gtaC

UniProt ID: Q75JZ1
Organism: Dictyostelium discoideum
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

GtaC is a GATA-family transcription factor of Dictyostelium discoideum that carries a single Cys2-Cys2 (type IV) zinc-finger domain and binds sequence-specific GATA-like cis-regulatory elements in the promoters of target genes. It is a nuclear DNA-binding transcription factor that activates and represses developmental gene expression, and it is essential for early development, since cells lacking gtaC fail to aggregate and arrest transcriptional and morphological progression. GtaC is a central effector that decodes oscillatory extracellular cAMP signals. During early development it undergoes rapid nucleocytoplasmic shuttling driven by cAMP-receptor occupancy and reversible phosphorylation (mediated by the atypical MAPK Erk2 and GskA), entering the nucleus during the falling phase of each cAMP wave and exiting during the rising phase. This shuttling converts pulsatile cAMP input into temporally patterned bursts of transcription and functions as a developmental timer, allowing cells to track low-frequency and filter out high-frequency signals. GtaC directly binds the promoters of thousands of genes, including central cAMP-signalling components such as the adenylyl cyclase acaA and cAMP receptor carA, and its DNA binding is highly dynamic across developmental stages. Beyond aggregation, GtaC contributes to later cell-type specification, acting downstream of the diffusible morphogen DIF-1 to regulate prestalk/basal-disc (stalk-related) differentiation, and it modulates chemotactic behaviour, suppressing chemotaxis toward folate.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000976 transcription cis-regulatory region binding
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic inference that GtaC binds cis-regulatory regions is correct and independently confirmed by direct ChIP-seq evidence in the same organism, where GtaC occupies GATA-like promoter elements genome-wide.
Reason: This IBA annotation transfers the conserved GATA-family DNA-binding function and is fully corroborated by direct experimental evidence (ChIP-seq) showing GtaC binds thousands of promoters at a GATA-like motif. This is a core molecular function.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
PMID:26144553
We identified 2,091 genes whose promoter regions were bound by GtaC
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nuclear localization inferred by phylogeny is correct; GtaC acts as a transcription factor in the nucleus and multiple direct studies show nuclear accumulation.
Reason: As a DNA-binding transcription factor, GtaC is active in the nucleus. This is directly supported by localization studies of GFP-GtaC.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0006357 regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033
ACCEPT
Summary: GtaC regulates developmental gene expression by binding promoter cis-regulatory elements and modulating transcription of target genes, so involvement in regulation of RNA polymerase II transcription is well founded.
Reason: Direct target identification (integrated ChIP-seq and RNA-seq) shows GtaC binding to promoters is associated with both up- and downregulation of target gene expression, establishing it as a bona fide transcriptional regulator. This is a core biological process.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO inference of transcriptional regulation from the GATA zinc-finger domain is correct but is a more general parent of the RNA polymerase II term already annotated.
Reason: The annotation is biologically accurate (GtaC regulates DNA-templated transcription) but is a less specific parent of GO:0006357 (regulation of transcription by RNA polymerase II), which is also annotated. It is retained as correct though non-preferred relative to the more specific term.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0008270 zinc ion binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: The GATA-type Cys2-Cys2 zinc finger of GtaC coordinates a zinc ion that is required for DNA binding, so zinc ion binding is correct but is a supporting activity rather than the core function.
Reason: GtaC contains a Cys2-Cys2 (type IV) GATA zinc finger whose structural zinc ion is required for sequence-specific DNA binding. The annotation is accurate but represents an underlying structural activity that enables the core DNA-binding transcription-factor function rather than a function in its own right.
Supporting Evidence:
PMID:26144553
mediates DNA binding with a zinc ion
GO:0043565 sequence-specific DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: GtaC binds a specific GATA-like DNA motif, as shown directly by ChIP-seq motif enrichment, so sequence-specific DNA binding is correct.
Reason: The InterPro2GO inference of sequence-specific DNA binding is directly confirmed by ChIP-seq, which identified enrichment of a GATA-like motif only in GtaC-bound regions. This underpins its transcription-factor activity.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
GO:0003700 DNA-binding transcription factor activity
IMP
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: GtaC is a DNA-binding transcription factor essential for developmental gene expression; this is a core molecular function established by multiple experimental studies.
Reason: The full text of PMID:39672161 is not available in the cache, but GtaC's identity as a DNA-binding transcription factor is firmly established by direct ChIP-seq and genetic evidence in other studies. Per repository policy the experimental (IMP) curator annotation is retained; the function is independently corroborated below.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
PMID:24653039
The insertion occurred in the second exon of the gtaC gene, which encodes a GATA family zinc finger transcription factor
GO:0005634 nucleus
IDA
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: Nuclear localization of GtaC is directly demonstrated; GtaC acts as a transcription factor in the nucleus.
