Affinage

SAP30

Histone deacetylase complex subunit SAP30 · UniProt O75446

Length
220 aa
Mass
23.3 kDa
Annotated
2026-04-28
22 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAP30 is a constitutive core subunit of the Sin3/HDAC histone deacetylase corepressor complex that functions as a multivalent scaffold bridging sequence-specific transcription factors, chromatin, and additional corepressors to regulate diverse transcriptional programs. SAP30 binds the mSin3A PAH3 domain through a tripartite SID motif forming a ~1400 Ų interface (PMID:21676866), contains a CCCH zinc finger that directly binds double-stranded DNA and core histones (PMID:19015240, PMID:19223330), and recruits transcription factors (YY1, PBF) and corepressors (N-CoR, UHRF1) to the complex to mediate gene silencing at specific loci including IFN-beta and the MYC antagonist MXD4 (PMID:9702189, PMID:12788099, PMID:18225953, PMID:36302855). Beyond its canonical corepressor role, SAP30 forms a homodimer in which one subunit engages SIN3A/3B while the other recruits MLL1 through Phe186/200 residues, enabling a SIN3-independent transcriptional coactivation function that promotes breast tumor progression (PMID:37655663). SAP30 activity is regulated by nuclear phosphoinositide binding, which modulates its DNA binding and chromatin association (PMID:19015240), and its mRNA abundance is controlled by METTL14-mediated m6A modification recognized by YTHDF1 (PMID:40289460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Identification of SAP30 as a subunit of the Sin3/HDAC complex established it as an integral component of histone deacetylase-based transcriptional repression, resolving how this complex is assembled from multiple protein partners.

    Evidence Biochemical purification and co-immunoprecipitation of the human Sin3/HDAC complex with in vitro deacetylase activity assays

    PMID:9651585

    Open questions at the time
    • Specific contribution of SAP30 versus other subunits to complex assembly unknown
    • No structural data on SAP30 at this stage
  2. 1998 High

    Demonstration that SAP30 directly bridges N-CoR to the Sin3 complex and is selectively required for repression by specific nuclear receptors revealed it as a pathway-specific adaptor rather than a generic complex subunit.

    Evidence Co-IP, GST pulldown, reporter gene assays, and dominant-negative SAP30 experiments with estrogen receptor, Rpx, and Pit-1

    PMID:9702189

    Open questions at the time
    • Structural basis for selectivity among different nuclear receptor pathways not resolved
    • No genome-wide target identification
  3. 2003 Medium

    Mapping the SAP30–YY1 interaction showed how a sequence-specific transcription factor recruits HDAC1 indirectly through SAP30, establishing SAP30 as a bridge between DNA-bound factors and the deacetylase machinery.

    Evidence Yeast two-hybrid, GST pulldown, in vivo co-IP, reporter assays, and domain mapping of YY1 and SAP30

    PMID:12788099

    Open questions at the time
    • Endogenous genomic targets of YY1–SAP30 repression not identified
    • No structural resolution of the YY1–SAP30 interface
  4. 2007 Medium

    The discovery that PBF directly binds SAP30 to recruit SIN3A-HDAC1 extended the repertoire of transcription factors that use SAP30 as a HDAC-recruiting adaptor.

    Evidence Co-IP, GST pulldown, reporter assays with TSA inhibitor validation, domain mapping

    PMID:17897615

    Open questions at the time
    • Physiological gene targets of PBF–SAP30 repression unknown
    • No in vivo validation
  5. 2008 High

    Identification of SAP30's zinc-coordinating module as a DNA/histone-binding domain and its nuclear localization signal as a phosphoinositide-binding element revealed dual regulatory inputs — chromatin engagement and lipid-mediated nucleocytoplasmic control — previously unknown for any Sin3 complex subunit.

    Evidence EMSA, mutagenesis of zinc-coordinating residues, PI-binding assays, ChIP, confocal microscopy, reporter assays

    PMID:19015240

    Open questions at the time
    • Identity of specific nuclear PI species regulating SAP30 in vivo not determined
    • Functional distinction between SAP30 and SAP30L DNA binding not fully resolved
  6. 2008 High

    Demonstration that the Rift Valley fever virus NSs protein hijacks SAP30–YY1 to suppress IFN-beta transcription provided the first evidence that SAP30's bridging function is co-opted by a pathogen to subvert innate immunity.

