CudA is a nuclear, sequence-specific DNA-binding transcription factor of the social amoeba Dictyostelium discoideum that is essential for normal culmination and for the differentiation of both prestalk and prespore cells. It is the founding member of a novel family of transcription factors (the CudA/PTS family) whose conserved central core region constitutes a presumptive DNA-binding domain that is structurally related to the DNA-binding region of plant STAT-like proteins. CudA binds an interrupted dyad element containing GAA half-sites and forms homodimers, and it directly activates target genes such as the cotC spore-coat gene in prespore cells and the expansin-like expl7 gene in the slug tip-organiser. CudA is expressed in the nuclei of the prestalk cells of the slug tip (the tip-organiser/pstA cells) and in prespore cells, and its tip-specific expression is induced by the STATa signalling pathway acting downstream of the ACA adenylyl cyclase. Cells lacking cudA fail to culminate, continue to migrate as slugs under conditions where wild-type slugs culminate, and are defective in both mature stalk and mature spore formation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of nuclear localization is correct and strongly corroborated by direct experimental evidence; CudA is a nuclear transcription factor. Reason: CudA is directly shown to be a nucleoplasmic/nuclear protein that binds chromatin (cotC promoter) in vivo, so the IBA nuclear annotation is fully consistent with the experimental data. Supporting Evidence: PMID:19757394 CudA is a nuclear protein which is expressed in prespore cells where it acts as a specific transcription factor. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: CudA is a sequence-specific DNA-binding transcription factor that regulates gene expression, so the general transcription-regulation term is appropriate. Direct evidence specifically supports a positive (activator) role. Reason: The IBA inference that CudA is involved in regulation of transcription is confirmed experimentally; CudA binds target promoters and controls their expression. The general term is correct; the more specific activator role is captured in the core functions and in the positive-regulation annotations. Supporting Evidence: PMID:19757394 STATa then induces expression of cudA and cudA directs the transcription of target genes such as expl7. |
| GO:0043565 sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sequence-specific DNA binding is a core molecular function of CudA and is directly demonstrated experimentally; the IBA inference is well supported. Reason: CudA binds a defined interrupted-dyad sequence in target promoters, as shown by DNA affinity chromatography, ChIP, and band-shift analysis. The IBA annotation matches the experimental evidence. Supporting Evidence: PMID:18701541 We conclude that the dyad, defined using ECudA, also forms part or all of a CudA binding site. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to nucleoplasm is correct and matches direct experimental evidence describing CudA as a nucleoplasmic protein. Reason: CudA was originally characterized as a nucleoplasmic protein, so the IEA nucleoplasm annotation derived from the UniProt subcellular location is accurate. Supporting Evidence: PMID:9226443 The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. |
| GO:0097696 cell surface receptor signaling pathway via STAT | IMP PMID:10821768 Analysis of the promoter of the cudA gene reveals novel mech... | KEEP AS NON CORE | Summary: CudA is the principal transcriptional effector/target of the STATa signalling pathway; STATa binds the cudA promoter and directly activates cudA transcription in prestalk cells. CudA thus acts within the STATa pathway as a downstream node, but this is not its core molecular function. Reason: The annotation reflects that CudA operates downstream of STATa signalling (STATa is a direct activator of cudA), which is an experimentally supported and biologically meaningful placement within the pathway. It is, however, a pathway-level/developmental involvement rather than CudA's core transcription-factor activity. Supporting Evidence: PMID:10821768 Dd-STATa appears therefore to serve as a direct activator of cudA transcription in prestalk cells |
| GO:0010628 positive regulation of gene expression | IMP PMID:27125566 Regulation of ecmF gene expression and genetic hierarchy amo... | ACCEPT | Summary: CudA acts as a positive regulator of gene expression, directly activating downstream target genes such as expL7 in prestalk cells. This is a direct consequence of its core transcription-factor activity. Reason: The abstract explicitly states that CudA directly activates expL7 gene expression, supporting positive regulation of gene expression as a genuine and central role of this activator. Supporting Evidence: PMID:27125566 The only verified upregulated target gene of STATa is cudA gene; CudA directly activates expL7 gene expression in prestalk cells. |
| GO:0031154 culmination involved in sorocarp development | IEP PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo... | KEEP AS NON CORE | Summary: This annotation is inferred from the expression pattern of cudA, which is sharply up-regulated during late (slug-to-culmination) development. The involvement of cudA in culmination is well established genetically, but this particular annotation rests only on expression timing. Reason: The expression-based (IEP) evidence corroborates a developmental role in culmination but is weaker than the mutant-based evidence, and culmination is a downstream developmental process rather than CudA's core molecular function. Supporting Evidence: PMID:25887420 At 16 h, cudA and mybE were up-regulated sharply |
