Cdc42 is an essential Rho-family small GTPase that is the master regulator of cell polarity and polarized (tip) growth in fission yeast. It cycles between an inactive GDP-bound and an active GTP-bound state; activation is catalyzed by the guanine nucleotide exchange factors Scd1 (local, tip-associated) and Gef1 (global), and inactivation is accelerated by GTPase-activating proteins such as Rga4. In its GTP-bound state Cdc42 binds and activates CRIB-domain effectors, including the p21-activated kinases Shk1/Pak1/Orb2 and Shk2/Pak2, the scaffold Scd2, and the formin For3, thereby organizing the actin cytoskeleton, polarized exocytosis (via the exocyst and delivery of glucan synthases Bgs1/Bgs4), and establishment of cell polarity. Active Cdc42 forms self-organizing zones that oscillate between cell tips to drive bipolar growth and set cell width, and is recruited to the cell division site where it coordinates cytokinesis and restrains premature Rho1 activation. During sexual reproduction Cdc42 explores the cell periphery for mate selection and is required for shmoo (mating projection) formation and cell-cell fusion. Cdc42 is geranylgeranylated at its C-terminal CAAX cysteine, which anchors it to the cytoplasmic face of the plasma membrane, concentrating at growing cell tips and the division site.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007015 actin filament organization | IBA GO_REF:0000033 | ACCEPT | Summary: Organization of the actin cytoskeleton is a core, conserved Cdc42 function. In fission yeast active Cdc42 at cell tips is accompanied by developed F-actin and acts through the formin For3 and PAK effectors to polarize actin. Reason: Well supported by phylogenetic inference and direct fission yeast evidence that Cdc42 organizes tip F-actin via For3/PAK effectors. Supporting Evidence: PMID:18328707 GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures, where the Rga4 GAP is excluded. |
| GO:0030010 establishment of cell polarity | IBA GO_REF:0000033 | ACCEPT | Summary: Establishment of cell polarity is the central function of Cdc42 in fission yeast, supported by both phylogenetic inference and direct experimental data (essential gene controlling polarized growth). Reason: Core conserved function, independently supported by IMP evidence below. Supporting Evidence: PMID:8289788 the cdc42 mutants did exhibit an abnormal morphological phenotype of large, misshapen cells, suggesting that S. pombe Cdc42p is involved in controlling polarized cell growth |
| GO:0006897 endocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cdc42 has conserved roles in endocytosis and is implicated in endocytic recycling in fission yeast. Retain as a genuine but non-core process for the pombe gene (its dominant role is polarity/tip growth). Reason: Phylogenetically conserved; fission yeast Cdc42 affects endosome recycling and membrane traffic, though endocytosis per se is a secondary role. Supporting Evidence: PMID:21899677 Cdc42 and the scaffold Pob1 are required for membrane trafficking and fusion, contributing to polarized secretion, endosome recycling, vacuole formation and growth |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cdc42 binds and activates CRIB-domain PAK kinases (Shk1/Pak1 and Shk2/Pak2) in fission yeast. 'Protein kinase binding' is correct but generic; the more informative function is its activator activity toward these kinases. Reason: The binding is real and conserved, but a more informative term (protein serine/threonine kinase activator activity) is annotated separately and better captures the function. Supporting Evidence: PMID:7597098 We provide genetic evidence for physical and functional interaction between Shk1 and the Cdc42 GTP-binding protein required for normal cell morphology and mating in S. pombe. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Cdc42 is a Rho-family small GTPase with intrinsic GTP hydrolysis activity (the molecular-switch core function), facilitated by GAPs. This is the central molecular function. Reason: Core molecular function, supported by InterPro and the GEF/GAP literature. Supporting Evidence: PMID:21849474 They have intrinsic GTPase activity and can hydrolyze GTP to GDP, but this hydrolysis is usually inefficient. It is facilitated when the small GTPase binds to a GTPase-activating protein (GAP) |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: 'G protein activity' (GO:0003925) was assigned by EC mapping (EC 3.6.5.2). Despite the historical name, GO:0003925 is the