    Evidence Yeast two-hybrid, co-IP, ChIP at IFN-beta promoter, confocal microscopy, recombinant virus with NSs deletion, mouse infection model

    PMID:18225953

    Open questions at the time
    • Whether SAP30 is required for IFN-beta repression in non-viral contexts not tested
    • No structure of NSs–SAP30 interface
  7. 2009 High

    The NMR solution structure of the SAP30 CCCH zinc finger as a novel treble-clef-like fold with strong dsDNA preference provided atomic-level understanding of how SAP30 engages chromatin.

    Evidence NMR structure determination with NMR-based ligand binding assays

    PMID:19223330

    Open questions at the time
    • No structure in complex with DNA
    • Specificity for particular DNA sequences not determined
  8. 2010 High

    CDK2-mediated phosphorylation of RBP1 was shown to release the SAP30·Sin3·HDAC complex from pRb, linking SAP30-dependent repression to cell cycle control at the G1-S transition.

    Evidence In vitro kinase assay, co-IP, phosphosite mutagenesis, cell cycle synchronization in MCF-7 cells

    PMID:21148318

    Open questions at the time
    • Direct consequences of complex release on E2F target gene expression not measured genome-wide
    • Whether SAP30 itself is phosphorylated during the cell cycle not addressed
  9. 2011 High

    The NMR structure of the mSin3A PAH3–SAP30 SID complex revealed a tripartite binding mode with a ~1400 Ų interface, explaining SAP30's constitutive association with Sin3 and its ability to simultaneously bind nucleic acids for rRNA gene silencing.

    Evidence NMR structure determination, ITC, NMR-based nucleic acid binding assays

    PMID:21676866

    Open questions at the time
    • rRNA gene silencing function not validated genome-wide
    • Whether SAP30 binding occludes other Sin3 PAH3 partners not tested
  10. 2022 High

    UHRF1 was shown to recruit SAP30 via its SRA domain (G572/F573) to repress MXD4, establishing a SAP30-dependent epigenetic axis essential for myeloid leukemia-initiating cell self-renewal.

    Evidence Co-IP, SRA domain mutagenesis, shRNA knockdown with rescue, ChIP, PDX mouse models

    PMID:36302855

    Open questions at the time
    • Full set of UHRF1–SAP30 co-regulated genes not defined
    • Whether UHRF1–SAP30 interaction depends on DNA methylation status not tested
  11. 2023 High

    Discovery of SAP30 homodimerization and MLL1 recruitment through Phe186/200 revealed a SIN3-independent coactivation function, overturning the view that SAP30 acts exclusively as a corepressor.

    Evidence Co-IP, Phe186/200 mutagenesis, ChIP, ATAC-seq, RNA Pol II ChIP-seq, breast cancer mouse models with rescue

    PMID:37655663

    Open questions at the time
    • How the balance between corepressor and coactivator functions is regulated is unknown
    • Whether the homodimer can simultaneously engage Sin3 and MLL1 at the same locus not resolved
  12. 2024 Medium

    SAP30 was found to transcriptionally regulate STX17, coupling its corepressor/coactivator function to autophagosome-lysosome fusion and autophagy in neuroblastoma.

    Evidence siRNA knockdown, overexpression, promoter-reporter assays, confocal microscopy, xenograft and PDX models

    PMID:40190355

    Open questions at the time
    • Whether SAP30 directly binds the STX17 promoter via its zinc finger or acts through an intermediary is unclear
    • Generalizability beyond neuroblastoma not tested
  13. 2025 Medium

    Two studies extended SAP30 biology in distinct directions: its SID-dependent deacetylation and suppression of foamy virus Tas transactivator, and its post-transcriptional regulation via METTL14-mediated m6A modification stabilized by YTHDF1 driving glycolysis and drug resistance in colorectal cancer.

