Affinage

SAP30BP

SAP30-binding protein · UniProt Q9UHR5

Length
308 aa
Mass
33.9 kDa
Annotated
2026-06-10
35 papers in source corpus 8 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAP30BP is a nuclear protein that bridges two distinct nuclear regulatory processes: pre-mRNA splicing through CDK11 activation and transcriptional silencing through the mSin3A–HDAC corepressor complex (PMID:15496587, PMID:38059508, PMID:38065061). As a critical CDK11 activator, SAP30BP forms a tight complex with CDK11 and cyclins L1/L2, ensuring cyclin stability and promoting their assembly with the kinase; acute degradation of SAP30BP phenocopies CDK11 loss and causes widespread pre-mRNA splicing defects, including dysregulation of short (<100 nt) mini-introns (PMID:38059508, PMID:38065061). The cryo-EM structure of the CDK11–cyclin L2–SAP30BP ternary complex shows that SAP30BP makes extensive contacts that stabilize cyclin L2 and critical contacts with the CDK11 C-terminal kinase lobe that drive complex assembly, enabling SF3B1 phosphorylation and the spliceosome B-to-Bact transition (PMID:42034640). Formation of this active complex depends on CDK11 T-loop phosphorylation at Thr595, which is required for SAP30BP association and is controlled upstream by CDK7 (PMID:41428738). Independently, SAP30BP acts as a transcriptional co-repressor by directly binding SAP30 within the mSin3A–HDAC complex, promoting histone H3 deacetylation at K9 and K14 in an HDAC-dependent manner to enforce gene silencing (PMID:15496587, PMID:21221920).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2004 Medium

    Established SAP30BP as a nuclear protein physically linked to transcriptional repression machinery, answering where the uncharacterized HSV-1-induced gene product localizes and what it binds.

    Evidence Yeast two-hybrid, pull-down, reciprocal Co-IP, and fluorescent fusion localization in HeLa cells

    PMID:15496587

    Open questions at the time
    • Did not define functional consequence of the SAP30 interaction on chromatin
    • No demonstration of HDAC recruitment or histone modification
  2. 2010 Medium

    Showed the SAP30BP–SAP30 interaction is functionally repressive, converting a binding observation into a chromatin-level silencing mechanism.

    Evidence Dual-luciferase reporter, qPCR, and ChIP for H3K9/K14 deacetylation

    PMID:21221920

    Open questions at the time
    • Repression demonstrated on a viral promoter; cellular gene targets unclear
    • Did not establish whether SAP30BP is an obligate subunit of the complex
  3. 2023 High

    Identified an entirely separate molecular role: SAP30BP as a critical CDK11 activator required for global pre-mRNA splicing, answering how cyclin L1/L2–CDK11 assembly is achieved.

    Evidence Degron-based acute degradation phenocopy, in vitro kinase assay, AP-MS, corroborated by independent same-year AP-MS

    PMID:38059508 PMID:38065061

    Open questions at the time
    • Structural basis of cyclin stabilization not yet resolved
    • Substrate scope of resulting CDK11 activity beyond splicing not defined
  4. 2025 Medium

    Placed the CDK11–SAP30BP complex in a regulatory cascade by showing CDK11 Thr595 phosphorylation gates SAP30BP association and that CDK7 acts upstream.

    Evidence Mutational analysis, SILAC phosphoproteomics, CDK7 inhibition

    PMID:41428738

    Open questions at the time
    • Direct kinase responsible for Thr595 phosphorylation not formally proven
    • Single-lab study
  5. 2025 Medium

    Connected SAP30BP's repressor activity to disease physiology, showing it silences MFN2 via HDAC1 to drive mitochondrial ferroptosis in diabetic cardiomyopathy.

    Evidence siRNA knockdown, RNA-seq, ChIP, mitochondrial fractionation, ferroptosis assays in DCM mouse and high-glucose cardiomyocyte models

    PMID:40774404

    Open questions at the time
    • Causal link in human disease not established
    • Whether splicing function contributes to the phenotype not addressed
  6. 2026 High

    Provided the atomic-resolution mechanism of CDK11 activation, defining how SAP30BP stabilizes cyclin L2 and promotes the assembly that drives spliceosome activation.