Reason: GtaC nuclear localization is directly observed (GFP-GtaC accumulates in the nucleus). Although the cited paper's full text is uncached, nuclear activity is well established by multiple direct studies.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0005829 cytosol
IDA
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: GtaC is found in the cytoplasm/cytosol during the cytoplasmic phase of its cAMP-driven nucleocytoplasmic shuttling.
Reason: GtaC shuttles between nucleus and cytoplasm; upon cAMP-receptor occupancy it exits the nucleus into the cytosol. Cytosolic localization is part of its normal shuttling behaviour and is directly documented.
Supporting Evidence:
PMID:24653039
GtaC shifted from the nucleus to the cytoplasm with a half-life of ~65 s
GO:0005634 nucleus
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: Direct imaging of GFP-GtaC demonstrates nuclear localization during early development, where GtaC acts as a transcription factor.
Reason: Cai et al. 2014 directly visualized GtaC oscillating into the nucleus during early development, consistent with its role as a nuclear transcription factor. This is a core localization.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0005737 cytoplasm
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: GtaC directly localizes to the cytoplasm during the cytoplasmic phase of its cAMP-driven shuttling cycle.
Reason: Cai et al. 2014 directly showed GtaC moving from nucleus to cytoplasm in response to cAMP-receptor occupancy. Cytoplasmic localization is an intrinsic part of the shuttling mechanism.
Supporting Evidence:
PMID:24653039
GtaC shifted from the nucleus to the cytoplasm with a half-life of ~65 s
GO:0043326 chemotaxis to folate
IMP
PMID:35916164
An atypical MAPK regulates translocation of a GATA transcrip...
KEEP AS NON CORE
Summary: Loss of GtaC enhances chemotactic movement toward folate, indicating GtaC negatively modulates folate chemotaxis; it acts upstream of this foraging process.
Reason: Hadwiger et al. 2022 showed that gtaC-null cells have enhanced folate chemotaxis, so GtaC influences (suppresses) this foraging response. The annotation is experimentally supported, but this modulatory foraging role is peripheral to GtaC's core function as a developmental transcription factor.
Supporting Evidence:
PMID:35916164
Loss of GtaC function resulted in enhanced chemotactic movement to folate, suggesting that GtaC suppresses responses to folate.
PMID:35916164
Erk2 was also found to be essential for the translocation of GtaC in response to external folate, a foraging signal that directs the chemotaxis of amoeba to bacteria.
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
KEEP AS NON CORE
Summary: GtaC is a downstream effector within the cAMP-receptor signalling pathway; its shuttling is driven by cAMP-receptor occupancy and it regulates expression of core cAMP-signalling genes such as acaA and carA.
Reason: GtaC participates in the cAMP GPCR signalling relay - its nucleocytoplasmic shuttling is driven by cAMP-receptor occupancy and it decodes cAMP pulses to regulate expression of cAMP-signalling components. The annotation captures a genuine signalling role, but the core molecular function of GtaC is transcriptional regulation, so this is retained as non-core.
Supporting Evidence:
PMID:24653039
nucleocytoplasmic shuttling of GtaC is driven by periodic occupancy of the surface receptor from self-organized cAMP oscillations.
PMID:26144553
GtaC is a key regulator that decodes extracellular cAMP pulses and establishes downstream signalling pathways, ensuring timely development.
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:26144553
The GATA transcription factor GtaC regulates early developme...
ACCEPT
Summary: Direct ChIP-seq evidence demonstrates GtaC binds cis-regulatory promoter regions at a GATA-like motif genome-wide. This is a core molecular function.
Reason: Santhanam et al. 2015 provided direct genome-wide evidence that GtaC binds thousands of promoter cis-regulatory regions, with enrichment for a GATA-like motif specifically in wild-type GtaC-bound regions. This is the strongest support for GtaC's core DNA-binding function.
Supporting Evidence:
PMID:26144553
We identified 2,091 genes whose promoter regions were bound by GtaC
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:26144553
The GATA transcription factor GtaC regulates early developme...
ACCEPT
Summary: GtaC binds specific promoter motifs and its binding is directly associated with up- and downregulation of target genes, establishing DNA-binding transcription factor activity. This is a core molecular function.
Reason: Integration of ChIP-seq and RNA-seq directly demonstrates that GtaC binding to GATA-like sequences regulates target gene expression, confirming its DNA-binding transcription-factor activity.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0005634 nucleus
IDA
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
ACCEPT
Summary: GtaC translocates to the nucleus (in response to the morphogen DIF), consistent with its role as a nuclear transcription factor.
Reason: Keller and Thompson 2008 directly showed GtaC rapidly translocating to the nucleus in response to DIF, supporting nuclear activity as a transcription factor.
Supporting Evidence:
PMID:18367552
GtaC rapidly translocates to the nucleus in response to DIF
GO:0005737 cytoplasm
IDA
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
ACCEPT
Summary: GtaC is cytoplasmic prior to signal-induced nuclear translocation, consistent with its regulated nucleocytoplasmic distribution.