    Evidence Co-IP, domain deletion, acetylation assays, promoter-reporter for PFV; m6A-RIP, siRNA/overexpression, glycolysis assays, xenograft for CRC

    PMID:40275313 PMID:40289460

    Open questions at the time
    • Endogenous glycolytic gene targets directly bound by SAP30 in CRC not identified by ChIP
    • Whether SAP30-mediated Tas deacetylation occurs in natural foamy virus infection unknown
    • Functional interplay between m6A-driven SAP30 upregulation and its coactivator vs. corepressor modes not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the switch between SAP30's corepressor (Sin3/HDAC) and coactivator (MLL1) functions is regulated at specific genomic loci, and whether phosphoinositide binding, post-translational modifications, or homodimerization dynamics govern this decision.
  • No genome-wide map of SAP30-bound loci distinguishing repressive from activating complexes
  • Post-translational modification landscape of SAP30 itself largely uncharacterized
  • No full-length structure of SAP30 in either complex context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0003677 DNA binding 3 GO:0008289 lipid binding 1 GO:0042393 histone binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
HDAC1MLL1NCOR1RBP1SAMSN1SIN3AUHRF1YY1
Complex memberships
SAP30 homodimer-MLL1 complexSin3/HDAC complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SAP30 is a component of the human Sin3/HDAC histone deacetylase complex that includes Sin3, HDAC1, HDAC2, RbAp46, and RbAp48. The complex is active in deacetylating core histone octamers but inactive on nucleosomal histones because RbAp46/48 cannot access nucleosomal histones. A yeast SAP30 homolog is functionally related to Sin3 and Rpd3. Biochemical purification, co-immunoprecipitation, in vitro histone deacetylase activity assay on core histones vs. nucleosomes Molecular cell High 9651585
1998 SAP30 binds directly to mSin3 and mediates transcriptional repression via histone deacetylases. SAP30 also binds the N-CoR corepressor and is required for N-CoR-mediated repression by antagonist-bound estrogen receptor and homeodomain protein Rpx, and for N-CoR suppression of Pit-1 transactivation, but is not required for N-CoR-mediated repression by unliganded retinoic acid receptor or thyroid hormone receptor. Co-immunoprecipitation, GST pulldown, reporter gene repression assays, dominant-negative SAP30 experiments Molecular cell High 9702189
2003 SAP30 associates with the transcription factor YY1 via the C-terminal 91 amino acids of SAP30 and the C-terminal segment (295-414) of YY1, enhancing YY1-mediated transcriptional repression in a dose-dependent manner. YY1, SAP30, and HDAC1 form a complex in vivo, providing a mechanism by which YY1 recruits HDAC1 indirectly through SAP30. Yeast two-hybrid, in vitro GST pulldown, in vivo co-immunoprecipitation, reporter gene assays, domain mapping Biochemical and biophysical research communications Medium 12788099
2008 SAP30 and SAP30L contain a zinc-coordinating structure necessary for direct binding to core histones and naked DNA, and for bending DNA. A sequence motif serving as a nuclear localization signal also functions as a phosphatidylinositol (PI)-binding element; binding of nuclear monophosphoinositides regulates DNA binding, chromatin association, repression activity, and nuclear-to-cytoplasmic translocation of SAP30L. In vitro DNA-binding assays, mutagenesis of zinc-coordinating residues, electrophoretic mobility shift assay, PI-binding assays, chromatin immunoprecipitation, confocal microscopy, reporter gene assays Molecular and cellular biology High 19015240
2008 RVFV nonstructural protein NSs interacts with SAP30, which in turn interacts with YY1. NSs, SAP30, and Sin3A-associated factors are recruited to the IFN-beta promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. Deletion of the NSs-SAP30 interaction domain abolished IFN-beta suppression and rendered the virus avirulent. Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, chromatin immunoprecipitation, reverse genetics (recombinant virus with NSs deletion), in vivo mouse infection PLoS pathogens High 18225953
2009 The solution structure of a novel CCCH zinc finger (ZnF) motif in SAP30 was determined by NMR. The ZnF adopts a fold with two beta-strands and two alpha-helices with a zinc organizing center remotely resembling the treble clef motif. NMR analysis showed the SAP30 ZnF has a strong preference for nucleic acid substrates, functioning as a double-stranded DNA-binding module. NMR structure determination, in silico surface analysis, NMR-based ligand binding assays Nucleic acids research High 19223330
