Polarity-associated protein SPA2 is a large, nonessential scaffolding protein required for normal establishment and maintenance of cell polarity in budding yeast. SPA2 localizes to sites of polarized growth (bud tip, mating projection, bud neck) where it functions as a core component of the polarisome complex together with Pea2p and Bud6p. SPA2 serves as a scaffold for recruiting and organizing multiple functional modules including actin cable assembly through interaction with formin Bni1, MAPK signaling pathway components (its N-terminal SHD1 domain docks a short linear motif in the MAPKKs Ste7 and Mkk1 and in the Rab GAPs Msb3/Msb4), the actin-nucleation factor Aip5, and proteins involved in bud site selection and cytokinesis. The protein contains multiple functional domains including conserved SHD (SPA2 Homology Domain) regions critical for protein-protein interactions and a C-terminal region containing tandem repeats.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000131 incipient cellular bud site | IBA GO_REF:0000033 | ACCEPT | Summary: SPA2 is a core component of the incipient bud site, localizing to sites of polarized growth before the bud is morphologically evident. This early and consistent localization is a defining characteristic of SPA2. Reason: Strong experimental evidence (IDA in primary literature) demonstrates SPA2 as an early marker of polarized growth sites. IBA assignment is appropriate for this well-conserved localization property across orthologs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places incipient cellular bud site localization on PTN001091461 with Saccharomyces and Candida Spa2 descendants, and yeast Spa2 is directly observed at the incipient bud site. Supporting Evidence: PMID:9214378 Spa2p is one of the first proteins involved in bud formation to localize to the incipient bud site before a bud is recognizable |
| GO:0005078 MAP kinase scaffold activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function as direct scaffold for Mpk1p/Slt2p MAPK pathway; recruits MEKs and MAPK to polarized growth sites for cell wall integrity signaling. Reason: Experimental evidence (IDA, IMP) shows that SPA2 directly binds and recruits Mpk1p MAPK pathway components to polarized growth sites. A 2026 study mapped the binding to a short linear motif in Ste7 and Mkk1 that docks on the Spa2 SHD1 domain, with a qualification from the same paper. The SHD1-Ste7 interaction is needed to hold Ste7 at the shmoo tip, but cells lacking it still arrest on pheromone like wild type, so no signalling output of that interaction was detected. Mkk1 binds SHD1 only weakly, much more weakly than the Rab GAPs Msb3/Msb4, and the Mkk1 and Mkk2 N-terminal regions did not measurably bind SHD1 in the in vitro overlay. The 2026 motif data therefore support SHD1 as a localization dock for MAPKKs rather than independently demonstrating signalling scaffold activity; the ACCEPT rests on the Mkk1/Mpk1 recruitment data of PMID:12361575. The scaffold activity is correct and core for S. cerevisiae Spa2, the IBD seed. Placing this IBD on the Eukaryota root node PTN004550576 over-reaches, however, because S. pombe Spa2 shows no MAPK interaction or MAPK-localization role (see genes/SCHPO/spa2). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000492368 · PTN000492368 SOURCE STALE OR MISSING GOA traces this 2017 IBA to PTN000492368, which is not recoverable in the current PTHR21601 PAINT TSV. PANTHER:PTN004550576 · PTN004550576 SUPPORTS TRANSFER Current PTHR21601 PAINT now places MAP kinase scaffold activity on the broad Eukaryota node PTN004550576 with S. cerevisiae SPA2 as the experimental seed, matching the direct Mpk1/Mkk1 recruitment evidence. The transfer is sound for SPA2 (but not for its paralog SPH1, which is not needed to localize Slt2 or Mkk1; see genes/yeast/SPH1), and the root-level placement is too deep for S. pombe Spa2, which has negative MAPK data. Supporting Evidence: PMID:12361575 Spa2p functions as a scaffold-like protein to recruit the Mpk1p MAP kinase module to sites of polarized growth PMID:9632790 Spa2p interacts with Ste11p (MAPK kinase [MEK] kinase) and Ste7p (MEK) of the mating signaling pathway as well as with the MEKs Mkk1p and Mkk2p of the Slt2p (Mpk1p) MAPK pathway PMID:41527849 We identified a conserved short linear motif in the Rab GTPase-activating proteins (RabGAPs) Msb3 and Msb4, and the MAP kinase kinases Ste7 and Mkk1, which mediates their interaction with Spa2. PMID:41527849 Although the interaction between Ste7 and Spa2 is required to attach Ste7 to the shmoo tip (Fig. 4C,D), cells lacking this interaction arrest the cell cycle upon pheromone treatment as is seen for wild-type cells and not like ste7Δ cells PMID:41527849 The N-terminal regions of Mkk1 or Mkk2 did not measurably interact with 6×His-SHD1Spa2 under these conditions PMID:41527849 Our assays demonstrate that Msb4, Msb3, Ste7 and Mkk1 bind to Spa2 with decreasing affinity PMID:25428987 We did not detect physical or genetic interactions between Spa2 and the S. pombe homologues of Bni1, Bud6, or MAP kinases |
| GO:0005826 actomyosin contractile ring | IBA GO_REF:0000033 | REMOVE | Summary: Budding-yeast Spa2 localizes to the bud neck but is not known to be a structural component of the actomyosin contractile ring itself. Reason: S. pombe Spa2 genuinely localizes to the division-site contractile ring, and current PTHR21601 PAINT carries the PomBase seed forward as GO:0120105 mitotic actomyosin contractile ring, intermediate layer on PTN004550576. S. cerevisiae Spa2 is instead supported directly at the bud tip, mating projection tip and bud neck; the old actomyosin-contractile-ring IBA is a cross-species transfer from the fission-yeast cytokinetic compartment to the wrong budding-yeast structure. Because GO:0120105 is now placed at the same Eukaryota node from only the S. pombe seed, that live placement should be narrowed away from budding-yeast SPA2 rather than used as a budding-yeast-compatible successor. