srfA

UniProt ID: Q54TY7
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene 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 Review

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

Core Functions

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.

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
  • PMID:9729488
    This gene plays an essential role in sporulation as its disruption leads to abnormal spore morphology and loss of viability

References

Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
A Serum Response Factor homolog is required for spore differentiation in Dictyostelium.
  • DdSRF is the Dictyostelium SRF homolog with a MADS-box highly conserved with human, Drosophila and yeast SRFs.
    "The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs"
  • srfA is expressed in prespore and spore cells and is essential for sporulation; disruption causes abnormal spores and loss of viability.
    "This gene plays an essential role in sporulation as its disruption leads to abnormal spore morphology and loss of viability"
  • SrfA participates in regulating expression of the spore-coat marker spiA and other maturation genes.
    "participates in the regulation of the expression of the spore-coat marker spiA"
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.
  • srfA is expressed in a complex, cell-type-specific pattern via alternative promoters across most cell types.
    "srfA displays a complex temporal and cell type-specific pattern of expression in Dictyostelium"
  • srfA is required for proper slug migration in addition to spore differentiation.
    "The study of knockout strains revealed that srfA is also required for proper slug migration"
Dictyostelium discoideum developmentally regulated genes whose expression is dependent on MADS box transcription factor SrfA.
  • SrfA is a MADS-box transcription factor required for spore differentiation in D. discoideum.
    "The MADS box transcription factor SrfA is required for spore differentiation in Dictyostelium discoideum"
  • Five SrfA-dependent genes were identified that are not expressed in srfA-null strains.
    "Five genes whose expression is dependent on SrfA have been isolated by differential hybridization"
  • SrfA induces spore-specific genes at the final steps of spore differentiation, possibly by direct promoter binding.
    "The regulation of the expression of sig genes by SrfA could be through direct binding to their promoters, which activates their expression"
The MADS-box transcription factor SrfA is required for actin cytoskeleton organization and spore coat stability during Dictyostelium sporulation.
  • srfA-null spores fail to form mature actin rods.
    "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"
  • The spore coat outer layer progressively degrades in srfA mutants, indicating a late spore-coat stability defect.
    "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"
  • SrfA is involved in late events of spore maturation necessary for spore stability.
    "these results suggest that SrfA is involved in late events of spore maturation necessary for spore stability"
Regulated expression of the MADS-box transcription factor SrfA mediates activation of gene expression by protein kinase A during Dictyostelium sporulation.
  • PKA activation during culmination induces srfA expression in prespore cells, placing srfA downstream of PKA in spore maturation.
    "Our results strongly suggest that PKA activation during culmination leads to the induction of the expression of srfA"
Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.

📄 View Raw YAML

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