RBBP4

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; OMA:RBBP4 - orthologs
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 129,200,893 bp [2] End 129,229,163 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone bone marrow cells right testis left testis monocyte epithelium of colon appendix islet of Langerhans stromal cell of endometrium Top expressed in Paneth cell medial ganglionic eminence condyle vestibular membrane of cochlear duct fossa vas deferens primitive streak renal corpuscle abdominal wall fetal liver hematopoietic progenitor cell More reference expression data BioGPS n/a
Gene ontology Molecular function RNA polymerase II cis-regulatory region sequence-specific DNA binding ATP-dependent activity, acting on DNA histone binding histone deacetylase binding protein binding nucleosomal DNA binding histone deacetylase activity Cellular component NuRD complex ESC/E(Z) complex CAF-1 complex Sin3 complex nucleoplasm NURF complex nucleus cytosol protein-containing complex Biological process chromatin remodeling regulation of transcription, DNA-templated CENP-A containing chromatin assembly transcription, DNA-templated regulation of cell cycle DNA replication-dependent chromatin assembly DNA replication negative regulation of gene expression, epigenetic cell cycle negative regulation of cell population proliferation regulation of signal transduction by p53 class mediator histone deacetylation 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: 129.2 – 129.23 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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. Using 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, et al. (September 1993). "A retinoblastoma-binding protein related to a negative regulator of Ras in yeast". Nature. 364 (6438): 648–52. Bibcode:1993Natur.364..648Q. doi:10.1038/364648a0. PMID   8350924. S2CID   4303062.
6. Barak O, Lazzaro MA, Lane WS, et al. (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, et al. (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, et al. (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. Bibcode:1999PNAS...96.5280B. 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. Bibcode:1999PNAS...96.4983Y. 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, et al. (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. S2CID   28512341.
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. Bibcode:1999PNAS...96.4868G. doi: 10.1073/pnas.96.9.4868 . PMC   21783 . PMID   10220385.
17. You A, Tong JK, Grozinger CM, et al. (2001). "CoREST is an integral component of the CoREST- human histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1454–8. Bibcode:2001PNAS...98.1454Y. doi: 10.1073/pnas.98.4.1454 . PMC   29278 . PMID   11171972.
18. Hassig CA, Fleischer TC, Billin AN, et al. (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. S2CID   14233219.
19. Ng HH, Zhang Y, Hendrich B, et al. (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. S2CID   6147725.
20. 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.
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, 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. Bibcode:1998PNAS...95.3519H. doi: 10.1073/pnas.95.7.3519 . PMC   19868 . PMID   9520398.
23. 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.
24. Hakimi MA, Dong Y, Lane WS, et al. (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, et al. (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. Bibcode:1998Natur.395..917T. doi:10.1038/27699. PMID   9804427. S2CID   4355885.
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, et al. (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, 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.
29. Kuzmichev A, Zhang Y, Erdjument-Bromage H, et al. (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)]". Bethesda, MD: National Center for Biotechnology Information (NCBI) . Retrieved 2013-09-06.
• 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. S2CID   24768114.
• 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. Bibcode:1999PNAS...96.4868G. 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. Bibcode:1998PNAS...95.3519H. 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. S2CID   41855774.
• 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. Bibcode:1996Sci...272..408T. doi:10.1126/science.272.5260.408. PMID   8602529. S2CID   25717734.
• Tong JK, Hassig CA, Schnitzler GR, et al. (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. Bibcode:1998Natur.395..917T. doi:10.1038/27699. PMID   9804427. S2CID   4355885.
• 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. Bibcode:1998CBio....8...96V. doi: 10.1016/S0960-9822(98)70040-5 . PMID   9427644. S2CID   201273.
• 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. S2CID   1416453.
• 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. Bibcode:1999PNAS...96.4983Y. 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. S2CID   18786866.
• 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. S2CID   28512341.