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001091460 · PTN001091460 SOURCE STALE OR MISSING GOA traces this old actomyosin-contractile-ring IBA to PTN001091460 and fission-yeast SPAC3G9.05; the current PTHR21601 PAINT export no longer contains PTN001091460 or a GO:0005826 IBD. PANTHER:PTN004550576 · PTN004550576 SUPPORTS SOURCE BUT NOT TARGET Current PAINT places GO:0120105 mitotic actomyosin contractile ring, intermediate layer at this Eukaryota node with PomBase:SPAC3G9.05 as the only IBD seed. That fission-yeast division-site component should not be exported to budding-yeast SPA2, even though SGD-seeded polarity and MAPK-scaffold assertions on the same node do transfer. PomBase:SPAC3G9.05 · S. pombe spa2 SUPPORTS SOURCE BUT NOT TARGET PMID:40931936 supports the source species by showing that "Spa2–GFP localized to cell tips and the contractile ring (CR)"; this validates fission-yeast contractile-ring localization rather than transfer to the budding-yeast polarisome. |
| GO:0005934 cellular bud tip | IBA GO_REF:0000033 | ACCEPT | Summary: Strong and consistent localization of SPA2 to bud tip where it organizes actin cables and polarity factors. Reason: Direct experimental evidence (IDA) for localization to bud tip; functionally essential for actin organization and polarized bud growth. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places cellular bud tip localization on PTN001091461, a Saccharomycetales-level node with S. cerevisiae SPA2 among the experimental descendants. Supporting Evidence: PMID:9214378 Our studies with Spa2GFP demonstrate that Spa2p localizes to the bud tip, forming a cup-like crescent, and the bud neck between mother and daughter cell, forming a donut-like ring. PMID:12361575 Spa2p-GFP is stably anchored at bud tips |
| GO:0005935 cellular bud neck | IBA GO_REF:0000033 | ACCEPT | Summary: SPA2 localizes to bud neck as ring structure during cytokinesis; interacts with septin components including Shs1p. Reason: Clear microscopic evidence (IDA) for bud neck localization, particularly during cytokinesis. Functions in septin ring organization and polarity maintenance. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places cellular bud neck localization on PTN001091461, consistent with the direct Spa2p-GFP bud-neck ring observed during cytokinesis. Supporting Evidence: PMID:9214378 During cytokinesis Spa2p is present as a ring at the mother-daughter bud neck |
| GO:0007121 bipolar cellular bud site selection | IBA GO_REF:0000033 | ACCEPT | Summary: SPA2 is essential for establishing bipolar budding pattern in diploid cells; mutants show defects in bud site selection. Reason: Strong genetic evidence (IMP) for role in bipolar bud site selection. IBA appropriately reflects conservation of this function across species. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places bipolar cellular bud site selection on PTN001091461 with S. cerevisiae SPA2 and SPH1 seeds, matching the Saccharomyces diploid bud-site phenotype. Supporting Evidence: PMID:8909546 SPA2 is required for the bipolar budding pattern PMID:9214378 Spa2p, a nonessential protein, has been shown to be involved in bud site selection |
| GO:0007124 pseudohyphal growth | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SPA2 is required for pseudohyphal growth morphology but this represents a secondary developmental process, not core polarity function. Reason: SPA2 is involved in pseudohyphal growth through maintenance of polarized growth capability under nutrient stress. However, this is a specialized developmental program secondary to core cell polarity establishment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places pseudohyphal growth on PTN001091461. The transfer is supported by Saccharomyces Spa2-family genetics, but pseudohyphal growth is a condition-specific polarity program. Supporting Evidence: PMID:9055077 Dissection of filamentous growth by transposon mutagenesis in Saccharomyces cerevisiae. PMID:9443897 The Spa2-related protein, Sph1p, is important for polarized growth in yeast |
| GO:0036267 invasive filamentous growth | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SPA2 is required for invasive filamentous growth; genetic interaction with Spa2-related protein Sph1p shows importance for this developmental pathway. Reason: Genetic interaction evidence (IGI) shows SPA2 role in invasive growth, but this is a specialized developmental process secondary to core polarity function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SUPPORTS TRANSFER Current PTHR21601 PAINT places invasive filamentous growth on PTN001091461 with Saccharomyces Spa2-family seeds; this is a valid non-core extension of Spa2's polarized-growth function. Supporting Evidence: PMID:9443897 sph1(Delta) spa2(Delta) double mutants also exhibit a strong haploid invasive growth defect and an exacerbated mating projection defect relative to either sph1(Delta) or spa2(Delta) single mutants. |
| GO:0043332 mating projection tip | IBA GO_REF:0000033 | ACCEPT | Summary: SPA2 localizes prominently to mating projection tip (shmoo); essential for directed growth toward mating partner. Reason: Direct evidence (IDA) for localization to mating projection; essential for pheromone response and efficient mating. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001091461 · PTN001091461 SOURCE STALE OR MISSING GOA traces this 2017 IBA to PTN001091461, but current PTHR21601 PAINT no longer places mating projection tip at that older node. PANTHER:PTN004550576 · PTN004550576 SUPPORTS TRANSFER Current PTHR21601 PAINT now places mating projection tip on the broad Eukaryota node PTN004550576 with S. cerevisiae SPA2 as the seed, in register with direct shmoo-tip localization. PTN004550576 carries five current IBDs; its PomBase-only GO:0120105 actomyosin-ring assertion is a separate division-site placement that should be narrowed away from budding-yeast SPA2 and does not support the old growing-tip cortex row. Supporting Evidence: PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth PMID:9214378 Spa2p is also found at the mother-daughter bud neck in cells undergoing cytokinesis file:yeast/SPA2/SPA2-deep-research-falcon.md During pheromone response, Spa2 is required for **focal** (narrow) polarization of the polarisome at the shmoo tip; Spa2 loss leads to wider projections consistent with reduced focusing of polarized secretion/transport. |
