sfgA

UniProt ID: Q3I5F3
Organism: Emericella nidulans
Review Status: DRAFT
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Gene Description

sfgA (suppressor of fluG) encodes a nuclear Gal4-type Zn(II)2Cys6 binuclear-cluster DNA-binding protein that acts as a negative regulator of asexual sporulation (conidiation) and sterigmatocystin production in Aspergillus nidulans. Loss-of-function sfgA mutations bypass the requirement for fluG in both processes, and overexpression of sfgA inhibits conidiation and delays conidiation- and ST-specific gene expression, showing that FluG acts by removing SfgA-imposed repression rather than by direct activation. Genetically SfgA functions downstream of FluG and upstream of the transcriptional activators FlbD, FlbC, FlbB and BrlA that drive normal conidiophore development.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000976 transcription cis-regulatory region binding
IEA
GO_REF:0000118
ACCEPT
Summary: Accept: transcription cis-regulatory region binding.
Reason: Zn(II)2Cys6 binuclear-cluster factors bind upstream activating and repressing sequences, so the prediction fits SfgA's domain. No SfgA DNA-binding assay is cited in this review, so the row rests on the domain call.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IEA
GO_REF:0000002
ACCEPT
Summary: Accept: DNA-binding transcription factor activity, RNA polymerase II-specific.
Reason: Pol II-specific TF activity predicted from the binuclear-cluster domain, and consistent with SfgA acting as a repressor whose removal is what permits FluG-dependent development.
GO:0003677 DNA binding
IEA
GO_REF:0000104
ACCEPT
Summary: Accept: DNA binding.
Reason: Unsigned keyword-level parent of the terms above; uninformative on its own.
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000118
ACCEPT
Summary: Accept: DNA-binding transcription factor activity.
Reason: General TF term, subsumed by the Pol II-specific call; kept as its parent.
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Accept: nucleus.
Reason: Expected compartment for a sequence-specific DNA-binding regulator, and the ARBA rule behind this call is recorded as the SUBCELLULAR LOCATION in the UniProt entry (sfgA-uniprot.txt:24). Note this remains a prediction - the primary sfgA paper is genetic and does not image SfgA localization.
GO:0006351 DNA-templated transcription
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: Borderline: SfgA regulates transcription rather than catalyzing it.
Reason: 'DNA-templated transcription' implies performing transcription; for a TF the regulation terms are preferred.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000120
ACCEPT
Summary: Accept: regulation of DNA-templated transcription.
Reason: Generic unsigned process parent. SfgA's characterised role is repression relieved by FluG signalling, so a signed negative-regulation term would be more informative than this one.
GO:0008270 zinc ion binding
IEA
GO_REF:0000002
ACCEPT
Summary: Accept: zinc ion binding.
Reason: The Gal4-type Zn(II)2Cys6 binuclear cluster is a zinc-coordinating fold by definition, and the motif is identified in SfgA directly (PMID:16387865) rather than only inferred from InterPro.
Supporting Evidence:
PMID:16387865
novel protein with the Gal4-type Zn(II) 2 Cys 6 binuclear cluster DNA-binding motif at the N terminus
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000118
MARK AS OVER ANNOTATED
Summary: Direction-specific term contradicted by the characterized biology; SfgA is a repressor, not an activator.
Reason: This is an IEA:TreeGrafter propagation from the PTHR37534 zinc-cluster family (whose named member is the transcriptional *activator* Uga3), not an SfgA-specific inference. The primary characterization of sfgA shows the opposite direction - loss of sfgA bypasses fluG and derepresses conidiation, and sfgA overexpression inhibits it - so a positive-regulation term over-propagates the family's activator role onto a repressor. The direction-neutral GO:0006355 already retained here covers what is safely supportable; if a directional MF is wanted, GO:0001227 (DNA-binding transcription repressor activity, RNA polymerase II-specific) would be the correctly signed term.
Supporting Evidence:
PMID:16387865
In accordance with the proposed regulatory role of SfgA, overexpression of sfgA inhibited conidiation and delayed/reduced expression of conidiation- and ST-specific genes.
GO:0075308 negative regulation of conidium formation
IMP
PMID:16387865
FluG-dependent asexual development in Aspergillus nidulans o...
NEW
Summary: Proposed new annotation. The characterized role of SfgA - the one thing GOA does not capture - is repression of conidiation; deletion and 31 other loss-of-function sfgA alleles bypass the requirement for fluG in conidiation, and sfgA overexpression inhibits it.
Reason: GOA holds only electronic, generic zinc-cluster transcription-factor terms for SfgA. This IMP-supported directional process term is the term the primary literature establishes, and it is already used for the other conidiation repressors in this module (velB, sfaD).
Supporting Evidence:
PMID:16387865
Deletion (Ξ”) and 31 other loss-of-function sfgA mutations bypassed the need for fluG in conidiation and production of ST.
PMID:16387865
In accordance with the proposed regulatory role of SfgA, overexpression of sfgA inhibited conidiation and delayed/reduced expression of conidiation- and ST-specific genes.

Core Functions

Nuclear Gal4-type Zn(II)2Cys6 binuclear-cluster DNA-binding protein acting as a negative regulator of conidiation: SfgA represses asexual development and sterigmatocystin production, and FluG-dependent signalling relieves that repression to permit conidiophore development.

Supporting Evidence:
  • PMID:16387865
    we unveiled that the FluG-dependent activation of asexual development in the model fungus A. nidulans requires removal of negative regulation imposed by the novel protein SfgA
  • PMID:16387865
    In accordance with the proposed regulatory role of SfgA, overexpression of sfgA inhibited conidiation and delayed/reduced expression of conidiation- and ST-specific genes.
  • file:EMENI/sfgA/sfgA-uniprot.txt
    Zn(2)-C6 fungal-type DNA-binding domain

References

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Notes

(sfgA-notes.md)

sfgA (Aspergillus nidulans) β€” curation notes

UniProt Q3I5F3 (SfgA). Zn(II)2Cys6 (zinc-cluster) transcription factor; negative
regulator of conidiation. Repressive input of the upstream-activation tier.

  • Zn(II)2Cys6 DNA-binding domain (UniProt: "Zn(2)-C6 fungal-type DNA-binding domain").
  • Suppressor of fluG: acts downstream of FluG and upstream of the Flb activators to
    repress conidiation until FluG signalling relieves the repression (literature role;
    NOT yet captured in GOA β€” all current GOA annotations are electronic/generic TF terms).
  • Core MF GO:0003700 (from the zinc-cluster domain). GO:0006351 DNA-templated
    transcription kept non-core (TF regulates rather than catalyzes transcription).

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