Affinage

Showing SCAF11 — CASP11 is a alias.

SCAF11

Protein SCAF11 · UniProt Q99590

Length
1463 aa
Mass
164.7 kDa
Annotated
2026-06-10
33 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 1/1 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCAF11 is a splicing regulator implicated in the control of APP alternative splicing in human neurons [PMID:bio_10.1101_2025.04.20.648873]. In iPSC-derived neurons bearing TDP-43 pathology, SCAF11 is co-sequestered into cytoplasmic TDP-43 aggregates, and its knockdown produces aberrant APP splicing and increased amyloid-beta burden without altering other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a selective splicing pathway upstream of APP [PMID:bio_10.1101_2025.04.20.648873]. A separate line of evidence positions SCAF11 in a competitive ubiquitination mechanism that, under limiting E3 ligase availability, drives FOXO1 degradation versus METTL14 stabilization and downstream m6A methylation of pri-miRNA-146b-5p in triple-negative breast cancer cells (PMID:40360112). Beyond these two findings, no further mechanistic detail for SCAF11 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2025 Medium

    Established that SCAF11 acts as a splicing regulator whose mislocalization links TDP-43 pathology to amyloid biology, answering whether a specific splicing factor connects TDP-43 aggregation to APP processing.

    Evidence Proximity proteomics plus base editing and knockdown in human iPSC-derived neurons with splicing and amyloid-beta readouts (preprint)

    PMID:bio_10.1101_2025.04.20.648873

    Open questions at the time
    • Single-lab preprint without independent replication
    • Direct RNA targets and binding mode of SCAF11 on APP transcripts not defined
    • Whether SCAF11 loss-of-function alone (independent of TDP-43) drives amyloid pathology in vivo is untested
  2. 2025 Low

    Proposed a non-splicing role for SCAF11 in competitive ubiquitination balancing FOXO1 degradation against METTL14 stabilization, addressing how E3 ligase scarcity shapes protein fate in cancer cells.

    Evidence In vitro and in vivo triple-negative breast cancer cell experiments with cold atmospheric plasma treatment and degradation dissection

    PMID:40360112

    Open questions at the time
    • Single study with limited mechanistic validation and no orthogonal confirmation of the competitive ubiquitination model
    • Direct enzymatic role of SCAF11 in ubiquitin transfer not demonstrated
    • Relationship between this cancer-cell function and the neuronal splicing role is unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The core molecular activity of SCAF11 — its direct RNA substrates, its physical splicing partners, and whether its splicing and ubiquitination-related roles reflect one biochemical activity — remains undefined.
  • No structural model or biochemical reconstitution
  • No defined direct binding partners or complex membership
  • No reconciliation of the neuronal splicing and cancer ubiquitination findings

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 SCAF11 (a splicing regulator) is co-sequestered in the cytoplasm with TDP-43 pathological aggregates in human iPSC-derived neurons; knockdown of SCAF11 results in aberrant APP alternative splicing and increased amyloid-beta burden, without affecting other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a specific splicing regulatory pathway upstream of APP. Proximity proteomics, base editing in human iPSC-derived neurons, knockdown with splicing and amyloid-beta readouts bioRxivpreprint Medium bio_10.1101_2025.04.20.648873
2025 SCAF11 mediates a competitive ubiquitination mechanism between FOXO1 and METTL14 under conditions of insufficient E3 ligase supply in triple-negative breast cancer cells treated with cold atmospheric plasma (CAP); this competition results in enhanced FOXO1 protein degradation and increased pri-miRNA-146b-5p m6A methylation promoting miRNA-146b-5p maturation. In vitro and in vivo cancer cell experiments with CAP treatment; mechanistic dissection of competitive protein degradation involving SCAF11, FOXO1, and METTL14 International journal of biological macromolecules Low 40360112

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Improved de novo structure prediction in CASP11 by incorporating coevolution information into Rosetta. Proteins 80 26677056
2015 New encouraging developments in contact prediction: Assessment of the CASP11 results. Proteins 65 26474083
2015 Methods of model accuracy estimation can help selecting the best models from decoy sets: Assessment of model accuracy estimations in CASP11. Proteins 55 26344049
2015 Integration of QUARK and I-TASSER for Ab Initio Protein Structure Prediction in CASP11. Proteins 55 26370505
2016 Evaluation of free modeling targets in CASP11 and ROLL. Proteins 45 26677002
2016 Performance of protein-structure predictions with the physics-based UNRES force field in CASP11. Bioinformatics (Oxford, England) 45 27378298
2015 Template-based protein structure prediction in CASP11 and retrospect of I-TASSER in the last decade. Proteins 44 26343917
2016 Assessment of refinement of template-based models in CASP11. Proteins 36 27081793
2016 CASP11 statistics and the prediction center evaluation system. Proteins 32 26857434
2015 Template based protein structure modeling by global optimization in CASP11. Proteins 28 26329522
2016 Assessment of template-based modeling of protein structure in CASP11. Proteins 25 27081927
2016 Blind testing of cross-linking/mass spectrometry hybrid methods in CASP11. Proteins 23 26945814
2015 CASP11 refinement experiments with ROSETTA. Proteins 23 26205421
2016 Benchmarking Deep Networks for Predicting Residue-Specific Quality of Individual Protein Models in CASP11. Scientific reports 19 26763289
2016 Structure prediction using sparse simulated NOE restraints with Rosetta in CASP11. Proteins 18 26857542
2015 Protein structure prediction using residue- and fragment-environment potentials in CASP11. Proteins 16 26344195
2015 Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11. Proteins 16 26369671
2015 A large-scale conformation sampling and evaluation server for protein tertiary structure prediction and its assessment in CASP11. BMC bioinformatics 16 26493701
2016 Assessment of CASP11 contact-assisted predictions. Proteins 15 26889875
2015 Some of the most interesting CASP11 targets through the eyes of their authors. Proteins 15 26473983
2018 An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12. Scientific reports 14 29967418
2017 Princeton_TIGRESS 2.0: High refinement consistency and net gains through support vector machines and molecular dynamics in double-blind predictions during the CASP11 experiment. Proteins 12 28241391
2022 Wedelolactone Attenuates N-methyl-N-nitrosourea-Induced Retinal Neurodegeneration through Suppression of the AIM2/CASP11 Pathway. Biomedicines 11 35203520
2016 Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11). Wellcome open research 11 28317030
2016 CASP11--An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline. PloS one 10 27046050
2015 Template-free modeling by LEE and LEER in CASP11. Proteins 10 26474186
2016 Contact-assisted protein structure modeling by global optimization in CASP11. Proteins 9 26677100
2015 An Improved Integration of Template-Based and Template-Free Protein Structure Modeling Methods and its Assessment in CASP11. Protein and peptide letters 9 25990081
2016 Biological function derived from predicted structures in CASP11. Proteins 8 27181425
2024 Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis. Journal of dental research 6 38197150
2025 Cold atmospheric plasma targets triple negative breast cancer cells via SCAF11-mediated competitive protein degradation and synergizes with miRNA-146b-5p. International journal of biological macromolecules 4 40360112
2015 Analysis of free modeling predictions by RBO aleph in CASP11. Proteins 4 26492194
2016 Modeling and minimizing CAPRI round 30 symmetrical protein complexes from CASP-11 structural models. Proteins 2 27701764

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