DimB is a basic-region leucine-zipper (bZIP) transcription factor that acts as a direct effector of the polyketide morphogen DIF-1 during Dictyostelium multicellular development. In unstimulated cells DimB is distributed through the cytoplasm, but exposure to DIF-1 triggers its rapid accumulation in the nucleus, where it binds sequence-specific cis-regulatory elements in target promoters. DimB can bind DNA as a homodimer and as a heterodimer with the related bZIP factor DimA. It functions as a dual-mode regulator that directly activates prestalk/basal-disc genes such as ecmB in pstB cells, spatially restricts expression of the prestalk gene ecmA, and directly represses prespore genes such as pspA. Through these activities DimB controls prestalk cell-type patterning, pstB/basal-disc and anterior-like-cell differentiation, and the choice between stalk and spore fate. Loss of DimB produces abnormally long, thin slugs and defective culmination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005634
nucleus
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference that DimB acts in the nucleus is consistent with direct experimental evidence that DimB accumulates in the nucleus upon DIF-1 stimulation and binds target promoters there. This is a core location.
Reason: Nuclear localization is directly demonstrated for DimB and is where its transcription factor activity is exerted; the IBA inference is fully corroborated.
Supporting Evidence:
PMID:16410410
In the absence of DIF-1, GFP was fairly uniformly distributed throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP exhibited nuclear accumulation
|
|
GO:0010468
regulation of gene expression
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: DimB regulates expression of multiple developmental genes (activating ecmB, repressing pspA and others). This general parent term is correct but a more specific descendant (regulation of DNA-templated transcription) better captures its mechanism.
Reason: The annotation is accurate as a broad statement of DimB's function as a transcriptional regulator; more specific transcription terms are also present.
Supporting Evidence:
PMID:22253818
In response to the signaling polyketide DIF-1 DimB directly activates transcription of the ecmB gene in pstB cells
|
|
GO:0043565
sequence-specific DNA binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: DimB was purified by affinity chromatography on ecmA promoter fragments and binds defined sites in the ecmA, ecmB and pspA promoters, directly demonstrating sequence-specific DNA binding. The IBA inference is well supported.
Reason: Sequence-specific DNA binding is a core molecular function of DimB, confirmed by direct experimental evidence.
Supporting Evidence:
PMID:16396914
We have purified a novel bZIP transcription factor, DimB, by affinity chromatography on two spatially separated ecmA promoter fragments
|
|
GO:0003700
DNA-binding transcription factor activity
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO inference from the bZIP domain. DimB is experimentally a DNA-binding transcription factor that both activates and represses target genes, so this is a correct core molecular function.
Reason: The bZIP domain-based inference matches the demonstrated function of DimB as a sequence-specific transcription factor regulating prestalk and prespore genes.
Supporting Evidence:
PMID:22253818
In response to the signaling polyketide DIF-1 DimB directly activates transcription of the ecmB gene in pstB cells
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: UniProt subcellular-location mapping to nucleus, corroborated by direct experimental evidence of DIF-1-induced nuclear accumulation.
Reason: Nuclear localization is a core, experimentally established location for DimB.
Supporting Evidence:
PMID:16410410
In the absence of DIF-1, GFP was fairly uniformly distributed throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP exhibited nuclear accumulation
|
|
GO:0006355
regulation of DNA-templated transcription
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO inference consistent with DimB's demonstrated role as a direct transcriptional activator and repressor of developmental genes.
Reason: DimB directly regulates transcription of ecmB (activation) and pspA (repression); this term accurately captures the process.
Supporting Evidence:
PMID:22253818
In response to the signaling polyketide DIF-1 DimB directly activates transcription of the ecmB gene in pstB cells
|
|
GO:0010629
negative regulation of gene expression
|
IMP
PMID:20300194 BTG interacts with retinoblastoma to control cell fate in Di... |
ACCEPT |
Summary: In dimB-null cells the ALC-marker gene btg is over-induced during development, indicating that DimB normally represses btg as part of the DIF signalling response. Supports negative regulation of gene expression.
Reason: Direct genetic evidence (mutant phenotype) shows DimB negatively regulates btg expression during development.
Supporting Evidence:
PMID:20300194
btg is overinduced in the DIF unresponsive mutants
|
|
GO:0043069
negative regulation of programmed cell death
|
IMP
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
KEEP AS NON CORE |
Summary: In an 8-Br-cAMP monolayer assay, DIF-1-treated dimB-null cells undergo non-vacuolar cell death (NVCD) that is normally suppressed by DimB, which instead directs vacuolised stalk-cell formation. This is a genuine but downstream developmental consequence rather than a core molecular function.
