RBBP4

Histone-binding protein RBBP4 (also known as RbAp48, or NURF55) is a protein that in humans is encoded by the RBBP4 gene.[5][6]

RBBP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2XU7, 3GFC, 4PBY, 4PBZ, 4PC0, 4R7A, 5FXY
Identifiers
Aliases	RBBP4, NURF55, RBAP48, lin-53, retinoblastoma binding protein 4, RB binding protein 4, chromatin remodeling factor
External IDs	OMIM: 602923 MGI: 1194912 HomoloGene: 21153 GeneCards: RBBP4
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p35.1 Start 32,651,142 bp[1] End 32,686,211 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.2 Start 129,307,100 bp[2] End 129,335,370 bp[2]
Gene ontology Molecular function • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • DNA-dependent ATPase activity • histone binding • histone deacetylase binding • GO:0001948 protein binding • nucleosomal DNA binding • histone deacetylase activity Cellular component • NuRD complex • ESC/E(Z) complex • CAF-1 complex • Sin3 complex • nucleoplasm • NURF complex • nuclear chromatin • cell nucleus • cytosol • macromolecular complex Biological process • chromatin assembly • chromatin remodeling • regulation of transcription, DNA-templated • CENP-A containing nucleosome assembly • transcription, DNA-templated • regulation of cell cycle • ATP-dependent chromatin remodeling • DNA replication-dependent nucleosome assembly • DNA replication • negative regulation of gene expression, epigenetic • cell cycle • DNA replication-independent nucleosome assembly • negative regulation of cell proliferation • regulation of signal transduction by p53 class mediator • histone deacetylation • covalent chromatin modification • response to growth hormone • negative regulation of G0 to G1 transition • chromatin organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5928	19646
Ensembl	ENSG00000162521	ENSMUSG00000057236
UniProt	Q09028	Q60972
RefSeq (mRNA)	NM_005610 NM_001135255 NM_001135256	NM_009030
RefSeq (protein)	NP_001128727 NP_001128728 NP_005601	NP_033056
Location (UCSC)	Chr 1: 32.65 – 32.69 Mb	Chr 4: 129.31 – 129.34 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a ubiquitously expressed nuclear protein that belongs to a highly conserved subfamily of WD-repeat proteins. It is present in protein complexes involved in histone acetylation and chromatin assembly. It is part of the Mi-2/NuRD complex that has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of corepressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of E2F-responsive genes.[7]

Clinical significance

A decrease of RbAp48 in the dentate gyrus (DG) of the hippocampus in the brain is suspected to be a main cause of memory loss in normal aging.[8] An age related decrease in RbAp48 is observed in the DG from human post-mortem tissue and also in mice. Furthermore, a gene knockin of a dominant negative form of RbAp48 of causes memory deficits in young mice similar to that observed in older mice. Finally lentiviral gene transfer to increase the expression of RbAp48 in the brain reverses memory deficits in older mice.[8]

RBBP4 works at least in part through the PKA-CREB1-CPB pathway.[8] Hence one possible therapeutic approach to restore age-related memory loss is the use of PKA-CREB1-CPB pathway stimulating drugs. It has previously been shown that dopamine D1/D5 agonists such as 6-Br-APB and SKF-38,393 that are positively coupled to adenylyl cyclase and the cAMP phosphodieserase inhibitor rolipram reduce memory defects in aged mice.[9]

Interactions

RBBP4 has been shown to interact with:

• BRCA1,[10]
• CREBBP,[11]
• GATAD2B,[12]
• HDAC1,[13][14][15][16][17][18][19][20][21][22][23]
• HDAC2,[13][21][24][25]
• HDAC3,[15]
• MTA2,[14][20]
• RB,[15][26][27]
• SAP30,[20][28][29] and
• SIN3A.[18][28]