Reason: In the DIF-signalling context, GtaC resides in the cytoplasm and translocates to the nucleus upon stimulation, consistent with its signal-regulated shuttling behaviour documented elsewhere.
Supporting Evidence:
PMID:18367552
GtaC rapidly translocates to the nucleus in response to DIF
GO:0006351 DNA-templated transcription
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
MODIFY
Summary: GtaC regulates transcription of target genes but does not itself perform DNA-templated transcription (it is a transcription factor, not the polymerase). The regulatory term is more appropriate.
Reason: GO:0006351 (DNA-templated transcription) denotes the catalytic process of synthesizing RNA from a DNA template, an activity of RNA polymerase, not of a sequence-specific transcription factor. GtaC controls the expression of target genes by binding cis-regulatory elements, so the regulatory term regulation of transcription by RNA polymerase II better captures its role.
Supporting Evidence:
PMID:24653039
receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0060176 regulation of aggregation involved in sorocarp development
IMP
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: gtaC-null cells are defective in aggregation and cannot progress through early development, establishing GtaC as an upstream regulator of aggregation during sorocarp development. This is a core developmental role.
Reason: Loss of gtaC impairs aggregation and arrests morphological and transcriptional progression; expression of GFP-GtaC rescues these defects. This directly places GtaC upstream of aggregation during sorocarp development.
Supporting Evidence:
PMID:26144553
Cells lacking gtaC are defective in aggregation and in morphological and transcriptional progression.
PMID:24653039
GtaC shuttling is required for proper control of developmental gene expression and development progression.
GO:0031152 aggregation involved in sorocarp development
IEP
PMID:25887420
Leaps and lulls in the developmental transcriptome of Dictyo...
KEEP AS NON CORE
Summary: gtaC transcript abundance is developmentally regulated with a peak during the aggregation phase, and gtaC is described as a master transcriptional regulator of aggregation-associated genes; this expression-pattern annotation is consistent with its established aggregation role.
Reason: The IEP annotation is based on gtaC's developmental expression profile, which peaks during aggregation, and its identification as a master regulator of aggregation genes. It corroborates GtaC's aggregation role but, being derived from an expression pattern, is retained as non-core relative to the direct genetic and molecular evidence (GO:0060176).
Supporting Evidence:
PMID:25887420
The master transcriptional regulator gtaC, and several of its putative target genes involved in aggregation (such as the cell-cell adhesion gene csaA), looked markedly different at different time scales
GO:0031149 sorocarp stalk cell differentiation
IMP
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
KEEP AS NON CORE
Summary: GtaC acts downstream of the morphogen DIF-1 to regulate prestalk (pstB) and basal-disc cell differentiation, a stalk-lineage cell-type role that is secondary to its core early-developmental transcriptional function.
Reason: Keller and Thompson 2008 showed that GtaC is required for DIF-dependent pstB and basal-disc (stalk-lineage) differentiation. The annotation is experimentally supported but represents a later, cell-type-specific role that is peripheral to GtaC's core function in early developmental gene regulation.
Supporting Evidence:
PMID:18367552
GtaC is instead required to regulate DIF-dependent pstB and basal disc cell differentiation.
PMID:18367552
gtaC expression is directly regulated by DIF, and GtaC rapidly translocates to the nucleus in response to DIF.

Core Functions

GtaC is a sequence-specific GATA-family transcription factor that binds GATA-like cis-regulatory elements in target-gene promoters via its Cys2-Cys2 zinc-finger domain, directly controlling developmental gene expression by both activating and repressing target genes.

Supporting Evidence:
  • PMID:26144553
    We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
  • PMID:26144553
    GtaC binding to GATA-like sequences has a direct role in upregulating gene expression

GtaC binds cis-regulatory promoter regions genome-wide and is essential for early development, acting upstream of aggregation; through cAMP-driven nucleocytoplasmic shuttling it decodes oscillatory cAMP pulses to time developmental gene expression.

Supporting Evidence:
  • PMID:26144553
    We identified 2,091 genes whose promoter regions were bound by GtaC
  • PMID:26144553
    Cells lacking gtaC are defective in aggregation and in morphological and transcriptional progression.
  • PMID:24653039
    nucleocytoplasmic shuttling of GtaC is driven by periodic occupancy of the surface receptor from self-organized cAMP oscillations.

References

Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Cell type specificity of a diffusible inducer is determined by a GATA family transcription factor.
  • GtaC is a DIF-regulated GATA transcription factor that translocates to the nucleus in response to the morphogen DIF.
    "gtaC expression is directly regulated by DIF, and GtaC rapidly translocates to the nucleus in response to DIF."
  • GtaC is required for DIF-dependent pstB and basal-disc (stalk lineage) cell differentiation.
    "GtaC is instead required to regulate DIF-dependent pstB and basal disc cell differentiation."
Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer.
