fluG

UniProt ID: P38094
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Review Status: DRAFT
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Gene Description

fluG encodes a cytoplasmic protein related to prokaryotic glutamine synthetase I (GSI) that is the upstream-most activator of asexual sporulation (conidiation) in Aspergillus nidulans. FluG is required for the production/accumulation of a small extracellular developmental signal; fluG-null strains fail to conidiate and grow as undifferentiated 'fluffy' colonies. Signalling from FluG relieves repression by SfgA and thereby permits induction of the Flb factors and the master regulator brlA. Although FluG belongs to the glutamine synthetase family, its role is signal biosynthesis; a classical in vivo glutamine synthetase activity has been experimentally excluded rather than merely left undemonstrated (A. nidulans glutamine synthesis is provided by GlnA). FluG also influences secondary metabolism (sterigmatocystin).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003824 catalytic activity
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Generic catalytic-activity term (uninformative).
Reason: Root-level electronic MF; FluG's activity is GSI-related, so this term adds no specific information.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: Accept: cytoplasm.
Reason: Consistent with FluG's role as the upstream-most activator of conidiation (extracellular signal production).
GO:0016787 hydrolase activity
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Likely incorrect MF: FluG is GSI-related (a ligase), not a hydrolase.
Reason: FluG belongs to the glutamine synthetase family (ligase, EC 6.3.1.-); the electronic 'hydrolase activity' mapping is inconsistent with this and is likely an incorrect InterPro2GO assignment.
GO:0010913 regulation of sterigmatocystin biosynthetic process
IMP
PMID:9305634
Aspergillus sporulation and mycotoxin production both requir...
KEEP AS NON CORE
Summary: Non-core regulatory role in sterigmatocystin biosynthesis.
Reason: FluG affects ST biosynthesis as an upstream regulator; a pleiotropic, non-core role.
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.
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: FluG regulates ST, it is not part of the biosynthetic pathway.
Reason: FluG influences sterigmatocystin only as an upstream regulator; captured precisely by GO:0010913/GO:0010914.
GO:0048315 conidium formation
IMP
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: Core process. FluG is required for conidium formation.
Reason: fluG-null strains are aconidial (fluffy); FluG is essential for the induction of conidiation.
Supporting Evidence:
PMID:7926755
Mutations in the Aspergillus nidulans fluG gene disrupt the programmed induction of asexual sporulation and result in formation of fluffy colonies that are characterized by undifferentiated cotton-like masses of vegetative cells.
PMID:7926755
We show that the fluG mutant phenotype is suppressed when fluG mutant colonies are grown next to wild-type colonies even if the two strains are separated by dialysis membrane with a 6000- to 8000-dalton pore size.
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: Broader parent of the ST-regulation role; non-core.
GO:0000905 sporocarp development involved in asexual reproduction
IMP
PMID:1508186
Isolation of a gene required for programmed initiation of de...
ACCEPT
Summary: Core process. FluG is required for conidiophore (asexual sporocarp) development.
Reason: FluG is required for development of the conidiophore, the asexual reproductive structure.
GO:0001896 autolysis
IMP
PMID:19486415
Asexual sporulation signalling regulates autolysis of Asperg...
KEEP AS NON CORE
Summary: Non-core downstream effect on autolysis.
Reason: Asexual-sporulation signalling (including fluG) modulates autolysis; downstream/non-core.
GO:0005737 cytoplasm
IDA
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: Accept: cytoplasm.
Reason: Consistent with FluG's role as the upstream-most activator of conidiation (extracellular signal production).
GO:0004356 glutamine synthetase activity
IMP NOT
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: NOT annotation. FluG does NOT have glutamine synthetase activity: despite belonging to the GS family and carrying a GS-like domain required for signal production, the mutant analysis EXCLUDED a physiological glutamine synthetase activity rather than leaving it undemonstrated.
Reason: A well-supported experimental negative, and the annotation should be read as such. The AspGD row is NOT|enables (IMP, PMID:7926755): fluG mutants are not glutamine auxotrophs and the GS-family similarity does not translate into the canonical activity. Accepting the negation is the correct action - KEEP_AS_NON_CORE would imply retaining a weak positive claim, which inverts what the annotation asserts. FluG's GS-like domain instead synthesises a distinct small diffusible developmental signal.
Supporting Evidence:
PMID:7926755
We consider it unlikely that FluG functions in synthesis of glutamine but instead propose that FluG functions as a GSI-related enzyme in synthesizing an extracellular signal directing asexual sporulation
GO:0075307 positive regulation of conidium formation
IMP
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: Core process. FluG positively regulates conidium formation.
Reason: As the upstream-most activator, FluG is a positive regulator of conidiation.
Supporting Evidence:
PMID:7926755
Mutations in the Aspergillus nidulans fluG gene disrupt the programmed induction of asexual sporulation and result in formation of fluffy colonies that are characterized by undifferentiated cotton-like masses of vegetative cells.
PMID:7926755
We show that the fluG mutant phenotype is suppressed when fluG mutant colonies are grown next to wild-type colonies even if the two strains are separated by dialysis membrane with a 6000- to 8000-dalton pore size.
GO:0075307 positive regulation of conidium formation
IGI
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: Core process. FluG positively regulates conidium formation (genetic interaction).
Reason: Genetic-interaction evidence consistent with FluG as a positive regulator of conidiation.
GO:1901704 L-glutamine biosynthetic process
IMP NOT
PMID:7926755
The Aspergillus nidulans fluG gene is required for productio...
ACCEPT
Summary: NOT annotation. FluG is NOT involved in L-glutamine biosynthesis - the process counterpart of the excluded glutamine synthetase activity above.
Reason: Same experimental negative as GO:0004356, on the process side. The AspGD row is NOT|acts_upstream_of_or_within (IMP, PMID:7926755). Accepting the negation records what was ruled out; KEEP_AS_NON_CORE would misread the annotation as a retained weak positive.
Supporting Evidence:
PMID:7926755
We consider it unlikely that FluG functions in synthesis of glutamine but instead propose that FluG functions as a GSI-related enzyme in synthesizing an extracellular signal directing asexual sporulation

Core Functions

Upstream-most activator of conidiation: FluG, a cytoplasmic glutamine-synthetase-I-related protein, is required for production of the extracellular developmental signal that (by relieving SfgA repression) triggers the Flb->BrlA conidiation cascade. A classical glutamine synthetase activity is not asserted as its core function.

Supporting Evidence:
  • PMID:7926755
    Mutations in the Aspergillus nidulans fluG gene disrupt the programmed induction of asexual sporulation and result in formation of fluffy colonies that are characterized by undifferentiated cotton-like masses of vegetative cells.
  • PMID:7926755
    We show that the fluG mutant phenotype is suppressed when fluG mutant colonies are grown next to wild-type colonies even if the two strains are separated by dialysis membrane with a 6000- to 8000-dalton pore size.
  • file:EMENI/fluG/fluG-uniprot.txt
    May function as a GSI-related enzyme in synthesizing a small

References

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Notes

(fluG-notes.md)

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