| GO:1902716 cell cortex of growing cell tip | IBA GO_REF:0000033 | MODIFY | Summary: SPA2 localizes to cortical polarized-growth sites in budding yeast, but those sites are better represented as the cellular bud tip and cell cortex than as the generic fission-yeast-style growing cell tip cortex. Reason: GOA links this row to the same stale PTN001091460 and PomBase:SPAC3G9.05 source combination as the actomyosin-contractile-ring row. Current PAINT no longer carries GO:1902716, and the fission-yeast Spa2 evidence supports tip and division-site localization in a tip-growing rod-shaped yeast rather than this composite cellular component for S. cerevisiae. Existing direct SGD annotations to cellular bud tip and cell cortex capture the supported budding-yeast location without preserving this over-transferred IBA. The live PomBase-only GO:0120105 IBD at PTN004550576 shows that the broad node still needs source-specific handling for fission-yeast division-site localization, even though the older GO:1902716 IBD itself has disappeared. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001091460 · PTN001091460 SOURCE STALE OR MISSING GOA traces this cell-cortex-of-growing-tip row to PTN001091460, which is absent from the current PTHR21601 PAINT export and has no live GO:1902716 successor there. PomBase:SPAC3G9.05 · S. pombe spa2 SUPPORTS SOURCE BUT NOT TARGET S. pombe Spa2 localizes to cell tips and the contractile ring in a tip-growing yeast, but this supports source-species cortical polarity and division-site localization rather than transfer of GO:1902716 to budding-yeast Spa2. Proposed replacements: cellular bud tip cell cortex Supporting Evidence: PMID:9214378 Our studies with Spa2GFP demonstrate that Spa2p localizes to the bud tip, forming a cup-like crescent, and the bud neck between mother and daughter cell, forming a donut-like ring. PMID:23673619 Spa2-GFP clusters in S. cerevisiae. |
| GO:0000165 MAPK cascade | IEA GO_REF:0000108 | ACCEPT | Summary: Indirect involvement in MAPK cascade through scaffolding the Mpk1p pathway components. Reason: IEA is appropriate; logical inference from GO:0005078 (MAP kinase scaffold activity) that SPA2 is involved in MAPK cascade as a central scaffold. Supporting Evidence: GO:0005078 Logical inference from MAP kinase scaffold activity |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000043 | ACCEPT | Summary: Regulation of cell shape through control of polarized growth and actin organization. Reason: IEA from UniProt keywords is appropriate. SPA2's role in polarized growth fundamentally determines cell morphology. Supporting Evidence: GO_REF:0000043 UniProt keyword mapping |
| GO:0051286 cell tip | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: SPA2 localizes to cell tip as core component of growth site organization. Reason: This old UniProt subcellular-location mapping was appropriate and consistent with direct microscopic evidence, but the generic cell-tip term is broader than the directly observed bud-tip and mating-projection-tip locations. Supporting Evidence: GO_REF:0000044 UniProt subcellular location mapping |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Generic protein binding annotation from interactome study; too vague and uninformative about mechanism. Reason: Too vague and uninformative. SPA2's specific molecular functions (MAP kinase scaffold activity, polarisome assembly, actin regulation) are better represented by mechanistic terms rather than generic binding. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | REMOVE | Summary: Generic protein binding from large-scale interactome study. Reason: Vague annotation better replaced by mechanistic function terms. Multiple duplicate entries for protein binding should be consolidated. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:21502521 Modular coherence of protein dynamics in yeast cell polarity... | REMOVE | Summary: Generic protein binding from modular proteomics study. Reason: Generic annotation not informative about molecular mechanism. Supporting Evidence: PMID:21502521 Modular coherence of protein dynamics in yeast cell polarity system. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic protein binding from large-scale interactome survey. Reason: Generic annotation; specific molecular functions should replace this. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome. |
| GO:0000753 cell morphogenesis involved in conjugation with cellular fusion | IMP PMID:8013906 Identification of genes required for normal pheromone-induce... | ACCEPT | Summary: SPA2 is required for proper morphogenesis during mating; essential for efficient cell fusion with mating partner. Reason: Direct genetic evidence (IMP) shows SPA2 is required for mating morphogenesis. spa2 mutants show defective shmoo formation and reduced mating efficiency. Supporting Evidence: PMID:8013906 Identification of genes required for normal pheromone-induced cell polarization in Saccharomyces cerevisiae |
| GO:0000753 cell morphogenesis involved in conjugation with cellular fusion | IMP PMID:8909546 Pea2 protein of yeast is localized to sites of polarized gro... | ACCEPT | Summary: SPA2 and Pea2p function together in cell morphogenesis during conjugation; interdependent localization. Reason: Complementary genetic evidence showing SPA2-Pea2p interdependent localization is critical for mating morphogenesis. Supporting Evidence: PMID:8909546 These results suggest that Pea2p and Spa2p function together as a complex to generate the bipolar budding pattern and to guarantee proper polarization during mating |