    Evidence 2.3 Å cryo-EM of CDK11–cyclin L2–SAP30BP with biochemical stability assays and inhibitor binding analysis

    PMID:42034640

    Open questions at the time
    • Function of the identified CDK11 pseudo-substrate sequence in vivo not fully resolved
    • Structure does not address the transcriptional co-repressor role

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SAP30BP partitions between its splicing-activator and chromatin-repressor functions, and whether these are coordinated within a single regulatory program, remains unresolved.
  • No study connects the CDK11/splicing and mSin3A/HDAC roles
  • Determinants of complex choice (e.g. the neural alternative exon) not mapped to either function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CCNL1CCNL2CDK11HDAC1SAP18SAP30SF3B1
Complex memberships
CDK11–cyclin L2–SAP30BP complexmSin3A–HDAC corepressor complex

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SAP30BP (HTRP) was cloned as an immediate-early gene product induced by HSV-1 binding in human embryo fibroblasts. Yeast two-hybrid, in vitro pull-down/Western blot, and in vivo immunoprecipitation experiments showed that SAP30BP directly interacts with SAP30, a component of the mSin3A co-repressor/HDAC complex, via SAP30BP's conserved domain. Fluorescent fusion-protein imaging confirmed nuclear localization of SAP30BP in HeLa cells. Yeast two-hybrid, pull-down/Western blot, co-immunoprecipitation, fluorescent fusion-protein localization Journal of biochemistry Medium 15496587
2010 SAP30BP (HTRP) promotes HDAC activity and inhibits transcription of a viral promoter by interacting with SAP30 (mSin3A-associated protein). ChIP experiments demonstrated that SAP30BP increases histone H3 deacetylation at lysine 9 and lysine 14, and the interaction with SAP30 synergistically enhances transcriptional repression in a manner dependent on HDAC enzyme activity. Dual-luciferase reporter assay, real-time PCR, chromatin immunoprecipitation (ChIP) Virologica Sinica Medium 21221920
2023 SAP30BP forms a tight complex with CDK11 and cyclins L1/L2. Acute degradation of SAP30BP (mirroring CDK11 depletion) causes widespread defects in pre-mRNA splicing. In vitro and in vivo experiments showed that SAP30BP facilitates CDK11 kinase activity by ensuring the stability of cyclins L1/L2 and promoting their assembly with CDK11, identifying SAP30BP as a critical CDK11 activator. Additionally, a neural alternative exon in SAP30BP modulates interactions with RNA processing factors and regulates splicing of short (<100 nt) 'mini-introns' that control nuclear RNA levels. Acute protein degradation (degron system), in vitro kinase assay, co-immunoprecipitation, affinity purification-mass spectrometry (AP-MS) The EMBO journal / Molecular cell High 38059508 38065061
2025 CDK11 T-loop threonine 595 (Thr595) phosphorylation is essential for formation of the active CDK11–cyclin L–SAP30BP complex. Mutational analysis showed that Thr595 is required for SAP30BP association, and CDK7 inhibition leads to sequential dephosphorylation of CDK11 Thr595 and SF3B1, implicating CDK7 in regulating the CDK11–SAP30BP complex upstream. Mutational analysis, SILAC-based phosphoproteomics, CDK7 inhibition experiments Nucleic acids research Medium 41428738
2026 Cryo-EM structure of the CDK11–cyclin L2–SAP30BP complex at 2.3 Å resolution revealed that SAP30BP forms extensive interactions with cyclin L2 (stabilizing it) and makes critical contacts with the C-terminal kinase lobe of CDK11 that promote complex assembly. Biochemical experiments confirmed that cyclin L2 is destabilized in the absence of SAP30BP. A pseudo-substrate sequence near the CDK11 C-terminus was also identified and implicated in CDK11 auto-regulation. The complex promotes spliceosome activation (B-to-Bact transition) via SF3B1 phosphorylation. Cryo-EM (2.3 Å), biochemical stability assays, inhibitor binding analysis Nature communications High 42034640
2025 SAP30BP expression is elevated in hearts of diabetic cardiomyopathy (DCM) mice and high-glucose-treated cardiomyocytes. Mechanistically, SAP30BP inhibits transcription of MFN2 through HDAC1-mediated histone deacetylation, causing mitochondrial dynamic disruption that hinders mitochondrial translocation of ACSL4 and promotes mitochondria-associated ferroptosis. Knockdown of SAP30BP ameliorated ferroptosis, oxidative stress, and cardiac dysfunction in DCM. siRNA knockdown, RNA-seq, ChIP (HDAC1-mediated deacetylation), mitochondrial fractionation, cellular ferroptosis assays European journal of pharmacology Medium 40774404
2024 BioID proximity mapping identified SAP30BP as an in vivo interactor of SAP18 within the SIN3 transcriptional repressor complex context, and complementary immunoprecipitation validated this interaction. BioID proximity labeling, mass spectrometry, co-immunoprecipitation Biochemical and biophysical research communications Low 39522233