| GO:0010628 positive regulation of gene expression | IMP PMID:19757394 Identification of a target for CudA, the transcription facto... | ACCEPT | Summary: CudA is required for expression of its target gene expl7; expl7 is not expressed in cudA-null slugs, and CudA binds the expl7 promoter, establishing CudA as a positive transcriptional regulator. Reason: Loss of cudA abolishes expl7 expression and CudA binds the expl7 promoter, providing strong support for a positive regulatory role over gene expression. This directly reflects CudA's activator function. Supporting Evidence: PMID:19757394 there is no detectable expression of expl7 in cudA null slugs |
| GO:0043565 sequence-specific DNA binding | IDA PMID:19757394 Identification of a target for CudA, the transcription facto... | ACCEPT | Summary: Direct evidence shows CudA binds a defined region (region B) of the expl7 promoter by DNA affinity chromatography of slug nuclear extracts. Reason: CudA from slug nuclear extracts binds specifically to a defined promoter fragment, directly supporting sequence-specific DNA binding as a core molecular function. Supporting Evidence: PMID:19757394 Region B binds CudA |
| GO:0043565 sequence-specific DNA binding | IDA PMID:18701541 A new family of transcription factors. | ACCEPT | Summary: CudA binds a specific interrupted-dyad element in the cotC promoter, as shown by in vivo ChIP and by DNA affinity chromatography; a conserved core domain constitutes the presumptive DNA-binding domain and CudA forms a homodimer consistent with the dyad binding site. Reason: This is the strongest evidence for sequence-specific DNA binding; in vivo promoter occupancy (ChIP), affinity chromatography, and mutational mapping of the binding site all support this core molecular function. Supporting Evidence: PMID:18701541 We conclude that the dyad, defined using ECudA, also forms part or all of a CudA binding site. PMID:18701541 Thus, CudA is bound at the promoter of the cotC gene. |
| GO:0005654 nucleoplasm | IDA PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | ACCEPT | Summary: CudA was directly characterized as a nucleoplasmic protein, supporting this localization annotation. Reason: Direct experimental evidence from the founding cudA study describes CudA as a nucleoplasmic protein, consistent with its role as a transcription factor. Supporting Evidence: PMID:9226443 The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. |
| GO:0030435 sporulation resulting in formation of a cellular spore | IMP PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | KEEP AS NON CORE | Summary: cudA-null cells are defective in spore formation, indicating that CudA is required for normal sporulation. This is a downstream developmental outcome of CudA's role as a prespore-gene transcriptional activator. Reason: The mutant phenotype supports a genuine requirement for cudA in spore formation, but sporulation is a pleiotropic developmental process that follows from CudA's core transcription-factor activity rather than being that core function itself. Supporting Evidence: PMID:9226443 cudA- mutant cells are indeed defective in both stalk and spore formation. |
| GO:0031154 culmination involved in sorocarp development | IMP PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | KEEP AS NON CORE | Summary: cudA is essential for normal culmination; cudA-null slugs continue to migrate under conditions where wild-type slugs culminate, and cudA was identified precisely as a culmination-deficient mutant. Reason: The requirement for cudA in culmination is strongly supported by mutant phenotype, but culmination is a downstream developmental process controlled by CudA's transcriptional activity rather than its core molecular function. Supporting Evidence: PMID:9226443 The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. PMID:9226443 the slugs formed by cudA- cells continue to migrate under environmental conditions where normal slugs culminate immediately |
| GO:0005634 nucleus | IDA PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | ACCEPT | Summary: CudA is directly localized to the nucleus (nucleoplasm), consistent with its function as a DNA-binding transcription factor. Reason: Direct evidence establishes CudA as a nuclear/nucleoplasmic protein, so the nucleus localization annotation is accurate. Supporting Evidence: PMID:9226443 The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. |
| GO:0030154 cell differentiation | IMP PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | KEEP AS NON CORE | Summary: CudA is required for the differentiation of both stalk and spore cells, acting on both pathways of cell-type differentiation as a transcriptional regulator. Reason: The mutant is defective in both stalk and spore differentiation, supporting a role in cell differentiation. This is, however, a very general developmental-process term downstream of CudA's core transcription-factor activity; the more specific developmental roles are captured by the culmination and sporulation annotations. Supporting Evidence: PMID:9226443 This unusual pattern of expression suggests a role on both the stalk and spore pathways of differentiation PMID:9226443 cudA- mutant cells are indeed defective in both stalk and spore formation. |
| GO:0031154 culmination involved in sorocarp development | IMP PMID:9226443 cudA: a Dictyostelium gene with pleiotropic effects on cellu... | KEEP AS NON CORE | Summary: Duplicate culmination annotation from the same study with a different qualifier; cudA is required for entry into culmination, a property of the tip-organiser cells in which CudA is expressed. Reason: As with the other culmination annotation, this is strongly supported by the mutant phenotype but represents a downstream developmental process rather than CudA's core molecular function. Supporting Evidence: PMID:9226443 the slugs formed by cudA- cells continue to migrate under environmental conditions where normal slugs culminate immediately |
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