Reason: DimB is required to repress NVCD in the stalk differentiation pathway, so the annotation is supported, but it reflects a cell-fate outcome of DimB's transcriptional activity rather than its direct function.
Supporting Evidence:
PMID:16410410
NVCD is repressed by DimB
|
|
GO:1903014
cellular response to differentiation-inducing factor 1
|
HDA
PMID:25518940 The Dictyostelium prestalk inducer differentiation-inducing ... |
ACCEPT |
Summary: DimB is a direct effector of DIF-1 that accumulates in the nucleus and is phosphorylated in response to DIF-1. This term accurately captures DimB's role in the cellular response to the DIF-1 morphogen.
Reason: DimB nuclear accumulation and phosphorylation are direct, rapid responses to DIF-1, placing DimB centrally in the cellular DIF-1 response.
Supporting Evidence:
PMID:25518940
DimB accumulates in the nuclei of cells induced with DIF-1 and is phosphorylated
|
|
GO:0031153
slug development involved in sorocarp development
|
IMP
PMID:16396914 The Dictyostelium bZIP transcription factor DimB regulates p... |
KEEP AS NON CORE |
Summary: dimB-null development proceeds normally to the finger stage, then produces extremely long, thin fingers/slugs, implicating DimB in normal slug morphogenesis. This is a downstream developmental phenotype.
Reason: The mutant slug phenotype supports a role in slug development, but this is an organismal-level consequence of DimB's transcriptional activity rather than its core molecular function.
Supporting Evidence:
PMID:16396914
DimB is not essential for normal expression of the ecmA gene, instead it spatially limits its expression
|
|
GO:0005634
nucleus
|
IDA
PMID:16396914 The Dictyostelium bZIP transcription factor DimB regulates p... |
ACCEPT |
Summary: Direct evidence that DimB rapidly accumulates in the nucleus upon DIF-1 exposure and associates with the ecmA promoter there. Core active location.
Reason: Nuclear localization where DimB exerts its transcription factor activity is directly demonstrated.
Supporting Evidence:
PMID:16396914
DimB rapidly accumulates in the nucleus when cells are exposed to DIF-1
|
|
GO:0005634
nucleus
|
IDA
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
ACCEPT |
Summary: Direct GFP-localization evidence shows DimB accumulates in the nucleus after DIF-1 treatment. Core active location.
Reason: Independent direct evidence confirms nuclear localization as the site of DimB action.
Supporting Evidence:
PMID:16410410
In the absence of DIF-1, GFP was fairly uniformly distributed throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP exhibited nuclear accumulation
|
|
GO:0005634
nucleus
|
IDA
PMID:21458438 DIF-1 regulates Dictyostelium basal disc differentiation by ... |
ACCEPT |
Summary: DimB is specifically nuclear enriched in pstB cells during normal development, where it activates basal-disc gene expression. Core active location.
Reason: Direct evidence places active DimB in the nucleus of the responding cells.
Supporting Evidence:
PMID:21458438
DimB is specifically nuclear enriched in the pstB cells
|
|
GO:0005737
cytoplasm
|
IDA
PMID:16396914 The Dictyostelium bZIP transcription factor DimB regulates p... |
KEEP AS NON CORE |
Summary: In the absence of DIF-1, DimB is distributed through the cytoplasm and only translocates to the nucleus upon DIF-1 stimulation. Cytoplasmic localization reflects the inactive/resting state rather than the functional compartment.
Reason: The cytoplasmic pool is the pre-stimulation reservoir; DimB's functional compartment is the nucleus. The localization is real but not the core site of action.
Supporting Evidence:
PMID:16410410
In the absence of DIF-1, GFP was fairly uniformly distributed throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP exhibited nuclear accumulation
|
|
GO:0031287
positive regulation of sorocarp stalk cell differentiation
|
IMP
PMID:16396914 The Dictyostelium bZIP transcription factor DimB regulates p... |
KEEP AS NON CORE |
Summary: DimB promotes prestalk/basal-disc differentiation, and dimB-null cells fail to make stalk cells in response to DIF-1. This is a genuine developmental role, but a downstream outcome of DimB's transcriptional activity.
Reason: Supported by mutant phenotype (loss of DIF-1-induced stalk differentiation), but represents an organismal cell-differentiation outcome rather than DimB's core molecular function.
Supporting Evidence:
PMID:21458438
leading to nuclear localization of DimB and direct activation of cell type-specific gene expression
|
|
GO:0043565
sequence-specific DNA binding
|
IDA
PMID:16396914 The Dictyostelium bZIP transcription factor DimB regulates p... |
ACCEPT |
Summary: DimB was purified by affinity chromatography on ecmA promoter fragments, directly demonstrating sequence-specific DNA binding. Core molecular function.
