEAKLDEYI AIAKEKHGYN MEQALGMLFW HKHNIEKSLA 190 200 210 220 230 240 DLPNFTPFPD EWTVEDKVLF EQAFSFHGKT FHRIQQMLPD KSIASLVKFY YSWKKTRTKT 250 260 270 280 290 300 SVMDRHARKQ KREREESEDE LEEANGNNPI DIEVDQNKES KKEVPPTETV PQVKKEKHST 310 320 330 340 350 360 QAKNRAKRKP PKGMFLSQED VEAVSANATA ATTVLRQLDM ELVSVKRQIQ NIKQTNSALK 370 380 390 400 410 420 EKLDGGIEPY RLPEVIQKCN ARWTTEEQLL AVQAIRKYGR DFQAISDVIG NKSVVQVKNF 430 440 450 460 470 480 FVNYRRRFNI DEVLQEWEAE HGKEETNGPS NQKPVKSPDN SIKMPEEEDE APVLDVRYAS AS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CoREST: a functional corepressor required for regulation of neural-specific gene expression." Andres M.E., Burger C., Peral-Rubio M.J., Battaglioli E., Anderson M.E., Grimes J., Dallman J., Ballas N., Mandel G. Proc. Natl. Acad. Sci. U.S.A. 96:9873-9878(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH REST, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-295. Tissue: Lymph.
[3]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 87-482. Tissue: Bone marrow.
[4]	"The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex." Grimes J.A., Nielsen S.J., Battaglioli E., Miska E.A., Speh J.C., Berry D.L., Atouf F., Holdener B.C., Mandel G., Kouzarides T. J. Biol. Chem. 275:9461-9467(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH REST.
[5]	"Regulation of neuronal traits by a novel transcriptional complex." Ballas N., Battaglioli E., Atouf F., Andres M.E., Chenoweth J., Anderson M.E., Burger C., Moniwa M., Davie J.R., Bowers W.J., Federoff H.J., Rose D.W., Rosenfeld M.G., Brehm P., Mandel G. Neuron 31:353-365(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HDAC1 AND HDAC2.
[6]	"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1." Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H. J. Biol. Chem. 276:6817-6824(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE BHC COMPLEX WITH HDAC1 AND KDM1A.
[7]	"CoREST is an integral component of the CoREST-human histone deacetylase complex." You A., Tong J.K., Grozinger C.M., Schreiber S.L. Proc. Natl. Acad. Sci. U.S.A. 98:1454-1458(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE BHC COMPLEX WITH HDAC1; HDAC2 AND KDM1A.
[8]	"REST repression of neuronal genes requires components of the hSWI.SNF complex." Battaglioli E., Andres M.E., Rose D.W., Chenoweth J.G., Rosenfeld M.G., Anderson M.E., Mandel G. J. Biol. Chem. 277:41038-41045(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMARCE1.
[9]	"A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes." Hakimi M.-A., Bochar D.A., Chenoweth J., Lane W.S., Mandel G., Shiekhattar R. Proc. Natl. Acad. Sci. U.S.A. 99:7420-7425(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE BHC COMPLEX WITH HDAC1; HDAC2; HMG20B; KDM1A AND PHF21A.
[10]	"Corepressor-dependent silencing of chromosomal regions encoding neuronal genes." Lunyak V.V., Burgess R., Prefontaine G.G., Nelson C., Sze S.-H., Chenoweth J., Schwartz P., Pevzner P.A., Glass C., Mandel G., Rosenfeld M.G. Science 298:1747-1752(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	Erratum Lunyak V.V., Burgess R., Prefontaine G.G., Nelson C., Sze S.-H., Chenoweth J., Schwartz P., Pevzner P.A., Glass C., Mandel G., Rosenfeld M.G. Science 299:1663-1663(2003)
[12]	"A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes." Hakimi M.-A., Dong Y., Lane W.S., Speicher D.W., Shiekhattar R. J. Biol. Chem. 278:7234-7239(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE BHC COMPLEX WITH HDAC1; HDAC2; HMG20B; KDM1A; PHF21A; ZMYM2; ZNF217; ZMYM3; KIAA0182 AND GTF2I.
[13]	"Regulation of LSD1 histone demethylase activity by its associated factors." Shi Y.-J., Matson C., Lan F., Iwase S., Baba T., Shi Y. Mol. Cell 19:857-864(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN, INTERACTION WITH KDM1A.
[14]	"An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation." Lee M.G., Wynder C., Cooch N., Shiekhattar R. Nature 437:432-435(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KDM1A.
[15]	"Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells." Gu H., Liang Y., Mandel G., Roizman B. Proc. Natl. Acad. Sci. U.S.A. 102:7571-7576(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH HSV-1 ICP0.
[16]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-257, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-257, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257 AND SER-457, MASS SPECTROMETRY.
[22]	"Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase." Yang M., Gocke C.B., Luo X., Borek D., Tomchick D.R., Machius M., Otwinowski Z., Yu H. Mol. Cell 23:377-387(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.57 ANGSTROMS) OF 286-482 IN COMPLEX WITH KDM1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF155595 mRNA. Translation: AAF01498.1.
BC051003 mRNA. Translation: AAH51003.1.
BC064495 mRNA. Translation: AAH64495.1. Sequence problems.
D31888 mRNA. Translation: BAA06686.1.

