Affinage

CWC15

Spliceosome-associated protein CWC15 homolog · UniProt Q9P013

Length
229 aa
Mass
26.6 kDa
Annotated
2026-06-09
18 papers in source corpus 4 papers cited in narrative 4 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

CWC15 (also known as AD002/HSPC148) is a stable component of the conserved Prp19/CDC5L spliceosomal complex that supports pre-mRNA splicing and, through its orthologs, couples the Prp19 complex to transcription (PMID:20176811, PMID:38627018). In humans, CWC15 co-purifies with hPrp19, CDC5L, PRL1, SPF27, CTNNBL1, and HSP73 as part of an elongated, asymmetric assembly built around a salt-stable core of CDC5L, hPrp19, PRL1, and SPF27 (PMID:20176811). Its incorporation is governed by CTNNBL1, which directly enhances the association of CWC15 with CDC5L and competes for an overlapping binding region on CDC5L, such that CTNNBL1 acts as a chaperone maintaining Prp19 complex integrity and CWC15-CDC5L contact in vivo (PMID:26130721). Work in the rice blast fungus and budding yeast extends the function beyond core splicing: the ortholog localizes to the nucleus via an essential NLS, interacts with Prp19-associated splicing factors, and is required for proper intron splicing of hundreds of genes (PMID:34056823), while yeast Cwc15 mediates the interaction of Prp19C with RNA polymerase II, ensures TREX occupancy at transcribed genes, and promotes transcription elongation (PMID:38627018).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2010 High

    Established that CWC15 is a bona fide subunit of the human Prp19/CDC5L complex and defined the architecture and stable core of that complex, placing CWC15 within the splicing machinery.

    Evidence Affinity purification of FLAG-tagged AD002 from HeLa cells with stoichiometric analysis, salt fractionation, limited proteolysis, and electron microscopy

    PMID:20176811

    Open questions at the time
    • Does not define CWC15's specific contact partners within the complex
    • No functional role for CWC15 in splicing chemistry assigned
    • Position of CWC15 relative to the salt-stable core unresolved
  2. 2015 High

    Answered how CWC15 is incorporated into the Prp19 complex by identifying CTNNBL1 as a chaperone that promotes CWC15-CDC5L binding via an overlapping site on CDC5L.

    Evidence Amine crosslinking and HDX coupled to mass spectrometry, in vitro binding assays, and co-immunoprecipitation in CTNNBL1-deficient cells

    PMID:26130721

    Open questions at the time
    • Mechanism of the proposed CTNNBL1/CWC15 exchange on CDC5L not directly demonstrated
    • Consequences for splicing of disrupted CWC15-CDC5L contact not quantified
    • Structural basis of the overlapping binding region not resolved at atomic detail
  3. 2021 Medium

    Showed that the CWC15 ortholog is required for genome-wide intron splicing and for development/virulence, and mapped its function to an NLS-dependent nuclear role with regulatory effects on partner abundance.

    Evidence Gene deletion, co-immunoprecipitation, GFP-fusion localization, NLS/phospho/sumoylation site mutagenesis, and RNA-seq splicing analysis in Magnaporthe oryzae

    PMID:34056823

    Open questions at the time
    • Mechanism by which MoCwf15 negatively regulates MoCyp1/MoCwf4 accumulation unknown
    • Findings in fungal ortholog not confirmed for human CWC15
    • How splicing defects translate to virulence phenotypes unresolved
  4. 2024 Medium

    Revealed a transcription-coupled function for the CWC15 ortholog, linking Prp19C to RNA polymerase II and TREX-dependent transcription elongation beyond its splicing role.

    Evidence Yeast deletion mutants with ChIP, co-immunoprecipitation, and genetic epistasis analysis (Dst1, Syf2)

    PMID:38627018

    Open questions at the time
    • Whether human CWC15 mediates a comparable Prp19C-Pol II/TREX link untested
    • Direct versus indirect basis of the Prp19C-Pol II interaction not separated
    • Molecular nature of the Cwc15-dependent TREX recruitment unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CWC15's role in spliceosome assembly is mechanistically coordinated with transcription elongation in human cells, and what its precise catalytic or scaffolding contribution within Prp19C is, remain open.
  • No defined biochemical activity for CWC15 itself
  • Transcription-elongation role demonstrated only in yeast ortholog
  • No structural model of CWC15 within the human spliceosome

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
CDC5LCTNNBL1PRL1PRP19SPF27
Complex memberships
Prp19/CDC5L complex (Prp19C)

