Affinage

SAP30

Histone deacetylase complex subunit SAP30 · UniProt O75446

Length
220 aa
Mass
23.3 kDa
Annotated
2026-06-10
22 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAP30 is a core subunit of the Sin3/HDAC histone deacetylase corepressor complex, where it associates with mSin3, HDAC1, HDAC2, and RbAp46/48 to mediate transcriptional repression through histone deacetylation (PMID:9651585, PMID:9702189). It binds the mSin3A PAH3 domain through a tripartite Sin3 interaction domain (SID) that buries an ~1400 Ų interface, accounting for its constitutive, high-affinity association with the complex (PMID:21676866). SAP30 functions as an adaptor that bridges the Sin3/HDAC machinery to diverse sequence-specific and corepressor partners — including N-CoR, where it is selectively required for repression by antagonist-bound estrogen receptor, Rpx, and Pit-1 (PMID:9702189); the transcription factor YY1, which recruits HDAC1 indirectly through SAP30 (PMID:12788099); RBP1, which tethers the complex to pRb to enforce E2F repression until CDK2 phosphorylation dissociates the bridge during G1-to-S progression (PMID:21148318); and UHRF1, which together with SAP30 represses the MYC antagonist MXD4 to sustain leukemia-initiating cell self-renewal (PMID:36302855). SAP30 carries a CCCH treble-clef zinc finger that directly binds naked DNA and core histones and bends DNA, with an embedded motif that doubles as a nuclear localization signal and a phosphoinositide-binding element regulating DNA binding, chromatin association, and nuclear-cytoplasmic shuttling (PMID:19015240, PMID:19223330). Beyond canonical silencing, SAP30 can act as a coactivator by homodimerizing so that one subunit engages SIN3 while the other recruits MLL1, enhancing chromatin accessibility and RNA Pol II occupancy at promoters driving cell motility and angiogenesis in breast cancer (PMID:37655663). SAP30 also transcriptionally controls STX17 to promote autophagosome-lysosome fusion and chemotherapy survival in neuroblastoma (PMID:40190355), and its own mRNA is upregulated by METTL14-deposited m6A read by YTHDF1, driving glycolysis and oxaliplatin resistance (PMID:40289460). It is additionally exploited or deployed in viral transcriptional control, connecting Rift Valley fever virus NSs to Sin3A/N-CoR/HDAC repression of the IFN-beta promoter via YY1 (PMID:18225953) and inhibiting foamy virus replication by deacetylating the Tas transactivator through its SID (PMID:40275313).

Mechanistic history

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

    Establishing SAP30 as a bona fide subunit of the Sin3/HDAC complex defined its core biochemical context as a histone deacetylase corepressor component.

    Evidence Biochemical purification, Co-IP, and in vitro histone deacetylase assays on the human Sin3/HDAC1/HDAC2/RbAp46/48 complex

    PMID:9651585

    Open questions at the time
    • Did not define which subunit confers substrate access or nucleosomal activity
    • SAP30's specific role within the complex left unresolved
  2. 1998 High

    Direct binding and functional assays showed SAP30 is required for a selective subset of corepressor-mediated repression events, framing it as an adaptor rather than a generic structural subunit.

    Evidence Cloning, Co-IP, and transcriptional repression/complementation assays with mSin3, N-CoR, and multiple transcription factors

    PMID:9702189

    Open questions at the time
    • Structural basis of selectivity for certain repressors not addressed
    • Mechanism distinguishing required vs. dispensable N-CoR pathways unknown
  3. 2003 Medium

    Identifying YY1 as a SAP30 partner explained how a sequence-specific factor recruits HDAC1 indirectly, mapping SAP30 as the recruitment bridge.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, and repression assays with domain mapping

    PMID:12788099

    Open questions at the time
    • Single lab
    • Genome-wide YY1/SAP30 co-target landscape not defined
  4. 2008 High

    Demonstrating direct DNA/histone binding via a zinc-coordinating motif, with phosphoinositide-regulated chromatin association and shuttling, established SAP30 as an active chromatin-engaging and regulatable module rather than a passive scaffold.

    Evidence In vitro DNA binding, zinc-chelation mutagenesis, PI-binding and subcellular localization assays on SAP30/SAP30L

    PMID:19015240

    Open questions at the time
    • Physiological lipid signals controlling shuttling in vivo not identified
    • Genomic DNA sequence specificity, if any, unresolved
  5. 2008 High

    Showing that RVFV NSs hijacks SAP30 to silence the IFN-beta promoter revealed how a viral protein exploits the SAP30-YY1-Sin3/HDAC axis for immune evasion.

