The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
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Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
DSF2 (systematic name YBR007C; UniProt P38213) encodes a protein in Saccharomyces cerevisiae (strain ATCC 204508 / S288c) whose full name is "Deletion Suppressor of MPT5 mutation protein 2." The gene was originally identified through genetic screens in which its deletion suppressed phenotypes associated with loss of MPT5 (also known as PUF5/HTR1/UTH4), an RNA-binding protein of the Pumilio family involved in mRNA regulation (coorey2012anovelhighthroughput pages 83-88, zhang2025theyeastgsk3 pages 14-15). DSF2 is a relatively undercharacterized gene, and no dedicated primary study of its molecular function has been published; instead, evidence about its function derives from high-throughput studies, phosphoproteomics, computational analyses, and comparative genomics.
The following table summarizes verified properties of DSF2:
| Gene Name | Systematic Name | UniProt ID | Organism | Protein Size | Key Domains | Subcellular Localization | Genetic Interactions | Phosphorylation Sites | Potential Kinase Regulators | Orthologs | Proposed Function |
|---|---|---|---|---|---|---|---|---|---|---|---|
| DSF2 | YBR007C (ORF alias reported by UniProt: YBR0113) | P38213 | Saccharomyces cerevisiae strain ATCC 204508 / S288c | Not established from the literature retrieved here; UniProt accession verified as the target protein | Sel1-like repeats, TPR-like helical domain superfamily, Mitotic_Regulator domain; these domains are most consistent with a protein-protein interaction scaffold/adaptor role rather than catalytic activity (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2, mittl2007sel1likerepeatproteins pages 6-8) | Localizes to the bud neck under standard conditions; reported to relocalize from the bud neck to the cytoplasm upon DNA replication stress, supporting a role in cell-cycle-linked cortical structures (mamun2023largescaleidentificationof pages 12-13, zhang2025theyeastgsk3 pages 14-15) | Originally identified as deletion suppressor of MPT5 mutation; thus genetically linked to MPT5/PUF5, an RNA regulatory factor (coorey2012anovelhighthroughput pages 83-88, gogl2015thestructureof pages 12-15) | S391, S395 detected in phosphoproteomic data (zhang2025theyeastgsk3 pages 13-14, zhang2025theyeastgsk3 pages 14-15) | Cbk1 is the strongest inferred regulator from sequence/pathway analysis: Dsf2 contains conserved Cbk1 phosphorylation consensus motifs but lacks the canonical Cbk1 docking motif; therefore it is a putative non-docking Cbk1 substrate rather than a confirmed direct substrate (gogl2015thestructureof pages 12-15, gogl2015thestructureof pages 15-17) | Nif1 in Schizosaccharomyces pombe and SppD in Aspergillus spp.; comparative analyses link this family to mitotic/cytokinetic functions, though septal-pore functions appear lineage-specialized in filamentous fungi (mamun2023largescaleidentificationof pages 12-13) | Best-supported current model: non-enzymatic adaptor/scaffold protein acting at the bud neck in processes related to cell division/cytokinesis and possibly integrated with the RAM/Cbk1 signaling network; precise molecular mechanism remains incompletely characterized (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2, mamun2023largescaleidentificationof pages 12-13, gogl2015thestructureof pages 12-15, zhang2025theyeastgsk3 pages 14-15) |
Table: This table summarizes the verified identity, domains, localization, genetic interactions, phosphorylation evidence, orthology, and best-supported functional interpretation for the yeast DSF2/YBR007C protein. It is useful as a compact reference for distinguishing experimentally supported facts from mechanistic inferences.
DSF2 harbors three notable domain annotations: Sel1-like repeats (SLR; InterPro IPR006597), a TPR-like helical domain superfamily (IPR011990), and a Mitotic Regulator domain (IPR052945). These domains provide strong functional clues.