  • GtaC is a GATA family zinc finger transcription factor essential for early development; its gene disruption blocks aggregation.
    "The insertion occurred in the second exon of the gtaC gene, which encodes a GATA family zinc finger transcription factor"
  • GtaC undergoes oscillatory nucleocytoplasmic shuttling during early development, driven by periodic cAMP-receptor occupancy.
    "nucleocytoplasmic shuttling of GtaC is driven by periodic occupancy of the surface receptor from self-organized cAMP oscillations."
  • cAMP-receptor occupancy drives GtaC out of the nucleus, producing a transient burst of transcription at each cAMP cycle (developmental timer).
    "receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle"
  • GtaC shuttling is required for proper developmental gene expression and progression.
    "GtaC shuttling is required for proper control of developmental gene expression and development progression."
Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  • gtaC is a master transcriptional regulator whose expression, together with aggregation target genes, is dynamically regulated during development.
    "The master transcriptional regulator gtaC, and several of its putative target genes involved in aggregation (such as the cell-cell adhesion gene csaA), looked markedly different at different time scales"
The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium.
  • GtaC binds the promoter regions of ~2,091 genes genome-wide, with highly dynamic stage-specific DNA binding.
    "We identified 2,091 genes whose promoter regions were bound by GtaC"
  • GtaC binds a GATA-like DNA motif; this motif is enriched only in wild-type GtaC-bound regions.
    "We found enrichment for a GATA-like motif only in regions bound by the WT GtaC"
  • GtaC binding to GATA-like sequences directly upregulates target gene expression.
    "GtaC binding to GATA-like sequences has a direct role in upregulating gene expression"
  • GtaC decodes extracellular cAMP pulses to establish downstream signalling and ensure timely development; gtaC-null cells fail to aggregate.
    "Cells lacking gtaC are defective in aggregation and in morphological and transcriptional progression."
An atypical MAPK regulates translocation of a GATA transcription factor in response to chemoattractant stimulation.
  • Loss of GtaC enhances folate chemotaxis, indicating GtaC suppresses responses to folate.
    "Loss of GtaC function resulted in enhanced chemotactic movement to folate, suggesting that GtaC suppresses responses to folate."
  • The atypical MAPK Erk2 is required for GtaC translocation in response to both cAMP and folate chemoattractants.
    "Erk2 was also found to be essential for the translocation of GtaC in response to external folate, a foraging signal that directs the chemotaxis of amoeba to bacteria."
Collective oscillatory signaling in Dictyostelium discoideum acts as a developmental timer initiated by weak coupling of a noisy pulsatile signal.

📄 View Raw YAML

id: Q75JZ1
gene_symbol: gtaC
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: GtaC is a GATA-family transcription factor of Dictyostelium discoideum
  that carries a single Cys2-Cys2 (type IV) zinc-finger domain and binds
  sequence-specific GATA-like cis-regulatory elements in the promoters of target
  genes. It is a nuclear DNA-binding transcription factor that activates and
  represses developmental gene expression, and it is essential for early
  development, since cells lacking gtaC fail to aggregate and arrest transcriptional
  and morphological progression. GtaC is a central effector that decodes oscillatory
  extracellular cAMP signals. During early development it undergoes rapid
  nucleocytoplasmic shuttling driven by cAMP-receptor occupancy and reversible
  phosphorylation (mediated by the atypical MAPK Erk2 and GskA), entering the
  nucleus during the falling phase of each cAMP wave and exiting during the rising
  phase. This shuttling converts pulsatile cAMP input into temporally patterned
  bursts of transcription and functions as a developmental timer, allowing cells
  to track low-frequency and filter out high-frequency signals. GtaC directly
  binds the promoters of thousands of genes, including central cAMP-signalling
  components such as the adenylyl cyclase acaA and cAMP receptor carA, and its DNA
  binding is highly dynamic across developmental stages. Beyond aggregation, GtaC
  contributes to later cell-type specification, acting downstream of the diffusible
  morphogen DIF-1 to regulate prestalk/basal-disc (stalk-related) differentiation,
  and it modulates chemotactic behaviour, suppressing chemotaxis toward folate.
existing_annotations:
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference that GtaC binds cis-regulatory regions is
      correct and independently confirmed by direct ChIP-seq evidence in the same
      organism, where GtaC occupies GATA-like promoter elements genome-wide.
    action: ACCEPT
    reason: This IBA annotation transfers the conserved GATA-family DNA-binding
      function and is fully corroborated by direct experimental evidence (ChIP-seq)
      showing GtaC binds thousands of promoters at a GATA-like motif. This is a
      core molecular function.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: We found enrichment for a GATA-like motif only in regions
        bound by the WT GtaC
    - reference_id: PMID:26144553
      supporting_text: We identified 2,091 genes whose promoter regions were bound
        by GtaC
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Nuclear localization inferred by phylogeny is correct; GtaC acts as a
      transcription factor in the nucleus and multiple direct studies show nuclear
      accumulation.
    action: ACCEPT
    reason: As a DNA-binding transcription factor, GtaC is active in the nucleus.