IPI

IPI00008531.

RefSeq

NP_055971.2. NM_015156.3.

UniGene

Hs.510521.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IW5	X-ray	2.57	B	286-482	[»]
2UXN	X-ray	2.72	B	286-482	[»]
2UXX	X-ray	2.74	B	286-482	[»]
2V1D	X-ray	3.10	B	305-482	[»]
2X0L	X-ray	3.00	B	308-440	[»]
2XAF	X-ray	3.25	B	1-482	[»]
2XAG	X-ray	3.10	B	1-482	[»]
2XAH	X-ray	3.10	B	1-482	[»]
2XAJ	X-ray	3.30	B	1-482	[»]
2XAQ	X-ray	3.20	B	1-482	[»]
2XAS	X-ray	3.20	B	1-482	[»]
2Y48	X-ray	3.00	B	305-482	[»]

ProteinModelPortal

Q9UKL0.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35263N.

IntAct

Q9UKL0. 11 interactions.

MINT

MINT-3081566.

STRING

9606.ENSP00000262241.

PTM databases

PhosphoSite

Q9UKL0.

Polymorphism databases

DMDM

74762776.

Proteomic databases

PaxDb

Q9UKL0.

PeptideAtlas

Q9UKL0.

PRIDE

Q9UKL0.

Protocols and materials databases

DNASU

23186.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000570597; ENSP00000459789; ENSG00000089902.

GeneID

23186.

KEGG

hsa:23186.

UCSC

uc001ymb.3. human.

Organism-specific databases

CTD

23186.

GeneCards

GC14P103059.

HGNC

HGNC:17441. RCOR1.

HPA

CAB001956.

MIM

607675. gene.

neXtProt

NX_Q9UKL0.

PharmGKB

PA34305.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG326181.

HOGENOM

HOG000065784.

HOVERGEN

HBG079800.

InParanoid

Q9UKL0.

KO

K11829.

OMA

TVPQIKK.

OrthoDB

EOG49ZXPF.

PhylomeDB

Q9UKL0.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

Q9UKL0.

Bgee

Q9UKL0.

CleanEx

HS_RCOR1.

Genevestigator

Q9UKL0.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR000949. ELM2_dom.
IPR009057. Homeodomain-like.
IPR001005. SANT/Myb.
IPR017884. SANT_dom.
[Graphical view]

Pfam

PF01448. ELM2. 1 hit.
PF00249. Myb_DNA-binding. 1 hit.
[Graphical view]

SMART

SM00717. SANT. 2 hits.
[Graphical view]

SUPFAM

SSF46689. Homeodomain_like. 2 hits.

PROSITE

PS51156. ELM2. 1 hit.
PS51293. SANT. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UKL0.

GenomeRNAi

23186.

NextBio

44655.

SOURCE

Search...

Entry information

Entry name

RCOR1_HUMAN

Accession

Primary (citable) accession number: Q9UKL0
Secondary accession number(s): Q15044, Q6P2I9, Q86VG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.