Sel1-like repeats are α-helical structural motifs related to tetratricopeptide repeats (TPRs). A comprehensive review of SLR proteins established that, despite their diverse cellular roles, all characterized SLR proteins function as adaptor or scaffold proteins that mediate protein-protein interactions and facilitate assembly of macromolecular complexes (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2). SLR domains achieve selectivity through a combination of short-range protein-peptide interactions and long-range electrostatic interactions, enabling discrimination between different target sequences (mittl2007sel1likerepeatproteins pages 6-8).
In yeast specifically, well-characterized SLR proteins include:
- Hrd3, which contains 12 Sel1-like repeats and functions as the ER-lumenal substrate recognition adaptor for the Hrd1 ubiquitin ligase complex in ER-associated degradation (ERAD) (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 6-8);
- Chs4, which contains 7 Sel1-like repeats and functions as a chitin synthase III activator, recruiting the activated Chs3/Chs4 complex to the septum via interaction with the Bni4/Cdc10 complex (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2);
- Nif1, which regulates mitosis in fission yeast (mittl2007sel1likerepeatproteins pages 1-2).
The SLR domain architecture of DSF2 thus strongly suggests it operates as a non-enzymatic adaptor or scaffold protein involved in protein-protein interactions at sites relevant to cell division.
The Mitotic Regulator domain (IPR052945) connects DSF2 to Nif1, its ortholog in Schizosaccharomyces pombe. Nif1 acts as a mitotic inhibitor through direct interaction with the Nim1 protein kinase, thereby regulating mitotic entry (mamun2023largescaleidentificationof pages 12-13). This domain assignment is consistent with a role for DSF2 in cell cycle regulation.
Dsf2 localizes to the bud neck under normal growth conditions (mamun2023largescaleidentificationof pages 12-13, zhang2025theyeastgsk3 pages 14-15). The bud neck is the constriction site between mother and daughter cells in budding yeast, where the septin ring, actomyosin ring, and cell wall remodeling machinery converge to execute cytokinesis. Phosphoproteomic data from Zhang et al. (2025) demonstrate that upon DNA replication stress, Dsf2 relocalizes from the bud neck to the cytoplasm, indicating that its localization is dynamically regulated in a cell cycle- and stress-dependent manner (zhang2025theyeastgsk3 pages 14-15). Phosphorylation at residues S391 and S395 was detected in phosphoproteomic analyses, suggesting regulation of Dsf2 by one or more kinases (zhang2025theyeastgsk3 pages 13-14, zhang2025theyeastgsk3 pages 14-15).
The bud neck localization places Dsf2 at the same subcellular site as other key regulators of cytokinesis and cell separation, including Chs4 (septum formation), Dbf2-Mob1 (mitotic exit network), and components of the actomyosin ring.
DSF2 was named for its property as a deletion suppressor of mpt5 mutations: deletion of DSF2 suppresses phenotypes caused by loss of MPT5/PUF5 (coorey2012anovelhighthroughput pages 83-88, zhang2025theyeastgsk3 pages 14-15). MPT5 is a member of the PUF (Pumilio and FBF) family of RNA-binding proteins that promotes mRNA decapping and deadenylation of target transcripts (gogl2015thestructureof pages 18-20). MPT5 targets include mRNAs encoding cell wall proteins and regulators of cell morphogenesis. The fact that loss of DSF2 can compensate for loss of MPT5 implies that DSF2 and MPT5 have opposing or balancing roles in a shared pathway, possibly related to post-transcriptional regulation of cell wall or cytokinesis-related transcripts.
A key study by Gögl et al. (2015) systematically analyzed substrates of the NDR/LATS family kinase Cbk1, a central component of the RAM (Regulation of Ace2 and cellular Morphogenesis) signaling network. This analysis revealed that Dsf2 contains conserved Cbk1 phosphorylation consensus sequences (Hx[RK]xx[ST]) but notably lacks the canonical Cbk1 core docking motif ([YF]xFP) (gogl2015thestructureof pages 12-15). DSF2 was grouped alongside Mpt5 and Sec3 as proteins with conserved Cbk1 consensus sites but no docking motif, suggesting these may represent a class of non-docking Cbk1 substrates (gogl2015thestructureof pages 12-15). While in vivo phosphorylation at Cbk1 consensus sites has been confirmed for Mpt5 and Sec3, such evidence for Dsf2 specifically remains indirect (gogl2015thestructureof pages 12-15).