      This is directly supported by localization studies of GFP-GtaC.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling
        during early development
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: GtaC regulates developmental gene expression by binding promoter
      cis-regulatory elements and modulating transcription of target genes, so
      involvement in regulation of RNA polymerase II transcription is well founded.
    action: ACCEPT
    reason: Direct target identification (integrated ChIP-seq and RNA-seq) shows
      GtaC binding to promoters is associated with both up- and downregulation of
      target gene expression, establishing it as a bona fide transcriptional
      regulator. This is a core biological process.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: GtaC binding to GATA-like sequences has a direct role in
        upregulating gene expression
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO inference of transcriptional regulation from the GATA
      zinc-finger domain is correct but is a more general parent of the RNA
      polymerase II term already annotated.
    action: ACCEPT
    reason: The annotation is biologically accurate (GtaC regulates DNA-templated
      transcription) but is a less specific parent of GO:0006357 (regulation of
      transcription by RNA polymerase II), which is also annotated. It is retained
      as correct though non-preferred relative to the more specific term.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: GtaC binding to GATA-like sequences has a direct role in
        upregulating gene expression
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The GATA-type Cys2-Cys2 zinc finger of GtaC coordinates a zinc ion
      that is required for DNA binding, so zinc ion binding is correct but is a
      supporting activity rather than the core function.
    action: KEEP_AS_NON_CORE
    reason: GtaC contains a Cys2-Cys2 (type IV) GATA zinc finger whose structural
      zinc ion is required for sequence-specific DNA binding. The annotation is
      accurate but represents an underlying structural activity that enables the
      core DNA-binding transcription-factor function rather than a function in its
      own right.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: mediates DNA binding with a zinc ion
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: GtaC binds a specific GATA-like DNA motif, as shown directly by
      ChIP-seq motif enrichment, so sequence-specific DNA binding is correct.
    action: ACCEPT
    reason: The InterPro2GO inference of sequence-specific DNA binding is directly
      confirmed by ChIP-seq, which identified enrichment of a GATA-like motif only
      in GtaC-bound regions. This underpins its transcription-factor activity.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: We found enrichment for a GATA-like motif only in regions
        bound by the WT GtaC
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IMP
  original_reference_id: PMID:39672161
  qualifier: enables
  review:
    summary: GtaC is a DNA-binding transcription factor essential for developmental
      gene expression; this is a core molecular function established by multiple
      experimental studies.
    action: ACCEPT
    reason: The full text of PMID:39672161 is not available in the cache, but GtaC's
      identity as a DNA-binding transcription factor is firmly established by direct
      ChIP-seq and genetic evidence in other studies. Per repository policy the
      experimental (IMP) curator annotation is retained; the function is
      independently corroborated below.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: We found enrichment for a GATA-like motif only in regions
        bound by the WT GtaC
    - reference_id: PMID:24653039
      supporting_text: The insertion occurred in the second exon of the gtaC gene,
        which encodes a GATA family zinc finger transcription factor
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:39672161
  qualifier: is_active_in
  review:
    summary: Nuclear localization of GtaC is directly demonstrated; GtaC acts as a
      transcription factor in the nucleus.
    action: ACCEPT
    reason: GtaC nuclear localization is directly observed (GFP-GtaC accumulates in
      the nucleus). Although the cited paper's full text is uncached, nuclear
      activity is well established by multiple direct studies.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling
        during early development
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:39672161
  qualifier: located_in
  review:
    summary: GtaC is found in the cytoplasm/cytosol during the cytoplasmic phase of
      its cAMP-driven nucleocytoplasmic shuttling.
    action: ACCEPT
    reason: GtaC shuttles between nucleus and cytoplasm; upon cAMP-receptor
      occupancy it exits the nucleus into the cytosol. Cytosolic localization is
      part of its normal shuttling behaviour and is directly documented.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: GtaC shifted from the nucleus to the cytoplasm with a
        half-life of ~65 s
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:24653039
  qualifier: is_active_in
  review:
    summary: Direct imaging of GFP-GtaC demonstrates nuclear localization during
      early development, where GtaC acts as a transcription factor.
    action: ACCEPT
    reason: Cai et al. 2014 directly visualized GtaC oscillating into the nucleus
      during early development, consistent with its role as a nuclear transcription
      factor. This is a core localization.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling
        during early development
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24653039
  qualifier: located_in
  review:
    summary: GtaC directly localizes to the cytoplasm during the cytoplasmic phase
      of its cAMP-driven shuttling cycle.
