Affinage

SAP130

Splicing factor 3B subunit 3 · UniProt Q15393

Length
1217 aa
Mass
135.6 kDa
Annotated
2026-06-10
13 papers in source corpus 3 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAP130 (Sin3A-associated protein 130) is a nuclear component of the SIN3A/HDAC chromatin-modifying complex that acts as a transcriptional repressor and promoter of cell proliferation (PMID:38172660). Its activity and abundance are controlled by SUMO1 modification at K794, K878, and K932; sumoylation destabilizes the protein and dampens its repressor function (PMID:38172660). Sumoylated SAP130 is recognized via the SIM motifs of FAF1, which drives its polyubiquitination and degradation and thereby mitigates SAP130-dependent transcriptional repression and proliferation; SUMO-site mutations abolish the FAF1 interaction without affecting Sin3A association or nuclear localization (PMID:38172660). In zebrafish, sap130a is required for Second Heart Field cell accretion and cardiomyocyte maturation during ventricular development, and it interacts genetically with hdac1, anchoring its developmental role within the SIN3A/HDAC1 complex (PMID:37711853, PMID:37034673).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2023 Medium

    Whether SAP130 has an essential developmental function in vivo was unresolved; loss-of-function in zebrafish established a specific requirement in cardiac morphogenesis.

    Evidence sap130a knockout with light-sheet imaging of cardiac output, SHF lineage tracing, and transcriptome profiling

    PMID:37034673 PMID:37711853

    Open questions at the time
    • Does not define the direct transcriptional targets controlled by sap130a in the heart
    • Mammalian developmental requirement not addressed
  2. 2023 Medium

    It was unclear whether SAP130's developmental role operates through the SIN3A/HDAC complex; genetic epistasis placed it functionally with hdac1.

    Evidence hdac1/sap130a double-mutant analysis with cardiac phenotype scoring in zebrafish

    PMID:37711853

    Open questions at the time
    • Genetic interaction does not establish a direct biochemical contact in the cardiac context
    • Other complex subunits not tested
  3. 2024 Medium

    How SAP130 stability and repressor activity are regulated was unknown; SUMO1 modification at three lysines was identified as a negative regulatory mark.

    Evidence In vitro and in vivo sumoylation assays with K→A mutagenesis, protein-stability/pulse-chase, and reporter assays

    PMID:38172660

    Open questions at the time
    • Single lab, no independent replication
    • SUMO E3 ligase responsible not identified
  4. 2024 Medium

    The functional consequence of SAP130 sumoylation was undefined; FAF1 was shown to read the SUMO mark and target SAP130 for ubiquitin-dependent degradation.

    Evidence Yeast two-hybrid, reciprocal co-IP, ubiquitination assay, and reporter assays with SUMO-site and SIM-dependent readouts

    PMID:38172660

    Open questions at the time
    • Single lab, no independent replication
    • E3 ubiquitin ligase mediating degradation not identified
    • Physiological context where FAF1 regulates SAP130 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SUMO-dependent FAF1 turnover of SAP130 connects to its developmental role in the SIN3A/HDAC1 complex remains unresolved.
  • No link drawn between the sumoylation/FAF1 axis and cardiac SHF function
  • Direct gene targets of the SAP130-containing complex not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-4839726 Chromatin organization 2 R-HSA-1266738 Developmental Biology 1
Partners
FAF1HDAC1SIN3ASUMO1
Complex memberships
SIN3A/HDAC complex

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 SAP130 (Sin3A-associated protein 130) is sumoylated by SUMO1 at lysine residues K794, K878, and K932, both in vitro and in vivo. Mutation of these three SUMO-accepting lysines abolished SAP130 interaction with FAF1 but did not affect SAP130 association with Sin3A or its nuclear localization. In vitro sumoylation assay, in vivo sumoylation (transfection), site-directed mutagenesis (K→A mutations), co-immunoprecipitation BMC molecular and cell biology Medium 38172660
2024 FAF1 interacts with sumoylated SAP130 (via FAF1's SIM motifs) and promotes SAP130 polyubiquitination and degradation in a sumoylation-dependent manner. FAF1 binding mitigates SAP130's transcriptional repressor activity and its cell proliferation-promoting function. Yeast two-hybrid screening (identification), co-immunoprecipitation, ubiquitination assay, transient transfection overexpression/knockdown, transcriptional reporter assay BMC molecular and cell biology Medium 38172660
2024 SUMO1-modified SAP130 is less stable than unmodified SAP130; sumoylation-deficient SAP130 mutants showed enhanced transcriptional repression and attenuated promotion of cell growth, indicating that sumoylation negatively regulates SAP130's repressor function and stability. Site-directed mutagenesis (SUMO-site mutants), pulse-chase/protein stability assay, transcriptional reporter assay, cell proliferation assay BMC molecular and cell biology Medium 38172660
2023 Zebrafish sap130a, ortholog of Sin3A-associated protein 130, is required for Second Heart Field (SHF) cell accretion to the growing ventricle and subsequent cardiomyocyte maturation; loss of sap130a results in smaller ventricle size and reduced cardiac output. Loss-of-function genetic mutant (sap130a knockout), confocal light sheet imaging of cardiac output, lineage tracing of SHF cells, transcriptome profiling Frontiers in cell and developmental biology Medium 37034673 37711853
2023 Genetic interaction between hdac1 and sap130a in zebrafish: double mutants show increased incidence of small ventricles, placing SAP130 functionally within the SIN3A/HDAC1 chromatin-modifying complex during cardiogenesis. Genetic epistasis (double mutant analysis), cardiac phenotype scoring Frontiers in cell and developmental biology Medium 37711853

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/Mincle signaling in acute kidney injury. Cell death & disease 35 34556635
2008 Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome. BMC biochemistry 34 18173839
2024 SAP130 released by ferroptosis tubular epithelial cells promotes macrophage polarization via Mincle signaling in sepsis acute kidney injury. International immunopharmacology 32 38320352
2009 A mutation in teg-4, which encodes a protein homologous to the SAP130 pre-mRNA splicing factor, disrupts the balance between proliferation and differentiation in the C. elegans germ line. Mechanisms of development 27 19368799
2001 Mutation in the prp12+ gene encoding a homolog of SAP130/SF3b130 causes differential inhibition of pre-mRNA splicing and arrest of cell-cycle progression in Schizosaccharomyces pombe. RNA (New York, N.Y.) 24 11350031
2024 SAP130 mediates crosstalk between hepatocyte ferroptosis and M1 macrophage polarization in PFOS-induced hepatotoxicity. The Science of the total environment 17 39163934
2013 Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130). Biology open 9 23951410
2021 Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130). Cells 5 33800128
2023 Sin3a associated protein 130 kDa, sap130, plays an evolutionary conserved role in zebrafish heart development. Frontiers in cell and developmental biology 2 37711853
2025 Sesamin attenuates liver inflammation caused by PFOS via regulating SAP130-mediated hepatocyte-macrophage crosstalk. Ecotoxicology and environmental safety 1 40773918
2024 Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function. BMC molecular and cell biology 1 38172660
2025 The SAP130/Mincle axis was involved in sevoflurane-induced neuronal death and microglial activation in juvenile mice. Frontiers in pharmacology 0 40792209
2023 Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development. bioRxiv : the preprint server for biology 0 37034673

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