Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Accept: nucleus. Reason: FRQ must enter the nucleus to inhibit the White Collar Complex, so nuclear localisation is intrinsic to the negative-feedback step. Electronic here, but well established for this protein.
GO:0005737 cytoplasm	IEA GO_REF:0000002	ACCEPT	Summary: Accept: cytoplasm. Reason: FRQ shuttles, and its cytoplasmic pool is where much of the progressive phosphorylation that sets period length occurs. The term is general, but the dual distribution is real.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: Accept: regulation of DNA-templated transcription. Reason: FRQ regulates transcription indirectly, by inhibiting the WCC rather than by binding DNA itself. The unsigned term is defensible, but a negative-regulation term would be the more accurate statement.
GO:0007623 circadian rhythm	IEA GO_REF:0000002	ACCEPT	Summary: Accept: circadian rhythm. Reason: The defining process for frq: it constitutes the negative arm of the Neurospora clock feedback loop. Correct, though electronic for a gene with extensive direct evidence.
GO:0005515 protein binding	IPI PMID:20807745 VIVID interacts with the WHITE COLLAR complex and FREQUENCY-...	KEEP AS NON CORE	Summary: Protein binding (uninformative MF) reflecting White Collar Complex / clock interactions. Reason: This IPI captures physical interactions within the White Collar Complex or clock; 'protein binding' is uninformative as a molecular function, so kept as non-core.
GO:0005634 nucleus	IDA PMID:38526948 Phosphorylation, disorder, and phase separation govern the b...	ACCEPT	Summary: Accept: nucleus. Reason: FRQ acts in the nucleus as part of the FFC repressor, which is where it engages the WCC. Supporting Evidence: PMID:38526948 The FFC enters the nucleus where it directly inhibits the WCC and thereby downregulates frq expression
GO:0042803 protein homodimerization activity	EXP PMID:38526948 Phosphorylation, disorder, and phase separation govern the b...	ACCEPT	Summary: Accept: protein homodimerization activity (phosphorylation-dependent). Reason: MALS shows the unphosphorylated protein is a dimer; note the activity is conditional — phosphorylation destabilizes the homodimer, so this is not a constitutive property across the circadian cycle. Supporting Evidence: PMID:38526948 Hence, purified np-FRQ dimerizes, whereas phosphorylation destabilizes this association.
GO:0140693 molecular condensate scaffold activity	IDA PMID:38526948 Phosphorylation, disorder, and phase separation govern the b...	ACCEPT	Summary: Accept: molecular condensate scaffold activity. Reason: FRQ phase-separates and, as a condensate, sequesters its FFC partners FRH and CK1 — the scaffolding role the term describes, demonstrated directly in the annotated reference. Supporting Evidence: PMID:38526948 Full-length FRQ undergoes liquid-liquid phase separation (LLPS) to sequester FRH and CK1 and influence CK1 enzymatic activity.
GO:0140694 membraneless organelle assembly	IDA PMID:38526948 Phosphorylation, disorder, and phase separation govern the b...	ACCEPT	Summary: Accept: membraneless organelle assembly. Reason: FRQ forms condensate foci in vivo, so it participates in assembly of a membraneless compartment rather than merely residing in one. Supporting Evidence: PMID:38526948 Live imaging of Neurospora hyphae reveals FRQ foci characteristic of condensates near the nuclear periphery.

Core Functions

Core circadian-clock negative-feedback protein: FRQ represses its White Collar Complex activator to generate the circadian oscillation, and scaffolds molecular condensates as part of clock function; the clock gates rhythmic conidiation.

Molecular Function:

molecular condensate scaffold activity

Directly Involved In:

circadian rhythm

Cellular Locations:

nucleus cytoplasm

Supporting Evidence:

PMID:38526948
Full-length FRQ undergoes liquid-liquid phase separation (LLPS) to sequester FRH and CK1 and influence CK1 enzymatic activity.
PMID:38526948
Live imaging of Neurospora hyphae reveals FRQ foci characteristic of condensates near the nuclear periphery.
PMID:38526948
The FFC enters the nucleus where it directly inhibits the WCC and thereby downregulates frq expression

References

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📚 Additional Documentation

Notes

(frq-notes.md)

frq / frequency (Neurospora crassa) — curation notes

UniProt P19970. Core circadian-clock negative-feedback protein. Neurospora variant, light/clock-gating tier.
- Autoregulatory negative feedback defining the circadian clock. PMID:8128244.
- Forms molecular condensates / membraneless organelles (recent IDA MF GO:0140693/GO:0140694, PMID:38526948). Core MF GO:0140693 molecular condensate scaffold activity; BP circadian rhythm. The clock gates rhythmic (banded) conidiation. Protein-binding IPI kept non-core.

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