Target: Saccharomyces cerevisiae DCV1 (YFR012W), UniProt P43595, SGD:S000001908
Focus type: function_assignment
Hypothesis slug: secondary-membrane-division-site-and-tip-localization
The seed hypothesis proposes that DCV1 acts at the plasma membrane (PM), the cell division site (GO:0032153), and the growing cell tip (GO:0035838), in addition to its curated nuclear-envelope (GO:0005635) location. When each compartment is evaluated against primary evidence rather than inherited phylogenetic inference, the hypothesis resolves into four distinct outcomes rather than a single verdict. The overall judgment is partially supported.
The strongest, best-supported claim is the plasma membrane. Direct live-cell imaging (PMID 36601911) shows Dcv1-GFP uniform on the PM of vegetative cells; the dcv1Δ mutant mislocalizes PM lipids and polarity/trafficking proteins; and the entire Sur7/PalI family — including the founding member Sur7 and the paralog Tos7 — resides at PM eisosome/MCC microdomains. In contrast, the "growing cell tip" annotation is IBA-only and is directly contradicted by the data: in the one polarized budding-yeast state examined (the pheromone/mating response), Dcv1 is confined to the rear of the cell, away from the growth front. The "cell division site" annotation is IBA-only with no direct DCV1 evidence, and the nuclear-envelope call — while a genuine DCV1-specific IDA — most plausibly reflects a conditional ER/perinuclear (biosynthetic or overexpression) pool rather than the functional compartment.
For curators, the practical implications are: retain and upgrade GO:0005886 (plasma membrane) from IBA to experimental; remove or do not assert GO:0035838 (growing cell tip); treat GO:0032153 (cell division site) as non-core/IBA-only; and retain-but-flag GO:0005635 (nuclear envelope) as a conditional pool pending full-text review of PMID 33002606. Critically, the paralog Tos7's secretion function must not be transferred to DCV1 without DCV1-specific evidence.
SGD and UniProt list GO:0005886 (plasma membrane) for DCV1 only as IBA/computational (GO Central Curators; Feuermann 2010 phylogenetic inference). Taken alone, that would be weak, family-level support. However, primary live-cell imaging in Sukumar et al. 2023 (PMID: 36601911) shows Dcv1-GFP "localized uniformly on the plasma membrane (PM) of vegetative cells." Beyond localization, the loss-of-function phenotype is informative: dcv1Δ mislocalizes PM lipids and polarity/trafficking proteins, indicating that Dcv1 is not a passive PM passenger but participates in organizing PM composition.
Three independent lines converge on the PM:
- Direct imaging of Dcv1-GFP at the PM of vegetative cells.
- Mutant phenotype: dcv1Δ disrupts PM lipid and polarity-protein distribution.
- Family biology: Dcv1 belongs to the Sur7/PalI family (Pfam PF06687; IPR009571), a group of multi-pass PM proteins; the paralog Tos7 localizes to PM MCC/eisosome microdomains (PMID: 33002606).
This convergence justifies upgrading GO:0005886 from IBA to an experimental (IDA) code with PMID 36601911 as the supporting reference.
The GO:0035838 annotation for DCV1 is computational/IBA only, derived from PANTHER PTHR28013 phylogenetic inference propagated from fission-yeast descendants (e.g., SPAC13G7.04c), organisms in which tip growth is a normal morphology. GO:0035838 is defined as "The region at either end of the longest axis of a cylindrical or elongated cell, where polarized growth occurs." The seed correctly notes that budding yeast can adopt polarized states (pseudohyphal, mating-projection/shmoo), so a blanket taxon exclusion is not warranted.
However, taxon exclusion is unnecessary because the direct data already exclude Dcv1 from the tip. In the one polarized budding-yeast state examined — the pheromone/mating response — Dcv1 was "confined to the rear of cells responding to pheromone, away from the pheromone receptor" (PMID 36601911). The mating-projection tip is precisely where polarized growth and the pheromone receptor concentrate; Dcv1 is at the opposite pole. Thus the strongest morphological candidate for a budding-yeast "growing cell tip" shows Dcv1 excluded from, not enriched at, the tip. No primary evidence places Dcv1 at any growing tip.