Reason: Direct biochemical evidence for sequence-specific promoter binding.
Supporting Evidence:
PMID:16396914
We have purified a novel bZIP transcription factor, DimB, by affinity chromatography on two spatially separated ecmA promoter fragments
|
|
GO:0045184
establishment of protein localization
|
IMP
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
KEEP AS NON CORE |
Summary: DimB is required for DIF-1-induced nuclear accumulation of its partner DimA; in dimB-null cells DimA fails to accumulate in the nucleus. The annotation captures this regulatory effect but with a very general term.
Reason: Supported by direct genetic evidence that DimB controls DimA nuclear localization, but this is a specialized downstream effect and the term is broad; not a core function.
Supporting Evidence:
PMID:16410410
nuclear accumulation of DimA in response to DIF-1 is dependent on DimB
|
|
GO:0005737
cytoplasm
|
IDA
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
KEEP AS NON CORE |
Summary: Consistent with the other cytoplasm annotation, DimB:GFP is uniformly distributed (including cytoplasm) before DIF-1 and translocates to the nucleus after stimulation.
Reason: Cytoplasmic localization is the resting-state distribution; the functional compartment is the nucleus.
Supporting Evidence:
PMID:16410410
In the absence of DIF-1, GFP was fairly uniformly distributed throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP exhibited nuclear accumulation
|
|
GO:0005515
protein binding
|
IPI
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
MODIFY |
Summary: This IPI annotation records the physical interaction of DimB with the bZIP factor DimA (UniProtKB:Q54XG7). Bare protein binding is uninformative; the interaction is bZIP heterodimerization, better captured by protein heterodimerization activity.
Reason: Pull-down assays show DimB forms heterodimeric complexes with DimA in vitro. Replacing the generic term with protein heterodimerization activity conveys the mechanistic nature (bZIP leucine-zipper dimerization) of the interaction.
Proposed replacements:
protein heterodimerization activity
Supporting Evidence:
PMID:16410410
Pull-down assays with purified proteins showed that DimA and DimB can form homodimeric and heterodimeric complexes in vitro
PMID:16410410
a second bZIP transcription factor (DimB) that can directly interact with DimA in vitro
|
|
GO:0000976
transcription cis-regulatory region binding
|
IDA
PMID:21458438 DIF-1 regulates Dictyostelium basal disc differentiation by ... |
ACCEPT |
Summary: ChIP analysis directly shows DimB binding to the ecmB cis-regulatory region (promoter) in DIF-1-induced cells. Core molecular function.
Reason: Direct in vivo evidence of DimB binding a defined promoter cis-regulatory region.
Supporting Evidence:
PMID:21458438
ChIP analysis shows that DimB binds to the ecmB promoter in DIF-induced cells
|
|
GO:0000976
transcription cis-regulatory region binding
|
IDA
PMID:22253818 Transcriptional repression by a bZIP protein regulates Dicty... |
ACCEPT |
Summary: ChIP analysis shows DIF-1-induced binding of DimB to the pspA promoter, confirming cis-regulatory region binding at a prespore-gene promoter. Core molecular function.
Reason: Independent direct in vivo evidence of DimB binding a promoter cis-regulatory region.
Supporting Evidence:
PMID:22253818
Thus DIF induces binding of DimB to the pspA promoter
|
|
GO:0010628
positive regulation of gene expression
|
IMP
PMID:21458438 DIF-1 regulates Dictyostelium basal disc differentiation by ... |
ACCEPT |
Summary: DimB directly activates ecmB transcription in pstB cells; in dimB-null cells ecmB is not DIF-inducible. Supports positive regulation of gene expression.
Reason: Direct activation of ecmB, supported by ChIP and mutant analysis, makes this a well-supported functional annotation.
Supporting Evidence:
PMID:22253818
In response to the signaling polyketide DIF-1 DimB directly activates transcription of the ecmB gene in pstB cells
|
|
GO:0010629
negative regulation of gene expression
|
IMP
PMID:20080085 A new Dictyostelium prestalk cell sub-type. |
ACCEPT |
Summary: Genome-wide microarray analysis of dimB-null cells identified genes that become DIF-inducible only when DimB is absent, i.e. genes normally under negative control by DimB. Supports negative regulation of gene expression.
Reason: Direct genetic (mutant) evidence that DimB represses a set of DIF-1 target genes.
