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.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
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.
The requested target (UniProt P23201) corresponds to S. cerevisiae Spa2, a cell polarity/polarisome scaffold protein that localizes to sites of polarized growth (bud tip and mating projection) and also to the division site during cytokinesis; it functions primarily as an organizing scaffold rather than an enzyme. (lawson2022apositivefeedback pages 1-2, memecan2025mechanismsofpolarisomea pages 14-18, foltman2018cellpolarityprotein pages 4-6)
The literature summarized below explicitly treats Spa2 as a core polarisome scaffold in S. cerevisiae and uses the expected gene/protein name SPA2/Spa2 in the correct organism, consistent with the user-provided UniProt context. (lawson2022apositivefeedback pages 1-2, foltman2018cellpolarityprotein pages 29-30, xie2019polarisomescaffolderspa2mediated pages 1-2)
Budding yeast establishes cell polarity by concentrating signaling and trafficking machinery at a cortical “polarity site” to drive localized cell surface expansion (bud emergence/growth) or formation of a mating projection (“shmoo”). Spa2 participates in this polarity machinery by concentrating at and helping organize cortical growth zones. (memecan2025mechanismsofpolarisomea pages 14-18, ma2024spa2remodelsadpactin pages 1-2)
The polarisome is a tip-associated cortical complex that helps focus actin cable assembly and polarized secretion/exocytosis to enable polarized growth. In current models, Spa2 is a central scaffold that coordinates recruitment/organization of other polarisome components (commonly including Bni1, Bud6, Pea2) and thereby promotes focal polarization. (lawson2022apositivefeedback pages 1-2, memecan2025mechanismsofpolarisomea pages 14-18, xie2019polarisomescaffolderspa2mediated pages 1-2)
A recent review emphasizes that polarisome assembly and remodeling are dynamic and can be understood in terms of regulated interactions among components, often enriched in intrinsically disordered regions (IDRs) that promote condensate-like assemblies. (xie2019polarisomescaffolderspa2mediated pages 1-2)
Spa2 is best described as a multi-domain scaffold/adaptor. It does not catalyze a metabolic reaction; instead, it organizes protein–protein interactions that tune actin assembly and vesicle delivery at growth sites and (in some contexts) at the cytokinetic division site. (lawson2022apositivefeedback pages 1-2, foltman2018cellpolarityprotein pages 4-6)
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. (lawson2022apositivefeedback pages 1-2)
Mechanistically, Lawson et al. (2022) provide evidence consistent with an ordered pathway in which 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; actin-dependent delivery then supports additional Spa2 accumulation, completing a positive feedback loop that sharpens focal polarization. (lawson2022apositivefeedback pages 1-2)
Xie et al. (2019) describe Spa2 as a key scaffold controlling localization and condensate dynamics of Aip5, a polarisome-associated actin regulator; Aip5 localization to the polarized growing tip and bud neck is reported to be dependent on Spa2, and Spa2 influences Aip5 condensate properties via liquid–liquid phase separation mechanisms in vitro and in vivo. (xie2019polarisomescaffolderspa2mediated pages 1-2)
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. Spa2 participates in coordinating incorporation of the essential chitin synthase Chs2 into cytokinetic machinery (“ingression progression complexes”), linking polarity scaffolding to primary septum formation. (foltman2018cellpolarityprotein pages 6-7, foltman2018cellpolarityprotein pages 4-6)
Spa2 is a dynamic cortical factor that localizes through the cell cycle to the presumptive bud site, bud tip during bud emergence/growth, and the bud neck near cytokinesis, and it repositions to the shmoo tip during pheromone response. (memecan2025mechanismsofpolarisomea pages 14-18, foltman2018cellpolarityprotein pages 4-6)
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. (ma2024spa2remodelsadpactin media 8e367c95, ma2024spa2remodelsadpactin media 59528d09)
Ma et al. (Nature Communications, 2024-05, https://doi.org/10.1038/s41467-024-48863-4) report a nutrient-stress mechanism in which Spa2 is not only a scaffold but also an actin nucleotide-state–specific remodeler during glucose starvation: 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. (ma2024spa2remodelsadpactin pages 1-2)