References

1. GRCh38: Ensembl release 89: ENSG00000162521 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057236 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Qian YW, Wang YC, Hollingsworth RE Jr, Jones D, Ling N, Lee EY (September 1993). "A retinoblastoma-binding protein related to a negative regulator of Ras in yeast". Nature. 364 (6438): 648–52. doi:10.1038/364648a0. PMID 8350924.
6. Barak O, Lazzaro MA, Lane WS, Speicher DW, Picketts DJ, Shiekhattar R (November 2003). "Isolation of human NURF: a regulator of Engrailed gene expression". EMBO J. 22 (22): 6089–100. doi:10.1093/emboj/cdg582. PMC 275440. PMID 14609955.
7. "Entrez Gene: RBBP4 retinoblastoma-binding protein 4".
8. Pavlopoulos E, Jones S, Kosmidis S, Close M, Kim C, Kovalerchik O, Small SA, Kandel ER (August 2013). "Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48". Sci Transl Med. 5 (200): 200ra115. doi:10.1126/scitranslmed.3006373. PMC 4940031. PMID 23986399.
9. Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, Mansuy I, Hawkins RD, Kandel ER (April 1999). "Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 5280–5. doi:10.1073/pnas.96.9.5280. PMC 21855. PMID 10220457.
10. Yarden RI, Brody LC (1999). "BRCA1 interacts with components of the histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
11. Zhang Q, Vo N, Goodman RH (2000). "Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB". Mol. Cell. Biol. 20 (14): 4970–8. doi:10.1128/MCB.20.14.4970-4978.2000. PMC 85947. PMID 10866654.
12. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (2002). "Identification and functional characterization of the p66/p68 components of the MeCP1 complex". Mol. Cell. Biol. 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549.
13. Zhang Y, Dufau ML (2003). "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". J. Steroid Biochem. Mol. Biol. 85 (2–5): 401–14. doi:10.1016/S0960-0760(03)00230-9. PMID 12943729.
14. Yao YL, Yang WM (2003). "The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity". J. Biol. Chem. 278 (43): 42560–8. doi:10.1074/jbc.M302955200. PMID 12920132.
15. Nicolas E, Ait-Si-Ali S, Trouche D (2001). "The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein". Nucleic Acids Res. 29 (15): 3131–6. doi:10.1093/nar/29.15.3131. PMC 55834. PMID 11470869.
16. Grozinger CM, Hassig CA, Schreiber SL (1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
17. You A, Tong JK, Grozinger CM, Schreiber SL (2001). "CoREST is an integral component of the CoREST- human histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1454–8. doi:10.1073/pnas.98.4.1454. PMC 29278. PMID 11171972.
18. Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE (1997). "Histone deacetylase activity is required for full transcriptional repression by mSin3A". Cell. 89 (3): 341–7. doi:10.1016/S0092-8674(00)80214-7. PMID 9150133.
19. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. hdl:1842/684. PMID 10471499.
20. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
21. Zhang Y, Dufau ML (2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". J. Biol. Chem. 277 (36): 33431–8. doi:10.1074/jbc.M204417200. PMID 12091390.
22. Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL (1998). "A role for histone deacetylase activity in HDAC1-mediated transcriptional repression". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3519–24. doi:10.1073/pnas.95.7.3519. PMC 19868. PMID 9520398.
23. Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (1997). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell. 89 (3): 357–64. doi:10.1016/S0092-8674(00)80216-0. PMID 9150135.
24. Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R (2003). "A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes". J. Biol. Chem. 278 (9): 7234–9. doi:10.1074/jbc.M208992200. PMID 12493763.
25. Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. doi:10.1038/27699. PMID 9804427.
26. Qian YW, Lee EY (1995). "Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast". J. Biol. Chem. 270 (43): 25507–13. doi:10.1074/jbc.270.43.25507. PMID 7503932.
27. Nicolas E, Morales V, Magnaghi-Jaulin L, Harel-Bellan A, Richard-Foy H, Trouche D (2000). "RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein". J. Biol. Chem. 275 (13): 9797–804. doi:10.1074/jbc.275.13.9797. PMID 10734134.
28. Zhang Y, Sun ZW, Iratni R, Erdjument-Bromage H, Tempst P, Hampsey M, Reinberg D (1998). "SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex". Mol. Cell. 1 (7): 1021–31. doi:10.1016/S1097-2765(00)80102-1. PMID 9651585.
29. Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D (2002). "Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)". Mol. Cell. Biol. 22 (3): 835–48. doi:10.1128/MCB.22.3.835-848.2002. PMC 133546. PMID 11784859.

Further reading

• "RBBP4 retinoblastoma binding protein 4 [Homo sapiens (human)]". Home - Gene - NCBI. Bethesda, MD: National Center for Biotechnology Information (NCBI). Retrieved 2013-09-06. External link in |work= (help)
• Bauw G, Rasmussen HH, van den Bulcke M, et al. (1990). "Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes". Electrophoresis. 11 (7): 528–36. doi:10.1002/elps.1150110703. PMID 1699755.
• Grozinger CM, Hassig CA, Schreiber SL (1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
• Hassig CA, Tong JK, Fleischer TC, et al. (1998). "A role for histone deacetylase activity in HDAC1-mediated transcriptional repression". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3519–24. doi:10.1073/pnas.95.7.3519. PMC 19868. PMID 9520398.
• Marheineke K, Krude T (1998). "Nucleosome assembly activity and intracellular localization of human CAF-1 changes during the cell division cycle". J. Biol. Chem. 273 (24): 15279–86. doi:10.1074/jbc.273.24.15279. PMID 9614144.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Qian YW, Lee EY (1995). "Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast". J. Biol. Chem. 270 (43): 25507–13. doi:10.1074/jbc.270.43.25507. PMID 7503932.
• Rasmussen HH, van Damme J, Puype M, et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Taunton J, Hassig CA, Schreiber SL (1996). "A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p". Science. 272 (5260): 408–11. doi:10.1126/science.272.5260.408. PMID 8602529.
• Tong JK, Hassig CA, Schnitzler GR, et al. (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. doi:10.1038/27699. PMID 9804427.
• Verreault A, Kaufman PD, Kobayashi R, Stillman B (1998). "Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase". Curr. Biol. 8 (2): 96–108. doi:10.1016/S0960-9822(98)70040-5. PMID 9427644.
• Verreault A, Kaufman PD, Kobayashi R, Stillman B (1996). "Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4". Cell. 87 (1): 95–104. doi:10.1016/S0092-8674(00)81326-4. PMID 8858152.
• Wolffe AP, Urnov FD, Guschin D (2001). "Co-repressor complexes and remodelling chromatin for repression". Biochem. Soc. Trans. 28 (4): 379–86. doi:10.1042/0300-5127:0280379. PMID 10961924.
• Yarden RI, Brody LC (1999). "BRCA1 interacts with components of the histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
• Zhang Y, Ng HH, Erdjument-Bromage H, et al. (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
• Zhang Y, Iratni R, Erdjument-Bromage H, et al. (1997). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell. 89 (3): 357–64. doi:10.1016/S0092-8674(00)80216-0. PMID 9150135.
• Zhang Y, Sun ZW, Iratni R, et al. (1998). "SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex". Mol. Cell. 1 (7): 1021–31. doi:10.1016/S1097-2765(00)80102-1. PMID 9651585.
• Zhang Y, LeRoy G, Seelig HP, et al. (1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell. 95 (2): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534.
• Zhang Y, Dufau ML (2003). "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". J. Steroid Biochem. Mol. Biol. 85 (2–5): 401–14. doi:10.1016/S0960-0760(03)00230-9. PMID 12943729.