general "molecular switch" function that cycles between active GTP-bound and inactive GDP-bound states and binds effectors; its narrow synonyms explicitly include "small monomeric GTPase activity" and "Ras superfamily protein", and EC 3.6.5.2 (small monomeric GTPase) maps to it. It therefore correctly applies to Cdc42, capturing the GTP/GDP molecular-switch behaviour that is central to Cdc42 function. It overlaps with the separately annotated GTPase activity (GO:0003924). Reason: Correct term: GO:0003925 covers small monomeric GTPases (EC 3.6.5.2), so it is valid for Cdc42 and captures its molecular-switch behaviour. Kept as non-core only because it overlaps with the GTPase activity (GO:0003924) annotation. (An earlier REMOVE call claiming this term is exclusive to heterotrimeric G proteins was incorrect.) Supporting Evidence: PMID:21849474 They have intrinsic GTPase activity and can hydrolyze GTP to GDP, but this hydrolysis is usually inefficient. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding is a core molecular function; Cdc42 has canonical P-loop GTP/GDP binding motifs and cycles between GTP- and GDP-bound states. Reason: Core conserved function; supported by sequence motifs and the switch mechanism. Supporting Evidence: PMID:18328707 the GTP-bound form of Cdc42 binds and activates a group of proteins with the CRIB (Cdc42/Rac-interactive binding) domain |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Cdc42 is prenyl-anchored to the cytoplasmic face of the plasma membrane, concentrating at cell tips and the division site. Plasma membrane localization is correct and core. Reason: Supported by direct localization of functional tagged Cdc42 and prenylation requirement. Supporting Evidence: PMID:25837586 Cdc42-mCherrySW was enriched at the cell tips and division sites. |
| GO:0005938 cell cortex | IEA GO_REF:0000117 | ACCEPT | Summary: Cdc42 localizes to the cell cortex (the cytoplasmic face of the plasma membrane and associated cortical structures), consistent with direct IDA evidence below. Reason: Supported by direct cortical localization evidence. Supporting Evidence: PMID:10961446 GFP-Cdc42p was observed at the medial region of the cell at the cell-division site early in cytokinesis and remained there through cell separation, and was also localized to the periphery of the cell and to internal membranes. |
| GO:0007264 small GTPase-mediated signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: Cdc42 is the prototypical small GTPase switch transducing signals to cytoskeletal and polarity effectors; this is a correct core process term. Reason: Core conserved process for a Rho-family GTPase; well supported. Supporting Evidence: PMID:7597098 signaling modules composed of small GTP-binding proteins and protein kinases related to Shk1, Ste20, and p65PAK, are highly conserved in evolution and participate in both cytoskeletal functions and mitogen-activated protein kinase signaling pathways |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cdc42 is present on internal/endomembranes (nuclear and vacuolar membranes, exocytic vesicles) in addition to the plasma membrane, consistent with its trafficking through the secretory pathway. A broad but accurate localization. Reason: Supported by direct imaging of internal membranes; the functionally important site is the plasma membrane of the cell tip, so endomembrane is non-core. Supporting Evidence: PMID:25837586 Significant levels of Cdc42-mCherrySW were also found along the cell sides and on internal membranes including the nuclear and presumably vacuolar membranes. |
| GO:0016020 membrane | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: 'Membrane' is a high-level parent of the experimentally supported plasma membrane localization and is uninformative on its own. Reason: Redundant generic parent term; the specific plasma membrane / cell tip membrane terms are annotated and preferred. Supporting Evidence: PMID:25837586 removal of the CAAX sequence yielded a diffuse, non-functional Cdc42 allele unable to complement the cdc42-1625 temperature-sensitive mutant |
| GO:0030010 establishment of cell polarity | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate of the establishment of cell polarity annotation (also IBA and IMP). Core function; accept. Reason: Redundant with IMP/IBA annotations of the same core function. Supporting Evidence: PMID:8289788 S. pombe Cdc42p is involved in controlling polarized cell growth |
