flbA

UniProt ID: P38093
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Review Status: DRAFT
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Gene Description

flbA encodes a Regulator of G-protein Signaling (RGS) domain protein that antagonizes FadA (G-alpha) signaling in Aspergillus nidulans, stimulating GTP hydrolysis to switch off proliferation signaling and thereby license asexual sporulation. flbA loss gives fluffy, aconidial colonies with low brlA; flbA overexpression activates brlA and premature development. FlbA also positively influences sterigmatocystin biosynthesis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005096 GTPase activator activity
IBA
GO_REF:0000033
ACCEPT
Summary: Accept: GTPase activator activity.
Reason: The defining molecular function of an RGS-domain protein: FlbA accelerates GTP hydrolysis on FadA, returning it to the inactive GDP state. This is FlbA's core function, and the reason loss of flbA gives an aconidial, proliferative phenotype.
GO:0009898 cytoplasmic side of plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Accept: cytoplasmic side of plasma membrane.
Reason: RGS proteins act where their G-alpha target is, at the inner leaflet of the plasma membrane. The location is appropriately specific and biologically expected, though it is not directly imaged in the studies cited here.
GO:0045744 negative regulation of G protein-coupled receptor signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Accept: negative regulation of G protein-coupled receptor signaling pathway.
Reason: Signed and pathway-specific: FlbA antagonises FadA signalling, and that antagonism is what licenses conidiation. The most informative process term in this set.
GO:0035556 intracellular signal transduction
IEA
GO_REF:0000002
ACCEPT
Summary: Accept: intracellular signal transduction.
Reason: General parent term. Correct, but far less informative than the negative-regulation-of-GPCR-signalling call above.
GO:0010914 positive regulation of sterigmatocystin biosynthetic process
IMP
PMID:9305634
Aspergillus sporulation and mycotoxin production both requir...
KEEP AS NON CORE
Summary: Non-core positive regulation of ST biosynthesis.
Reason: FlbA influences ST via its effect on G-protein signaling; non-core.
GO:0010914 positive regulation of sterigmatocystin biosynthetic process
IMP
PMID:9339347
Dominant mutations affecting both sporulation and sterigmato...
KEEP AS NON CORE
Summary: Non-core positive regulation of ST biosynthesis (duplicate).
Reason: Pleiotropic secondary-metabolism regulatory role.
GO:0045461 sterigmatocystin biosynthetic process
IMP
PMID:9305634
Aspergillus sporulation and mycotoxin production both requir...
MARK AS OVER ANNOTATED
Summary: Over-annotated: regulator of sterigmatocystin, not part of the biosynthetic pathway.
Reason: This subunit influences sterigmatocystin only via G-protein signaling (regulatory); the biosynthetic-process annotation overstates the role. The regulation term is more accurate.
GO:0045574 sterigmatocystin catabolic process
IMP
PMID:9339347
Dominant mutations affecting both sporulation and sterigmato...
MARK AS OVER ANNOTATED
Summary: Likely spurious: 'sterigmatocystin catabolic process' is inconsistent with FlbA's positive-regulatory role in ST biosynthesis.
Reason: FlbA positively regulates ST biosynthesis (GO:0010914); an ST-catabolic-process annotation contradicts this and is likely a curation artifact of the acts_upstream_of_or_within qualifier. Flagged for review.
GO:0048315 conidium formation
IMP
PMID:7830576
Overexpression of flbA, an early regulator of Aspergillus as...
ACCEPT
Summary: Core process. FlbA is required for conidium formation.
Reason: flbA-null strains are aconidial (fluffy, low brlA); FlbA is required for conidiation.
Supporting Evidence:
PMID:8895563
flbA encodes an Aspergillus nidulans RGS (regulator of G protein signaling) domain protein that is required for control of mycelial proliferation and activation of asexual sporulation
GO:1900376 regulation of secondary metabolite biosynthetic process
IMP
PMID:9339347
Dominant mutations affecting both sporulation and sterigmato...
KEEP AS NON CORE
Summary: Non-core secondary-metabolite regulatory role.
Reason: Regulatory reach over secondary metabolism; non-core.
GO:0006357 regulation of transcription by RNA polymerase II
IMP
PMID:21624998
Regulation of conidiation by light in Aspergillus nidulans.
KEEP AS NON CORE
Summary: Indirect effect on transcription (via signaling).
Reason: FlbA is an RGS protein, not a transcription factor; its effect on brlA transcription is indirect (relieving G-protein repression). Kept non-core.
GO:0035556 intracellular signal transduction
IMP
PMID:7830576
Overexpression of flbA, an early regulator of Aspergillus as...
ACCEPT
Summary: Accept: intracellular signal transduction.
Reason: flbA overexpression activates brlA and sporulation, which is a signalling readout. The term is general, but the mutational evidence that FlbA acts within a signalling pathway is genuine.
GO:0030436 asexual sporulation
IMP
PMID:9305634
Aspergillus sporulation and mycotoxin production both requir...
ACCEPT
Summary: Core process. FlbA is required for asexual sporulation.
Reason: FlbA attenuation of FadA signaling is required for asexual sporulation.
Supporting Evidence:
PMID:7830576
We have identified a gene called flbA (for fluffy low brlA expression) that is required for initiation of A. nidulans conidiophore development.
PMID:7830576
Overexpression of flbA using an inducible promoter resulted in misscheduled expression of brlA in vegetative cells and caused hyphal tips to differentiate into spore-producing structures.
GO:0075306 regulation of conidium formation
IMP
PMID:7830576
Overexpression of flbA, an early regulator of Aspergillus as...
ACCEPT
Summary: Core process. FlbA regulates conidium formation.
Reason: FlbA controls the timing/onset of conidiation by antagonizing G-protein proliferation signaling.
Supporting Evidence:
PMID:8895563
flbA encodes an Aspergillus nidulans RGS (regulator of G protein signaling) domain protein that is required for control of mycelial proliferation and activation of asexual sporulation.

Core Functions

RGS-domain attenuator of G-protein signaling: FlbA stimulates FadA GTP hydrolysis to switch off proliferation signaling, which is required to license brlA induction and asexual sporulation.

Supporting Evidence:
  • PMID:8895563
    flbA encodes an Aspergillus nidulans RGS (regulator of G protein signaling) domain protein that is required for control of mycelial proliferation and activation of asexual sporulation
  • PMID:7830576
    We have identified a gene called flbA (for fluffy low brlA expression) that is required for initiation of A. nidulans conidiophore development.
  • PMID:7830576
    Overexpression of flbA using an inducible promoter resulted in misscheduled expression of brlA in vegetative cells and caused hyphal tips to differentiate into spore-producing structures.

References

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Notes

(flbA-notes.md)

flbA (Aspergillus nidulans) β€” curation notes

UniProt P38093 (FLBA_EMENI). RGS protein; repressive gating tier (attenuates FadA).
- RGS domain protein antagonizing FadA to block proliferation and allow development. PMID:8895563. Overexpression activates brlA prematurely PMID:7830576.
- Core MF GO:0005096 GTPase activator activity. GO:0045461 ST biosynthetic process over-annotation; GO:0045574 sterigmatocystin catabolic process flagged likely-spurious (contradicts FlbA's positive-regulatory role in ST biosynthesis).

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