| GO:0006903 vesicle targeting | NAS PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | KEEP AS NON CORE | Summary: SPA2 polarisome coordinates with secretory machinery through Msb3/4 interaction; indirect role in vesicle targeting. Reason: NAS from ComplexPortal is appropriate but SPA2's role in vesicle targeting is indirect through organizing polarisome that coordinates with exocytosis. Not a primary function. Supporting Evidence: PMID:16166638 Msb3 and Msb4 regulate polarized growth by multiple mechanisms, directly regulating exocytosis through their GAP activity toward Sec4 |
| GO:0030010 establishment of cell polarity | NAS PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | ACCEPT | Summary: SPA2 is core scaffolding component of polarisome complex essential for establishing cell polarity. Reason: NAS from ComplexPortal is appropriate for well-characterized complex annotation. SPA2 is definitional component of the polarisome. Supporting Evidence: PMID:16166638 Here we show that the Rab GTPase-activating proteins (GAPs) Msb3 and Msb4 interact directly with Spa2, a scaffold protein of the "polarisome" that also interacts with the formin Bni1. file:yeast/SPA2/SPA2-deep-research-falcon.md Spa2 helps focus the polarisome at cortical growth zones, promotes **formin-dependent actin cable assembly**, recruits or stabilizes partners |
| GO:0030950 establishment or maintenance of actin cytoskeleton polarity | NAS PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | ACCEPT | Summary: SPA2 as polarisome component is essential for organizing and maintaining actin cytoskeleton polarity. Reason: NAS from ComplexPortal is appropriate. SPA2-Bud6p directly regulate actin organization at growth sites. Supporting Evidence: PMID:16166638 Here we show that the Rab GTPase-activating proteins (GAPs) Msb3 and Msb4 interact directly with Spa2, a scaffold protein of the "polarisome" that also interacts with the formin Bni1. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | ACCEPT | Summary: SPA2 regulates actin cable organization and recovery of actin structures under stress through scaffold function. Reason: SPA2 is essential for actin recovery and bud emergence under osmotic stress; core function in actin organization. Beyond scaffolding, recent work (Ma et al. 2024) shows Spa2 can directly remodel actin in a nucleotide-state-specific manner under glucose starvation, reinforcing a direct role in actin cytoskeleton organization. Supporting Evidence: PMID:12857882 Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p file:yeast/SPA2/SPA2-deep-research-falcon.md Spa2 promotes rapid **ADP-actin monomer nucleation** via a dimeric core region (aa 281–535) and bundles ADP-F-actin through an N-terminal IDR-driven condensation (“wetting”) process, dependent on the actin D-loop. PMID:38802374 Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast |
| GO:0032956 regulation of actin cytoskeleton organization | IGI PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | ACCEPT | Summary: Genetic interaction with actin pathway genes demonstrates SPA2's role in actin cytoskeleton organization. Reason: IGI evidence shows genetic interaction with cytoskeleton components; supports core actin regulation function. Supporting Evidence: PMID:12857882 Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:19633059 Importance of polarisome proteins in reorganization of actin... | ACCEPT | Summary: SPA2 is critical for reorganization of actin cytoskeleton in response to acid stress; maintains polarity under environmental challenge. Reason: Shows SPA2 function in actin reorganization under environmental stress; represents core polarity maintenance. Supporting Evidence: PMID:19633059 Importance of polarisome proteins in reorganization of actin cytoskeleton at low pH in Saccharomyces cerevisiae |
| GO:0071468 cellular response to acidic pH | IMP PMID:19633059 Importance of polarisome proteins in reorganization of actin... | KEEP AS NON CORE | Summary: SPA2 involved in maintaining polarized growth and actin organization under acidic conditions. Reason: SPA2 helps maintain actin organization and polarity under acid stress, but this is a stress response secondary to core polarity function. Supporting Evidence: PMID:19633059 Importance of polarisome proteins in reorganization of actin cytoskeleton at low pH in Saccharomyces cerevisiae. |
| GO:0071474 cellular hyperosmotic response | IGI PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: SPA2 participates in osmotic stress response through maintaining actin and polarity. Reason: Genetic interaction evidence; SPA2 helps cells recover polarity and actin under osmotic stress, secondary to core function. Supporting Evidence: PMID:12857882 Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p |
| GO:0005934 cellular bud tip | IMP PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | ACCEPT | Summary: SPA2 localization to bud tip is functionally required for polarized growth. Reason: Functional requirement for bud tip localization consistent with direct evidence; SPA2 organizing polarity at tip. Supporting Evidence: PMID:16166638 Spa2 is required for the polarized localization of Msb3 and Msb4 at the bud tip |
| GO:0032880 regulation of protein localization | IMP PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | ACCEPT | Summary: SPA2 acts as scaffold for polarized localization of multiple proteins including Msb3/4, formins, and kinases. Reason: SPA2 as scaffold protein directly regulates protein localization to growth sites through protein-protein interactions. Supporting Evidence: PMID:16166638 Spa2 is required for the polarized localization of Msb3 and Msb4 at the bud tip |
| GO:0032880 regulation of protein localization | IMP PMID:9571251 Rho1p-Bni1p-Spa2p interactions: implication in localization ... | ACCEPT | Summary: SPA2 regulates Bni1p formin localization to bud site through Rho1p-Bni1p-Spa2p interaction network. Reason: Direct evidence for SPA2 role in regulating formin localization; essential for actin cable assembly. Supporting Evidence: PMID:9571251 Rho1p-Bni1p-Spa2p interactions: implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae. file:yeast/SPA2/SPA2-deep-research-falcon.md an N-terminal Spa2 homology domain (SHD) recruits Msb3/4, promoting Sec4-dependent delivery of Bud6 to the polarisome, where Bud6 stimulates the formin Bni1 to generate actin cables |
