Reviewed, UniProtKB/Swiss-Prot Q09028 (RBBP4_HUMAN)

Names and origin

Protein names

Recommended name:
    Histone-binding protein RBBP4
Alternative name(s):
    Retinoblastoma-binding protein 4
      Short name=RBBP-4
    Retinoblastoma-binding protein p48
    Chromatin assembly factor 1 subunit C
      Short name=CAF-1 subunit C
    Chromatin assembly factor I p48 subunit
    CAF-I 48 kDa subunit
    CAF-I p48
    Nucleosome-remodeling factor subunit RBAP48

Gene names

Name:	RBBP4
Synonyms:	RBAP48

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex. Ref.20
Subunit structure	Interacts with SUV39H1 and HDAC7 By similarity. Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin. Subunit of the chromatin assembly factor 1 (CAF-1) complex, which is composed of RBBP4, CHAF1B and CHAF1A. Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex. The core HDAC complex may also associate with MTA2, MBD3, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylase complex (the NuRD complex). The NuRD complex may also interact with MBD3L1 and MBD3L2. Interacts with MTA1. Subunit of the PRC2/EED-EZH2 complex, which is composed of at least EED, EZH2, RBBP4, RBBP7 and SUZ12. The PRC2/EED-EZH2 complex may also associate with HDAC1. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. Part of the nucleosome remodeling factor (NURF) complex which consists of SMARCA1; BPTF; RBBP4 and RBBP7. Interacts with the viral protein-binding domain of the retinoblastoma protein (RB1). Interacts with SPEN/MINT. Interacts with BRCA1. Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2.
Subcellular location	Nucleus.
Sequence similarities	Belongs to the WD repeat RBAP46/RBAP48/MSI1 family. Contains 6 WD repeats.

Ontologies

Keywords
Biological process	Cell cycle DNA replication Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat WD repeat
Molecular function	Chromatin regulator Repressor
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW chromatin remodeling Ref.27 Inferred from direct assay. Source: HGNC negative regulation of cell proliferation Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.27 Inferred from direct assay. Source: HGNC
Molecular function	protein binding Ref.10 Ref.27 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASF1B	Q9NVP2	1	EBI-620823,EBI-1055650
HDAC1	Q13547	1	EBI-620823,EBI-301834