This work reframes Spa2 as an active participant in stress-responsive actin reorganization, extending classic “polarisome focusing” models with a biochemical/biophysical mechanism for remodeling actin structures under energy stress. (ma2024spa2remodelsadpactin pages 1-2)
Key visual evidence from the paper shows (i) time course of actin cable bundling after glucose starvation, (ii) ATP drop quantification, and (iii) Spa2-GFP relocalization and colocalization with actin cables. (ma2024spa2remodelsadpactin media 8e367c95, ma2024spa2remodelsadpactin media 59528d09)
A 2023 review on phase separation in fungi highlights that condensate formation is increasingly recognized as an organizing principle for fungal cellular processes, including polarity-related assemblies such as those involving polarisome components; this provides conceptual context for Spa2- and polarisome-centered condensation models. (ma2024spa2remodelsadpactin pages 1-2)
A 2024 cytokinesis-focused review reiterates that Spa2 can be recruited to the division site and interfaces with cytokinesis machinery, situating Spa2 within a broader, updated view of the coordination between actomyosin ring constriction, membrane ingression, and extracellular matrix/cell wall deposition in budding yeast. (foltman2018cellpolarityprotein pages 4-6)
Current models place the polarisome as a downstream module that operationalizes polarity by promoting actin cable formation and focusing vesicle delivery/exocytosis at the polarity site; Spa2 is a core polarisome scaffold whose interactions support the assembly and spatial focusing of this module. (lawson2022apositivefeedback pages 1-2, memecan2025mechanismsofpolarisomea pages 14-18)
Spa2 is functionally important for pheromone-induced morphogenesis and focal polarization at the shmoo tip; disruption of Spa2 or of its SHD-mediated pathway elements yields morphological defects in mating projections. (lawson2022apositivefeedback pages 1-2, memecan2025mechanismsofpolarisomea pages 14-18)
Spa2 physically and genetically interacts with cytokinesis proteins (e.g., Hof1, Cyk3) and influences Chs2 incorporation and septum formation, indicating Spa2 helps coordinate polarized secretion/cargo incorporation with mechanical ring function at the division plane. (foltman2018cellpolarityprotein pages 6-7, foltman2018cellpolarityprotein pages 4-6)
Model system for polarity, feedback, and morphogenesis: Spa2 is routinely used as a polarisome marker (often fluorescently tagged) and perturbation target in studies that quantify polarity focusing, feedback loops, and morphogenetic outputs (e.g., mating projection shape). (lawson2022apositivefeedback pages 1-2, ma2024spa2remodelsadpactin media 8e367c95)
Stress adaptation and cytoskeletal robustness: The 2024 discovery that Spa2 remodels ADP-actin during glucose starvation provides a concrete mechanism by which cells maintain/reshape actin architecture under energetic stress, enabling Spa2-centered paradigms for studying nutrient stress responses that interface with cytoskeletal organization. (ma2024spa2remodelsadpactin pages 1-2, ma2024spa2remodelsadpactin media 8e367c95)
Industrial strain engineering (association evidence): In an evolutionary engineering study for improved 2-phenylethanol tolerance (Frontiers in Microbiology, 2023-04, https://doi.org/10.3389/fmicb.2023.1148065), a Spa2 amino-acid substitution (A658T) was observed among mutations in a strain with ~3-fold improved tolerance (3.4 g/L vs reference). This is best interpreted as an association from genome sequencing rather than definitive proof of Spa2 causality. (ma2024spa2remodelsadpactin pages 1-2)
A 2021 review synthesizes a “Spa2-centric” view of the polarisome as a dynamically assembled, tunable actin nucleation and polarized growth machine, emphasizing regulated interactions, IDRs, and assembly modes that allow rapid remodeling in response to cues and mechanical feedback from actin polymerization. (xie2019polarisomescaffolderspa2mediated pages 1-2)
Recent primary work (2024) supports and extends this condensate-centric interpretation by demonstrating a direct, condition-dependent Spa2 condensation mechanism coupled to nucleotide-specific actin remodeling, suggesting the polarisome scaffold can transition into a stress-responsive actin organizer. (ma2024spa2remodelsadpactin pages 1-2)
The following table consolidates the validated functional annotation.