| GO:0032880 regulation of protein localization | IMP PMID:9632790 Spa2p interacts with cell polarity proteins and signaling co... | ACCEPT | Summary: SPA2 is component of polarisome complex that localizes actin and signaling proteins to growth sites. Reason: SPA2-Pea2p-Bud6p complex functions to organize protein localization at polarization sites. Supporting Evidence: PMID:9632790 We thus propose that Spa2p, Pea2p, and Bud6p function together, perhaps as a complex, to promote polarized morphogenesis through regulation of the actin cytoskeleton and signaling pathways. |
| GO:0032880 regulation of protein localization | IMP PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | ACCEPT | Summary: SPA2 is required for proper protein localization during recovery from osmotic stress. Reason: SPA2 scaffold function maintains protein organization at growth sites under stress conditions. Supporting Evidence: PMID:12857882 Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p |
| GO:0071474 cellular hyperosmotic response | IMP PMID:12857882 Actin recovery and bud emergence in osmotically stressed cel... | KEEP AS NON CORE | Summary: SPA2 scaffold function maintains polarity and actin organization under hyperosmotic conditions. Reason: SPA2 participates in osmotic stress response as secondary effect of maintaining polarity and actin organization. Supporting Evidence: PMID:12857882 Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p/MTK1 and the scaffold protein Spa2p |
| GO:0005938 cell cortex | IDA PMID:23673619 Spatial segregation of polarity factors into distinct cortic... | ACCEPT | Summary: Direct evidence for SPA2 localization to cell cortex at growth sites through spatial segregation of polarity factors. Reason: IDA from microscopy demonstrates SPA2 is cortical protein that segregates into distinct cortical clusters at growth sites. Supporting Evidence: PMID:23673619 Spatial segregation of polarity factors into distinct cortical clusters is required for cell polarity control file:yeast/SPA2/SPA2-deep-research-falcon.md Under acute energy/glucose starvation, Spa2 can depolarize from the bud tip and relocalize into **filamentous/punctate structures that overlap actin cables**, indicating condition-dependent remodeling of its spatial organization. |
| GO:0005078 MAP kinase scaffold activity | IDA PMID:12361575 Spa2p functions as a scaffold-like protein to recruit the Mp... | ACCEPT | Summary: Direct biochemical and localization evidence for SPA2 scaffold activity for MAP kinase pathway. Reason: IDA demonstrates direct recruitment and physical interaction with MAPK pathway components. Supporting Evidence: PMID:12361575 Spa2p interacts with Mkk1p and Mpk1p, and membrane bound Spa2p is sufficient to recruit Mkk1p and Mpk1p but not other MAP kinases to the cell cortex |
| GO:0005078 MAP kinase scaffold activity | IMP PMID:12361575 Spa2p functions as a scaffold-like protein to recruit the Mp... | ACCEPT | Summary: Functional requirement for SPA2 in MAPK pathway signaling and localization. Reason: IMP evidence shows SPA2 is required for proper MAPK localization and function during polarized growth. Supporting Evidence: PMID:12361575 Spa2p functions as a scaffold-like protein for the cell wall integrity pathway during polarized growth |
| GO:0032880 regulation of protein localization | IMP PMID:11740491 Yeast formins regulate cell polarity by controlling the asse... | ACCEPT | Summary: Yeast formins regulate cell polarity through actin cable assembly; SPA2 localizes and organizes Bni1p formin. Reason: SPA2 regulates formin localization as part of core actin cable organization for polarity. Supporting Evidence: PMID:11740491 Yeast formins regulate cell polarity by controlling the assembly of actin cables |
| GO:0007118 budding cell apical bud growth | IMP PMID:10866679 Polarized growth controls cell shape and bipolar bud site se... | ACCEPT | Summary: SPA2 is essential for polarized bud growth; controls actin cable organization and apical growth direction. Reason: Direct evidence that SPA2 is required for apical bud growth morphogenesis; mutants show defective polarized growth. Supporting Evidence: PMID:10866679 Polarized growth controls cell shape and bipolar bud site selection in Saccharomyces cerevisiae |
| GO:0007118 budding cell apical bud growth | IGI PMID:10866679 Polarized growth controls cell shape and bipolar bud site se... | ACCEPT | Summary: Genetic interactions show SPA2 functions with other polarity components in bud growth. Reason: IGI evidence demonstrates SPA2 genetic interaction with actin and morphogenesis genes critical for apical growth. Supporting Evidence: PMID:10866679 We found that the polarity genes SPA2, PEA2, BUD6, and BNI1 participate in a crucial step of bud morphogenesis, apical growth. |
| GO:0032880 regulation of protein localization | IMP PMID:10085294 The cortical localization of the microtubule orientation pro... | ACCEPT | Summary: SPA2 is required for proper cortical protein localization including Kar9p; actin-dependent mechanism. Reason: SPA2 scaffold function essential for organizing actin and associated proteins including microtubule orieintation proteins at cell cortex. Supporting Evidence: PMID:10085294 The cortical localization of the microtubule orientation protein, Kar9p, is dependent upon actin and proteins required for polarization |
| GO:0007121 bipolar cellular bud site selection | IMP PMID:8909546 Pea2 protein of yeast is localized to sites of polarized gro... | ACCEPT | Summary: SPA2 is required for bipolar bud site selection in diploid cells; functions with Pea2p in site recognition. Reason: Strong genetic evidence showing SPA2 and Pea2p work together to establish and maintain bipolar budding pattern. Supporting Evidence: PMID:8909546 These results suggest that Pea2p and Spa2p function together as a complex to generate the bipolar budding pattern |