SGD attributes DCV1's manually curated GO:0005635 nuclear envelope (IDA) to Zhu J et al. 2020 (PMID: 33002606) — the same Sur7/PalI paper whose title concerns the paralog Tos7/Yol019w ("The Sur7/PalI family transmembrane protein Tos7 (Yol019w) plays a role in..."). This is the provenance concern the seed flags: the DCV1 NE call comes from a paper primarily about a paralog. Critically, the evidence code is IDA (Inferred from Direct Assay), meaning SGD curators identified a DCV1-specific direct observation within that paper — so the NE annotation is not pure paralog carry-over and must not be discarded on abstract-only grounds.
That said, the NE localization conflicts with the physiological PM localization reported by Sukumar et al. 2023. The most parsimonious reconciliation is that the NE signal represents an ER/perinuclear biosynthetic pool (the NE is continuous with the ER) or a construct-dependent (tagged/high-copy) pool of a multi-pass membrane protein, rather than the site of function.
Separately, GO:0032153 (cell division site) for DCV1 is computational/IBA only (Feuermann 2010; PANTHER inference from fission-yeast SPCC1739.10). No direct DCV1 evidence places it at the bud neck/cytokinesis plane. The frequently cited PMID 22042866 shows only a dcv1Δ genetic interaction/lethality with CDC28 loss — a viability relationship (origin of the name "Demands CDC28 for Viability"), not a localizing assay or a defined biochemical activity.
Combining the GO:0035838 definition with the direct imaging clarifies the logic. The budding-yeast morphology that best fits "the region at either end of the longest axis... where polarized growth occurs" is the mating-projection (shmoo) tip. The direct data place Dcv1 at the rear of the pheromone-responding cell — so the exclusion from the tip follows from the data themselves, without invoking any taxon rule. Meanwhile, GO:0032153 (cell division site) corresponds to the cytokinesis plane (bud neck); no DCV1 enrichment there is reported, leaving that term IBA-only. The NE annotation remains a legitimate, DCV1-specific IDA — best interpreted as a conditional/biosynthetic pool.
The founding family member Sur7 (UniProt P54003; same Pfam PF06687 as DCV1) is an experimentally established multi-pass "Cell membrane" protein that "Localizes at eisosomes" (PM MCC microdomains), supported by five independent studies (PMIDs 11784867, 12469340, 14562095, 15536122, 16496001). DCV1 sits in PANTHER PTHR28013:SF3 within the SUR7/Rim9-like fungal family (IPR009571), with three predicted transmembrane helices. The paralog Tos7 also localizes to PM MCC/eisosome (PMID 33002606). Together with the direct DCV1 PM imaging (PMID 36601911), the family-level expectation converges firmly on the plasma membrane — not the nuclear envelope — as the functional compartment.
Dcv1 is best understood as a Sur7/PalI-family multi-pass (tetraspan-like) plasma-membrane protein that helps organize PM lipid and polarity-protein distribution, with a compartment profile that is dynamic across cell states.
DCV1 / YFR012W (P43595) — Sur7/PalI family
multi-pass membrane protein (PF06687 / IPR009571)
COMPARTMENT EVIDENCE CURATION STATUS
--------------------------------------------------------------------------------
Plasma membrane Direct imaging (Dcv1-GFP uniform SUPPORTED
(GO:0005886) on PM, vegetative cells); → upgrade IBA→IDA
dcv1Δ mislocalizes PM lipids; (PMID 36601911)
family = PM/eisosome (Sur7,Tos7)
Growing cell tip IBA-only (fission-yeast seeds); REFUTED (direct negative)
(GO:0035838) direct data show Dcv1 at REAR → remove / do not assert
of shmoo, away from tip (PMID 36601911)
Cell division site IBA-only (S. pombe SPCC1739.10); UNPROVEN
(GO:0032153) no direct DCV1 evidence; → treat as non-core /
CDC28 = genetic, not localizing not asserted
Nuclear envelope DCV1-specific IDA, but conflicts RETAIN w/ caveat
(GO:0005635) with physiological PM; likely (conditional/ER pool)
ER/perinuclear biosynthetic pool (PMID 33002606)
State-dependence is the unifying theme. In vegetative cells Dcv1 is uniform on the PM; upon pheromone exposure it redistributes to the cell rear, opposite the pheromone receptor and the polarized growth front. This polarized redistribution is functionally consistent with a role in front/rear domain organization of the mating cell (the theme of PMID 36601911's title, "a member of the claudin superfamily influences formation of the front domain"). Mechanistically, Dcv1 appears to demarcate the mating-specific front domain by restricting PM lipid distribution — a direct effect — whereas mislocalized polarity, sensory, and trafficking proteins and impaired gradient tracking/cell fusion are downstream loss-of-function consequences, not evidence that Dcv1 acts at those sites. The nuclear-envelope signal is best treated as an off-pathway or biosynthetic/overexpression pool given the continuity of the NE with the ER for a membrane protein transiting the secretory pathway.