    action: ACCEPT
    reason: Cai et al. 2014 directly showed GtaC moving from nucleus to cytoplasm in
      response to cAMP-receptor occupancy. Cytoplasmic localization is an intrinsic
      part of the shuttling mechanism.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: GtaC shifted from the nucleus to the cytoplasm with a
        half-life of ~65 s
- term:
    id: GO:0043326
    label: chemotaxis to folate
  evidence_type: IMP
  original_reference_id: PMID:35916164
  qualifier: acts_upstream_of_or_within
  review:
    summary: Loss of GtaC enhances chemotactic movement toward folate, indicating
      GtaC negatively modulates folate chemotaxis; it acts upstream of this
      foraging process.
    action: KEEP_AS_NON_CORE
    reason: Hadwiger et al. 2022 showed that gtaC-null cells have enhanced folate
      chemotaxis, so GtaC influences (suppresses) this foraging response. The
      annotation is experimentally supported, but this modulatory foraging role is
      peripheral to GtaC's core function as a developmental transcription factor.
    supported_by:
    - reference_id: PMID:35916164
      supporting_text: Loss of GtaC function resulted in enhanced chemotactic
        movement to folate, suggesting that GtaC suppresses responses to folate.
    - reference_id: PMID:35916164
      supporting_text: Erk2 was also found to be essential for the translocation of
        GtaC in response to external folate, a foraging signal that directs the
        chemotaxis of amoeba to bacteria.
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IDA
  original_reference_id: PMID:24653039
  qualifier: involved_in
  review:
    summary: GtaC is a downstream effector within the cAMP-receptor signalling
      pathway; its shuttling is driven by cAMP-receptor occupancy and it regulates
      expression of core cAMP-signalling genes such as acaA and carA.
    action: KEEP_AS_NON_CORE
    reason: GtaC participates in the cAMP GPCR signalling relay - its
      nucleocytoplasmic shuttling is driven by cAMP-receptor occupancy and it
      decodes cAMP pulses to regulate expression of cAMP-signalling components. The
      annotation captures a genuine signalling role, but the core molecular function
      of GtaC is transcriptional regulation, so this is retained as non-core.
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: nucleocytoplasmic shuttling of GtaC is driven by periodic
        occupancy of the surface receptor from self-organized cAMP oscillations.
    - reference_id: PMID:26144553
      supporting_text: GtaC is a key regulator that decodes extracellular cAMP
        pulses and establishes downstream signalling pathways, ensuring timely
        development.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IDA
  original_reference_id: PMID:26144553
  qualifier: enables
  review:
    summary: Direct ChIP-seq evidence demonstrates GtaC binds cis-regulatory
      promoter regions at a GATA-like motif genome-wide. This is a core molecular
      function.
    action: ACCEPT
    reason: Santhanam et al. 2015 provided direct genome-wide evidence that GtaC
      binds thousands of promoter cis-regulatory regions, with enrichment for a
      GATA-like motif specifically in wild-type GtaC-bound regions. This is the
      strongest support for GtaC's core DNA-binding function.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: We identified 2,091 genes whose promoter regions were bound
        by GtaC
    - reference_id: PMID:26144553
      supporting_text: We found enrichment for a GATA-like motif only in regions
        bound by the WT GtaC
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:26144553
  qualifier: enables
  review:
    summary: GtaC binds specific promoter motifs and its binding is directly
      associated with up- and downregulation of target genes, establishing
      DNA-binding transcription factor activity. This is a core molecular function.
    action: ACCEPT
    reason: Integration of ChIP-seq and RNA-seq directly demonstrates that GtaC
      binding to GATA-like sequences regulates target gene expression, confirming
      its DNA-binding transcription-factor activity.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: GtaC binding to GATA-like sequences has a direct role in
        upregulating gene expression
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18367552
  qualifier: is_active_in
  review:
    summary: GtaC translocates to the nucleus (in response to the morphogen DIF),
      consistent with its role as a nuclear transcription factor.
    action: ACCEPT
    reason: Keller and Thompson 2008 directly showed GtaC rapidly translocating to
      the nucleus in response to DIF, supporting nuclear activity as a transcription
      factor.
    supported_by:
    - reference_id: PMID:18367552
      supporting_text: GtaC rapidly translocates to the nucleus in response to DIF
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18367552
  qualifier: located_in
  review:
    summary: GtaC is cytoplasmic prior to signal-induced nuclear translocation,
      consistent with its regulated nucleocytoplasmic distribution.
    action: ACCEPT
    reason: In the DIF-signalling context, GtaC resides in the cytoplasm and
      translocates to the nucleus upon stimulation, consistent with its
      signal-regulated shuttling behaviour documented elsewhere.
    supported_by:
    - reference_id: PMID:18367552
      supporting_text: GtaC rapidly translocates to the nucleus in response to DIF
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:24653039
  qualifier: involved_in
  review:
    summary: GtaC regulates transcription of target genes but does not itself
      perform DNA-templated transcription (it is a transcription factor, not the
      polymerase). The regulatory term is more appropriate.