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 425	424	Histone-binding protein RBBP4		PRO_0000051186
Regions
	Repeat	122 – 155	34	WD 1
	Repeat	175 – 206	32	WD 2
	Repeat	225 – 256	32	WD 3
	Repeat	271 – 302	32	WD 4
	Repeat	315 – 346	32	WD 5
	Repeat	372 – 403	32	WD 6
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.6
	Cross-link	4		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.33
Experimental info
	Sequence conflict	7	1	Missing in BAD96499. Ref.4
	Sequence conflict	61	1	F → G in AAH15123. Ref.5
	Sequence conflict	405 – 425	21	AENIY…EGQGS → MELVLDH Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q09028-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B71E2D55A444C360	FASTA	425	47,656
	10 20 30 40 50 60 MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD 70 80 90 100 110 120 FSIHRLVLGT HTSDEQNHLV IASVQLPNDD AQFDASHYDS EKGEFGGFGS VSGKIEIEIK 130 140 150 160 170 180 INHEGEVNRA RYMPQNPCII ATKTPSSDVL VFDYTKHPSK PDPSGECNPD LRLRGHQKEG 190 200 210 220 230 240 YGLSWNPNLS GHLLSASDDH TICLWDISAV PKEGKVVDAK TIFTGHTAVV EDVSWHLLHE 250 260 270 280 290 300 SLFGSVADDQ KLMIWDTRSN NTSKPSHSVD AHTAEVNCLS FNPYSEFILA TGSADKTVAL 310 320 330 340 350 360 WDLRNLKLKL HSFESHKDEI FQVQWSPHNE TILASSGTDR RLNVWDLSKI GEEQSPEDAE 370 380 390 400 410 420 DGPPELLFIH GGHTAKISDF SWNPNEPWVI CSVSEDNIMQ VWQMAENIYN DEDPEGSVDP EGQGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A retinoblastoma-binding protein related to a negative regulator of Ras in yeast." Qian Y.-W., Wang Y.-C.J., Hollingsworth R.E. Jr., Jones D., Ling N., Lee E.Y.-H.P. Nature 364:648-652(1993) [PubMed: 8350924] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 134-158 AND 254-271.
[2]	"Molecular cloning and expression of two novel human cDNAs encoding proteins containing WD-40 repeats and sharing similarity to yeast MSI1 a negative regulation of the RAS-cAMP pathway." Nielsen M.S., Rasmussen H.H., Celis J.E., Leffers H. Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow, Brain, Eye and Uterus.
[6]	Bienvenut W.V. Submitted (FEB-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15 AND 297-304, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes." Bauw G., Rasmussen H.H., van den Bulcke M., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 11:528-536(1990) [PubMed: 1699755] [Abstract] Cited for: PROTEIN SEQUENCE OF 60-65; 144-160 AND 221-240. Tissue: Keratinocyte.
[8]	"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes." Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 13:960-969(1992) [PubMed: 1286667] [Abstract] Cited for: PROTEIN SEQUENCE OF 60-65; 144-160 AND 221-240. Tissue: Keratinocyte.
[9]	"Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4." Verreault A., Kaufman P.D., Kobayashi R., Stillman B. Cell 87:95-104(1996) [PubMed: 8858152] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, IDENTIFICATION IN THE CAF-1 COMPLEX, INTERACTION WITH HISTONE H4.
[10]	"Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex." Zhang Y., Iratni R., Erdjument-Bromage H., Tempst P., Reinberg D. Cell 89:357-364(1997) [PubMed: 9150135] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, IDENTIFICATION IN THE SIN3 HDAC COMPLEX.
[11]	"Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast." Qian Y.-W., Lee E.Y.-H.P. J. Biol. Chem. 270:25507-25513(1995) [PubMed: 7503932] [Abstract] Cited for: INTERACTION WITH RB1.
[12]	"A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p." Taunton J., Hassig C.A., Schreiber S.L. Science 272:408-411(1996) [PubMed: 8602529] [Abstract] Cited for: INTERACTION WITH HDAC1.
[13]	"The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities." Zhang Y., LeRoy G., Seelig H.-P., Lane W.S., Reinberg D. Cell 95:279-289(1998) [PubMed: 9790534] [Abstract] Cited for: IDENTIFICATION IN THE NURD COMPLEX.
[14]	"Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase." Verreault A., Kaufman P.D., Kobayashi R., Stillman B. Curr. Biol. 8:96-108(1998) [PubMed: 9427644] [Abstract] Cited for: INTERACTION WITH HISTONE H4.
[15]	"SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex." Zhang Y., Sun Z.-W., Iratni R., Erdjument-Bromage H., Tempst P., Hampsey M., Reinberg D. Mol. Cell 1:1021-1031(1998) [PubMed: 9651585] [Abstract] Cited for: IDENTIFICATION IN THE SIN3 HDAC COMPLEX.
[16]	"A role for histone deacetylase activity in HDAC1-mediated transcriptional repression." Hassig C.A., Tong J.K., Fleischer T.C., Owa T., Grable P.G., Ayer D.E., Schreiber S.L. Proc. Natl. Acad. Sci. U.S.A. 95:3519-3524(1998) [PubMed: 9520398] [Abstract] Cited for: INTERACTION WITH HDAC1.
[17]	"Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation." Zhang Y., Ng H.-H., Erdjument-Bromage H., Tempst P., Bird A., Reinberg D. Genes Dev. 13:1924-1935(1999) [PubMed: 10444591] [Abstract] Cited for: IDENTIFICATION IN THE NURD COMPLEX.
[18]	"BRCA1 interacts with components of the histone deacetylase complex." Yarden R.I., Brody L.C. Proc. Natl. Acad. Sci. U.S.A. 96:4983-4988(1999) [PubMed: 10220405] [Abstract] Cited for: INTERACTION WITH BRCA1.
[19]	"RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein." Nicolas E., Morales V., Magnaghi-Jaulin L., Harel-Bellan A., Richard-Foy H., Trouche D. J. Biol. Chem. 275:9797-9804(2000) [PubMed: 10734134] [Abstract] Cited for: INTERACTION WITH HDAC1 AND RB1.
[20]	"Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB." Zhang Q., Vo N., Goodman R.H. Mol. Cell. Biol. 20:4970-4978(2000) [PubMed: 10866654] [Abstract] Cited for: FUNCTION, INTERACTION WITH CREBBP.
[21]	"Sharp, an inducible cofactor that integrates nuclear receptor repression and activation." Shi Y., Downes M., Xie W., Kao H.-Y., Ordentlich P., Tsai C.-C., Hon M., Evans R.M. Genes Dev. 15:1140-1151(2001) [PubMed: 11331609] [Abstract] Cited for: INTERACTION WITH SPEN.
[22]	"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: 11102443] [Abstract] Cited for: IDENTIFICATION IN THE NURD COMPLEX.
[23]	"Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex." Skowyra D., Zeremski M., Neznanov N., Li M., Choi Y., Uesugi M., Hauser C.A., Gu W., Gudkov A.V., Qin J. J. Biol. Chem. 276:8734-8739(2001) [PubMed: 11118440] [Abstract] Cited for: IDENTIFICATION IN A SIN3 HDAC COMPLEX.
[24]	"Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein." Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D. Genes Dev. 16:2893-2905(2002) [PubMed: 12435631] [Abstract] Cited for: IDENTIFICATION IN THE PRC2/EED-EZH2 COMPLEX WITH EED; EZH2; RBBP7 AND SUZ12, TRANSIENT INTERACTION WITH HDAC1, METHYLTRANSFERASE ACTIVITY OF THE COMPLEX.
[25]	"Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)." Kuzmichev A., Zhang Y., Erdjument-Bromage H., Tempst P., Reinberg D. Mol. Cell. Biol. 22:835-848(2002) [PubMed: 11784859] [Abstract] Cited for: IDENTIFICATION IN MULTIPLE SIN3 HDAC COMPLEXES.
[26]	"Role of histone H3 lysine 27 methylation in Polycomb-group silencing." Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P., Jones R.S., Zhang Y. Science 298:1039-1043(2002) [PubMed: 12351676] [Abstract] Cited for: IDENTIFICATION IN THE PRC2/EED-EZH2 COMPLEX WITH AEBP2; EED; EZH2 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE COMPLEX.
[27]	"Isolation of human NURF: a regulator of Engrailed gene expression." Barak O., Lazzaro M.A., Lane W.S., Speicher D.W., Picketts D.J., Shiekhattar R. EMBO J. 22:6089-6100(2003) [PubMed: 14609955] [Abstract] Cited for: IDENTIFICATION IN THE NURF COMPLEX, MASS SPECTROMETRY.
[28]	"The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity." Yao Y.-L., Yang W.-M. J. Biol. Chem. 278:42560-42568(2003) [PubMed: 12920132] [Abstract] Cited for: INTERACTION WITH MTA1.
[29]	"MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex." Jiang C.-L., Jin S.-G., Pfeifer G.P. J. Biol. Chem. 279:52456-52464(2004) [PubMed: 15456747] [Abstract] Cited for: INTERACTION WITH MBD3L1.
[30]	"MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing." Jin S.-G., Jiang C.-L., Rauch T., Li H., Pfeifer G.P. J. Biol. Chem. 280:12700-12709(2005) [PubMed: 15701600] [Abstract] Cited for: INTERACTION WITH MBD3L2.
[31]	"LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes." Schmit F., Korenjak M., Mannefeld M., Schmitt K., Franke C., von Eyss B., Gagrica S., Haenel F., Brehm A., Gaubatz S. Cell Cycle 6:1903-1913(2007) [PubMed: 17671431] [Abstract] Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[32]	"Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence." Litovchick L., Sadasivam S., Florens L., Zhu X., Swanson S.K., Velmurugan S., Chen R., Washburn M.P., Liu X.S., DeCaprio J.A. Mol. Cell 26:539-551(2007) [PubMed: 17531812] [Abstract] Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[33]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-4, MASS SPECTROMETRY.
[34]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X74262 mRNA. Translation: CAA52321.1.
X71810 mRNA. Translation: CAA50685.1.
BT007309 mRNA. Translation: AAP35973.1.
AK222779 mRNA. Translation: BAD96499.1.
BC003092 mRNA. Translation: AAH03092.1.
BC015123 mRNA. Translation: AAH15123.1.
BC053904 mRNA. Translation: AAH53904.1.
BC075836 mRNA. Translation: AAH75836.1.

