SrfA (DdSRF) is the Dictyostelium discoideum homolog of Serum Response Factor, a MADS-box transcription factor. Its MADS-box DNA-binding domain (residues 67-127) is highly conserved with the human, Drosophila and yeast SRF homologs, although several DNA-binding residues have diverged, likely altering its target-sequence specificity relative to animal SRFs (the animal CArG box is not found in its Dictyostelium targets). SrfA acts in the nucleus as a sequence-specific RNA polymerase II transcription factor that activates a subset of late, prespore/spore-specific genes (for example the spore-coat marker spiA and the SrfA-dependent sigA/sigB/sigC/sigD genes). It is expressed in a complex, promoter-dependent pattern across prestalk, prespore and spore cells, with a strong induction in prespore cells at culmination that is driven by cAMP-dependent protein kinase A (PKA). SrfA is essential for terminal spore differentiation and maturation, since srfA-null strains form rounded spores with reduced viability, defective actin-rod formation, and progressively degrading spore coats, and the mutants also show defective slug migration and a delay in culmination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005634
nucleus
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Nuclear localization is where a sequence-specific transcription factor acts. Consistent with the MADS-box/SRF family and with the independent IC and UniProt-based nucleus annotations for this protein.
Reason: SrfA is a MADS-box RNA polymerase II transcription factor; the nucleus is its site of action. This is well supported across evidence types.
Supporting Evidence:
PMID:9729488
A homolog of the Serum Response Factor (SRF) has been isolated from Dictyostelium discoideum
|
|
GO:0000978
RNA polymerase II cis-regulatory region sequence-specific DNA binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: SrfA is a MADS-box protein that binds cis-regulatory regions of target genes; the SrfA-dependent sig genes are proposed to be directly activated through binding to their promoters. Note that DNA-binding residues have diverged from animal SRF, so the recognized element likely differs from the animal CArG box.
Reason: Sequence-specific cis-regulatory DNA binding is the core biochemical activity of a MADS-box/SRF transcription factor and is consistent with the proposed direct promoter binding of SrfA targets.
Supporting Evidence:
PMID:14665466
The regulation of the expression of sig genes by SrfA could be through direct binding to their promoters, which activates their expression
|
|
GO:0000981
DNA-binding transcription factor activity, RNA polymerase II-specific
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This is the core molecular function of SrfA - a sequence-specific RNA polymerase II DNA-binding transcription factor of the MADS-box/SRF family, corroborated by experimental IMP evidence (GO:0003700).
Reason: SrfA is an SRF-family MADS-box transcription factor that activates RNA polymerase II transcription of late developmental genes. This is its defining function.
Supporting Evidence:
PMID:14665466
The MADS box transcription factor SrfA is required for spore differentiation in Dictyostelium discoideum
|
|
GO:0045944
positive regulation of transcription by RNA polymerase II
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: SrfA induces (activates) the expression of spore-specific genes at the final steps of spore differentiation; five SrfA-dependent genes are not expressed in srfA-null strains, consistent with a positive/activating role.
Reason: Experimental data show SrfA is required for the expression of its target genes and induces spore-specific genes, supporting a positive-regulation role.
Supporting Evidence:
PMID:14665466
These data are in agreement with the hypothesis that SrfA induces the expression of a number of spore-specific genes at the final steps of spore differentiation
|
|
GO:0000981
DNA-binding transcription factor activity, RNA polymerase II-specific
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO annotation from the SRF-like MADS-box domain (IPR033897). Redundant with the IBA and experimental (IMP/ISS) transcription-factor annotations and biologically correct.
Reason: The SRF-like MADS-box domain is a well-characterized RNA polymerase II DNA-binding transcription factor domain; the electronic inference is correct and matches experimental evidence.
Supporting Evidence:
PMID:14665466
The MADS box transcription factor SrfA is required for spore differentiation in Dictyostelium discoideum
|
|
GO:0000987
cis-regulatory region sequence-specific DNA binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO annotation for sequence-specific cis-regulatory DNA binding. Correct but more general than the RNA polymerase II-specific term (GO:0000978) also annotated to this protein.
Reason: SrfA binds cis-regulatory regions of its targets. The annotation is biologically correct; the Pol II-specific child term is the more informative version of the same activity.
Supporting Evidence:
PMID:14665466
The regulation of the expression of sig genes by SrfA could be through direct binding to their promoters, which activates their expression
|
|
GO:0003677
DNA binding
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: General DNA binding inferred from the MADS-box domain. Correct but uninformative given the more specific sequence-specific and RNA polymerase II-specific DNA-binding terms already annotated.
