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.
| 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.
Proposed replacements:
regulation of transcription by RNA polymerase II
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.
|
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.