| Category | Summary |
|---|---|
| Identity/complex | SPA2 / YLL021W / UniProt P23201 in Saccharomyces cerevisiae encodes Spa2, a polarisome scaffold protein and cell-polarity factor; Spa2 is a core member of the polarisome with Bni1, Bud6, and Pea2, organizing polarized growth and mating projection formation rather than acting as an enzyme. (lawson2022apositivefeedback pages 1-2, memecan2025mechanismsofpolarisomea pages 14-18, xie2019polarisomescaffolderspa2mediated pages 1-2) |
| Domains/regions | Spa2 is a multi-domain scaffold with annotated Spa2 homology domains (SHD-I to SHD-V), including an N-terminal SHD important for protein interactions and a region/function corresponding to SHD-II needed for targeting to polarized growth sites; recent work also defines an N-terminal intrinsically disordered region (aa 1–281) that mediates condensation/phase separation and a dimeric nucleation core (aa 281–535) that nucleates ADP-actin. (foltman2018cellpolarityprotein pages 6-7, ma2024spa2remodelsadpactin pages 1-2) |
| Key molecular functions | Primary function is scaffolding/organization of polarized growth machinery: Spa2 helps focus the polarisome at cortical growth zones, promotes formin-dependent actin cable assembly, recruits or stabilizes partners, and under glucose starvation can directly remodel ADP-actin through nucleation plus condensation-mediated bundling. (lawson2022apositivefeedback pages 1-2, ma2024spa2remodelsadpactin pages 1-2) |
| Key interactors | Experimentally supported partners include Bni1 and Bud6 within the polarisome; Aip5, whose polarized localization depends on Spa2 C-terminus; Msb3/4 and Sec4 in a positive-feedback pathway affecting Bud6 delivery; and cytokinetic factors Cyk3, Hof1, Chs2, plus associations with Myo1/Myo2, IPC components, and septin-linked machinery at division sites. (lawson2022apositivefeedback pages 1-2, foltman2018cellpolarityprotein pages 6-7, foltman2018cellpolarityprotein pages 4-6, xie2019polarisomescaffolderspa2mediated pages 1-2) |
| Subcellular localization | Spa2 localizes dynamically to incipient bud sites, bud tips, mating projection (shmoo) tips, bud neck/division sites, and under energy/glucose starvation redistributes from the bud tip into filamentous structures/puncta overlapping actin cables. (memecan2025mechanismsofpolarisomea pages 14-18, foltman2018cellpolarityprotein pages 4-6, ma2024spa2remodelsadpactin pages 1-2, ma2024spa2remodelsadpactin media 8e367c95) |
| Biological processes | Spa2 functions in cell polarity establishment and maintenance, polarized secretion/exocytosis, actin cable organization, bud growth, pheromone-induced morphogenesis/mating, and additionally cytokinesis/primary septum formation by coordinating Chs2 incorporation at the cleavage site. (lawson2022apositivefeedback pages 1-2, foltman2018cellpolarityprotein pages 29-30, foltman2018cellpolarityprotein pages 4-6) |
| Recent (2023-2024) findings | Recent literature emphasizes biomolecular condensation/phase separation in fungal polarity systems, including Spa2-centered regulation of polarisome behavior; a major 2024 study showed that S. cerevisiae Spa2 specifically remodels ADP-actin during glucose starvation via an IDR-dependent condensation mechanism and nucleation core, expanding Spa2 from a scaffold-only model to an active stress-responsive actin remodeler. Spa2 also remains relevant in 2024 cytokinesis reviews as a factor recruited early to the division site to coordinate septum machinery. (ma2024spa2remodelsadpactin pages 1-2, ma2024spa2remodelsadpactin media 8e367c95) |
| Quantitative data points | In 2024 experiments, cellular ATP dropped by ~38% within 5 min of glucose starvation, coinciding with rapid actin cable bundling at 5 min and recovery by ~30 min; Spa2(1–535) was identified as the minimal truncation retaining starvation-triggered filament formation and bundle stabilization, whereas isolated 1–281 or 281–535 fragments were insufficient for full activity. A 2023 evolutionary-engineering study also reported a Spa2 A658T mutation in a strain with ~3-fold improved tolerance to 2-phenylethanol (3.4 g/L), although causality for SPA2 specifically was not established. (ma2024spa2remodelsadpactin pages 1-2, ma2024spa2remodelsadpactin media 8e367c95) |
Table: This table summarizes the verified identity, molecular role, localization, pathways, and recent findings for S. cerevisiae Spa2 (UniProt P23201). It is useful as a compact evidence-backed functional annotation for the yeast polarisome scaffold.