Reason: DNA binding is a true but very general parent term. The specific sequence-specific transcription-factor DNA-binding terms better capture the core function, so this general term is retained as non-core.
Supporting Evidence:
PMID:9729488
The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Nuclear localization from the UniProt subcellular-location mapping, consistent with the transcription-factor function and the IC and IBA nucleus annotations.
Reason: SrfA is a nuclear transcription factor; nuclear localization is well supported across multiple evidence lines.
Supporting Evidence:
PMID:9729488
A homolog of the Serum Response Factor (SRF) has been isolated from Dictyostelium discoideum
|
|
GO:0045944
positive regulation of transcription by RNA polymerase II
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO inference of positive regulation of RNA polymerase II transcription from the SRF-like domain. Redundant with the IBA annotation and supported by experimental data showing SrfA induces target-gene expression.
Reason: Consistent with experimental evidence that SrfA activates its target genes; the electronic inference matches the biology.
Supporting Evidence:
PMID:14665466
These data are in agreement with the hypothesis that SrfA induces the expression of a number of spore-specific genes at the final steps of spore differentiation
|
|
GO:0046983
protein dimerization activity
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: MADS-box/SRF proteins bind DNA as dimers, so dimerization activity is a plausible domain-based inference. However there is no direct experimental evidence for SrfA dimerization, and it is an ancillary capability supporting DNA binding rather than a core function.
Reason: Dimerization is a general property of the MADS-box fold that supports DNA binding, but it is an accessory biochemical capability inferred only from domain presence, not a core evolved function of SrfA.
Supporting Evidence:
PMID:9729488
The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs
|
|
GO:0031247
actin rod assembly
|
IMP
PMID:14706699 The MADS-box transcription factor SrfA is required for actin... |
KEEP AS NON CORE |
Summary: srfA-null spores fail to form mature actin rods and show strongly reduced actin phosphorylation. This is a genuine mutant phenotype, but it is a downstream consequence of SrfA's transcriptional function rather than a direct molecular role of SrfA in rod assembly.
Reason: The phenotype is well documented experimentally, but SrfA is a transcription factor acting upstream; the actin-rod defect reflects loss of target-gene expression. Retained as a non-core, downstream developmental role.
Supporting Evidence:
PMID:14706699
SrfA mutant spores showed the initial stages of rod formation but no mature rods were found in older spores either in the nucleus or the cytoplasm
PMID:14706699
phosphorylation of actin, that is believed to stabilize the actin rods, is strongly reduced in the mutant
|
|
GO:0042244
spore wall assembly
|
IMP
PMID:14706699 The MADS-box transcription factor SrfA is required for actin... |
KEEP AS NON CORE |
Summary: srfA-null spores form basically normal trilaminar coats initially but the outer layer becomes wavier and progressively degrades as the spore ages, indicating a late defect in spore-coat stability. As with actin rods, this is a downstream effect of the loss of SrfA-dependent transcription.
Reason: The spore-coat stability defect is experimentally supported, but SrfA acts as an upstream transcription factor; the coat phenotype is an indirect consequence. Retained as a non-core developmental role.
Supporting Evidence:
PMID:14706699
the outer layer gets wavier as the spore ages and suffers a progressive degradation suggesting a late defect in the stability of the spore coat
|
|
GO:0043945
positive regulation of asexual sporulation resulting in formation of a cellular spore
|
IMP
PMID:14706699 The MADS-box transcription factor SrfA is required for actin... |
ACCEPT |
Summary: SrfA is required for late events of spore maturation and for full spore viability, and it positively drives expression of spore-specific genes. This captures its regulatory role in sporulation.
Reason: SrfA is essential for spore differentiation/maturation and positively regulates spore-gene expression; a positive-regulation-of-sporulation term is appropriate and reflects a core aspect of its biology.
Supporting Evidence:
PMID:14706699
these results suggest that SrfA is involved in late events of spore maturation necessary for spore stability
|
|
GO:0006357
regulation of transcription by RNA polymerase II
|
IMP
PMID:14665466 Dictyostelium discoideum developmentally regulated genes who... |
ACCEPT |
Summary: This study isolated five SrfA-dependent genes that are expressed in wild-type but not srfA-null strains, directly demonstrating that SrfA regulates RNA polymerase II transcription of target genes.
Reason: Direct experimental evidence that SrfA is required for the expression of a defined set of target genes supports its role in regulation of RNA polymerase II transcription.
Supporting Evidence:
PMID:14665466
Five genes whose expression is dependent on SrfA have been isolated by differential hybridization
|
|
GO:0006357
regulation of transcription by RNA polymerase II
|
ISS
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: Sequence-similarity inference from human SRF (UniProtKB:P11831). SrfA's MADS-box is highly conserved with the human, Drosophila and yeast homologs, supporting a conserved transcription-factor role.