| GO:0030427 site of polarized growth | IEA GO_REF:0000117 | ACCEPT | Summary: Cdc42 localizes to and acts at the site of polarized growth (cell tips). Supported by direct IDA evidence below. Reason: Supported by direct localization; redundant with IDA annotation. Supporting Evidence: PMID:25837586 Cdc42-mCherrySW was enriched at the cell tips and division sites. |
| GO:0051286 cell tip | IEA GO_REF:0000117 | ACCEPT | Summary: Cell tip localization is a hallmark of active Cdc42 in fission yeast. Supported by direct IDA evidence. Reason: Core localization; redundant with IDA annotation. Supporting Evidence: PMID:20870879 a group of proteins involved in the growth process and actin regulation, comprising Spo20, Bgs4, activated Cdc42, and Crn1, are all concentrated at the growing tip |
| GO:0005515 protein binding | IPI PMID:12529446 Gef1p, a new guanine nucleotide exchange factor for Cdc42p, ... | MARK AS OVER ANNOTATED | Summary: Represents the Cdc42-Gef1 (GEF) interaction. 'Protein binding' is uninformative; the meaningful relationship is that Gef1 is a GEF that activates Cdc42. Reason: Bare protein binding is uninformative; the underlying Gef1-Cdc42 GEF interaction is captured by GTPase/signal-transduction functions. Supporting Evidence: PMID:12529446 Gef1p binds to inactive Cdc42p but not to other Rho GTPases in two-hybrid assays. |
| GO:0005515 protein binding | IPI PMID:12972551 Gef1p and Scd1p, the Two GDP-GTP exchange factors for Cdc42p... | MARK AS OVER ANNOTATED | Summary: Represents Cdc42 interaction with the GEFs Gef1/Scd1 at the division site. Uninformative bare protein-binding term. Reason: Bare protein binding; specific functions captured elsewhere. Supporting Evidence: PMID:12972551 recruitment of Cdc42p to the cell division site follows the shrinking Gef1p/Scd1p ring; the Cdc42p accumulates like a closing iris |
| GO:0005515 protein binding | IPI PMID:17363901 Hob3p, the fission yeast ortholog of human BIN3, localizes C... | MARK AS OVER ANNOTATED | Summary: Represents the direct Cdc42-Hob3p interaction that localizes Cdc42 to the division site. Uninformative bare protein-binding term. Reason: Bare protein binding; the biologically relevant role (division-site recruitment) is captured by cellular-component and cytokinesis annotations. Supporting Evidence: PMID:17363901 Hob3p also interacts directly with Cdc42p independently of Gef1p. |
| GO:0000755 cytogamy | IMP PMID:41855172 Distinct Cdc42 protein levels differentially regulate polari... | KEEP AS NON CORE | Summary: Cdc42 is required for cell-cell fusion (cytogamy) during sexual reproduction, concentrating at the fusion site; mating/fusion require higher Cdc42 levels than mitotic growth. A genuine but specialized (non-core) developmental role. Reason: Directly supported by mutant phenotype, but a specialized sexual-reproduction role rather than the core mitotic polarity function. Supporting Evidence: PMID:41855172 Cdc42 also functions in cell-cell fusion during Schizosaccharomyces pombe sexual reproduction |
| GO:0070867 mating projection tip membrane | EXP PMID:41855172 Distinct Cdc42 protein levels differentially regulate polari... | KEEP AS NON CORE | Summary: During mating, active Cdc42 concentrates at the mating projection tip/fusion-site membrane. A specialized localization supporting its cell fusion role. Reason: Specialized mating localization, directly observed. Supporting Evidence: PMID:41855172 concentrates at the fusion site through mechanisms distinct from those proposed in Saccharomyces cerevisiae |
| GO:0032153 cell division site | IDA PMID:37039135 Cdc42 prevents precocious Rho1 activation during cytokinesis... | ACCEPT | Summary: Active Cdc42 at the division site coordinates cytokinesis, including preventing precocious Rho1 activation via Pak1. Correct, well-supported localization. Reason: Directly observed active Cdc42 at the division site with functional consequence. Supporting Evidence: PMID:37039135 We show that Cdc42 prevents early Rho1 activation during fission yeast cytokinesis. |
| GO:0035591 signaling adaptor activity | EXP PMID:31719163 A novel interplay between GEFs orchestrates Cdc42 activity d... | KEEP AS NON CORE | Summary: Active Cdc42 acts as a hub in a feedforward loop that recruits the scaffold Scd2 (and thereby the GEF Scd1), coordinating its own activators during polarity and cytokinesis. This adaptor/hub role is supported, though it is a consequence of GTP-Cdc42 effector binding rather than a distinct activity. Reason: Supported by the feedforward-recruitment data; non-core relative to the GTPase switch function. Supporting Evidence: PMID:31719163 Gef1 promotes Scd1 localization to the division site during cytokinesis through recruitment of the scaffold protein Scd2, via a Cdc42 feedforward pathway |