Supporting Evidence:
PMID:20080085
these genes fall under negative control by the same two transcription factors
|
|
GO:0010629
negative regulation of gene expression
|
IMP
PMID:22253818 Transcriptional repression by a bZIP protein regulates Dicty... |
ACCEPT |
Summary: DimB directly represses the prespore gene pspA; DIF-1-dependent repression of pspA is abrogated in a dimB-null strain, and DimB binds the pspA promoter. Core repressive activity.
Reason: Direct in vivo binding plus mutant analysis establish DimB as a direct repressor of pspA.
Supporting Evidence:
PMID:22253818
DIF-1 represses pspA gene expression in a suspension cell assay but this repression is abrogated in a dimB null strain
|
|
GO:0042802
identical protein binding
|
IPI
PMID:16410410 bZIP transcription factor interactions regulate DIF response... |
ACCEPT |
Summary: Pull-down assays show DimB can form homodimeric complexes (self- interaction; UniProtKB:Q54ER9), consistent with bZIP homodimerization. This is informative (unlike bare protein binding) and supported.
Reason: Direct in vitro evidence of DimB homodimerization; retained as an informative interaction annotation reflecting bZIP dimerization behavior.
Supporting Evidence:
PMID:16410410
Pull-down assays with purified proteins showed that DimA and DimB can form homodimeric and heterodimeric complexes in vitro
|
|
GO:0030587
sorocarp development
|
IEP
PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo... |
KEEP AS NON CORE |
Summary: An IEP annotation based on dimB's developmentally regulated expression trajectory in a genome-wide transcriptome study. Expression-based inference of a broad developmental role.
Reason: The developmental-transcriptome correlation is consistent with a role in sorocarp development, but this very general term rests on expression pattern rather than direct functional evidence and is not a core function.
Supporting Evidence:
PMID:25887420
dimB and dstC continued on a more graded trajectory
|
id: Q54ER9
gene_symbol: dimB
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:44689
label: Dictyostelium discoideum
description: DimB is a basic-region leucine-zipper (bZIP) transcription factor that
acts as a direct effector of the polyketide morphogen DIF-1 during Dictyostelium
multicellular development. In unstimulated cells DimB is distributed through the
cytoplasm, but exposure to DIF-1 triggers its rapid accumulation in the nucleus,
where it binds sequence-specific cis-regulatory elements in target promoters. DimB
can bind DNA as a homodimer and as a heterodimer with the related bZIP factor DimA.
It functions as a dual-mode regulator that directly activates prestalk/basal-disc
genes such as ecmB in pstB cells, spatially restricts expression of the prestalk
gene ecmA, and directly represses prespore genes such as pspA. Through these
activities DimB controls prestalk cell-type patterning, pstB/basal-disc and
anterior-like-cell differentiation, and the choice between stalk and spore fate.
Loss of DimB produces abnormally long, thin slugs and defective culmination.
existing_annotations:
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Phylogenetic inference that DimB acts in the nucleus is consistent with
direct experimental evidence that DimB accumulates in the nucleus upon DIF-1
stimulation and binds target promoters there. This is a core location.
action: ACCEPT
reason: Nuclear localization is directly demonstrated for DimB and is where its
transcription factor activity is exerted; the IBA inference is fully corroborated.
supported_by:
- reference_id: PMID:16410410
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- term:
id: GO:0010468
label: regulation of gene expression
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: DimB regulates expression of multiple developmental genes (activating
ecmB, repressing pspA and others). This general parent term is correct but a
more specific descendant (regulation of DNA-templated transcription) better
captures its mechanism.
action: ACCEPT
reason: The annotation is accurate as a broad statement of DimB's function as a
transcriptional regulator; more specific transcription terms are also present.
supported_by:
- reference_id: PMID:22253818
supporting_text: In response to the signaling polyketide DIF-1 DimB directly
activates transcription of the ecmB gene in pstB cells
- term:
id: GO:0043565
label: sequence-specific DNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: DimB was purified by affinity chromatography on ecmA promoter fragments
and binds defined sites in the ecmA, ecmB and pspA promoters, directly
demonstrating sequence-specific DNA binding. The IBA inference is well
supported.
action: ACCEPT
reason: Sequence-specific DNA binding is a core molecular function of DimB,
confirmed by direct experimental evidence.
supported_by:
- reference_id: PMID:16396914
supporting_text: We have purified a novel bZIP transcription factor, DimB, by
affinity chromatography on two spatially separated ecmA promoter fragments
- term:
id: GO:0003700
label: DNA-binding transcription factor activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: InterPro2GO inference from the bZIP domain. DimB is experimentally a
DNA-binding transcription factor that both activates and represses target genes,
so this is a correct core molecular function.
action: ACCEPT
reason: The bZIP domain-based inference matches the demonstrated function of DimB
as a sequence-specific transcription factor regulating prestalk and prespore
genes.