Reason: The conserved MADS-box and demonstrated target-gene dependence support the transcription-factor role transferred by similarity from human SRF.
Supporting Evidence:
PMID:9729488
The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs
|
|
GO:0006357
regulation of transcription by RNA polymerase II
|
IMP
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: srfA disruption reduces expression of the spore marker spiA and impairs spore maturation, indicating SrfA regulates the transcription of target genes.
Reason: Loss-of-function evidence that SrfA is needed for target-gene (spiA) expression supports its role in regulation of RNA polymerase II transcription.
Supporting Evidence:
PMID:9729488
participates in the regulation of the expression of the spore-coat marker spiA
|
|
GO:0042331
phototaxis
|
IMP
PMID:11437439 The MADS-box gene srfA is expressed in a complex pattern und... |
KEEP AS NON CORE |
Summary: srfA-null strains have a slug-migration defect; phototaxis is a slug-migration-associated behavior assessed in this study of srfA's developmental roles. This is a downstream, non-core developmental phenotype of the transcription factor.
Reason: SrfA acts upstream of slug behaviors as a transcription factor. The phototaxis/migration phenotype is a real but indirect developmental role, not the core molecular function. Experimental IMP annotation retained as non-core.
Supporting Evidence:
PMID:11437439
The study of knockout strains revealed that srfA is also required for proper slug migration
|
|
GO:0031154
culmination involved in sorocarp development
|
IEP
PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo... |
UNDECIDED |
Summary: This is a genome-wide developmental transcriptome study (Rosengarten et al. 2015) that profiles thousands of genes but does not specifically discuss srfA in the available text. The culmination association is an expression-pattern (IEP) inference that cannot be verified for srfA from this source.
Reason: The cited large-scale transcriptome paper does not mention srfA in the cached text, so its specific contribution to culmination cannot be verified here. SrfA's culmination-stage role is separately supported by other references (its PKA-driven induction and expression in prespore cells at culmination), but this particular IEP annotation cannot be independently confirmed.
|
|
GO:0031154
culmination involved in sorocarp development
|
IMP
PMID:11437439 The MADS-box gene srfA is expressed in a complex pattern und... |
KEEP AS NON CORE |
Summary: SrfA is expressed in a complex pattern that includes strong induction in spores by the end of culmination, and srfA is required for several developmental functions. Its role at culmination is a developmental, non-core function downstream of its transcription-factor activity.
Reason: Experimental (IMP) annotation of a developmental-stage role. SrfA acts upstream as a transcription factor; culmination involvement is a non-core developmental role rather than its core molecular function.
Supporting Evidence:
PMID:11437439
the correct spatial and temporal pattern of expression of srfA is essential for the different functions that this transcription factor plays in development
|
|
GO:0030435
sporulation resulting in formation of a cellular spore
|
IMP
PMID:14706699 The MADS-box transcription factor SrfA is required for actin... |
ACCEPT |
Summary: SrfA is required for late events of spore maturation necessary for spore stability; srfA-null spores are abnormal and lose viability. Sporulation is the central biological process in which SrfA acts.
Reason: Sporulation/spore differentiation is the core developmental process requiring SrfA, supported by multiple loss-of-function studies.
Supporting Evidence:
PMID:14706699
these results suggest that SrfA is involved in late events of spore maturation necessary for spore stability
|
|
GO:0003700
DNA-binding transcription factor activity
|
IMP
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: Experimental (IMP) support for SrfA acting as a DNA-binding transcription factor, based on the requirement of srfA for target-gene (spiA) expression. The RNA polymerase II-specific child term (GO:0000981) is the more precise form of the same activity.
Reason: DNA-binding transcription factor activity is the core molecular function of SrfA and is experimentally supported by its requirement for target-gene expression.
Supporting Evidence:
PMID:9729488
participates in the regulation of the expression of the spore-coat marker spiA
|
|
GO:0005634
nucleus
|
IC
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: Nuclear localization inferred by curators (IC) from the DNA-binding transcription factor activity of SrfA. Consistent with the IBA and UniProt nucleus annotations.
Reason: As a MADS-box transcription factor, SrfA acts in the nucleus; the IC inference is sound and corroborated by independent evidence.
Supporting Evidence:
PMID:9729488
A homolog of the Serum Response Factor (SRF) has been isolated from Dictyostelium discoideum
|
|
GO:0030435
sporulation resulting in formation of a cellular spore
|
IMP
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: srfA disruption causes abnormal spore morphology and loss of viability, establishing an essential role in sporulation. Duplicate process annotation supported by the original characterization of the gene.