| GO:0032456 endocytic recycling | IMP PMID:23060961 Cdc42 regulation of polarized traffic in fission yeast. | KEEP AS NON CORE | Summary: Cdc42 is required for transport/recycling of glucan synthases Bgs1/Bgs4 to the plasma membrane and for endosome recycling. A genuine membrane-traffic role, secondary to the core polarity function. Reason: Supported by mutant traffic phenotypes; a downstream effector process. Supporting Evidence: PMID:23060961 Cdc42 is required for the correct transport/recycling to the plasma membrane of the glucan synthases Bgs1 and Bgs4 |
| GO:0003924 GTPase activity | EXP PMID:18328707 Pom1 DYRK regulates localization of the Rga4 GAP to ensure b... | ACCEPT | Summary: GTPase activity / GTP-GDP cycling is the core molecular function; this paper demonstrates Cdc42 functions as a GTP-loaded switch regulated by its GAP Rga4 and detected via CRIB-GFP. Reason: Core function supported by the GAP-regulated switch behavior. Supporting Evidence: PMID:18328707 Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator of F-actin |
| GO:0042815 bipolar cell growth | EXP PMID:18328707 Pom1 DYRK regulates localization of the Rga4 GAP to ensure b... | ACCEPT | Summary: Bipolar Cdc42 activation at both cell ends drives bipolar growth; Pom1 ensures bipolar Cdc42 activation by localizing the GAP Rga4. A core fission-yeast process. Reason: Directly supported; central to fission yeast polarized growth. Supporting Evidence: PMID:18328707 Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42 |
| GO:2000769 regulation of establishment or maintenance of cell polarity regulating cell shape | EXP PMID:18328707 Pom1 DYRK regulates localization of the Rga4 GAP to ensure b... | ACCEPT | Summary: The spatial gradient of active Cdc42 at cell tips controls cell shape/width. A specific and well-supported facet of the core polarity function. Reason: Supported by Cdc42-activation gradient determining cell shape/width. Supporting Evidence: PMID:18328707 GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:9660818 Characterization of Pak2p, a pleckstrin homology domain-cont... | ACCEPT | Summary: GTP-Cdc42 binds and activates PAK serine/threonine kinases (Pak2/Shk2, Shk1/Pak1). This is an informative molecular function downstream of the GTPase switch. Reason: Directly supported; captures Cdc42's effector-activation function better than bare protein/kinase binding. Supporting Evidence: PMID:9660818 the membrane localization of Pak2p, directed by its interactions with membrane lipids and Cdc42p, is critical to its biological activity |
| GO:0005515 protein binding | IPI PMID:18328707 Pom1 DYRK regulates localization of the Rga4 GAP to ensure b... | MARK AS OVER ANNOTATED | Summary: Bare protein-binding annotation derived from interactions reported in the Rga4/Pom1 study. Uninformative; more specific functions are annotated. Reason: Bare protein binding term. Supporting Evidence: PMID:18328707 Rga4 functions as GAP for the Cdc42 GTPase |
| GO:1902716 cell cortex of growing cell tip | IDA PMID:18328707 Pom1 DYRK regulates localization of the Rga4 GAP to ensure b... | ACCEPT | Summary: Active Cdc42 (CRIB-GFP) is concentrated at the cortex of growing cell tips. Specific and well-supported localization. Reason: Directly observed active Cdc42 at the growing-tip cortex. Supporting Evidence: PMID:18328707 GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures |
| GO:0031520 plasma membrane of cell tip | EXP PMID:21849474 Spatial control of Cdc42 activation determines cell width in... | ACCEPT | Summary: A gradient of active Cdc42 within the cell-tip plasma membrane sets cell width; this is the principal site of Cdc42 action. Core localization. Reason: Directly supported core localization. Supporting Evidence: PMID:21849474 the GAP Rga4 and the GEF Scd1 establish a gradient of activated Cdc42 within the cellular tip plasma membrane, and it is this gradient that determines cell growth-zone size and normal cell width |
| GO:0005938 cell cortex | IDA PMID:29930085 Local and global Cdc42 guanine nucleotide exchange factors f... | ACCEPT | Summary: Active Cdc42 localizes at the cell cortex. Directly supported. Reason: Direct localization evidence. Supporting Evidence: PMID:10961446 GFP-Cdc42p was observed at the medial region of the cell at the cell-division site early in cytokinesis and remained there through cell separation, and was also localized to the periphery of the cell and to internal membranes. |