supported_by:
- reference_id: PMID:22253818
supporting_text: In response to the signaling polyketide DIF-1 DimB directly
activates transcription of the ecmB gene in pstB cells
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: UniProt subcellular-location mapping to nucleus, corroborated by direct
experimental evidence of DIF-1-induced nuclear accumulation.
action: ACCEPT
reason: Nuclear localization is a core, experimentally established location for
DimB.
supported_by:
- reference_id: PMID:16410410
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- 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 consistent with DimB's demonstrated role as a
direct transcriptional activator and repressor of developmental genes.
action: ACCEPT
reason: DimB directly regulates transcription of ecmB (activation) and pspA
(repression); this term accurately captures the process.
supported_by:
- reference_id: PMID:22253818
supporting_text: In response to the signaling polyketide DIF-1 DimB directly
activates transcription of the ecmB gene in pstB cells
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:20300194
qualifier: involved_in
review:
summary: In dimB-null cells the ALC-marker gene btg is over-induced during
development, indicating that DimB normally represses btg as part of the DIF
signalling response. Supports negative regulation of gene expression.
action: ACCEPT
reason: Direct genetic evidence (mutant phenotype) shows DimB negatively regulates
btg expression during development.
supported_by:
- reference_id: PMID:20300194
supporting_text: btg is overinduced in the DIF unresponsive mutants
- term:
id: GO:0043069
label: negative regulation of programmed cell death
evidence_type: IMP
original_reference_id: PMID:16410410
qualifier: involved_in
review:
summary: In an 8-Br-cAMP monolayer assay, DIF-1-treated dimB-null cells undergo
non-vacuolar cell death (NVCD) that is normally suppressed by DimB, which
instead directs vacuolised stalk-cell formation. This is a genuine but
downstream developmental consequence rather than a core molecular function.
action: KEEP_AS_NON_CORE
reason: DimB is required to repress NVCD in the stalk differentiation pathway, so
the annotation is supported, but it reflects a cell-fate outcome of DimB's
transcriptional activity rather than its direct function.
supported_by:
- reference_id: PMID:16410410
supporting_text: NVCD is repressed by DimB
- term:
id: GO:1903014
label: cellular response to differentiation-inducing factor 1
evidence_type: HDA
original_reference_id: PMID:25518940
qualifier: involved_in
review:
summary: DimB is a direct effector of DIF-1 that accumulates in the nucleus and
is phosphorylated in response to DIF-1. This term accurately captures DimB's
role in the cellular response to the DIF-1 morphogen.
action: ACCEPT
reason: DimB nuclear accumulation and phosphorylation are direct, rapid responses
to DIF-1, placing DimB centrally in the cellular DIF-1 response.
supported_by:
- reference_id: PMID:25518940
supporting_text: DimB accumulates in the nuclei of cells induced with DIF-1 and
is phosphorylated
- term:
id: GO:0031153
label: slug development involved in sorocarp development
evidence_type: IMP
original_reference_id: PMID:16396914
qualifier: acts_upstream_of_or_within
review:
summary: dimB-null development proceeds normally to the finger stage, then
produces extremely long, thin fingers/slugs, implicating DimB in normal slug
morphogenesis. This is a downstream developmental phenotype.
action: KEEP_AS_NON_CORE
reason: The mutant slug phenotype supports a role in slug development, but this is
an organismal-level consequence of DimB's transcriptional activity rather than
its core molecular function.
supported_by:
- reference_id: PMID:16396914
supporting_text: DimB is not essential for normal expression of the ecmA gene,
instead it spatially limits its expression
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:16396914
qualifier: is_active_in
review:
summary: Direct evidence that DimB rapidly accumulates in the nucleus upon DIF-1
exposure and associates with the ecmA promoter there. Core active location.
action: ACCEPT
reason: Nuclear localization where DimB exerts its transcription factor activity
is directly demonstrated.
supported_by:
- reference_id: PMID:16396914
supporting_text: DimB rapidly accumulates in the nucleus when cells are exposed
to DIF-1
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:16410410
qualifier: is_active_in
review:
summary: Direct GFP-localization evidence shows DimB accumulates in the nucleus
after DIF-1 treatment. Core active location.
action: ACCEPT
reason: Independent direct evidence confirms nuclear localization as the site of
DimB action.
supported_by:
- reference_id: PMID:16410410
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:21458438
qualifier: is_active_in
review:
summary: DimB is specifically nuclear enriched in pstB cells during normal
development, where it activates basal-disc gene expression. Core active
location.
action: ACCEPT
reason: Direct evidence places active DimB in the nucleus of the responding
cells.
