Affinage

PEF1

Peflin · UniProt Q9UBV8

Length
284 aa
Mass
30.4 kDa
Annotated
2026-06-10
10 papers in source corpus 3 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

PEF1 is a penta-EF-hand Ca2+-binding protein that functions in the maintenance and repair of plasma membrane integrity in fungi (PMID:31270133). In Neurospora crassa, GFP-tagged PEF1 accumulates at sites of plasma membrane injury in a Ca2+-dependent manner, and mutation of its Ca2+-binding EF-hand domains abolishes both this spatial recruitment and the protein's membrane-repair function, establishing that Ca2+ sensing through the EF-hands drives localization and activity (PMID:31270133). Loss of PEF1 compromises membrane integrity during cell-cell fusion and upon challenge with pore-forming agents such as tomatine (PMID:31270133). In Candida albicans, the ortholog localizes to sites of polarized growth and redistributes into punctate membrane spots upon membrane perturbation by amphotericin B or tomatine [PMID:bio_10.1101_2024.09.06.611525], and is required for hyphal plasma membrane integrity in serum and for full virulence, operating downstream of calcineurin A (Cna1) but independently of the Crz1 transcription factor (PMID:41920808). Beyond this Ca2+-dependent membrane-repair role, no molecular partners or biochemical mechanism of PEF1 have been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2019 High

    Established that a fungal penta-EF-hand protein acts as a Ca2+-triggered effector at sites of membrane damage, linking Ca2+ sensing to membrane repair.

    Evidence Live-cell imaging of GFP-PEF1 with site-directed mutagenesis of EF-hand Ca2+-binding domains and deletion-mutant membrane integrity assays in Neurospora crassa

    PMID:31270133

    Open questions at the time
    • No direct biochemical demonstration of Ca2+ binding or the membrane species engaged
    • Molecular mechanism of repair (membrane resealing partners) not identified
    • No interacting proteins characterized
  2. 2024 Medium

    Extended the membrane-perturbation response to a second fungal species and connected PEF1 recruitment to polarized growth sites and the calcineurin pathway.

    Evidence Live-cell imaging of GFP-Pef1 with pharmacological membrane disruption (amphotericin B, tomatine) and cna1Δ deletion in Candida albicans (preprint)

    PMID:bio_10.1101_2024.09.06.611525

    Open questions at the time
    • Preprint status lowers certainty
    • Functional consequence of polarized-growth localization not resolved
    • Direct epistasis with calcineurin not yet established at this stage
  3. 2026 Medium

    Defined PEF1's physiological role in hyphal membrane integrity and virulence and placed it genetically downstream of calcineurin A but separate from Crz1.

    Evidence pef1Δ deletion with serum membrane-integrity assays, epistasis with cna1Δ and crz1Δ, and an insect larvae virulence model in Candida albicans

    PMID:41920808

    Open questions at the time
    • Crz1-independent branch of calcineurin signaling acting through PEF1 not molecularly defined
    • How calcineurin regulates PEF1 (direct dephosphorylation vs. indirect) unknown
    • Relevance to mammalian ortholog ALG-2/PEF1A not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular partners and biochemical mechanism by which PEF1 promotes membrane resealing, and how calcineurin controls it, remain unresolved.
  • No physical interaction partners or substrates identified
  • No structural model of Ca2+-bound PEF1 or its membrane engagement
  • Mechanistic link between calcineurin A activity and PEF1 recruitment undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 4

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 The penta-EF-hand protein PEF1 of Neurospora crassa accumulates at sites of plasma membrane injury in a Ca2+-dependent manner, as shown by live-cell imaging of GFP-tagged PEF1. Site-directed mutagenesis of Ca2+-binding EF-hand domains abolished both the spatial dynamics and the membrane-repair function of the protein. Live-cell fluorescence imaging of GFP-PEF1, site-directed mutagenesis of Ca2+-binding domains, deletion mutant analysis with membrane integrity assays Genetics Medium 31270133
2019 Deletion of pef1 in Neurospora crassa impairs plasma membrane integrity during cell-cell fusion and in the presence of pore-forming drugs (e.g., tomatine), establishing PEF1 as required for membrane repair in fungi. Gene knockout, cell-cell fusion assays, pore-forming drug (tomatine) treatment with viability/integrity readouts Genetics Medium 31270133
2024 In Candida albicans, GFP-tagged Pef1 (penta-EF-hand protein, ortholog of human ALG-2/PEF1) localizes to sites of polarized growth in yeast and hyphal cells, and redistributes to punctate membrane spots upon treatment with amphotericin B or tomatine, indicating Ca2+-dependent recruitment to sites of membrane perturbation. Live-cell fluorescence imaging of GFP-Pef1, pharmacological membrane disruption (amphotericin B, tomatine), genetic deletion of calcineurin (cna1Δ) bioRxivpreprint Medium bio_10.1101_2024.09.06.611525
2026 Deletion of PEF1 in C. albicans does not affect filamentation but causes failure to maintain plasma membrane integrity in serum (specifically in hyphae), and attenuates virulence in an insect larvae infection model, placing PEF1 in a membrane integrity pathway downstream of calcineurin A (Cna1) but not Crz1. Gene deletion (pef1Δ), membrane integrity assays in serum, genetic epistasis with cna1Δ and crz1Δ mutants, insect larvae virulence model G3 (Bethesda, Md.) Medium 41920808

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The enhancer in the long control region of human papillomavirus type 16 is up-regulated by PEF-1 and down-regulated by Oct-1. Journal of virology 38 7769658
2020 The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy. Journal of cell science 11 32788233
2006 Molecular analysis of the 21-kb bacteriocin-encoding plasmid pEF1 from Enterococcus faecium 6T1a. Plasmid 10 16893567
2019 Plasma Membrane Integrity During Cell-Cell Fusion and in Response to Pore-Forming Drugs Is Promoted by the Penta-EF-Hand Protein PEF1 in Neurospora crassa. Genetics 7 31270133
2024 Characterization of Two Novel Endolysins from Bacteriophage PEF1 and Evaluation of Their Combined Effects on the Control of Enterococcus faecalis Planktonic and Biofilm Cells. Antibiotics (Basel, Switzerland) 4 39335057
2021 The S. pombe CDK5 Orthologue Pef1 Cooperates with Three Cyclins, Clg1, Pas1 and Psl1, to Promote Pre-Meiotic DNA Replication. Biomolecules 3 33445784
2020 The CDK Pef1 and protein phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes. eLife 3 31895039
1998 PEF-1, an epithelial cell transcription factor which activates the long control region of human papillomavirus type 16, is glycosylated with N-acetylglucosamine. The Journal of general virology 2 9820151
2026 The penta-EF-hand protein Pef1 of Candida albicans functions at sites of membrane perturbation to support polarized growth and membrane integrity. G3 (Bethesda, Md.) 0 41920808
2024 In Vivo Proximity Labeling Identifies a New Function for the Lifespan and Autophagy-regulating Kinase Pef1, an Ortholog of Human Cdk5. bioRxiv : the preprint server for biology 0 38915521

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