| GO:0030010 establishment of cell polarity | IMP PMID:8909546 Pea2 protein of yeast is localized to sites of polarized gro... | ACCEPT | Summary: SPA2 required for cell polarity establishment during both budding and mating morphogenesis. Reason: Strong genetic evidence (IMP) showing SPA2 is essential for polarity in multiple developmental contexts. Supporting Evidence: PMID:8909546 These results suggest that Pea2p and Spa2p function together as a complex to generate the bipolar budding pattern and to guarantee proper polarization during mating. |
| GO:0032880 regulation of protein localization | IMP PMID:8909546 Pea2 protein of yeast is localized to sites of polarized gro... | ACCEPT | Summary: SPA2-Pea2p complex regulates protein localization during budding and mating morphogenesis. Reason: Demonstrates SPA2's protein localization regulatory function in multiple polarity contexts. Supporting Evidence: PMID:8909546 Pea2p is not stably produced in spa2 mutants. |
| GO:0030010 establishment of cell polarity | IMP PMID:8013906 Identification of genes required for normal pheromone-induce... | ACCEPT | Summary: SPA2 is essential for establishing polarity during mating morphogenesis; required for directed growth toward mating partner. Reason: Demonstrates SPA2's requirement for directed polarized growth toward pheromone source during mating. Supporting Evidence: PMID:8013906 Identification of genes required for normal pheromone-induced cell polarization |
| GO:0000131 incipient cellular bud site | IDA PMID:9214378 A small conserved domain in the yeast Spa2p is necessary and... | ACCEPT | Summary: SPA2 is early marker of incipient bud site, localizing before morphological bud emergence. Reason: Defining property of SPA2; localizes to single edge in unbudded cells and incipient sites as verified by confocal microscopy. Supporting Evidence: PMID:9214378 Spa2p localizes to one edge of unbudded cells and subsequently is observable in the bud tip |
| GO:0000133 polarisome | IDA PMID:9632790 Spa2p interacts with cell polarity proteins and signaling co... | ACCEPT | Summary: SPA2 is core structural component of polarisome complex along with Pea2p and Bud6p. Reason: Coimmunoprecipitation and sedimentation evidence confirms SPA2 as integral polarisome component forming large multiprotein complex. Supporting Evidence: PMID:9632790 Velocity sedimentation experiments suggest that a significant portion of Spa2p, Pea2p, and Bud6p cosediment, raising the possibility that these proteins form a large, 12S multiprotein complex file:yeast/SPA2/SPA2-deep-research-falcon.md Spa2 is a central scaffold that coordinates recruitment/organization of other polarisome components (commonly including Bni1, Bud6, Pea2) and thereby promotes focal polarization. |
| GO:0005934 cellular bud tip | IDA PMID:12361575 Spa2p functions as a scaffold-like protein to recruit the Mp... | ACCEPT | Summary: Direct evidence for stable SPA2 localization to bud tip from fluorescence recovery analysis. Reason: FRAP analysis confirms SPA2 is stably anchored at bud tips; foundational evidence for scaffold function at growth sites. Supporting Evidence: PMID:12361575 FRAP analysis shows that Spa2p-GFP is stably anchored at bud tips, whereas Mpk1p binds transiently |
| GO:0005934 cellular bud tip | IDA PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth. | ACCEPT | Summary: Early direct evidence establishing SPA2 as growth-site localized protein. Reason: Seminal work showing SPA2 localizes to sites of cell growth; foundational observation for polarity field. Supporting Evidence: PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth |
| GO:0005935 cellular bud neck | IDA PMID:9214378 A small conserved domain in the yeast Spa2p is necessary and... | ACCEPT | Summary: SPA2 localizes as ring at mother-daughter bud neck during cytokinesis as verified by microscopy. Reason: Direct microscopic evidence for bud neck localization during cell division; shows SPA2 role at septation sites. Falcon synthesis adds that Spa2 is recruited to the division site in late cell cycle and directly binds cytokinetic factors Cyk3 and Hof1, coordinating Chs2 incorporation for primary septum formation. Supporting Evidence: PMID:9214378 During cytokinesis Spa2p is present as a ring at the mother-daughter bud neck file:yeast/SPA2/SPA2-deep-research-falcon.md Foltman et al. (2018) show Spa2 is recruited to the division site in late cell cycle and directly binds cytokinetic factors, including **Cyk3** and **Hof1**, via Spa2 N-terminal regions containing Spa2 homology domains. file:yeast/SPA2/SPA2-deep-research-falcon.md Spa2 participates in coordinating incorporation of the essential chitin synthase **Chs2** into cytokinetic machinery (“ingression progression complexes”), linking polarity scaffolding to primary septum formation. |
| GO:0007124 pseudohyphal growth | IMP PMID:9055077 Dissection of filamentous growth by transposon mutagenesis i... | KEEP AS NON CORE | Summary: SPA2 is required for pseudohyphal growth morphology in response to nutrient starvation. Reason: Genetic evidence for involvement in developmental program; secondary to core polarity establishment function. Supporting Evidence: PMID:9055077 Dissection of filamentous growth by transposon mutagenesis in Saccharomyces cerevisiae. |
| GO:0007124 pseudohyphal growth | IMP PMID:9443897 The Spa2-related protein, Sph1p, is important for polarized ... | KEEP AS NON CORE | Summary: SPA2-related protein Sph1p plays role in pseudohyphal growth; demonstrates family function in filamentous growth. Reason: Shows SPA2 family role in filamentous growth but represents specialized developmental function secondary to core polarity. Supporting Evidence: PMID:9443897 The Spa2-related protein, Sph1p, is important for polarized growth in yeast |