    Evidence Co-IP, confocal colocalization, ChIP, and reverse-genetics NSs deletion virus

    PMID:18225953

    Open questions at the time
    • Whether other innate immune promoters are co-targeted not defined
  6. 2009 High

    Solving the NMR structure of the SAP30 CCCH zinc finger defined a novel treble-clef-like fold with a basic nucleic-acid-binding surface, providing the structural basis for its DNA-engaging activity.

    Evidence NMR solution structure with in silico surface analysis and NMR ligand-binding

    PMID:19223330

    Open questions at the time
    • No structure of the ZnF bound to a defined DNA target
    • Sequence preference of bound nucleic acids not determined
  7. 2010 High

    Demonstrating CDK2-driven phosphorylation of the RBP1 bridge that releases the Sin3/HDAC complex from pRb placed SAP30 within cell-cycle-regulated E2F repression.

    Evidence In vitro kinase assay, Co-IP, cell-cycle fractionation, and site-directed mutagenesis

    PMID:21148318

    Open questions at the time
    • Direct SAP30 contribution vs. RBP1-pRb axis not isolated
    • Single lab
  8. 2011 High

    The NMR structure of the PAH3-SID complex explained the constitutive, high-affinity tethering of SAP30 to mSin3A through a tripartite, large-interface interaction.

    Evidence NMR solution structure, NMR binding assays, and interface area calculation

    PMID:21676866

    Open questions at the time
    • Dynamics of SID engagement during complex assembly not captured
    • Single lab
  9. 2022 High

    Identifying the UHRF1-SAP30 complex repressing MXD4 to sustain leukemia-initiating cell self-renewal connected SAP30 to a defined oncogenic transcriptional program with epistatic validation.

    Evidence Reciprocal Co-IP, UHRF1 SRA-domain mutagenesis, knockdown/MXD4-rescue, and in vivo leukemia model

    PMID:36302855

    Open questions at the time
    • Whether repression here uses the canonical Sin3/HDAC enzymatic output not dissected
    • Single lab
  10. 2023 High

    Demonstrating a SAP30 homodimer that bridges SIN3 and MLL1 to open chromatin redefined SAP30 as capable of coactivation independent of its silencing function.

    Evidence Co-IP, Phe186/200 mutagenesis, ATAC-seq, RNA Pol II ChIP, and in vivo mouse tumor models

    PMID:37655663

    Open questions at the time
    • Signals that switch SAP30 between repressor and coactivator modes unknown
    • Single lab
  11. 2025 Medium

    Linking SAP30 to STX17 transcription tied it to autophagosome-lysosome fusion and chemotherapy survival, extending its role beyond classical chromatin output.

    Evidence siRNA knockdown, overexpression, autophagy flux assays, and PDX xenografts in neuroblastoma

    PMID:40190355

    Open questions at the time
    • Whether SAP30 binds the STX17 promoter directly not shown
    • Single lab
  12. 2025 Medium

    Showing METTL14/YTHDF1 m6A control of SAP30 mRNA placed its own expression under post-transcriptional regulation driving glycolysis and drug resistance.

    Evidence m6A-seq/MeRIP, knockdown/overexpression, glycolysis assays, and in vivo xenograft in colorectal cancer

    PMID:40289460

    Open questions at the time
    • Downstream SAP30 target genes mediating glycolysis not defined
    • Single lab
  13. 2025 Medium

    Demonstrating SAP30-mediated deacetylation of the foamy virus Tas transactivator via its SID showed SAP30 can restrict viral transcription, contrasting its pro-viral role in RVFV.