| GO:0110085 mitotic actomyosin contractile ring | IDA PMID:29930085 Local and global Cdc42 guanine nucleotide exchange factors f... | KEEP AS NON CORE | Summary: Active Cdc42 is present at the mitotic actomyosin (contractile) ring, where it contributes to cytokinesis. Supported localization, non-core relative to tip polarity. Reason: Directly observed; part of the cytokinesis role. Supporting Evidence: PMID:10961446 medial GFP-Cdc42p localization was eliminated in a number of cytokinesis mutants, including strains defective in assembling the medial actinomyosin ring, medial ring contraction, and septum assembly. |
| GO:0005515 protein binding | IPI PMID:9660817 Cloning and characterization of shk2, a gene encoding a nove... | MARK AS OVER ANNOTATED | Summary: Represents the Cdc42-Shk2/Pak2 interaction. Bare protein binding; uninformative relative to the PAK-activator function. Reason: Bare protein binding; captured by kinase-activator activity. Supporting Evidence: PMID:9660817 Like other known PAKs, Shk2 binds to Cdc42 in vivo and in vitro. |
| GO:1902917 positive regulation of mating projection assembly | IMP PMID:24147005 The coordination of cell growth during fission yeast mating ... | KEEP AS NON CORE | Summary: Cdc42 promotes mating projection (shmoo) assembly; coordinating active Cdc42 into a single growth zone is required for proper projection formation during mating. A genuine but specialized developmental role. Reason: Supported by mating-specific phenotypes; specialized sexual-reproduction role. Supporting Evidence: PMID:24147005 We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. |
| GO:1902917 positive regulation of mating projection assembly | IMP PMID:7923372 Cooperative interaction of S. pombe proteins required for ma... | KEEP AS NON CORE | Summary: Cdc42, together with Scd1/Scd2/Ras1, is required for mating and morphology, consistent with promotion of mating projection assembly. Duplicate mating-projection annotation; non-core specialized role. Reason: Supported via the Ras1-Scd1-Scd2-Cdc42 mating pathway; non-core. Supporting Evidence: PMID:7923372 scd1, scd2, cdc42sp, and ras1, in its GTP-bound state, act cooperatively to form a protein complex |
| GO:0032153 cell division site | IDA PMID:26941334 Unique spatiotemporal activation pattern of Cdc42 by Gef1 an... | ACCEPT | Summary: Active Cdc42 localizes to the cell division site with a Gef1/Scd1-dependent spatiotemporal pattern during cytokinesis. Supported localization. Reason: Directly observed; redundant with other division-site annotations. Supporting Evidence: PMID:26941334 The Rho-family GTPase Cdc42 regulates cell polarity and localizes to the cell division site. |
| GO:0032154 cleavage furrow | IDA PMID:26941334 Unique spatiotemporal activation pattern of Cdc42 by Gef1 an... | ACCEPT | Summary: Active Cdc42 (Scd1-dependent) localizes to the ingressing membrane/cleavage furrow during cytokinetic furrowing. Supported localization. Reason: Directly observed at the ingressing membrane during furrowing. Supporting Evidence: PMID:26941334 Scd1 localizes to the broader region of ingressing membrane during cytokinetic furrowing. |
| GO:0032153 cell division site | IDA PMID:25837586 Spontaneous Cdc42 polarization independent of GDI-mediated e... | ACCEPT | Summary: Functional tagged Cdc42 is enriched at division sites. Supported localization; redundant with other division-site annotations. Reason: Directly observed division-site enrichment of functional Cdc42. Supporting Evidence: PMID:25837586 Cdc42-mCherrySW was enriched at the cell tips and division sites. |
| GO:1902917 positive regulation of mating projection assembly | EXP PMID:23200991 Cdc42 explores the cell periphery for mate selection in fiss... | KEEP AS NON CORE | Summary: Cdc42 exploration of the cell periphery orients polarized growth toward a mating partner, promoting mating projection formation. Non-core specialized role. Reason: Directly supported mating-projection function; specialized role. Supporting Evidence: PMID:23200991 active Cdc42, its GEF Scd1, and scaffold Scd2 form colocalizing dynamic zones that sample the periphery of the cell |