| GO:0036267 invasive filamentous growth | IGI PMID:9443897 The Spa2-related protein, Sph1p, is important for polarized ... | KEEP AS NON CORE | Summary: Genetic interaction evidence for SPA2 in invasive growth; Spa2-Sph1 interaction shows redundancy. Reason: Secondary developmental function; interaction with Sph1p suggests role in specialized growth program. Supporting Evidence: PMID:9443897 sph1(Delta) spa2(Delta) double mutants also exhibit a strong haploid invasive growth defect and an exacerbated mating projection defect relative to either sph1(Delta) or spa2(Delta) single mutants. |
| GO:0043332 mating projection tip | IDA PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth. | ACCEPT | Summary: SPA2 localizes prominently to mating projection tip as discrete patch. Reason: Early direct evidence for localization to shmoo tip; essential for mating morphogenesis. Supporting Evidence: PMID:2647769 When a-cells are induced to form schmoos with alpha-factor, the SPA2 protein is found at the tip of the schmoo. |
| GO:0043332 mating projection tip | IDA PMID:9214378 A small conserved domain in the yeast Spa2p is necessary and... | ACCEPT | Summary: SPA2 localizes to mating projection tip in response to pheromone and is essential for shmoo formation. Reason: Consistent direct evidence from multiple studies; essential for directed growth toward mating partner. Supporting Evidence: PMID:9214378 A small conserved domain in the yeast Spa2p is necessary and sufficient for its polarized localization. |
| GO:0000133 polarisome | NAS PMID:16166638 Regulation of cell polarity by interactions of Msb3 and Msb4... | ACCEPT | Summary: ComplexPortal-supported membership in the polarisome, where Spa2 is a core scaffold for actin-assembly and vesicle-targeting factors at polarized growth sites. Reason: The ComplexPortal NAS row is consistent with direct SGD evidence that Spa2 is part of the polarisome. Tcheperegine et al. describe Spa2 as a polarisome scaffold that binds the Sec4 RabGAPs Msb3/Msb4 and the formin Bni1, supporting retention of the complex-membership annotation. Supporting Evidence: PMID:16166638 Spa2, a scaffold protein of the "polarisome" that also interacts with the formin Bni1. |
| GO:0005515 protein binding | IPI PMID:31362951 YFR016c/Aip5 is part of an actin nucleation complex in yeast... | REMOVE | Summary: Aip5 binds directly to Spa2 through its N-terminal Spa2-binding region, but a generic protein-binding row is not informative for Spa2's scaffold activity. Reason: The Aip5-Spa2 interaction is well supported and functionally localizes Aip5 into a Bud6/Spa2 actin-assembly complex. GO:0005515 protein binding is too generic to describe that mechanism for Spa2; the review already captures Spa2 as a MAPK and polarisome scaffold and keeps the Aip5 paper under the more informative protein-localization and apical-bud-growth rows. Supporting Evidence: PMID:31362951 Aip5 binds with its N-terminal region to Spa2 and with its C-terminal region to Bud6. |
| GO:0005934 cellular bud tip | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to the bud tip recapitulates the experimentally observed Spa2 polarized-growth localization. Reason: Spa2 is repeatedly observed at bud tips, and the UniProt SubCell mapping is a conservative electronic restatement of that core localization. Supporting Evidence: PMID:9214378 Our studies with Spa2GFP demonstrate that Spa2p localizes to the bud tip, forming a cup-like crescent, and the bud neck between mother and daughter cell, forming a donut-like ring. |
| GO:0005935 cellular bud neck | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to the bud neck recapitulates the experimentally observed Spa2 ring at the mother-bud neck during cytokinesis. Reason: Direct microscopy supports Spa2 localization to the bud neck, and the UniProt SubCell-derived IEA is consistent with that experimentally established localization. Supporting Evidence: PMID:9214378 During cytokinesis Spa2p is present as a ring at the mother-daughter bud neck |
| GO:0007118 budding cell apical bud growth | IGI PMID:10866679 Polarized growth controls cell shape and bipolar bud site se... | ACCEPT | Summary: Genetic-interaction evidence with another polarity gene supports Spa2's role in apical bud growth. Reason: The PMID:10866679 experiments identify SPA2, PEA2, BUD6 and BNI1 as apical-growth components whose deletion impairs bud elongation and focused Sec4 localization. This duplicate IGI row differs only in the interacting gene recorded by GOA and is consistent with Spa2's core polarized-growth role. Supporting Evidence: PMID:10866679 We found that the polarity genes SPA2, PEA2, BUD6, and BNI1 participate in a crucial step of bud morphogenesis, apical growth. |
| GO:0007118 budding cell apical bud growth | IGI PMID:10866679 Polarized growth controls cell shape and bipolar bud site se... | ACCEPT | Summary: Genetic-interaction evidence with another polarity gene supports Spa2's role in apical bud growth. Reason: The PMID:10866679 experiments identify SPA2, PEA2, BUD6 and BNI1 as apical-growth components whose deletion impairs bud elongation and focused Sec4 localization. This duplicate IGI row differs only in the interacting gene recorded by GOA and is consistent with Spa2's core polarized-growth role. Supporting Evidence: PMID:10866679 We found that the polarity genes SPA2, PEA2, BUD6, and BNI1 participate in a crucial step of bud morphogenesis, apical growth. |
| GO:0007118 budding cell apical bud growth | IPI PMID:31362951 YFR016c/Aip5 is part of an actin nucleation complex in yeast... | ACCEPT | Summary: The direct Spa2-Aip5 interaction places Aip5 in the Bud6/Spa2 actin-cable nucleation complex that supports polar bud growth. Reason: Glomb et al. show that Aip5 binds Spa2 and Bud6, that both interactions localize Aip5 to bud tip and bud neck, and that they are needed to stimulate actin-cable formation. The row is therefore a specific functional use of the Spa2-Aip5 interaction, not merely a generic binding assertion. Supporting Evidence: PMID:31362951 Both interactions collaborate to localize Aip5 at bud tip and neck, and are required to stimulate the formation of actin cables. |