The RAM network, through Cbk1 phosphorylation of the mRNA-binding protein Ssd1 and the transcription factor Ace2, coordinates cell wall biogenesis, cell separation, and polarized growth (gogl2015thestructureof pages 17-18, gogl2015thestructureof pages 18-20, gogl2015thestructureof pages 11-12). Cbk1 phosphorylation of Ssd1 permits translation of mRNAs encoding cell wall proteins required for bud growth, while phosphorylation of Ace2 activates transcription of cell separation genes (gogl2015thestructureof pages 12-15). The connection of DSF2 to this network—through conserved phosphorylation motifs, bud neck localization, and genetic interaction with MPT5—suggests Dsf2 participates in this signaling axis, potentially as a scaffold or adaptor that facilitates pathway component interactions at the site of cytokinesis.
Comparative genomic and phylogenetic analyses have identified orthologs of DSF2 in other fungi, providing additional functional insight:
| Protein Name | Organism | Domain Architecture | Subcellular Localization | Known Function | Relationship to DSF2 |
|---|---|---|---|---|---|
| Dsf2 | Saccharomyces cerevisiae | Sel1-like repeats; TPR-like helical domain; Mitotic_Regulator domain | Bud neck; relocalizes to cytoplasm upon DNA replication stress | Best-supported as a non-enzymatic adaptor/scaffold protein associated with bud-neck/cell-division functions; genetically linked to MPT5 and inferred to connect to the Cbk1/RAM network (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2, gogl2015thestructureof pages 12-15, zhang2025theyeastgsk3 pages 14-15) | Self |
| Nif1 | Schizosaccharomyces pombe | Sel1-like repeats | Not clearly established in the retrieved evidence | Mitotic inhibitor acting via interaction with Nim1 protein kinase (mamun2023largescaleidentificationof pages 12-13) | Ortholog |
| SppD | Aspergillus oryzae | 3 SEL1 domain repeats | Septum / septal pore; accumulates at septal structures involved in wound response | Required for septal pore plugging upon wounding; proposed to have evolved in Pezizomycotina by gene duplication from a yeast-like orthologous lineage (mamun2023largescaleidentificationof pages 7-8, mamun2023largescaleidentificationof pages 12-13) | Ortholog; likely lineage-specialized derivative |
| Hrd3 | Saccharomyces cerevisiae | 12 Sel1-like repeats | ER membrane / ER lumenal HRD complex | ERAD substrate-recognition adaptor/scaffold in the Hrd1 complex; Sel1-like repeats mediate substrate and partner recognition (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 6-8) | Same Sel1-like repeat protein family |
| Chs4 | Saccharomyces cerevisiae | 7 Sel1-like repeats | Septum / bud neck | Activator and recruitment factor for chitin synthase III during septum formation; adaptor/scaffold role in cytokinetic cell-wall assembly (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2) | Same Sel1-like repeat protein family |
Table: This table compares DSF2 with orthologous or domain-related fungal Sel1-like repeat proteins to clarify what is directly known about DSF2 versus what can be inferred from better-characterized family members. It is useful for interpreting DSF2 as a likely scaffold/adaptor protein involved in cell division-related processes.
In Schizosaccharomyces pombe, the ortholog Nif1 functions as a mitotic inhibitor through interaction with the Nim1 protein kinase, establishing a direct connection between this protein family and cell cycle control (mamun2023largescaleidentificationof pages 12-13). In Aspergillus oryzae, the ortholog SppD contains three SEL1 domain repeats and was identified in a large-scale screening of genes involved in septal pore plugging upon hyphal wounding (mamun2023largescaleidentificationof pages 7-8). Mamun et al. (2023) specifically noted that "Nif1 and Dsf2 are orthologs of SppD in fission and budding yeasts, respectively," and that "Nif1 acts as a mitotic inhibitor via interaction with Nim1 protein kinase, whereas Dsf2 localizes to the bud neck, the site of cytokinesis," suggesting a possible role of SppD in cell-cycle regulation or cytokinesis (mamun2023largescaleidentificationof pages 12-13). However, the SppD subclade in Pezizomycotina is distinct from the subclade containing yeast orthologs, and the authors hypothesize that SppD evolved through gene duplication to perform septal pore-related functions specific to filamentous fungi (mamun2023largescaleidentificationof pages 12-13).