2011 The solution structure of the mSin3A PAH3 domain in complex with the SAP30 Sin3 interaction domain (SID) was determined by NMR. The SAP30 SID binds to PAH3 via a tripartite structural motif (C-terminal helix targeting the canonical PAH hydrophobic cleft, two other helices, and an N-terminal extension), resulting in a large protein-protein interface (~1400 Ų) accounting for constitutive association. The mSin3A PAH3-SAP30 SID complex also binds nucleic acids, implicating the nucleolar localization sequence in rRNA gene silencing. NMR structure determination, isothermal titration calorimetry, NMR-based nucleic acid binding assays The Journal of biological chemistry High 21676866
2007 Papillomavirus binding factor (PBF/HDBP2) directly binds to SAP30 via amino acids 263-312 of PBF, and this interaction recruits the SIN3A-HDAC1 complex to mediate transcriptional repression. TSA (HDAC inhibitor) relieves PBF-mediated repression, demonstrating that HDAC activity is required. Co-immunoprecipitation, GST pulldown, reporter gene repression assays, TSA inhibitor treatment, domain mapping Archives of biochemistry and biophysics Medium 17897615
2010 RBP1 acts as a bridging protein between pRb and SAP30 (within the mSin3·HDAC complex). CDK2 phosphorylates RBP1 on serines 864 and 1007, destabilizing the RBP1-pRb interaction in vitro; concurrent phosphorylation of both RBP1 and pRb causes their dissociation, releasing the SAP30·mSin3·HDAC repressor complex from pRb to alleviate E2F transcriptional repression during G1-S progression. In vitro kinase assay, co-immunoprecipitation, mutagenesis of CDK phosphorylation sites, cell cycle synchronization, immunoprecipitation from MCF-7 cells The Journal of biological chemistry High 21148318
2010 In the nucleus, SLy2 (SAMSN1/HACS1) interacts with the SAP30/HDAC1 complex and regulates HDAC1 activity. Phosphorylated SLy2 is retained in the cytoplasm by 14-3-3 proteins, controlling its nuclear access and thus its regulation of the SAP30/HDAC1 complex. Co-immunoprecipitation, subcellular fractionation, protein interaction assays, HDAC activity assay The international journal of biochemistry & cell biology Medium 20478393
2022 UHRF1 directly interacts with SAP30 through two critical amino acids (G572 and F573) in its SRA domain to repress gene expression. This UHRF1-SAP30 interaction is required for myeloid leukemogenesis; depletion of either UHRF1 or SAP30 derepresses MXD4 (a MYC antagonist), suppressing leukemia-initiating cell self-renewal. Co-immunoprecipitation, mutagenesis of UHRF1 SRA domain, shRNA knockdown, rescue experiments, chromatin immunoprecipitation, PDX mouse model Cell research High 36302855
2023 SAP30 forms a homodimer with one subunit binding to SIN3A/3B and another recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. This SAP30-MLL1 interaction is required for SAP30-mediated transcriptional coactivation (enhancing chromatin accessibility and RNA Pol II occupancy at promoters) and breast tumor progression, independent of the canonical SIN3-HDAC gene silencing function. Co-immunoprecipitation, mutagenesis of Phe186/200, chromatin immunoprecipitation, ATAC-seq, RNA Pol II ChIP-seq, breast cancer mouse models, rescue experiments The Journal of clinical investigation High 37655663
2024 SAP30 transcriptionally regulates STX17 (a SNARE protein required for autophagosome-lysosome fusion). Silencing SAP30 decreases STX17 expression, inhibits its translocation to the autophagic membrane, and blocks autophagosome-lysosome fusion, thereby inhibiting autophagy in neuroblastoma cells. siRNA knockdown, ectopic overexpression, reporter/promoter assays, western blotting, confocal microscopy, in vivo xenograft and PDX models Molecular therapy. Oncology Medium 40190355
2025 SAP30 interacts with the prototype foamy virus Tas transactivator protein and induces its deacetylation, thereby suppressing Tas-mediated transactivation of PFV LTR and internal promoters. The Sin3 interaction domain (SID) at the C-terminus of SAP30 is the critical domain for inhibiting PFV transcription. PFV infection also upregulates SAP30 via Tas-mediated enhancement of the SAP30 promoter. Co-immunoprecipitation, overexpression and knockdown experiments, promoter-reporter assays, acetylation assays, domain deletion analysis Cell & bioscience Medium 40275313
2025 SAP30 mRNA is upregulated in colorectal cancer via METTL14-mediated m6A modification of SAP30 mRNA, which is recognized and stabilized by the m6A reader YTHDF1. Elevated SAP30 promotes glycolysis (upregulating LDHA, HK1, HK2, GLUT1, GLUT4) and oxaliplatin resistance; SAP30 knockout impairs tumor growth in vivo. m6A methylation assays, RIP (RNA immunoprecipitation), siRNA/overexpression, glycolysis assays, in vivo xenograft, GLUT1 inhibitor rescue Journal of gastroenterology and hepatology Medium 40289460
2009 Phylogenetic and biochemical analysis shows that SAP30 has diverged functionally from its paralog SAP30L by accumulating mutations that attenuate association with the nuclear matrix. This function is mediated by a nuclear matrix association sequence consisting of a conserved C-terminal motif adjacent to a nucleolar localization signal (NoLS). Phylogenetic sequence analysis, biochemical nuclear matrix association assays BMC evolutionary biology Low 19566944