supported_by:
- reference_id: PMID:21458438
supporting_text: DimB is specifically nuclear enriched in the pstB cells
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:16396914
qualifier: located_in
review:
summary: In the absence of DIF-1, DimB is distributed through the cytoplasm and
only translocates to the nucleus upon DIF-1 stimulation. Cytoplasmic
localization reflects the inactive/resting state rather than the functional
compartment.
action: KEEP_AS_NON_CORE
reason: The cytoplasmic pool is the pre-stimulation reservoir; DimB's functional
compartment is the nucleus. The localization is real but not the core site of
action.
supported_by:
- reference_id: PMID:16410410
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- term:
id: GO:0031287
label: positive regulation of sorocarp stalk cell differentiation
evidence_type: IMP
original_reference_id: PMID:16396914
qualifier: involved_in
review:
summary: DimB promotes prestalk/basal-disc differentiation, and dimB-null cells
fail to make stalk cells in response to DIF-1. This is a genuine developmental
role, but a downstream outcome of DimB's transcriptional activity.
action: KEEP_AS_NON_CORE
reason: Supported by mutant phenotype (loss of DIF-1-induced stalk differentiation),
but represents an organismal cell-differentiation outcome rather than DimB's
core molecular function.
supported_by:
- reference_id: PMID:21458438
supporting_text: leading to nuclear localization of DimB and direct activation
of cell type-specific gene expression
- term:
id: GO:0043565
label: sequence-specific DNA binding
evidence_type: IDA
original_reference_id: PMID:16396914
qualifier: enables
review:
summary: DimB was purified by affinity chromatography on ecmA promoter fragments,
directly demonstrating sequence-specific DNA binding. Core molecular function.
action: ACCEPT
reason: Direct biochemical evidence for sequence-specific promoter binding.
supported_by:
- reference_id: PMID:16396914
supporting_text: We have purified a novel bZIP transcription factor, DimB, by
affinity chromatography on two spatially separated ecmA promoter fragments
- term:
id: GO:0045184
label: establishment of protein localization
evidence_type: IMP
original_reference_id: PMID:16410410
qualifier: involved_in
review:
summary: DimB is required for DIF-1-induced nuclear accumulation of its partner
DimA; in dimB-null cells DimA fails to accumulate in the nucleus. The annotation
captures this regulatory effect but with a very general term.
action: KEEP_AS_NON_CORE
reason: Supported by direct genetic evidence that DimB controls DimA nuclear
localization, but this is a specialized downstream effect and the term is broad;
not a core function.
supported_by:
- reference_id: PMID:16410410
supporting_text: nuclear accumulation of DimA in response to DIF-1 is dependent
on DimB
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:16410410
qualifier: located_in
review:
summary: Consistent with the other cytoplasm annotation, DimB:GFP is uniformly
distributed (including cytoplasm) before DIF-1 and translocates to the nucleus
after stimulation.
action: KEEP_AS_NON_CORE
reason: Cytoplasmic localization is the resting-state distribution; the functional
compartment is the nucleus.
supported_by:
- reference_id: PMID:16410410
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16410410
qualifier: enables
review:
summary: This IPI annotation records the physical interaction of DimB with the
bZIP factor DimA (UniProtKB:Q54XG7). Bare protein binding is uninformative;
the interaction is bZIP heterodimerization, better captured by protein
heterodimerization activity.
action: MODIFY
reason: Pull-down assays show DimB forms heterodimeric complexes with DimA in
vitro. Replacing the generic term with protein heterodimerization activity
conveys the mechanistic nature (bZIP leucine-zipper dimerization) of the
interaction.
proposed_replacement_terms:
- id: GO:0046982
label: protein heterodimerization activity
supported_by:
- reference_id: PMID:16410410
supporting_text: Pull-down assays with purified proteins showed that DimA and
DimB can form homodimeric and heterodimeric complexes in vitro
- reference_id: PMID:16410410
supporting_text: a second bZIP transcription factor (DimB) that can directly
interact with DimA in vitro
- term:
id: GO:0000976
label: transcription cis-regulatory region binding
evidence_type: IDA
original_reference_id: PMID:21458438
qualifier: enables
review:
summary: ChIP analysis directly shows DimB binding to the ecmB cis-regulatory
region (promoter) in DIF-1-induced cells. Core molecular function.
action: ACCEPT
reason: Direct in vivo evidence of DimB binding a defined promoter cis-regulatory
region.