Reason: Sporulation is the core developmental process requiring SrfA; this loss-of-function evidence directly supports the annotation.
Supporting Evidence:
PMID:9729488
This gene plays an essential role in sporulation as its disruption leads to abnormal spore morphology and loss of viability
|
|
GO:0003700
DNA-binding transcription factor activity
|
ISS
PMID:9729488 A Serum Response Factor homolog is required for spore differ... |
ACCEPT |
Summary: Sequence-similarity inference of DNA-binding transcription factor activity from human SRF (UniProtKB:P11831), consistent with the highly conserved MADS-box domain and the experimental IMP annotation of the same activity.
Reason: The conserved MADS-box supports transfer of the DNA-binding transcription-factor activity from human SRF; this is the core molecular function of SrfA.
Supporting Evidence:
PMID:9729488
The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs
|
id: Q54TY7
gene_symbol: srfA
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:44689
label: Dictyostelium discoideum
description: SrfA (DdSRF) is the Dictyostelium discoideum homolog of Serum Response
Factor, a MADS-box transcription factor. Its MADS-box DNA-binding domain (residues
67-127) is highly conserved with the human, Drosophila and yeast SRF homologs,
although several DNA-binding residues have diverged, likely altering its
target-sequence specificity relative to animal SRFs (the animal CArG box is not
found in its Dictyostelium targets). SrfA acts in the nucleus as a sequence-specific
RNA polymerase II transcription factor that activates a subset of late,
prespore/spore-specific genes (for example the spore-coat marker spiA and the
SrfA-dependent sigA/sigB/sigC/sigD genes). It is expressed in a complex,
promoter-dependent pattern across prestalk, prespore and spore cells, with a strong
induction in prespore cells at culmination that is driven by cAMP-dependent protein
kinase A (PKA). SrfA is essential for terminal spore differentiation and maturation,
since srfA-null strains form rounded spores with reduced viability, defective
actin-rod formation, and progressively degrading spore coats, and the mutants also
show defective slug migration and a delay in culmination.
existing_annotations:
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Nuclear localization is where a sequence-specific transcription factor
acts. Consistent with the MADS-box/SRF family and with the independent IC and
UniProt-based nucleus annotations for this protein.
action: ACCEPT
reason: SrfA is a MADS-box RNA polymerase II transcription factor; the nucleus is
its site of action. This is well supported across evidence types.
supported_by:
- reference_id: PMID:9729488
supporting_text: A homolog of the Serum Response Factor (SRF) has been isolated
from Dictyostelium discoideum
- term:
id: GO:0000978
label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: SrfA is a MADS-box protein that binds cis-regulatory regions of target
genes; the SrfA-dependent sig genes are proposed to be directly activated through
binding to their promoters. Note that DNA-binding residues have diverged from
animal SRF, so the recognized element likely differs from the animal CArG box.
action: ACCEPT
reason: Sequence-specific cis-regulatory DNA binding is the core biochemical
activity of a MADS-box/SRF transcription factor and is consistent with the
proposed direct promoter binding of SrfA targets.
supported_by:
- reference_id: PMID:14665466
supporting_text: The regulation of the expression of sig genes by SrfA could be
through direct binding to their promoters, which activates their expression
- term:
id: GO:0000981
label: DNA-binding transcription factor activity, RNA polymerase II-specific
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: This is the core molecular function of SrfA - a sequence-specific RNA
polymerase II DNA-binding transcription factor of the MADS-box/SRF family,
corroborated by experimental IMP evidence (GO:0003700).
action: ACCEPT
reason: SrfA is an SRF-family MADS-box transcription factor that activates RNA
polymerase II transcription of late developmental genes. This is its defining
function.
supported_by:
- reference_id: PMID:14665466
supporting_text: The MADS box transcription factor SrfA is required for spore
differentiation in Dictyostelium discoideum
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: SrfA induces (activates) the expression of spore-specific genes at the
final steps of spore differentiation; five SrfA-dependent genes are not expressed
in srfA-null strains, consistent with a positive/activating role.
action: ACCEPT
reason: Experimental data show SrfA is required for the expression of its target
genes and induces spore-specific genes, supporting a positive-regulation role.
supported_by:
- reference_id: PMID:14665466
supporting_text: These data are in agreement with the hypothesis that SrfA
induces the expression of a number of spore-specific genes at the final steps
of spore differentiation
- term:
id: GO:0000981
label: DNA-binding transcription factor activity, RNA polymerase II-specific
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: InterPro2GO annotation from the SRF-like MADS-box domain (IPR033897).