    Evidence Co-IP, overexpression/knockdown, promoter-reporter assays, and domain-deletion mapping

    PMID:40275313

    Open questions at the time
    • Direct deacetylase responsible for Tas modification not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SAP30 is toggled between Sin3/HDAC-dependent repression and MLL1-dependent coactivation, and which signals dictate context-specific target selection, remains unresolved.
  • No structural/biochemical account of the repressor-to-coactivator switch
  • Genome-wide direct binding map across cell contexts lacking
  • Physiological signals controlling PI-regulated shuttling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2 GO:0008289 lipid binding 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
HDAC1MLL1NCOR1RBBP4RBP1SIN3AUHRF1YY1
Complex memberships
N-CoR corepressor complexSAP30-SIN3-MLL1 coactivator complexSin3/HDAC corepressor complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SAP30 is a component of the human histone deacetylase complex containing Sin3, HDAC1, HDAC2, RbAp46, and RbAp48. The complex is active in deacetylating core histone octamers but inactive on nucleosomal histones due to the inability of RbAp46/RbAp48 to access nucleosomal histones. A yeast SAP30 homolog was also identified as functionally related to Sin3 and Rpd3. Biochemical purification, Co-IP, in vitro histone deacetylase activity assay Molecular cell High 9651585
1998 SAP30 directly binds 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, the homeodomain protein Rpx, and POU domain protein Pit-1, but is not required for N-CoR-mediated repression by unliganded retinoic acid receptor or thyroid hormone receptor. Cloning, Co-IP, transcriptional repression assays, functional complementation assays Molecular cell High 9702189
2003 SAP30 interacts with the transcription factor YY1 via the C-terminal segment of YY1 (residues 295–414) and the C-terminal 91 amino acids of SAP30, enhancing YY1-mediated repression in a dose-dependent manner. YY1, SAP30, and HDAC1 form a complex in vivo, indicating YY1 recruits HDAC1 indirectly through SAP30. Yeast two-hybrid screening, in vitro GST pulldown, co-immunoprecipitation, transcriptional repression assay Biochemical and biophysical research communications Medium 12788099
2008 RVFV nonstructural protein NSs interacts with SAP30, which connects NSs to Sin3A/NCoR/HDAC repressor complexes and to YY1. NSs, SAP30, and Sin3A-associated factors are recruited to the IFN-beta promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation of IFN-beta. Deletion of the NSs domain that interacts with SAP30 rendered the virus unable to inhibit the IFN response. Co-IP, confocal microscopy colocalization, chromatin immunoprecipitation (ChIP), reverse genetics deletion mutant virus PLoS pathogens High 18225953
2008 SAP30 (and SAP30L) can directly bind core histones and naked DNA. A zinc-coordinating structure is required for DNA binding, which causes DNA bending. A sequence motif functioning as a nuclear localization signal also acts as a phosphatidylinositol (PI)-binding element; binding of specific nuclear monophosphoinositides regulates DNA binding, chromatin association, repression activity, and nuclear-to-cytoplasmic translocation of SAP30L. In vitro DNA binding assays, zinc chelation mutagenesis, PI binding assays, chromatin association assays, subcellular fractionation/localization Molecular and cellular biology High 19015240
2009 The solution structure of a novel CCCH zinc finger (ZnF) motif in SAP30 was determined by NMR. The fold comprises two beta-strands and two alpha-helices with a zinc organizing center resembling the treble clef motif. The conserved basic surface of the ZnF shows strong preference for nucleic acid substrates by NMR-based ligand analysis. NMR solution structure determination, in silico surface analysis, NMR-based ligand binding assay Nucleic acids research High 19223330
2007 Papillomavirus binding factor (PBF/HDBP2) directly binds SAP30 via amino acids 263–312 of PBF. This interaction recruits the mSIN3A-HDAC1 complex to repress HPV transcription; TSA treatment (HDAC inhibitor) relieved PBF-mediated repression. Co-IP, domain mapping, transcriptional repression assay, TSA inhibitor treatment Archives of biochemistry and biophysics Medium 17897615
2010 RBP1 binds to SAP30 (as part of the mSin3·HDAC complex) and to pRb, acting as a bridging protein. CDK2 phosphorylates RBP1 on serines 864 and 1007, destabilizing the RBP1–pRb interaction in vitro. Concurrent phosphorylation of both RBP1 and pRb by CDK2 leads to their dissociation, thereby releasing the mSin3·HDAC transcriptional repressor complex from pRb and alleviating E2F repression during G1-to-S phase progression. In vitro kinase assay, Co-IP, cell cycle fractionation, site-directed mutagenesis The Journal of biological chemistry High 21148318