supported_by:
- reference_id: PMID:21458438
supporting_text: ChIP analysis shows that DimB binds to the ecmB promoter in
DIF-induced cells
- term:
id: GO:0000976
label: transcription cis-regulatory region binding
evidence_type: IDA
original_reference_id: PMID:22253818
qualifier: enables
review:
summary: ChIP analysis shows DIF-1-induced binding of DimB to the pspA promoter,
confirming cis-regulatory region binding at a prespore-gene promoter. Core
molecular function.
action: ACCEPT
reason: Independent direct in vivo evidence of DimB binding a promoter
cis-regulatory region.
supported_by:
- reference_id: PMID:22253818
supporting_text: Thus DIF induces binding of DimB to the pspA promoter
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:21458438
qualifier: involved_in
review:
summary: DimB directly activates ecmB transcription in pstB cells; in dimB-null
cells ecmB is not DIF-inducible. Supports positive regulation of gene
expression.
action: ACCEPT
reason: Direct activation of ecmB, supported by ChIP and mutant analysis, makes
this a well-supported functional annotation.
supported_by:
- reference_id: PMID:22253818
supporting_text: In response to the signaling polyketide DIF-1 DimB directly
activates transcription of the ecmB gene in pstB cells
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:20080085
qualifier: involved_in
review:
summary: Genome-wide microarray analysis of dimB-null cells identified genes that
become DIF-inducible only when DimB is absent, i.e. genes normally under
negative control by DimB. Supports negative regulation of gene expression.
action: ACCEPT
reason: Direct genetic (mutant) evidence that DimB represses a set of DIF-1
target genes.
supported_by:
- reference_id: PMID:20080085
supporting_text: these genes fall under negative control by the same two
transcription factors
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:22253818
qualifier: involved_in
review:
summary: DimB directly represses the prespore gene pspA; DIF-1-dependent
repression of pspA is abrogated in a dimB-null strain, and DimB binds the pspA
promoter. Core repressive activity.
action: ACCEPT
reason: Direct in vivo binding plus mutant analysis establish DimB as a direct
repressor of pspA.
supported_by:
- reference_id: PMID:22253818
supporting_text: DIF-1 represses pspA gene expression in a suspension cell assay
but this repression is abrogated in a dimB null strain
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:16410410
qualifier: enables
review:
summary: Pull-down assays show DimB can form homodimeric complexes (self-
interaction; UniProtKB:Q54ER9), consistent with bZIP homodimerization. This
is informative (unlike bare protein binding) and supported.
action: ACCEPT
reason: Direct in vitro evidence of DimB homodimerization; retained as an
informative interaction annotation reflecting bZIP dimerization behavior.
supported_by:
- reference_id: PMID:16410410
supporting_text: Pull-down assays with purified proteins showed that DimA and
DimB can form homodimeric and heterodimeric complexes in vitro
- term:
id: GO:0030587
label: sorocarp development
evidence_type: IEP
original_reference_id: PMID:25887420
qualifier: acts_upstream_of_or_within
review:
summary: An IEP annotation based on dimB's developmentally regulated expression
trajectory in a genome-wide transcriptome study. Expression-based inference of
a broad developmental role.
action: KEEP_AS_NON_CORE
reason: The developmental-transcriptome correlation is consistent with a role in
sorocarp development, but this very general term rests on expression pattern
rather than direct functional evidence and is not a core function.
supported_by:
- reference_id: PMID:25887420
supporting_text: dimB and dstC continued on a more graded trajectory
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: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: PMID:16396914
title: The Dictyostelium bZIP transcription factor DimB regulates prestalk-specific
gene expression.
findings:
- statement: DimB is a bZIP transcription factor purified by affinity chromatography
on ecmA promoter fragments; it spatially restricts ecmA expression rather than
being essential for it.
supporting_text: DimB is not essential for normal expression of the ecmA gene,
instead it spatially limits its expression
- statement: DimB accumulates rapidly in the nucleus upon DIF-1 exposure and
associates with the ecmA promoter in vivo.
supporting_text: DimB rapidly accumulates in the nucleus when cells are exposed
to DIF-1
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed abstract confirms DimB as a DIF-1-regulated bZIP transcription
factor that binds the ecmA promoter and spatially patterns ecmA expression;
basis for the DNA-binding, nuclear and prestalk-patterning annotations.