Redundant with the IBA and experimental (IMP/ISS) transcription-factor
annotations and biologically correct.
action: ACCEPT
reason: The SRF-like MADS-box domain is a well-characterized RNA polymerase II
DNA-binding transcription factor domain; the electronic inference is correct and
matches experimental evidence.
supported_by:
- reference_id: PMID:14665466
supporting_text: The MADS box transcription factor SrfA is required for spore
differentiation in Dictyostelium discoideum
- term:
id: GO:0000987
label: cis-regulatory region sequence-specific DNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: InterPro2GO annotation for sequence-specific cis-regulatory DNA binding.
Correct but more general than the RNA polymerase II-specific term (GO:0000978)
also annotated to this protein.
action: ACCEPT
reason: SrfA binds cis-regulatory regions of its targets. The annotation is
biologically correct; the Pol II-specific child term is the more informative
version of the same activity.
supported_by:
- reference_id: PMID:14665466
supporting_text: The regulation of the expression of sig genes by SrfA could be
through direct binding to their promoters, which activates their expression
- term:
id: GO:0003677
label: DNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: General DNA binding inferred from the MADS-box domain. Correct but
uninformative given the more specific sequence-specific and RNA polymerase
II-specific DNA-binding terms already annotated.
action: KEEP_AS_NON_CORE
reason: DNA binding is a true but very general parent term. The specific
sequence-specific transcription-factor DNA-binding terms better capture the core
function, so this general term is retained as non-core.
supported_by:
- reference_id: PMID:9729488
supporting_text: The MADS-box region of Dictyostelium SRF (DdSRF) is highly
conserved with those of the human, Drosophila and yeast homologs
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Nuclear localization from the UniProt subcellular-location mapping,
consistent with the transcription-factor function and the IC and IBA nucleus
annotations.
action: ACCEPT
reason: SrfA is a nuclear transcription factor; nuclear localization is well
supported across multiple evidence lines.
supported_by:
- reference_id: PMID:9729488
supporting_text: A homolog of the Serum Response Factor (SRF) has been isolated
from Dictyostelium discoideum
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: InterPro2GO inference of positive regulation of RNA polymerase II
transcription from the SRF-like domain. Redundant with the IBA annotation and
supported by experimental data showing SrfA induces target-gene expression.
action: ACCEPT
reason: Consistent with experimental evidence that SrfA activates its target
genes; the electronic inference matches the biology.
supported_by:
- reference_id: PMID:14665466
supporting_text: These data are in agreement with the hypothesis that SrfA
induces the expression of a number of spore-specific genes at the final steps
of spore differentiation
- term:
id: GO:0046983
label: protein dimerization activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: MADS-box/SRF proteins bind DNA as dimers, so dimerization activity is a
plausible domain-based inference. However there is no direct experimental
evidence for SrfA dimerization, and it is an ancillary capability supporting DNA
binding rather than a core function.
action: KEEP_AS_NON_CORE
reason: Dimerization is a general property of the MADS-box fold that supports DNA
binding, but it is an accessory biochemical capability inferred only from domain
presence, not a core evolved function of SrfA.
supported_by:
- reference_id: PMID:9729488
supporting_text: The MADS-box region of Dictyostelium SRF (DdSRF) is highly
conserved with those of the human, Drosophila and yeast homologs
- term:
id: GO:0031247
label: actin rod assembly
evidence_type: IMP
original_reference_id: PMID:14706699
qualifier: involved_in
review:
summary: srfA-null spores fail to form mature actin rods and show strongly reduced
actin phosphorylation. This is a genuine mutant phenotype, but it is a downstream
consequence of SrfA's transcriptional function rather than a direct molecular
role of SrfA in rod assembly.
action: KEEP_AS_NON_CORE
reason: The phenotype is well documented experimentally, but SrfA is a
transcription factor acting upstream; the actin-rod defect reflects loss of
target-gene expression. Retained as a non-core, downstream developmental role.
supported_by:
- reference_id: PMID:14706699
supporting_text: SrfA mutant spores showed the initial stages of rod formation
but no mature rods were found in older spores either in the nucleus or the
cytoplasm
- reference_id: PMID:14706699
supporting_text: phosphorylation of actin, that is believed to stabilize the
actin rods, is strongly reduced in the mutant
- term:
id: GO:0042244
label: spore wall assembly
evidence_type: IMP
original_reference_id: PMID:14706699
qualifier: involved_in
review:
summary: srfA-null spores form basically normal trilaminar coats initially but the
outer layer becomes wavier and progressively degrades as the spore ages,
indicating a late defect in spore-coat stability. As with actin rods, this is a
downstream effect of the loss of SrfA-dependent transcription.