| GO:0043332 mating projection tip | IDA PMID:23200991 Cdc42 explores the cell periphery for mate selection in fiss... | KEEP AS NON CORE | Summary: Active Cdc42 localizes to the mating projection tip during pheromone response. Supported specialized localization. Reason: Directly observed mating-specific localization. Supporting Evidence: PMID:23200991 active Cdc42, its GEF Scd1, and scaffold Scd2 form colocalizing dynamic zones that sample the periphery of the cell |
| GO:0090726 cortical dynamic polarity patch | IDA PMID:23200991 Cdc42 explores the cell periphery for mate selection in fiss... | ACCEPT | Summary: During mate selection, active Cdc42 forms dynamic cortical polarity patches that explore the cell periphery. Directly observed and specific. Reason: Directly observed dynamic cortical Cdc42 patches. Supporting Evidence: PMID:23200991 active Cdc42, its GEF Scd1, and scaffold Scd2 form colocalizing dynamic zones that sample the periphery of the cell |
| GO:0030427 site of polarized growth | IDA PMID:25837586 Spontaneous Cdc42 polarization independent of GDI-mediated e... | ACCEPT | Summary: Active Cdc42 acts at the site of polarized growth (cell tips). Core localization, directly observed. Reason: Directly observed; core site of action. Supporting Evidence: PMID:25837586 Cdc42-mCherrySW was enriched at the cell tips and division sites. |
| GO:0005886 plasma membrane | IDA PMID:25837586 Spontaneous Cdc42 polarization independent of GDI-mediated e... | ACCEPT | Summary: Cdc42 is active at the plasma membrane (cell tips, division site). Core localization with direct evidence. Reason: Directly observed plasma-membrane localization of functional Cdc42. Supporting Evidence: PMID:25837586 Cdc42-mCherrySW was enriched at the cell tips and division sites. |
| GO:0012505 endomembrane system | IDA PMID:25837586 Spontaneous Cdc42 polarization independent of GDI-mediated e... | KEEP AS NON CORE | Summary: Cdc42 is found on internal/endomembranes (nuclear, vacuolar) and exocytic vesicles, consistent with secretory-pathway trafficking. Non-core relative to plasma-membrane action. Reason: Directly observed internal-membrane localization; not the primary site of action. Supporting Evidence: PMID:25837586 on internal membranes including the nuclear and presumably vacuolar membranes |
| GO:0070382 exocytic vesicle | IDA PMID:25837586 Spontaneous Cdc42 polarization independent of GDI-mediated e... | KEEP AS NON CORE | Summary: Cdc42 is trafficked on exocytic vesicles, demonstrated by sub-apical accumulation upon exocyst (Sec8) depletion. Supported localization, consistent with its secretion role. Reason: Directly demonstrated vesicle association; secondary to plasma-membrane action. Supporting Evidence: PMID:25837586 In cells depleted of the exocyst member Sec8, in which exocytic vesicles accumulate but fail to fuse at the cell tip [41,42], Cdc42-mCherrySW accumulated sub-apically, confirming that Cdc42 is trafficked on exocytic vesicles (Fig. 1G). |
| GO:0005515 protein binding | IPI PMID:7923372 Cooperative interaction of S. pombe proteins required for ma... | MARK AS OVER ANNOTATED | Summary: Represents Cdc42 interaction within the Scd1-Scd2-Cdc42-Ras1 complex. Bare protein binding; the informative annotation is membership in the Cdc42 GTPase (Scd1/Scd2) complex. Reason: Bare protein binding; complex membership captured by Cdc42 GTPase complex term. Supporting Evidence: PMID:7923372 scd2 forms complexes with both scd1 and cdc42sp |
| GO:0030010 establishment of cell polarity | IMP PMID:7923372 Cooperative interaction of S. pombe proteins required for ma... | ACCEPT | Summary: Cdc42 (with Scd1/Scd2/Ras1) is required for normal cell morphology and polarity. Core function, directly supported. Reason: Core function supported by mutant morphology phenotypes. Supporting Evidence: PMID:7923372 We isolated two S. pombe genes, scd1 and scd2, that are required for normal morphology and mating. |
| GO:0071521 Cdc42 GTPase complex | IPI PMID:8943016 The highly conserved skb1 gene encodes a protein that intera... | ACCEPT | Summary: Cdc42 forms a complex with its PAK effector Shk1 and Skb1 (and with Scd1/Scd2). Membership in the Cdc42 GTPase complex is informative and well supported. Reason: Directly supported ternary/effector complex membership. Supporting Evidence: PMID:8943016 Shk1, Cdc42, and Skb1 are able to form a ternary complex in vivo |
| GO:0005515 protein binding | IPI PMID:7597098 Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and ma... | MARK AS OVER ANNOTATED | Summary: Represents the Cdc42-Shk1/Pak1 interaction. Bare protein binding; uninformative relative to the PAK kinase-activator function. Reason: Bare protein binding; captured by kinase-activator activity / complex terms. Supporting Evidence: PMID:7597098 physical and functional interaction between Shk1 and the Cdc42 GTP-binding protein |