    action: MODIFY
    reason: GO:0006351 (DNA-templated transcription) denotes the catalytic process
      of synthesizing RNA from a DNA template, an activity of RNA polymerase, not of
      a sequence-specific transcription factor. GtaC controls the expression of
      target genes by binding cis-regulatory elements, so the regulatory term
      regulation of transcription by RNA polymerase II better captures its role.
    proposed_replacement_terms:
    - id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: PMID:24653039
      supporting_text: receptor occupancy promotes nuclear exit of GtaC, which leads
        to a transient burst of transcription at each cAMP cycle
    - reference_id: PMID:26144553
      supporting_text: GtaC binding to GATA-like sequences has a direct role in
        upregulating gene expression
- term:
    id: GO:0060176
    label: regulation of aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:24653039
  qualifier: acts_upstream_of_or_within
  review:
    summary: gtaC-null cells are defective in aggregation and cannot progress
      through early development, establishing GtaC as an upstream regulator of
      aggregation during sorocarp development. This is a core developmental role.
    action: ACCEPT
    reason: Loss of gtaC impairs aggregation and arrests morphological and
      transcriptional progression; expression of GFP-GtaC rescues these defects.
      This directly places GtaC upstream of aggregation during sorocarp development.
    supported_by:
    - reference_id: PMID:26144553
      supporting_text: Cells lacking gtaC are defective in aggregation and in
        morphological and transcriptional progression.
    - reference_id: PMID:24653039
      supporting_text: GtaC shuttling is required for proper control of developmental
        gene expression and development progression.
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: acts_upstream_of_or_within
  review:
    summary: gtaC transcript abundance is developmentally regulated with a peak
      during the aggregation phase, and gtaC is described as a master transcriptional
      regulator of aggregation-associated genes; this expression-pattern annotation
      is consistent with its established aggregation role.
    action: KEEP_AS_NON_CORE
    reason: The IEP annotation is based on gtaC's developmental expression profile,
      which peaks during aggregation, and its identification as a master regulator of
      aggregation genes. It corroborates GtaC's aggregation role but, being derived
      from an expression pattern, is retained as non-core relative to the direct
      genetic and molecular evidence (GO:0060176).
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: The master transcriptional regulator gtaC, and several of its
        putative target genes involved in aggregation (such as the cell-cell
        adhesion gene csaA), looked markedly different at different time scales
- term:
    id: GO:0031149
    label: sorocarp stalk cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:18367552
  qualifier: acts_upstream_of_or_within
  review:
    summary: GtaC acts downstream of the morphogen DIF-1 to regulate prestalk (pstB)
      and basal-disc cell differentiation, a stalk-lineage cell-type role that is
      secondary to its core early-developmental transcriptional function.
    action: KEEP_AS_NON_CORE
    reason: Keller and Thompson 2008 showed that GtaC is required for DIF-dependent
      pstB and basal-disc (stalk-lineage) differentiation. The annotation is
      experimentally supported but represents a later, cell-type-specific role that
      is peripheral to GtaC's core function in early developmental gene regulation.
    supported_by:
    - reference_id: PMID:18367552
      supporting_text: GtaC is instead required to regulate DIF-dependent pstB and
        basal disc cell differentiation.
    - reference_id: PMID:18367552
      supporting_text: gtaC expression is directly regulated by DIF, and GtaC rapidly
        translocates to the nucleus in response to DIF.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: PMID:18367552
  title: Cell type specificity of a diffusible inducer is determined by a GATA family
    transcription factor.
  findings:
  - statement: GtaC is a DIF-regulated GATA transcription factor that translocates
      to the nucleus in response to the morphogen DIF.
    supporting_text: gtaC expression is directly regulated by DIF, and GtaC rapidly
      translocates to the nucleus in response to DIF.
  - statement: GtaC is required for DIF-dependent pstB and basal-disc (stalk lineage)
      cell differentiation.
    supporting_text: GtaC is instead required to regulate DIF-dependent pstB and
      basal disc cell differentiation.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text cached and verified; establishes GtaC as a DIF-regulated
      GATA factor controlling a subset of cell-type-specific (stalk-related)
      differentiation events.
- id: PMID:24653039
  title: Nucleocytoplasmic shuttling of a GATA transcription factor functions as a
    development timer.
  findings:
  - statement: GtaC is a GATA family zinc finger transcription factor essential for
      early development; its gene disruption blocks aggregation.
    supporting_text: The insertion occurred in the second exon of the gtaC gene,
      which encodes a GATA family zinc finger transcription factor
  - statement: GtaC undergoes oscillatory nucleocytoplasmic shuttling during early
      development, driven by periodic cAMP-receptor occupancy.
    supporting_text: nucleocytoplasmic shuttling of GtaC is driven by periodic
      occupancy of the surface receptor from self-organized cAMP oscillations.