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. Molecular cell 250 9651585
1998 SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Molecular cell 187 9702189
2008 A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells. PLoS pathogens 175 18225953
2008 DNA-binding and -bending activities of SAP30L and SAP30 are mediated by a zinc-dependent module and monophosphoinositides. Molecular and cellular biology 49 19015240
2022 Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia. Cell research 34 36302855
2004 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 32 15005689
2011 Structure of the 30-kDa Sin3-associated protein (SAP30) in complex with the mammalian Sin3A corepressor and its role in nucleic acid binding. The Journal of biological chemistry 31 21676866
2003 Modulation of YY1 activity by SAP30. Biochemical and biophysical research communications 31 12788099
2010 Cyclin-dependent kinase-mediated phosphorylation of RBP1 and pRb promotes their dissociation to mediate release of the SAP30·mSin3·HDAC transcriptional repressor complex. The Journal of biological chemistry 21 21148318
2007 Papillomavirus binding factor binds to SAP30 and represses transcription via recruitment of the HDAC1 co-repressor complex. Archives of biochemistry and biophysics 20 17897615
2010 SLy2 targets the nuclear SAP30/HDAC1 complex. The international journal of biochemistry & cell biology 15 20478393
2009 Solution structure of a novel zinc finger motif in the SAP30 polypeptide of the Sin3 corepressor complex and its potential role in nucleic acid recognition. Nucleic acids research 14 19223330
2000 Mouse scrapie responsive gene 1 (Scrg1): genomic organization, physical linkage to sap30, genetic mapping on chromosome 8, and expression in neuronal primary cell cultures. Genomics 14 11087671
2020 Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2. Frontiers of medicine 12 32820380
2009 Phylogenetic analysis of the SAP30 family of transcriptional regulators reveals functional divergence in the domain that binds the nuclear matrix. BMC evolutionary biology 10 19566944
2023 SAP30 promotes breast tumor progression by bridging the transcriptional corepressor SIN3 complex and MLL1. The Journal of clinical investigation 8 37655663
2023 Reveal the correlation between hub hypoxia/immune-related genes and immunity and diagnosis, and the effect of SAP30 on cell apoptosis, ROS and MDA production in cerebral ischemic stroke. Aging 4 38154101
2025 The METTL14-YTHDF1-SAP30 Axis Promotes Glycolysis and Oxaliplatin Resistance in Colorectal Adenocarcinoma via m6A Modification. Journal of gastroenterology and hepatology 1 40289460
2025 SAP30 promotes clear cell renal cell carcinoma proliferation and inhibits apoptosis through the MT1G axis. European journal of medical research 0 40247376
2025 SAP30 deacetylates the Tas protein to inhibit PFV replication. Cell & bioscience 0 40275313
2024 SAP30, a novel autophagy regulatory gene in neuroblastoma. Molecular therapy. Oncology 0 40190355
2021 SAP30 Gene Is a Probable Regulator of Muscle Hypertrophy in Chickens. Frontiers in genetics 0 34646299