DSF2 (YBR007C) is a 736-residue protein of the budding yeast Saccharomyces cerevisiae composed of a large intrinsically disordered / low-complexity N-terminal half (~residues 1-461) and a C-terminal Sel1-like tetratricopeptide (TPR) repeat solenoid (~residues 560-736). Sel1/TPR repeats are alpha-helical scaffolds that typically mediate protein-protein interactions, and DSF2 has no predicted catalytic domain. The protein localizes to the bud tip and bud neck of growing cells and moves to the cytoplasm during DNA-replication stress. It is a low-abundance phosphoprotein. Its molecular function and the biological process it participates in are not experimentally established. DSF2 belongs to a Sel1-repeat protein family (PANTHER PTHR43628) whose best-characterized member is the fission-yeast mitotic inhibitor Nif1, which negatively regulates entry into mitosis; whether DSF2 has an analogous cell-cycle role in S. cerevisiae has not been demonstrated. DSF2 was originally identified as a deletion suppressor of the puf5/mpt5 RNA-binding-protein deletion, a genetic relationship that does not by itself define its own function. Despite the shared "Dsf" name, DSF2 is not a homolog of DSF1 (YEL070W, a mannitol dehydrogenase); both were merely recovered in the same suppressor screen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0010972 negative regulation of G2/M transition of mitotic cell cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference propagated from the fission-yeast ortholog Nif1 (PomBase:SPBC23G7.04c), which negatively regulates mitotic entry. DSF2 and Nif1 share only Sel1-like/TPR repeats, and no S. cerevisiae experiment shows DSF2 acting on Swe1/Cdc28 or a Nim1-family kinase. The inference is plausible but uncorroborated for budding yeast, so it is kept as a non-core annotation rather than removed (per guidance not to REMOVE on distant-ortholog grounds alone). Reason: Legitimate IBA transfer from Nif1 but not experimentally supported in S. cerevisiae; DSF2's own biological process is unknown, so this cannot be treated as a core function. Supporting Evidence: PMID:16328373 dsf1 (YEL070W), dsf2 (YBR007C) |
| GO:0032153 cell division site | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA inference from the same Nif1 ortholog. It is loosely consistent with the experimentally observed bud-tip / bud-neck localization of DSF2, but "is_active_in the cell division site" asserts a functional activity there that has not been demonstrated for DSF2. Retained as non-core given the supporting localization but flagged as unverified for activity. Reason: Distant-ortholog IBA; the localization component is consistent with HDA bud-tip data, but no DSF2 activity at the division site is established. |
| GO:0005934 cellular bud tip | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: Direct high-throughput GFP-localization evidence (HDA) that Dsf2 localizes to the bud tip (and bud neck), from a genome-wide imaging screen. This is the best-supported annotation for DSF2 and is accepted; it is the anchor for the protein's cellular location, although localization alone does not define molecular function. Reason: Experimental (HDA) localization for DSF2 itself; consistent with SGD's bud-tip/bud-neck localization and the replication-stress relocalization. Supporting Evidence: PMID:22842922 one that reflects movement away from the budneck or bud tip |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular_function annotation with ND (no biological data) evidence, correctly recording that DSF2's molecular function is unknown. This is an honest placeholder and is retained: no specific MF term is defensible from current evidence (the Sel1/TPR architecture suggests a protein-interaction module but no partner or activity has been shown). Reason: Accurately reflects the genuine absence of molecular-function knowledge for this dark gene. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process annotation with ND evidence, correctly recording that DSF2's biological process is unknown at the level of direct evidence. The only BP signal is the distant-ortholog IBA (negative regulation of G2/M), which is not corroborated in S. cerevisiae, so retaining the ND root is the honest position. Reason: Accurately reflects the genuine absence of direct biological-process knowledge for this dark gene. |
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Download this section (compressed HTML)Q: What are the physiological binding partners of Dsf2, and do they define it as a scaffold/adaptor at the bud tip or bud neck?
Q: Does DSF2 have any role in the budding-yeast G2/M transition (e.g. through Swe1 or Cdc28), as its phylogenetic annotation from Nif1 would predict?
Q: By what mechanism does dsf2 deletion suppress the temperature and hydroxyurea sensitivity of a puf5/mpt5 deletion?
Experiment: Affinity purification-mass spectrometry (or proximity labeling such as BioID/TurboID) of endogenously tagged Dsf2 in log-phase and replication-stress conditions to identify stable and stress-dependent interactors.
Hypothesis: Dsf2 uses its Sel1/TPR solenoid to scaffold a specific partner at the bud tip/neck; identifying that partner would define its molecular function.
Type: affinity purification-mass spectrometry
Experiment: Quantitative cell-morphology and cell-cycle profiling of dsf2 deletion and overexpression strains, plus genetic-interaction tests with SWE1 and CDC28, to test the phylogenetically inferred negative regulation of G2/M.