IPI

IPI00328319.

PIR

S36112.

RefSeq

NP_001128727.1.
NP_005601.1.

UniGene

Hs.647652

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GFC	X-ray	2.30	A	1-425	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q09028. 20 interactions.

PTM databases

PhosphoSite

Q09028.

2-D gel databases

Aarhus/Ghent-2DPAGE

8303. IEF.
9306. IEF.

Proteomic databases

PRIDE

Q09028.

Genome annotation databases

Ensembl

ENSG00000162521. Homo sapiens. [Contig view]

GeneID

5928.

UCSC

uc001bvr.1. human.

Organism-specific databases

GeneCards

GC01P032889.
GC05M014849.

H-InvDB

HIX0000377.

HGNC

HGNC:9887. RBBP4.

HPA

CAB006264.

MIM

602923. gene.

PharmGKB

PA34251.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q09028.

HOVERGEN

Q09028.

OMA

Q09028. DRRLHVW.

Enzyme and pathway databases

Pathway_Interaction_DB

hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpress

Q09028.

Bgee

Q09028.

CleanEx

HS_RBBP4.

GermOnline

ENSG00000162521. Homo sapiens.

Family and domain databases

InterPro

IPR015943. WD40/YVTN_repeat-like.
IPR001680. WD40_repeat.
IPR019782. WD40_repeat_2.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_region.
IPR019781. WD40_repeat_sg.
[Graphical view]

Gene3D

G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.

Pfam

PF00400. WD40. 5 hits.
[Graphical view]

ProDom

PD000018. WD40. 3 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00320. WD40. 6 hits.
[Graphical view]

PROSITE

PS00678. WD_REPEATS_1. 3 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

23094.

SOURCE

Search...

Entry information

Entry name

RBBP4_HUMAN

Accession

Primary (citable) accession number: Q09028
Secondary accession number(s): P31149, Q53H02, Q96BV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 102 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)