2010 SLy2 (HACS1/NASH1/SAMSN1) interacts with the SAP30/HDAC1 complex in the nucleus and regulates HDAC1 activity. 14-3-3 proteins control nucleo-cytoplasmic shuttling of SLy2 by retaining phosphorylated SLy2 in the cytoplasm, modulating its nuclear access to SAP30/HDAC1. Co-IP, nuclear/cytoplasmic fractionation, HDAC1 activity assay The international journal of biochemistry & cell biology Medium 20478393
2011 The NMR solution structure of the complex formed by the mSin3A PAH3 domain and the SAP30 Sin3 interaction domain (SID) was determined. The SAP30 SID binds PAH3 via a tripartite motif: a C-terminal helix targets the canonical PAH hydrophobic cleft, while two other helices and an N-terminal extension target a discrete surface on PAH3 α2, α3, and α3' helices. The interface is ~1400 Ų, explaining the high-affinity constitutive association. The PAH3–SID complex can also bind nucleic acids by NMR. NMR solution structure, NMR binding assay, interface area calculation The Journal of biological chemistry High 21676866
2009 Phylogenetic and biochemical analysis showed that SAP30 has diverged from ancestral SAP30L by accumulating mutations that attenuate nuclear matrix association. This function is mediated by a nuclear matrix association sequence in the C-terminus adjacent to the nucleolar localization signal (NoLS). SAP30 shows reduced nuclear matrix association compared to SAP30L. Phylogenetic analysis combined with biochemical nuclear matrix association assay BMC evolutionary biology Medium 19566944
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 complex represses MXD4 (a MYC antagonist), maintaining leukemia-initiating cell self-renewal. Depletion of either UHRF1 or SAP30 de-represses MXD4, suppressing leukemogenesis, which can be rescued by MXD4 knockdown. Co-IP, site-directed mutagenesis of UHRF1, genetic knockdown/rescue experiments, chromatin analysis Cell research High 36302855
2023 SAP30 forms a homodimer in which one subunit binds SIN3A/3B while the other subunit recruits MLL1 through specific Phe186 and Phe200 residues in its transactivation domain. This SAP30–SIN3–MLL1 complex enhances chromatin accessibility and RNA polymerase II occupancy at promoters, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis in breast cancer. The canonical gene silencing function (via SIN3) was not required for tumor-promoting activity. Co-IP, site-directed mutagenesis (Phe186/200), chromatin accessibility assay (ATAC-seq), RNA Pol II ChIP, genetic loss-of-function in mouse tumor models The Journal of clinical investigation High 37655663
2025 SAP30 transcriptionally regulates STX17, a protein required for autophagosome-lysosome fusion. SAP30 knockdown reduces STX17 expression and inhibits its translocation to the autophagic membrane, blocking autophagosome-lysosome fusion. Conversely, SAP30 overexpression induces autophagy. SAP30-mediated autophagy promotes cell survival under chemotherapy in neuroblastoma. siRNA knockdown, ectopic overexpression, autophagy flux assays, in vivo PDX xenograft Molecular therapy. Oncology Medium 40190355
2025 SAP30 inhibits prototype foamy virus (PFV) replication by interacting with the viral Tas transactivator protein and inducing its deacetylation, thereby suppressing Tas-mediated transactivation of PFV LTR and IP promoters. The Sin3 interaction domain (SID) at the C-terminus of SAP30 is the critical domain for this inhibition. Co-IP, overexpression/knockdown assays, promoter-reporter transcriptional assays, domain deletion mapping Cell & bioscience Medium 40275313
2025 SAP30 inhibits MT1G transcription in clear cell renal cell carcinoma. Reduced MT1G impairs zinc delivery to p53 and attenuates MT1G-mediated inhibition of MDM2, destabilizing p53 activity and promoting tumor progression. Gene knockdown, gene expression analysis, functional p53 pathway assays European journal of medical research Low 40247376
2025 METTL14 upregulates SAP30 mRNA levels via m6A modification, stabilized by the m6A reader YTHDF1. Elevated SAP30 promotes glycolysis and oxaliplatin resistance in colorectal cancer cells. SAP30 knockout in vivo impairs tumor growth and reduces glycolytic markers. m6A-seq/MeRIP, knockdown/overexpression, glycolysis assays, in vivo tumor xenograft Journal of gastroenterology and hepatology Medium 40289460
2025 In Saccharomyces cerevisiae, deletion of SAP30 attenuated the biased non-allelic homologous recombination (NAHR) behavior at Chr7R, implicating yeast Sap30 in chromatin organization relevant to chromosomal rearrangement propensity. Yeast genetics, CNV assay, deletion mutation analysis bioRxivpreprint Low

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 176 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 36 36302855
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 33 21676866
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
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 15 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 9 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

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