  - statement: cAMP-receptor occupancy drives GtaC out of the nucleus, producing a
      transient burst of transcription at each cAMP cycle (developmental timer).
    supporting_text: receptor occupancy promotes nuclear exit of GtaC, which leads to
      a transient burst of transcription at each cAMP cycle
  - statement: GtaC shuttling is required for proper developmental gene expression
      and progression.
    supporting_text: GtaC shuttling is required for proper control of developmental
      gene expression and development progression.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text cached and verified; the definitive mechanistic study of
      GtaC as a cAMP-decoding developmental timer.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: gtaC is a master transcriptional regulator whose expression, together
      with aggregation target genes, is dynamically regulated during development.
    supporting_text: The master transcriptional regulator gtaC, and several of its
      putative target genes involved in aggregation (such as the cell-cell adhesion
      gene csaA), looked markedly different at different time scales
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text cached; provides fine-scale developmental expression
      profiling supporting gtaC's aggregation-phase expression and master-regulator
      status (basis of the IEP annotation).
- id: PMID:26144553
  title: The GATA transcription factor GtaC regulates early developmental gene expression
    dynamics in Dictyostelium.
  findings:
  - statement: GtaC binds the promoter regions of ~2,091 genes genome-wide, with
      highly dynamic stage-specific DNA binding.
    supporting_text: We identified 2,091 genes whose promoter regions were bound by
      GtaC
  - statement: GtaC binds a GATA-like DNA motif; this motif is enriched only in
      wild-type GtaC-bound regions.
    supporting_text: We found enrichment for a GATA-like motif only in regions bound
      by the WT GtaC
  - statement: GtaC binding to GATA-like sequences directly upregulates target gene
      expression.
    supporting_text: GtaC binding to GATA-like sequences has a direct role in
      upregulating gene expression
  - statement: GtaC decodes extracellular cAMP pulses to establish downstream
      signalling and ensure timely development; gtaC-null cells fail to aggregate.
    supporting_text: Cells lacking gtaC are defective in aggregation and in
      morphological and transcriptional progression.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text cached and verified; direct genome-wide ChIP-seq/RNA-seq
      evidence for GtaC's core DNA-binding and transcriptional-regulatory functions.
- id: PMID:35916164
  title: An atypical MAPK regulates translocation of a GATA transcription factor in
    response to chemoattractant stimulation.
  findings:
  - statement: Loss of GtaC enhances folate chemotaxis, indicating GtaC suppresses
      responses to folate.
    supporting_text: Loss of GtaC function resulted in enhanced chemotactic movement
      to folate, suggesting that GtaC suppresses responses to folate.
  - statement: The atypical MAPK Erk2 is required for GtaC translocation in response
      to both cAMP and folate chemoattractants.
    supporting_text: Erk2 was also found to be essential for the translocation of
      GtaC in response to external folate, a foraging signal that directs the
      chemotaxis of amoeba to bacteria.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text cached and verified; establishes Erk2-dependent
      regulation of GtaC translocation and a negative role of GtaC in folate
      chemotaxis (basis of the folate chemotaxis annotation).
- id: PMID:39672161
  title: Collective oscillatory signaling in Dictyostelium discoideum acts as a developmental
    timer initiated by weak coupling of a noisy pulsatile signal.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: Full text not available in cache (abstract is focused on Hbx5). The
      GtaC IMP/IDA annotations attributed to this paper (DNA-binding TF activity,
      nucleus, cytosol) are experimental curator annotations and are corroborated by
      other cached studies; specific supporting text from this paper could not be
      verified.
core_functions:
- description: GtaC is a sequence-specific GATA-family transcription factor that
    binds GATA-like cis-regulatory elements in target-gene promoters via its
    Cys2-Cys2 zinc-finger domain, directly controlling developmental gene
    expression by both activating and repressing target genes.
  molecular_function:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  locations:
  - id: GO:0005634
    label: nucleus
  directly_involved_in:
  - id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  supported_by:
  - reference_id: PMID:26144553
    supporting_text: We found enrichment for a GATA-like motif only in regions bound
      by the WT GtaC
  - reference_id: PMID:26144553
    supporting_text: GtaC binding to GATA-like sequences has a direct role in
      upregulating gene expression
- description: GtaC binds cis-regulatory promoter regions genome-wide and is essential
    for early development, acting upstream of aggregation; through cAMP-driven
    nucleocytoplasmic shuttling it decodes oscillatory cAMP pulses to time
    developmental gene expression.
  molecular_function:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  locations:
  - id: GO:0005634
    label: nucleus
  directly_involved_in:
  - id: GO:0060176
    label: regulation of aggregation involved in sorocarp development
  supported_by:
  - reference_id: PMID:26144553
    supporting_text: We identified 2,091 genes whose promoter regions were bound by
      GtaC
  - reference_id: PMID:26144553
    supporting_text: Cells lacking gtaC are defective in aggregation and in
      morphological and transcriptional progression.
  - reference_id: PMID:24653039
    supporting_text: nucleocytoplasmic shuttling of GtaC is driven by periodic
      occupancy of the surface receptor from self-organized cAMP oscillations.