| GO:0008104 intracellular protein localization | IPI PMID:31362951 YFR016c/Aip5 is part of an actin nucleation complex in yeast... | KEEP AS NON CORE | Summary: Spa2 helps localize Aip5 to polarized bud-tip and bud-neck sites. Reason: The Aip5 paper directly shows that Spa2 collaborates with Bud6 to recruit Aip5 to polar growth sites. This is a specific intracellular protein-localization result for Aip5, while the several GO:0032880 regulation of protein localization rows capture Spa2's broader recruitment activity, so GO:0008104 remains correct as a non-core consequence of Spa2's polarisome scaffold role. Supporting Evidence: PMID:31362951 Spa2 localizes Aip5 to sites of polar growth |
| GO:0030427 site of polarized growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA maps Spa2 to the generic polarized-growth site that subsumes its bud-tip, bud-neck and mating-projection-tip localizations. Reason: The location is biologically true but broader than the directly observed and curated bud-tip, bud-neck and mating-projection-tip locations, so it should be kept as a correct non-core electronic roll-up rather than treated as primary evidence for a distinct compartment. Supporting Evidence: PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth |
| GO:0051286 cell tip | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: True: entailed by mating projection tip, kept in this review; non-core, as for the other cell-tip row. Reason: Mating projection tip, accepted in this review, is a kind of cell tip, so the claim is true for Spa2. KEEP_AS_NON_CORE, matching the UniProt-mapping row for this term, rather than REMOVE. The ARBA transfer adds nothing beyond the specific tip terms: it mirrors the fission-yeast-style cell-tip transfer seen in the PomBase-derived PAINT rows, and the current UniProt record no longer carries the generic Cell tip location line. Supporting Evidence: PMID:2647769 The SPA2 protein of yeast localizes to sites of cell growth |
| GO:0120105 mitotic actomyosin contractile ring, intermediate layer | IBA GO_REF:0000033 | REMOVE | Summary: Budding-yeast Spa2 is not known to localize to the fission-yeast mitotic actomyosin contractile-ring intermediate layer. Reason: This live GOA row replaces the older GO:0005826 actomyosin-contractile-ring IBA with a more specific fission-yeast division-site component, but the propagation problem remains. PTHR21601 PAINT now places the PomBase-only GO:0120105 IBD at a broad Eukaryota node in the family export. Foltman et al. show that S. cerevisiae Spa2 is recruited to the budding-yeast division site and directly binds the cytokinetic factors Cyk3, Hof1 and Chs2, but this is a Chs2/secretory-vesicle incorporation role in budding-yeast ingression progression complexes, not membership in the S. pombe actomyosin contractile-ring intermediate layer. The IBD should therefore be narrowed to the fission-yeast branch instead of being exported to budding-yeast SPA2. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001091459 · PTN001091459 SOURCE STALE OR MISSING The refreshed GOA row names PTN001091459, but the current PTHR21601 PAINT TSV no longer exposes that node. PANTHER:PTN004550576 · PTN004550576 SUPPORTS SOURCE BUT NOT TARGET The current PTHR21601 PAINT export places GO:0120105 at this broad Eukaryota node with PomBase:SPAC3G9.05 as the only experimental seed. The seed supports S. pombe contractile-ring localization, but not propagation of this cytokinetic-ring compartment to S. cerevisiae Spa2. PomBase:SPAC3G9.05 · S. pombe spa2 SUPPORTS SOURCE BUT NOT TARGET PMID:40931936 shows fission-yeast Spa2 at the contractile ring, which validates the source-side PomBase annotation but highlights the species-specific localization being over-transferred. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:31362951 YFR016c/Aip5 is part of an actin nucleation complex in yeast... | NEW | Summary: Spa2 links polarity and actin-assembly partners (the Aip5-Bud6-Bni1 nucleation module and the Rab GAPs Msb3/Msb4) and places them at bud tip and neck. This is broader than its MAPK-module scaffolding. Reason: Spa2's best-characterized activity beyond MAPK scaffolding is bringing polarity and actin-nucleation proteins together at growth sites, which GO:0005078 does not cover. The fission-yeast ortholog already carries GO:0030674 by PomBase EXP (PMID:40931936, Gyp3 and Pos1 recruitment), so this fills the corresponding budding-yeast function and matches the existing core function. Supporting Evidence: PMID:31362951 Both interactions collaborate to localize Aip5 at bud tip and neck, and are required to stimulate the formation of actin cables. PMID:16166638 Msb3 and Msb4 interact directly with Spa2, a scaffold protein of the "polarisome" that also interacts with the formin Bni1. PMID:41527849 We identified a conserved short linear motif in the Rab GTPase-activating proteins (RabGAPs) Msb3 and Msb4, and the MAP kinase kinases Ste7 and Mkk1, which mediates their interaction with Spa2. |
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Download this section (compressed HTML)Q: Should the PomBase-only GO:0120105 mitotic actomyosin contractile ring, intermediate layer IBD reported by GOA from PTHR21601 node PTN001091459, and present in the current PAINT export on PTN004550576, be narrowed or constrained so fission-yeast Spa2 division-site localization is not propagated from a Eukaryota node to budding-yeast SPA2?
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Download this section (compressed HTML)Component of the polarisome; functions in actin cytoskeletal organization during polarized growth; acts as a scaffold for Mkk1p and Mpk1p cell wall integrity signaling components; potential Cdc28p substrate; coding sequence contains length polymorphisms in different strains; SPA2 has a paralog, SPH1, that arose from the whole genome duplication
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