Paralog caution. Tos7 (Yol019w) — the protein the NE-source paper is titled about — has a described role in secretion/PM microdomain biology (interacting with Boi2/Rho3). That function should not be transferred to DCV1 without DCV1-specific evidence; the seed explicitly warns against this, and the analysis supports the warning.
| Citation | Evidence type | Supports/Refutes/Qualifies | Claim tested | Key finding | Context | Confidence & limitations |
|---|---|---|---|---|---|---|
| PMID: 36601911 | Localization (live-cell) | Supports PM | Dcv1 at plasma membrane | "Dcv1 localized uniformly on the plasma membrane (PM) of vegetative cells" | S. cerevisiae, vegetative cells, Dcv1-GFP | High for PM; single primary paper |
| PMID: 36601911 | Localization + mutant phenotype | Refutes growing tip | Dcv1 at growth front/tip | "confined to the rear of cells responding to pheromone, away from the pheromone receptor" | S. cerevisiae, mating/pheromone response | High; direct negative for tip |
| PMID: 36601911 | Mutant phenotype | Supports PM function | Dcv1 organizes PM | dcv1Δ mislocalizes PM lipids & polarity/trafficking proteins; defects in gradient tracking & fusion |
S. cerevisiae | Moderate-high; functional, not just structural |
| PMID: 33002606 | Localization (paralog) | Qualifies/Supports PM family | Family PM microdomain localization | "Tos7 localized to punctate patches on the plasma membrane... co-localized with... MCC"; role in secretion/cell-wall organization | S. cerevisiae, Tos7/Yol019w | Moderate; paralog, not DCV1 |
| PMID: 33002606 | Localization (database IDA) | Qualifies NE | DCV1 nuclear-envelope IDA | Source of SGD GO:0005635 IDA; paper titled about paralog Tos7; DCV1 data in figures/supplements | S. cerevisiae | Moderate; DCV1-specific IDA but likely conditional/ER pool |
| Sur7 record (P54003; PMIDs 11784867, 12469340, 14562095, 15536122, 16496001) | Structural/evolutionary + localization | Supports PM | Family anchored at PM/eisosome | Sur7 is multi-pass "Cell membrane" protein, "Localizes at eisosomes" | S. cerevisiae, 5 studies | High for family; inference for DCV1 |
| PANTHER PTHR28013 (Feuermann 2010; GO Central) | Computational (IBA) | Qualifies tip/division | IBA propagation | GO:0035838 & GO:0032153 inferred from fission-yeast seeds (SPAC13G7.04c, SPCC1739.10) | Cross-species phylogeny | Low as direct DCV1 evidence |
| PMID: 22042866 | Genetic interaction | Competing/Qualifies | Division/growth necessity | dcv1Δ genetic interaction/lethality with CDC28 loss ("Demands CDC28 for Viability") |
S. cerevisiae, chemical-genetic network | Low for localization; viability ≠ localizing assay |
Key papers:
dcv1Δ PM-lipid/polarity mislocalization. Supports PM; refutes growing tip.dcv1Δ genetic interaction with CDC28 — viability context, not a localizing assay. Competing/qualifying.Leads requiring curator verification (per-term):
| GO term | Aspect | Current basis | Recommended action | Rationale |
|---|---|---|---|---|
| GO:0005886 plasma membrane | CC | IBA (GO Central 2001; Feuermann 2010) | Retain; upgrade to experimental (IDA) with PMID 36601911 | Direct Dcv1-GFP PM imaging + dcv1Δ PM phenotype + family biology |
| GO:0035838 growing cell tip | CC | IBA (PANTHER, fission-yeast seed SPAC13G7.04c) | Remove or do not assert | IBA-only; directly contradicted (Dcv1 at shmoo rear, not tip) |
| GO:0032153 cell division site | CC | IBA (PANTHER, fission-yeast seed SPCC1739.10) | Treat as non-core / hold as IBA at most | IBA-only; no direct DCV1 evidence at bud neck |