Based on the convergent lines of evidence, Dsf2 is best understood as a non-enzymatic adaptor/scaffold protein that functions at the bud neck in processes related to cell division and cytokinesis. Its Sel1-like repeat architecture is consistent with a role as a protein-protein interaction platform, analogous to other yeast SLR proteins such as Hrd3 (ERAD substrate recognition) and Chs4 (chitin synthase III activation at the septum) (mittl2007sel1likerepeatproteins pages 5-6, mittl2007sel1likerepeatproteins pages 1-2, mittl2007sel1likerepeatproteins pages 6-8). Its dynamic localization—from the bud neck to the cytoplasm upon DNA replication stress—implies cell-cycle-dependent regulation (zhang2025theyeastgsk3 pages 14-15).
The genetic interaction with MPT5 (a PUF-family mRNA regulator) and the presence of conserved Cbk1 phosphorylation consensus sites place Dsf2 within the broader Cbk1/RAM signaling network that coordinates post-transcriptional control of cell wall biogenesis and cell separation with cell cycle progression (gogl2015thestructureof pages 12-15, gogl2015thestructureof pages 18-20). The Mitotic Regulator domain annotation and orthology with the fission yeast mitotic inhibitor Nif1 further support a cell-cycle regulatory function (mamun2023largescaleidentificationof pages 12-13).
It is important to note that DSF2 remains incompletely characterized. Key unresolved questions include:
In summary, DSF2 encodes a Sel1-like repeat-containing adaptor protein that localizes to the bud neck during cell division, is integrated into the Cbk1/RAM signaling network through conserved phosphorylation motifs, and functions in a pathway that intersects with MPT5-mediated post-transcriptional regulation. Its precise molecular role likely involves scaffolding protein-protein interactions at the site of cytokinesis, consistent with the established functions of the SLR protein family across eukaryotes.
References
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(gogl2015thestructureof pages 17-18): Gergő Gógl, Kyle D. Schneider, Brian J. Yeh, Nashida Alam, Alex N. Nguyen Ba, Alan M. Moses, Csaba Hetényi, Attila Reményi, and Eric L. Weiss. The structure of an ndr/lats kinase–mob complex reveals a novel kinase–coactivator system and substrate docking mechanism. PLOS Biology, 13:e1002146, May 2015. URL: https://doi.org/10.1371/journal.pbio.1002146, doi:10.1371/journal.pbio.1002146. This article has 57 citations and is from a highest quality peer-reviewed journal.
(gogl2015thestructureof pages 11-12): Gergő Gógl, Kyle D. Schneider, Brian J. Yeh, Nashida Alam, Alex N. Nguyen Ba, Alan M. Moses, Csaba Hetényi, Attila Reményi, and Eric L. Weiss. The structure of an ndr/lats kinase–mob complex reveals a novel kinase–coactivator system and substrate docking mechanism. PLOS Biology, 13:e1002146, May 2015. URL: https://doi.org/10.1371/journal.pbio.1002146, doi:10.1371/journal.pbio.1002146. This article has 57 citations and is from a highest quality peer-reviewed journal.
(mamun2023largescaleidentificationof pages 7-8): Md. Abdulla Al Mamun, Wei Cao, Shugo Nakamura, and Jun-ichi Maruyama. Large-scale identification of genes involved in septal pore plugging in multicellular fungi. Nature Communications, Mar 2023. URL: https://doi.org/10.1038/s41467-023-36925-y, doi:10.1038/s41467-023-36925-y. This article has 16 citations and is from a highest quality peer-reviewed journal.