action: KEEP_AS_NON_CORE
reason: The spore-coat stability defect is experimentally supported, but SrfA acts
as an upstream transcription factor; the coat phenotype is an indirect
consequence. Retained as a non-core developmental role.
supported_by:
- reference_id: PMID:14706699
supporting_text: the outer layer gets wavier as the spore ages and suffers a
progressive degradation suggesting a late defect in the stability of the spore
coat
- term:
id: GO:0043945
label: positive regulation of asexual sporulation resulting in formation of a
cellular spore
evidence_type: IMP
original_reference_id: PMID:14706699
qualifier: involved_in
review:
summary: SrfA is required for late events of spore maturation and for full spore
viability, and it positively drives expression of spore-specific genes. This
captures its regulatory role in sporulation.
action: ACCEPT
reason: SrfA is essential for spore differentiation/maturation and positively
regulates spore-gene expression; a positive-regulation-of-sporulation term is
appropriate and reflects a core aspect of its biology.
supported_by:
- reference_id: PMID:14706699
supporting_text: these results suggest that SrfA is involved in late events of
spore maturation necessary for spore stability
- term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
evidence_type: IMP
original_reference_id: PMID:14665466
qualifier: involved_in
review:
summary: This study isolated five SrfA-dependent genes that are expressed in
wild-type but not srfA-null strains, directly demonstrating that SrfA regulates
RNA polymerase II transcription of target genes.
action: ACCEPT
reason: Direct experimental evidence that SrfA is required for the expression of a
defined set of target genes supports its role in regulation of RNA polymerase II
transcription.
supported_by:
- reference_id: PMID:14665466
supporting_text: Five genes whose expression is dependent on SrfA have been
isolated by differential hybridization
- term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
evidence_type: ISS
original_reference_id: PMID:9729488
qualifier: involved_in
review:
summary: Sequence-similarity inference from human SRF (UniProtKB:P11831). SrfA's
MADS-box is highly conserved with the human, Drosophila and yeast homologs,
supporting a conserved transcription-factor role.
action: ACCEPT
reason: The conserved MADS-box and demonstrated target-gene dependence support the
transcription-factor role transferred by similarity from human SRF.
supported_by:
- reference_id: PMID:9729488
supporting_text: The MADS-box region of Dictyostelium SRF (DdSRF) is highly
conserved with those of the human, Drosophila and yeast homologs
- term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
evidence_type: IMP
original_reference_id: PMID:9729488
qualifier: involved_in
review:
summary: srfA disruption reduces expression of the spore marker spiA and impairs
spore maturation, indicating SrfA regulates the transcription of target genes.
action: ACCEPT
reason: Loss-of-function evidence that SrfA is needed for target-gene (spiA)
expression supports its role in regulation of RNA polymerase II transcription.
supported_by:
- reference_id: PMID:9729488
supporting_text: participates in the regulation of the expression of the
spore-coat marker spiA
- term:
id: GO:0042331
label: phototaxis
evidence_type: IMP
original_reference_id: PMID:11437439
qualifier: acts_upstream_of_or_within
review:
summary: srfA-null strains have a slug-migration defect; phototaxis is a
slug-migration-associated behavior assessed in this study of srfA's developmental
roles. This is a downstream, non-core developmental phenotype of the
transcription factor.
action: KEEP_AS_NON_CORE
reason: SrfA acts upstream of slug behaviors as a transcription factor. The
phototaxis/migration phenotype is a real but indirect developmental role, not
the core molecular function. Experimental IMP annotation retained as non-core.
supported_by:
- reference_id: PMID:11437439
supporting_text: The study of knockout strains revealed that srfA is also
required for proper slug migration
- term:
id: GO:0031154
label: culmination involved in sorocarp development
evidence_type: IEP
original_reference_id: PMID:25887420
qualifier: acts_upstream_of_or_within
review:
summary: This is a genome-wide developmental transcriptome study (Rosengarten et
al. 2015) that profiles thousands of genes but does not specifically discuss
srfA in the available text. The culmination association is an expression-pattern
(IEP) inference that cannot be verified for srfA from this source.
action: UNDECIDED
reason: The cited large-scale transcriptome paper does not mention srfA in the
cached text, so its specific contribution to culmination cannot be verified here.
SrfA's culmination-stage role is separately supported by other references (its
PKA-driven induction and expression in prespore cells at culmination), but this
particular IEP annotation cannot be independently confirmed.