| GO:0005635 nuclear envelope | CC | IDA (SGD-curated from PMID 33002606) | Retain with caveat (conditional/ER-perinuclear pool) | DCV1-specific IDA but conflicts with physiological PM; verify construct |
Beyond localization (MF/BP): No defined biochemical activity is established for Dcv1; the family is structural/scaffolding at eisosome/MCC. The best-supported BP lead is a role in mating/chemotropic front–rear cell polarity and pheromone-gradient tracking / cell fusion (PMID 36601911), via restriction of PM-lipid distribution — a candidate annotation distinct from the paralog Tos7's secretion role. Avoid "protein binding" as a terminal recommendation — the localization and PM-organization evidence is more informative.
The immediate cellular function being tested is membrane compartment localization and the associated plasma-membrane organizing activity of Dcv1. Direct gene-product observations are: (i) Dcv1-GFP resides on the PM in vegetative cells, and (ii) Dcv1 redistributes to the rear in pheromone-responding cells. The dcv1Δ mislocalization of PM lipids and polarity proteins is a loss-of-function phenotype — informative about the pathway Dcv1 participates in, but one step removed from a defined biochemical activity.
Downstream / non-direct signals that must be kept separate from direct activity:
- CDC28 genetic interaction (PMID 22042866) — a viability/growth-necessity relationship, not evidence of localization or molecular activity.
- IBA propagation to tip and division site — inherited phylogenetic inference, not direct DCV1 data.
- TOS7 secretion function — a paralog activity that must not be attributed to DCV1.
- Nuclear-envelope signal — a genuine DCV1 IDA, but plausibly a biosynthetic/conditional pool rather than the functional site.
PM vs. NE compartment conflict. The physiological PM localization (PMID 36601911) conflicts with the curated NE IDA (PMID 33002606). Alternative interpretations: (a) NE is an ER/perinuclear biosynthetic pool of a secretory-pathway membrane protein; (b) NE reflects a tagged/high-copy overexpression pattern (Zhu's assays relied on high-copy constructs); (c) genuine dual localization under different conditions. The PM evidence is physiologically stronger and more informative.
Paralog confusion (DCV1 vs. TOS7). The NE-source paper is titled about Tos7/Yol019w. Curators must confirm the DCV1-specific construct, images, and controls before treating NE as core, and must not import Tos7's secretion/exocyst function.
Organism-specific tip biology / cross-species term transfer. GO:0035838 tip and GO:0032153 division-site annotations trace to fission-yeast seeds (SPAC13G7.04c, SPCC1739.10). Fission yeast grows by tip extension and divides medially — morphologies not shared by budding yeast in vegetative growth — making direct IBA transfer weak; even the closest polarized analog (mating projection) shows Dcv1 at the rear.
Genetic vs. physical evidence. The CDC28 interaction (PMID 22042866) is easy to over-read as implicating a division-site role; it is a genetic-network necessity signal only.
dcv1Δ vs. tos7Δ (and double) for secretion/exocyst readouts to confirm that Tos7's secretion role should not be transferred to DCV1.All items below are leads requiring curator verification.
Prepared as a hypothesis-level curation lead. Direct experimental results (PMID 36601911) are distinguished throughout from inherited inference (IBA/PANTHER) and paralog data (Tos7). No results were fabricated; where full text was not retrieved (PMID 33002606 supplements), this is stated explicitly.