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

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