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron 329 8663995
1995 Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS letters 285 7589464
1998 Identification of tryptophan oxidation products in bovine alpha-crystallin. Protein science : a publication of the Protein Society 158 9828005
2001 Peptide folding induces high and selective affinity of a linear and small beta-peptide to the human somatostatin receptor 4. Journal of medicinal chemistry 110 11448228
1992 Biosynthesis of riboflavin: cloning, sequencing, and expression of the gene coding for 3,4-dihydroxy-2-butanone 4-phosphate synthase of Escherichia coli. Journal of bacteriology 76 1597419
2015 Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms. Journal of shoulder and elbow surgery 42 26350878
2017 Genetic and familial predisposition to rotator cuff disease: a systematic review. Journal of shoulder and elbow surgery 37 28162885
2016 Serotonin biosynthesis as a predictive marker of serotonin pharmacodynamics and disease-induced dysregulation. Scientific reports 32 27444653
2019 Genetic basis of rotator cuff injury: a systematic review. BMC medical genetics 30 31477042
2015 Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence. ACS medicinal chemistry letters 24 26005535
1991 The Escherichia coli htrP gene product is essential for bacterial growth at high temperatures: mapping, cloning, sequencing, and transcriptional regulation of htrP. Journal of bacteriology 22 1917833
2020 How tryptophan levels in plant-based aquafeeds affect fish physiology, metabolism and proteome. Journal of proteomics 19 32304777
2004 Comparative metabolism of alpha- and beta-peptides in the insect Heliothis virescens and in plant cells of black Mexican sweet maize. Chemistry & biodiversity 19 17191917
2019 Overexpression of ThSAP30BP from Tamarix hispida improves salt tolerance. Plant physiology and biochemistry : PPB 18 31743857
2016 Panel of SEREX-defined antigens for breast cancer autoantibodies profile detection. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 18 27775439
2004 HTRP--an immediate-early gene product induced by HSV1 infection in human embryo fibroblasts, is involved in cellular co-repressors. Journal of biochemistry 18 15496587
2023 Systematic analysis of alternative exon-dependent interactome remodeling reveals multitasking functions of gene regulatory factors. Molecular cell 17 38065061
2021 Capillary electrochromatography-mass spectrometry of kynurenine pathway metabolites. Journal of chromatography. A 16 34098249
2023 CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing. The EMBO journal 15 38059508
2005 Apolipoprotein E genotypes as predictors of high-risk groups for developing hyperlipidemia in kidney transplant recipients undergoing sirolimus treatment. Transplantation 15 16378065
2020 Effect of phosphorus supply on root traits of two Brassica oleracea L. genotypes. BMC plant biology 8 32758143
2010 Transcriptional regulation by HSV-1 induced HTRP via acetylation system. Virologica Sinica 8 21221920
2002 Complementary combining site contact residue mutations of the anti-digoxin Fab 26-10 permit high affinity wild-type binding. The Journal of biological chemistry 8 11854275
2020 Can ocular OCT findings be as a predictor for end-organ damage in systemic hypertension? Clinical and experimental hypertension (New York, N.Y. : 1993) 7 32579082
2014 Selection of reference genes for normalization of quantitative polymerase chain reaction data in mouse models of heart failure. Molecular medicine reports 7 25338732
2014 Establishment of the method for screening the potential targets and effective components of huatuo reconstruction pill. Interdisciplinary sciences, computational life sciences 5 25172450
2012 A novel paramagnetic substrate for detecting myeloperoxidase activity in vivo. Molecular imaging 5 22954188
2025 SAP30BP aggravates mitochondrial-related ferroptosis in diabetic cardiomyopathy by regulating MFN2-ACSL4 axis. European journal of pharmacology 4 40774404
2020 SAP30BP gene is associated with the susceptibility of rotator cuff tear: a case-control study based on Han Chinese population. Journal of orthopaedic surgery and research 4 32843068
2025 CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing. Nucleic acids research 3 41428738
2023 Are commercial genetic injury tests premature? Scandinavian journal of medicine & science in sports 3 37243491
2024 BioID proximity mapping reveals novel SAP18 interactions in the prespliceosomal complex. Biochemical and biophysical research communications 2 39522233
2023 Association between the rs820218 Variant within the SAP30BP Gene and Rotator Cuff Rupture in an Amazonian Population. Genes 2 36833294
2021 Environmental impact of amino acids on selenate-bearing hydrocalumite: Experimental and DFT studies. Environmental pollution (Barking, Essex : 1987) 1 34280745
2026 Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation. Nature communications 0 42034640

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