- term:
id: GO:0031154
label: culmination involved in sorocarp development
evidence_type: IMP
original_reference_id: PMID:11437439
qualifier: acts_upstream_of_or_within
review:
summary: SrfA is expressed in a complex pattern that includes strong induction in
spores by the end of culmination, and srfA is required for several developmental
functions. Its role at culmination is a developmental, non-core function
downstream of its transcription-factor activity.
action: KEEP_AS_NON_CORE
reason: Experimental (IMP) annotation of a developmental-stage role. SrfA acts
upstream as a transcription factor; culmination involvement is a non-core
developmental role rather than its core molecular function.
supported_by:
- reference_id: PMID:11437439
supporting_text: the correct spatial and temporal pattern of expression of srfA
is essential for the different functions that this transcription factor plays
in development
- term:
id: GO:0030435
label: sporulation resulting in formation of a cellular spore
evidence_type: IMP
original_reference_id: PMID:14706699
qualifier: acts_upstream_of_or_within
review:
summary: SrfA is required for late events of spore maturation necessary for spore
stability; srfA-null spores are abnormal and lose viability. Sporulation is the
central biological process in which SrfA acts.
action: ACCEPT
reason: Sporulation/spore differentiation is the core developmental process
requiring SrfA, supported by multiple loss-of-function studies.
supported_by:
- reference_id: PMID:14706699
supporting_text: these results suggest that SrfA is involved in late events of
spore maturation necessary for spore stability
- term:
id: GO:0003700
label: DNA-binding transcription factor activity
evidence_type: IMP
original_reference_id: PMID:9729488
qualifier: enables
review:
summary: Experimental (IMP) support for SrfA acting as a DNA-binding transcription
factor, based on the requirement of srfA for target-gene (spiA) expression. The
RNA polymerase II-specific child term (GO:0000981) is the more precise form of
the same activity.
action: ACCEPT
reason: DNA-binding transcription factor activity is the core molecular function of
SrfA and is experimentally supported by its requirement for target-gene
expression.
supported_by:
- reference_id: PMID:9729488
supporting_text: participates in the regulation of the expression of the
spore-coat marker spiA
- term:
id: GO:0005634
label: nucleus
evidence_type: IC
original_reference_id: PMID:9729488
qualifier: located_in
review:
summary: Nuclear localization inferred by curators (IC) from the DNA-binding
transcription factor activity of SrfA. Consistent with the IBA and UniProt
nucleus annotations.
action: ACCEPT
reason: As a MADS-box transcription factor, SrfA acts in the nucleus; the IC
inference is sound and corroborated by independent evidence.
supported_by:
- reference_id: PMID:9729488
supporting_text: A homolog of the Serum Response Factor (SRF) has been isolated
from Dictyostelium discoideum
- term:
id: GO:0030435
label: sporulation resulting in formation of a cellular spore
evidence_type: IMP
original_reference_id: PMID:9729488
qualifier: acts_upstream_of_or_within
review:
summary: srfA disruption causes abnormal spore morphology and loss of viability,
establishing an essential role in sporulation. Duplicate process annotation
supported by the original characterization of the gene.
action: ACCEPT
reason: Sporulation is the core developmental process requiring SrfA; this
loss-of-function evidence directly supports the annotation.
supported_by:
- reference_id: PMID:9729488
supporting_text: This gene plays an essential role in sporulation as its
disruption leads to abnormal spore morphology and loss of viability
- term:
id: GO:0003700
label: DNA-binding transcription factor activity
evidence_type: ISS
original_reference_id: PMID:9729488
qualifier: enables
review:
summary: Sequence-similarity inference of DNA-binding transcription factor activity
from human SRF (UniProtKB:P11831), consistent with the highly conserved MADS-box
domain and the experimental IMP annotation of the same activity.
action: ACCEPT
reason: The conserved MADS-box supports transfer of the DNA-binding
transcription-factor activity from human SRF; this is the core molecular function
of SrfA.
supported_by:
- reference_id: PMID:9729488
supporting_text: The MADS-box region of Dictyostelium SRF (DdSRF) is highly
conserved with those of the human, Drosophila and yeast homologs
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:9729488
title: A Serum Response Factor homolog is required for spore differentiation in
Dictyostelium.
findings:
- statement: DdSRF is the Dictyostelium SRF homolog with a MADS-box highly conserved
with human, Drosophila and yeast SRFs.
supporting_text: The MADS-box region of Dictyostelium SRF (DdSRF) is highly
conserved with those of the human, Drosophila and yeast homologs
- statement: srfA is expressed in prespore and spore cells and is essential for
sporulation; disruption causes abnormal spores and loss of viability.
supporting_text: This gene plays an essential role in sporulation as its
disruption leads to abnormal spore morphology and loss of viability
- statement: SrfA participates in regulating expression of the spore-coat marker
spiA and other maturation genes.
supporting_text: participates in the regulation of the expression of the
spore-coat marker spiA
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Original characterization of srfA; establishes it as an SRF/MADS-box
transcription factor required for spore differentiation. Abstract-only in cache.
