Biology:SAP30

Generic protein structure example

Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.

Function

Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3A, SAP18, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This complex is active in deacetylating core histone octamers, but inactive in deacetylating nucleosomal histones. A pseudogene of this gene is located on chromosome 3.

Mammals have one paralog of SAP30, named SAP30-like (SAP30L), which shares 70% sequence identity with SAP30. SAP30 and SAP30L together constitute a well-conserved SAP30 protein family. Also SAP30L interacts with several components of the Sin3A corepressor complex and induces transcriptional repression via recruitment of Sin3A and histone deacetylases.

Proteins of the SAP30 family (SAP30 proteins) have a functional nucleolar localization signal and they are able to target Sin3A to the nucleolus. SAP30 proteins have sequence-independent contact with DNA by their N-terminal zinc-dependent module and their acidic central region contributes to histone and nucleosome interactions. The DNA binding of SAP30 proteins is regulated by the nuclear signalling lipids, phosphoinositides (PI). SAP30 proteins provide the first example in which the DNA and PIs seem to stand in a mutually antagonizing interrelationship in regard to their interaction with zinc finger proteins and thus exemplifies the molecular mechanism how these lipids can contribute for gene regulation.

Interactions

SAP30 has been shown to interact with:

• HDAC1,
• Histone deacetylase 2,
• ING1 and
• Nuclear receptor co-repressor 1,
• RBBP4,
• RBBP7,
• SIN3A, and
• YY1.

Further reading

• "Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3". Cell 80 (5): 767–76. Mar 1995. doi:10.1016/0092-8674(95)90355-0. PMID 7889570. 
• "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell 89 (3): 357–64. May 1997. doi:10.1016/S0092-8674(00)80216-0. PMID 9150135. 
• "SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex". Molecular Cell 1 (7): 1021–31. Jun 1998. doi:10.1016/S1097-2765(00)80102-1. PMID 9651585. 
• "SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors". Molecular Cell 2 (1): 33–42. Jul 1998. doi:10.1016/S1097-2765(00)80111-2. PMID 9702189. 
• "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell 95 (2): 279–89. Oct 1998. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534. 
• "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature 395 (6705): 917–21. Oct 1998. doi:10.1038/27699. PMID 9804427. 
• "CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex". Proceedings of the National Academy of Sciences of the United States of America 96 (1): 23–8. Jan 1999. doi:10.1073/pnas.96.1.23. PMID 9874765. 
• "Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin". Human Molecular Genetics 8 (9): 1647–55. Sep 1999. doi:10.1093/hmg/8.9.1647. PMID 10441327. 
• "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development 13 (15): 1924–35. Aug 1999. doi:10.1101/gad.13.15.1924. PMID 10444591. 
• "Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells". Journal of Virology 74 (20): 9637–45. Oct 2000. doi:10.1128/JVI.74.20.9637-9645.2000. PMID 11000236. 
• "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". The Journal of Biological Chemistry 275 (51): 40463–70. Dec 2000. doi:10.1074/jbc.M007864200. PMID 11013263. 
• "Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1". The Journal of Biological Chemistry 276 (9): 6817–24. Mar 2001. doi:10.1074/jbc.M007372200. PMID 11102443. 
• "Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex". The Journal of Biological Chemistry 276 (12): 8734–9. Mar 2001. doi:10.1074/jbc.M007664200. PMID 11118440. 
• "Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex". Molecular and Cellular Biology 21 (13): 4110–8. Jul 2001. doi:10.1128/MCB.21.13.4110-4118.2001. PMID 11390640. 
• "Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)". Molecular and Cellular Biology 22 (3): 835–48. Feb 2002. doi:10.1128/MCB.22.3.835-848.2002. PMID 11784859. 
• "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". The Journal of Biological Chemistry 277 (38): 35434–9. Sep 2002. doi:10.1074/jbc.M203455200. PMID 12124384. 
• "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1". Genes & Development 17 (7): 896–911. Apr 2003. doi:10.1101/gad.252103. PMID 12670868. 
• "Modulation of YY1 activity by SAP30". Biochemical and Biophysical Research Communications 306 (1): 267–75. Jun 2003. doi:10.1016/S0006-291X(03)00966-5. PMID 12788099. 
• "Loss of heterozygosity on chromosome 4q32-35 in sporadic basal cell carcinomas: evidence for the involvement of p33ING2/ING1L and SAP30 genes". Journal of Cutaneous Pathology 31 (4): 318–22. Apr 2004. doi:10.1111/j.0303-6987.2004.0187.x. PMID 15005689.