Hypothesis: If the Nif1-based inference holds, perturbing DSF2 will change cell length or G2/M timing and interact genetically with the Swe1-Cdc28 axis.
Type: genetic interaction / cell-cycle phenotyping
Experiment: Epistasis analysis of the dsf2-mediated suppression of puf5/mpt5 phenotypes, testing dependence on known mpt5-suppression modifiers (e.g. PUF4, IME4) and whether Dsf2 abundance/localization changes in a puf5 background.
Hypothesis: dsf2 suppression of mpt5 operates through a definable branch of the Puf-family regulatory network rather than a nonspecific fitness effect.
Type: genetic epistasis
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular function of DSF2 is undetermined: no catalytic activity, no specific binding partner, and no scaffold/adaptor role has been experimentally demonstrated. The only structural clue is a C-terminal Sel1-like/TPR repeat solenoid, a generic protein-interaction module that does not specify an activity or a partner.
OPEN BIOLOGY MF_DARK
What is known: Established: DSF2 is a 736-aa protein with a disordered N-terminal half and a C-terminal Sel1-like/TPR-repeat region (UniProt P38213: SMART SEL1, InterPro IPR006597/IPR011990, SUPFAM HCP-like), it is a detected phosphoprotein, and it localizes to the bud tip/neck. SGD lists molecular function as Unknown.
Significance: DSF2 is a conserved (fungal-to-bacterial Sel1-repeat) yet functionally dark protein; identifying its binding partner(s) would convert a structural guess into an actual molecular function and likely explain its cell-cycle-adjacent annotations.
What would resolve it: Affinity purification / proximity labeling of Dsf2 to identify stable interactors, followed by testing whether it acts as a scaffold for the identified partner(s); a defensible specific MF term (e.g. a protein-binding adaptor term) could then replace the MF root.
Provenance (the field's own admissions):
Gap: The biological process DSF2 participates in is unknown. The sole process annotation (negative regulation of the G2/M transition) is a phylogenetic (IBA) inference from the distant fission-yeast ortholog Nif1 and has never been tested in S. cerevisiae; whether DSF2 regulates the budding-yeast cell cycle (e.g. via Swe1/Cdc28) is undetermined.
OPEN BIOLOGY BP_DARK
What is known: Established: the IBA is transferred from Nif1 (PomBase:SPBC23G7.04c), a Sel1-repeat mitotic inhibitor. DSF2 shares only Sel1/TPR repeats with Nif1, and there is no budding-yeast experimental link between DSF2 and the Swe1-Cdc28 or Nim1-kinase machinery.
Significance: Confirming or refuting a cell-cycle role would either validate the cross-species inference or reveal that DSF2's bud-tip localization serves an unrelated process.
What would resolve it: Epistasis and cell-length/cell-cycle phenotyping of dsf2 mutants combined with genetic interaction tests against SWE1/CDC28; direct assay of whether Dsf2 binds or modulates Swe1 or Cdc28.
Provenance (the field's own admissions):
Gap: The mechanism by which loss of DSF2 suppresses the temperature- and hydroxyurea-sensitivity of a puf5/mpt5 deletion is unknown. It is not established whether this reflects a direct functional relationship between Dsf2 and the Puf5 RNA-binding pathway or an indirect, downstream effect.
OPEN BIOLOGY BP_DARK
What is known: Established: dsf2 was recovered as a deletion suppressor of mpt5/puf5 temperature-sensitivity, and DSF2 loss partially suppresses mpt5 HU sensitivity (PMID:16328373; UniProt P38213 disruption phenotype). No molecular mechanism for this suppression has been reported.
Significance: Puf5/Mpt5 is a well-studied Puf-family translational repressor; explaining how a bud-tip Sel1-repeat protein feeds into its pathway could place DSF2 in a defined regulatory network.
What would resolve it: Dissect the suppression genetically (is it PUF4/IME4-dependent, as for other mpt5 suppressors?) and test whether Dsf2 abundance or localization changes in a puf5 background.
Provenance (the field's own admissions):
Gap: The functional significance of DSF2 relocalizing from the bud tip/neck to the cytoplasm during DNA-replication stress (HU/MMS) is unknown; it is not known whether this movement is part of a stress response or an incidental consequence of bud-neck disassembly.
OPEN BIOLOGY CC_DARK
What is known: Established: a genome-wide GFP screen scored DSF2 among proteins that lose bud-neck/bud-tip localization under replication stress (PMID:22842922; SGD). No follow-up has tested the consequence of this relocalization.
Significance: Stress-induced relocalization is often functionally informative; resolving it could link DSF2's location to a specific process.
What would resolve it: Test whether blocking DSF2 relocalization (or deleting DSF2) alters replication-stress survival, and identify the signal driving the move.
Provenance (the field's own admissions):
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