| GO:0097575 lateral cell cortex | IDA PMID:24146635 Hsp70-Hsp40 chaperone complex functions in controlling polar... | KEEP AS NON CORE | Summary: Under heat stress (or constitutive Hsf1 activation) Cdc42 activity shifts to a monopolar pattern with altered lateral cortex distribution. A condition-specific localization, non-core. Reason: Stress-condition-specific lateral localization; not the normal site of action. Supporting Evidence: PMID:24146635 dynamic adaptation to thermal stress resulting in a period of decreased Cdc42 activity and altered, monopolar growth |
| GO:1902716 cell cortex of growing cell tip | IDA PMID:24146635 Hsp70-Hsp40 chaperone complex functions in controlling polar... | ACCEPT | Summary: Active Cdc42 localizes at the cortex of the growing cell tip; under heat stress this is reduced/monopolar. Supported core localization. Reason: Directly observed growing-tip cortex localization. Supporting Evidence: PMID:24146635 a period of decreased Cdc42 activity and altered, monopolar growth |
| GO:0051285 cell cortex of cell tip | IDA PMID:24146635 Hsp70-Hsp40 chaperone complex functions in controlling polar... | ACCEPT | Summary: Active Cdc42 localizes to the cortex of the cell tip. Supported core localization. Reason: Directly observed cell-tip cortex localization. Supporting Evidence: PMID:24146635 the cellular polarity machinery in the fission yeast Schizosaccharomyces pombe undergoes dynamic adaptation to thermal stress |
| GO:0006893 Golgi to plasma membrane transport | IMP PMID:23060961 Cdc42 regulation of polarized traffic in fission yeast. | KEEP AS NON CORE | Summary: Cdc42 is required for transport of glucan synthases Bgs1/Bgs4 to the plasma membrane (post-Golgi/exocyst-dependent secretion). A genuine but downstream traffic role. Reason: Supported by traffic phenotype; downstream effector process. Supporting Evidence: PMID:23060961 Cdc42 is required for the correct transport/recycling to the plasma membrane of the glucan synthases Bgs1 and Bgs4 |
| GO:0006887 exocytosis | IGI PMID:21899677 Cdc42 regulates multiple membrane traffic events in fission ... | KEEP AS NON CORE | Summary: Cdc42 (with scaffold Pob1) is required for exocyst function and polarized secretion; cdc42L160S has secretion defects and exocyst mislocalization. A genuine downstream role in polarized exocytosis. Reason: Supported by secretion/exocyst phenotypes; downstream of the polarity switch. Supporting Evidence: PMID:21899677 This strain has decreased acid phosphatase (AP) secretion, intracellular accumulation of vesicles and fragmentation of vacuoles. In addition, the exocyst is not localized to the tips of these cells. |
| GO:0003924 GTPase activity | IDA PMID:18793338 Rga2 is a Rho2 GAP that regulates morphogenesis and cell int... | ACCEPT | Summary: GTPase activity is the core molecular function of Cdc42. However, the cited reference (PMID:18793338) characterizes Rga2 as a GAP for Rho2 and does not directly assay Cdc42 GTPase activity, so the supporting reference is weak. The function itself is correct and is supported elsewhere. Reason: Core function is correct (Rho-family GTPase). The specific reference is a poor source for an IDA on Cdc42 GTPase activity, but the annotation should be retained based on the broader GEF/GAP-cycle evidence. Supporting Evidence: PMID:21849474 They have intrinsic GTPase activity and can hydrolyze GTP to GDP, but this hydrolysis is usually inefficient. |
| GO:0051285 cell cortex of cell tip | IDA PMID:19646873 The conserved NDR kinase Orb6 controls polarized cell growth... | ACCEPT | Summary: Cdc42 is normally restricted to the cell-tip cortex by Orb6; loss of Orb6 activity relocates Cdc42 to the cell sides. Supported core localization. Reason: Directly observed cell-tip cortex localization (Orb6-dependent restriction). Supporting Evidence: PMID:19646873 Loss of Orb6 kinase activity leads to the recruitment of Cdc42 GTPase and the Cdc42-dependent formin For3, normally found only at the cell tips, to the cell sides. |