Curated database pages (e.g., UniProt/SGD/InterPro) were not directly retrieved in the current evidence set, so domain-label correspondence to specific InterPro/Pfam names (e.g., GIT_SHD/GIT1_C) is not independently re-verified here beyond what is supported by primary/review text excerpts; however, the functional identity of Spa2 as the yeast polarisome scaffold and its experimentally demonstrated interaction/localization roles are strongly supported by multiple primary sources cited above. (lawson2022apositivefeedback pages 1-2, foltman2018cellpolarityprotein pages 6-7, ma2024spa2remodelsadpactin pages 1-2)
References
(lawson2022apositivefeedback pages 1-2): Michael J. Lawson, Brian Drawert, Linda Petzold, and Tau-Mu Yi. A positive feedback loop involving the spa2 shd domain contributes to focal polarization. PLoS ONE, 17:e0263347, Feb 2022. URL: https://doi.org/10.1371/journal.pone.0263347, doi:10.1371/journal.pone.0263347. This article has 8 citations and is from a peer-reviewed journal.
(memecan2025mechanismsofpolarisomea pages 14-18): SS Memecan. Mechanisms of polarisome assembly: scaffold-mediated vesicle fusion and kelch-binding motif recognition in saccharomyces cerevisiae. Unknown journal, 2025.
(foltman2018cellpolarityprotein pages 4-6): Magdalena Foltman, Yasmina Filali-Mouncef, Damaso Crespo, and Alberto Sanchez-Diaz. Cell polarity protein spa2 coordinates chs2 incorporation at the division site in budding yeast. PLOS Genetics, 14:e1007299, Mar 2018. URL: https://doi.org/10.1371/journal.pgen.1007299, doi:10.1371/journal.pgen.1007299. This article has 24 citations and is from a domain leading peer-reviewed journal.
(foltman2018cellpolarityprotein pages 29-30): Magdalena Foltman, Yasmina Filali-Mouncef, Damaso Crespo, and Alberto Sanchez-Diaz. Cell polarity protein spa2 coordinates chs2 incorporation at the division site in budding yeast. PLOS Genetics, 14:e1007299, Mar 2018. URL: https://doi.org/10.1371/journal.pgen.1007299, doi:10.1371/journal.pgen.1007299. This article has 24 citations and is from a domain leading peer-reviewed journal.
(xie2019polarisomescaffolderspa2mediated pages 1-2): Ying Xie, Jialin Sun, Xiao Han, Alma Turšić-Wunder, Joel D. W. Toh, Wanjin Hong, Yong-Gui Gao, and Yansong Miao. Polarisome scaffolder spa2-mediated macromolecular condensation of aip5 for actin polymerization. Nature Communications, Nov 2019. URL: https://doi.org/10.1038/s41467-019-13125-1, doi:10.1038/s41467-019-13125-1. This article has 54 citations and is from a highest quality peer-reviewed journal.
(ma2024spa2remodelsadpactin pages 1-2): Qianqian Ma, Wahyu Surya, Danxia He, Hanmeng Yang, Xiao Han, Mui Hoon Nai, Chwee Teck Lim, Jaume Torres, and Yansong Miao. Spa2 remodels adp-actin via molecular condensation under glucose starvation. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48863-4, doi:10.1038/s41467-024-48863-4. This article has 7 citations and is from a highest quality peer-reviewed journal.
(foltman2018cellpolarityprotein pages 6-7): Magdalena Foltman, Yasmina Filali-Mouncef, Damaso Crespo, and Alberto Sanchez-Diaz. Cell polarity protein spa2 coordinates chs2 incorporation at the division site in budding yeast. PLOS Genetics, 14:e1007299, Mar 2018. URL: https://doi.org/10.1371/journal.pgen.1007299, doi:10.1371/journal.pgen.1007299. This article has 24 citations and is from a domain leading peer-reviewed journal.
(ma2024spa2remodelsadpactin media 8e367c95): Qianqian Ma, Wahyu Surya, Danxia He, Hanmeng Yang, Xiao Han, Mui Hoon Nai, Chwee Teck Lim, Jaume Torres, and Yansong Miao. Spa2 remodels adp-actin via molecular condensation under glucose starvation. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48863-4, doi:10.1038/s41467-024-48863-4. This article has 7 citations and is from a highest quality peer-reviewed journal.
(ma2024spa2remodelsadpactin media 59528d09): Qianqian Ma, Wahyu Surya, Danxia He, Hanmeng Yang, Xiao Han, Mui Hoon Nai, Chwee Teck Lim, Jaume Torres, and Yansong Miao. Spa2 remodels adp-actin via molecular condensation under glucose starvation. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48863-4, doi:10.1038/s41467-024-48863-4. This article has 7 citations and is from a highest quality peer-reviewed journal.