- id: PMID:16410410
title: bZIP transcription factor interactions regulate DIF responses in Dictyostelium.
findings:
- statement: DimB directly interacts with DimA and both proteins form homo- and
heterodimeric complexes in vitro.
supporting_text: Pull-down assays with purified proteins showed that DimA and
DimB can form homodimeric and heterodimeric complexes in vitro
- statement: DimB (and DimA) rapidly accumulate in the nucleus after DIF-1
treatment, being uniformly distributed beforehand.
supporting_text: In the absence of DIF-1, GFP was fairly uniformly distributed
throughout the cells. However, after DIF-1 treatment, both DimA:GFP and DimB:GFP
exhibited nuclear accumulation
- statement: DimB represses non-vacuolar cell death and is required for DimA nuclear
accumulation.
supporting_text: nuclear accumulation of DimA in response to DIF-1 is dependent
on DimB
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Full text (PMC3531922) verifies DimA-DimB dimerization, DIF-1-induced
nuclear accumulation, DimB-dependence of DimA localization, and NVCD repression.
- id: PMID:20080085
title: A new Dictyostelium prestalk cell sub-type.
findings:
- statement: Genome-wide analysis of dimB-null cells shows DimB acts as both an
inducer and a repressor of DIF-1 target genes.
supporting_text: these genes fall under negative control by the same two
transcription factors
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Full text supports the negative-regulation annotation via
microarray comparison of parental and dimB-null cells.
- id: PMID:20300194
title: BTG interacts with retinoblastoma to control cell fate in Dictyostelium.
findings:
- statement: The ALC gene btg is over-induced in dimB-null cells during development,
indicating DimB normally represses btg.
supporting_text: btg is overinduced in the DIF unresponsive mutants
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Full text shows btg overinduction in dimB-null development,
supporting DimB's negative regulation of gene expression.
- id: PMID:21458438
title: DIF-1 regulates Dictyostelium basal disc differentiation by inducing the
nuclear accumulation of a bZIP transcription factor.
findings:
- statement: DimB is nuclear enriched in pstB cells and directly activates ecmB by
binding its promoter, driving basal-disc differentiation.
supporting_text: ChIP analysis shows that DimB binds to the ecmB promoter in
DIF-induced cells
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Full text (PMC3107940) establishes DimB as a direct activator of
ecmB and driver of pstB/basal-disc differentiation.
- id: PMID:22253818
title: Transcriptional repression by a bZIP protein regulates Dictyostelium prespore
differentiation.
findings:
- statement: DimB binds the pspA promoter and directly represses pspA, while the
same pathway activates ecmB.
supporting_text: Thus DIF induces binding of DimB to the pspA promoter
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Full text (PMC3253789) demonstrates direct DimB repression of the
prespore gene pspA via promoter binding.
- id: PMID:25518940
title: The Dictyostelium prestalk inducer differentiation-inducing factor-1 (DIF-1)
triggers unexpectedly complex global phosphorylation changes.
findings:
- statement: DimB accumulates in nuclei of DIF-1-induced cells and is phosphorylated
in response to DIF-1.
supporting_text: DimB accumulates in the nuclei of cells induced with DIF-1 and
is phosphorylated
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Full text supports DimB as a phosphorylated nuclear effector of the
DIF-1 signalling pathway (HDA cellular response annotation).
- id: PMID:25887420
title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
findings:
- statement: dimB shows a graded developmental expression trajectory during the
developmental time course.
supporting_text: dimB and dstC continued on a more graded trajectory
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: Transcriptome study; provides only expression-timing context (basis
for the IEP sorocarp-development annotation).
core_functions:
- description: DimB is a DIF-1-responsive bZIP transcription factor that binds
sequence-specific cis-regulatory elements in target promoters (ecmA, ecmB, pspA)
and acts as a dual-mode regulator, directly activating prestalk/basal-disc genes
(e.g. ecmB) and directly repressing prespore genes (e.g. pspA), thereby patterning
cell-type gene expression in response to the DIF-1 morphogen.
molecular_function:
id: GO:0003700
label: DNA-binding transcription factor activity
locations:
- id: GO:0005634
label: nucleus
supported_by:
- reference_id: PMID:22253818
supporting_text: In response to the signaling polyketide DIF-1 DimB directly
activates transcription of the ecmB gene in pstB cells
- reference_id: PMID:22253818
supporting_text: DIF-1 represses pspA gene expression in a suspension cell assay
but this repression is abrogated in a dimB null strain
- description: DimB binds defined cis-regulatory (promoter) regions of its target
genes in a sequence-specific, DIF-1-induced manner, as shown by affinity
purification on the ecmA promoter and ChIP at the ecmB and pspA promoters.
molecular_function:
id: GO:0000976
label: transcription cis-regulatory region binding
locations:
- id: GO:0005634
label: nucleus
supported_by:
- reference_id: PMID:21458438
supporting_text: ChIP analysis shows that DimB binds to the ecmB promoter in
DIF-induced cells
- reference_id: PMID:16396914
supporting_text: We have purified a novel bZIP transcription factor, DimB, by
affinity chromatography on two spatially separated ecmA promoter fragments