- id: PMID:11437439
title: The MADS-box gene srfA is expressed in a complex pattern under the control
of alternative promoters and is essential for different aspects of Dictyostelium
development.
findings:
- statement: srfA is expressed in a complex, cell-type-specific pattern via
alternative promoters across most cell types.
supporting_text: srfA displays a complex temporal and cell type-specific pattern
of expression in Dictyostelium
- statement: srfA is required for proper slug migration in addition to spore
differentiation.
supporting_text: The study of knockout strains revealed that srfA is also
required for proper slug migration
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Establishes expression pattern and additional developmental roles
(slug migration) beyond sporulation. Abstract-only in cache.
- id: PMID:14665466
title: Dictyostelium discoideum developmentally regulated genes whose expression
is dependent on MADS box transcription factor SrfA.
findings:
- statement: SrfA is a MADS-box transcription factor required for spore
differentiation in D. discoideum.
supporting_text: The MADS box transcription factor SrfA is required for spore
differentiation in Dictyostelium discoideum
- statement: Five SrfA-dependent genes were identified that are not expressed in
srfA-null strains.
supporting_text: Five genes whose expression is dependent on SrfA have been
isolated by differential hybridization
- statement: SrfA induces spore-specific genes at the final steps of spore
differentiation, possibly by direct promoter binding.
supporting_text: The regulation of the expression of sig genes by SrfA could be
through direct binding to their promoters, which activates their expression
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Full text available; identifies SrfA-dependent target genes and
supports the positive-regulation transcription-factor role.
- id: PMID:14706699
title: The MADS-box transcription factor SrfA is required for actin cytoskeleton
organization and spore coat stability during Dictyostelium sporulation.
findings:
- statement: srfA-null spores fail to form mature actin rods.
supporting_text: SrfA mutant spores showed the initial stages of rod formation
but no mature rods were found in older spores either in the nucleus or the
cytoplasm
- statement: The spore coat outer layer progressively degrades in srfA mutants,
indicating a late spore-coat stability defect.
supporting_text: the outer layer gets wavier as the spore ages and suffers a
progressive degradation suggesting a late defect in the stability of the spore
coat
- statement: SrfA is involved in late events of spore maturation necessary for
spore stability.
supporting_text: these results suggest that SrfA is involved in late events of
spore maturation necessary for spore stability
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Structural analysis of srfA-null spores; documents actin-rod and
spore-coat phenotypes downstream of the transcription-factor function.
- id: PMID:12204259
title: Regulated expression of the MADS-box transcription factor SrfA mediates
activation of gene expression by protein kinase A during Dictyostelium
sporulation.
findings:
- statement: PKA activation during culmination induces srfA expression in prespore
cells, placing srfA downstream of PKA in spore maturation.
supporting_text: Our results strongly suggest that PKA activation during
culmination leads to the induction of the expression of srfA
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Establishes PKA-dependent regulation of srfA induction at
culmination; contextual background for its developmental role. Abstract-only in
cache.
- id: PMID:25887420
title: Leaps and lulls in the developmental transcriptome of Dictyostelium
discoideum.
findings: []
reference_review:
relevance: LOW
correctness: MISCITED
review_notes: Genome-wide developmental transcriptome study that does not
specifically discuss srfA in the cached full text. It is cited as the IEP source
for a culmination annotation, but srfA cannot be verified from this reference.
core_functions:
- description: SrfA is a MADS-box/SRF-family sequence-specific RNA polymerase II
transcription factor that acts in the nucleus to positively regulate transcription
of a subset of late, prespore/spore-specific genes (e.g. spiA and the
SrfA-dependent sig genes), thereby driving terminal spore differentiation and
maturation during Dictyostelium development.
molecular_function:
id: GO:0000981
label: DNA-binding transcription factor activity, RNA polymerase II-specific
locations:
- id: GO:0005634
label: nucleus
directly_involved_in:
- id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
- id: GO:0030435
label: sporulation resulting in formation of a cellular spore
supported_by:
- reference_id: PMID:14665466
supporting_text: These data are in agreement with the hypothesis that SrfA induces
the expression of a number of spore-specific genes at the final steps of spore
differentiation
- reference_id: PMID:9729488
supporting_text: This gene plays an essential role in sporulation as its
disruption leads to abnormal spore morphology and loss of viability