| GO:0051286 cell tip | IDA PMID:20870879 Reorganization of the growth pattern of Schizosaccharomyces ... | ACCEPT | Summary: Activated Cdc42 concentrates at the growing cell tip (here, the single tip of invasive filaments). Supported core localization. Reason: Directly observed cell-tip localization of activated Cdc42. Supporting Evidence: PMID:20870879 Spo20, Bgs4, activated Cdc42, and Crn1, are all concentrated at the growing tip |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:10961446 The Cdc42p GTPase is targeted to the site of cell division i... | ACCEPT | Summary: Cdc42 (prenyl-anchored) localizes to the cytoplasmic face of the plasma membrane and the cell-division site. Supported core localization. Reason: Directly observed; consistent with C-terminal prenyl membrane anchoring. Supporting Evidence: PMID:10961446 GFP-Cdc42p was observed at the medial region of the cell at the cell-division site early in cytokinesis and remained there through cell separation, and was also localized to the periphery of the cell |
| GO:0032951 regulation of beta-glucan biosynthetic process | IGI PMID:8887550 Rho 1 GTPase activates the (1-3)beta-D-glucan synthase and i... | MARK AS OVER ANNOTATED | Summary: PMID:8887550 explicitly shows that neither cdc42+ nor constitutively active cdc42 alleles affect (1-3)beta-D-glucan synthase activity (Rho1 is the direct activator). Any role of Cdc42 in beta-glucan biosynthesis is indirect, via trafficking of the Bgs glucan synthases to the plasma membrane. This IGI annotation overstates a direct regulatory role. Reason: The cited paper shows Cdc42 does NOT directly affect glucan synthase; the connection is indirect (Bgs1/Bgs4 trafficking), so a direct regulation term is an over-annotation. Supporting Evidence: PMID:8887550 Neither cdc42+ nor the cdc42-V12G or cdc42-Q61L constitutively active mutant alleles affect (1-3)beta-D-glucan synthase activity when overexpressed in S.pombe. |
| GO:0032153 cell division site | IDA PMID:10961446 The Cdc42p GTPase is targeted to the site of cell division i... | ACCEPT | Summary: GFP-Cdc42p localizes to the medial cell-division site during cytokinesis. Supported localization; redundant with other division-site annotations. Reason: Directly observed division-site localization. Supporting Evidence: PMID:10961446 GFP-Cdc42p was observed at the medial region of the cell at the cell-division site early in cytokinesis and remained there through cell separation |
| GO:0032878 regulation of establishment or maintenance of cell polarity | IMP PMID:8289788 Cdc42p GTPase is involved in controlling polarized cell grow... | ACCEPT | Summary: cdc42 mutants display abnormal morphology and disrupted polarized growth, directly implicating Cdc42 in regulation of cell polarity. Core function. Reason: Core function supported by loss/gain-of-function mutant phenotypes. Supporting Evidence: PMID:8289788 the cdc42 mutants did exhibit an abnormal morphological phenotype of large, misshapen cells, suggesting that S. pombe Cdc42p is involved in controlling polarized cell growth |
| GO:0032955 regulation of division septum assembly | IMP PMID:8887550 Rho 1 GTPase activates the (1-3)beta-D-glucan synthase and i... | KEEP AS NON CORE | Summary: Cdc42 has a genuine role in cytokinesis/septation (recruiting Cdc42 effectors and Bgs1 to the division site, restraining Rho1), but the cited reference (PMID:8887550) is a Rho1 paper and is a poor source for this specific IMP. Retain the process as a non-core function supported by the broader cytokinesis literature. Reason: Septum regulation is a real non-core Cdc42 role (cytokinesis literature), but the cited reference is weak for this annotation. Supporting Evidence: PMID:26941334 Scd1 promotes normal septum formation, andscd1Ξcells display aberrant septa with reduced Bgs1 localization. |
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Download this section (compressed HTML)Q: What is the relative contribution of intrinsic versus GAP-stimulated GTP hydrolysis to spatial restriction of Cdc42 activity, and which GAP(s) besides Rga4 act on Cdc42 in vivo?
Q: How is the switch-like (all-or-none) response of mating/cell fusion to Cdc42 protein levels, versus the linear response of mitotic growth, encoded molecularly?
Experiment: Quantitative in vitro GTPase assays of purified S. pombe Cdc42 with and without candidate GAPs (e.g., Rga4) and GEFs (Scd1, Gef1) to directly measure intrinsic and stimulated nucleotide cycling rates for the fission yeast protein.
Experiment: Proximity-labeling (TurboID) of active versus inactive Cdc42 (using GTP- and GDP-locked alleles) at cell tips and the division site to define the state-specific effector interactome and distinguish core effectors from context-specific partners.
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