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 CWC15 (AD002) is a component of the human Prp19/CDC5L complex, which contains hPrp19, CDC5L, PRL1, AD002 (CWC15), SPF27, CTNNBL1, and HSP73. Native complexes were purified from HeLa cells stably expressing FLAG-tagged AD002, revealing the complex contains four copies of hPrp19 and has an elongated, asymmetric shape (~20 nm). A stable core comprised of CDC5L, hPrp19, PRL1, and SPF27 was identified by salt treatment. Affinity purification of FLAG-tagged AD002 from HeLa cells, stoichiometric analysis, salt fractionation, limited proteolysis, electron microscopy Molecular and cellular biology High 20176811
2015 CTNNBL1 directly enhances the association of CWC15 with CDC5L in vitro, and there is an overlapping region on CDC5L that binds either CTNNBL1 or CWC15, suggesting the two proteins may exchange places in the Prp19 complex. In vivo, CTNNBL1 is required to maintain normal levels of the Prp19 complex and to facilitate the interaction of CWC15 with CDC5L, identifying a chaperone function for CTNNBL1 in maintaining Prp19 complex integrity. Amine crosslinking and hydrogen-deuterium exchange coupled to mass spectrometry, in vitro binding assays, CTNNBL1-deficient cell lines, co-immunoprecipitation Nucleic acids research High 26130721
2024 In yeast, Cwc15 (the ortholog of human CWC15) is a nonessential Prp19C-associated protein required for: (1) the interaction of Prp19C with RNA polymerase II, (2) TREX occupancy at transcribed genes, and (3) transcription elongation. Cwc15 functions in the Prp19C-TREX interaction and genetically interacts with the transcription elongation factor Dst1. Epistasis analysis showed Δcwc15 and Δsyf2 have a genetic interaction, with partially overlapping but distinct functions. Yeast genetics (deletion mutants), ChIP, co-immunoprecipitation, genetic interaction/epistasis analysis RNA (New York, N.Y.) Medium 38627018
2021 In the rice blast fungus Magnaporthe oryzae, MoCwf15 (ortholog of CWC15) localizes to the nucleus via a nuclear localization signal (NLS), physically interacts with Prp19-associated splicing factors MoCwf4, MoSsa1, and MoCyp1, negatively regulates protein accumulation of MoCyp1 and MoCwf4, and is required for proper intron splicing of ~400 genes. Deletion of MoCWF15 causes aberrant splicing of genes involved in fungal development and virulence. The NLS sequence (but not predicted phosphorylation or sumoylation sites) was essential for MoCwf15 biological function. Gene deletion, co-immunoprecipitation, subcellular localization (GFP fusion), mutagenesis of NLS/phosphorylation/sumoylation sites, RNA-seq splicing analysis Environmental microbiology Medium 34056823

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Molecular architecture of the human Prp19/CDC5L complex. Molecular and cellular biology 113 20176811
2013 Identification of a nonsense mutation in CWC15 associated with decreased reproductive efficiency in Jersey cattle. PloS one 75 23349982
2019 Effect of vitrification temperature and cryoprotectant concentrations on the mRNA transcriptome of bovine mature oocytes after vitrifying at immature stage. Theriogenology 21 31761539
2015 CTNNBL1 facilitates the association of CWC15 with CDC5L and is required to maintain the abundance of the Prp19 spliceosomal complex. Nucleic acids research 18 26130721
2021 A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis. Islets 16 34241569
2021 Prp19-associated splicing factor Cwf15 regulates fungal virulence and development in the rice blast fungus. Environmental microbiology 13 34056823
2008 Immunoscreening of urinary bladder cancer cDNA library and identification of potential tumor antigen. World journal of urology 10 18828023
2022 Alternative Splicing: A New Therapeutic Target for Ovarian Cancer. Technology in cancer research & treatment 9 35343831
2022 Genome-Wide Screening and Stability Verification of the Robust Internal Control Genes for RT-qPCR in Filamentous Fungi. Journal of fungi (Basel, Switzerland) 9 36135677
2015 Screening for JH1 genetic defect carriers in Jersey cattle by a polymerase chain reaction and restriction fragment length polymorphism assay. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 7 26179100
2015 Directed evolution of human scFvs in DT40 cells. Protein engineering, design & selection : PEDS 7 26519451
2024 The Prp19C/NTC subunit Syf2 and the Prp19C/NTC-associated protein Cwc15 function in TREX occupancy and transcription elongation. RNA (New York, N.Y.) 4 38627018
2023 Probable human origin of the SARS-CoV-2 polybasic furin cleavage motif. BMC genomic data 4 37990144
2025 A Validated Proteomic Signature of Basal-like Triple-Negative Breast Cancer Subtypes Obtained from Publicly Available Data. Cancers 1 40867231
2026 MOV10-mediated alternative splicing regulates mesangial cell proliferation in diabetic kidney disease. Biochimica et biophysica acta. Gene regulatory mechanisms 0 41638360
2026 Heterozygous TREM2 (p.W44X) and PSEN1 (p.A431T) mutations in two Peruvian families with familial Alzheimer's disease: expanding the genetic landscape in underrepresented populations. Frontiers in neuroscience 0 41704845
2025 Comprehensive analysis of molecular characteristics between primary and breast-derived metastatic ovarian cancer. Translational cancer research 0 40225000
2020 Alternate PCR assays for screening of JH1 mutation associated with embryonic death in Jersey cattle. Molecular and cellular probes 0 33279530

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