frq (frequency) encodes the central negative-feedback component of the Neurospora crassa circadian clock. FRQ, activated by the White Collar Complex, feeds back to inhibit WCC activity, generating the ~22 h oscillation that gates rhythmic (banded) conidiation. FRQ is an intrinsically disordered protein that homodimerizes and forms molecular condensates (membraneless organelles) as part of clock function.
| 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 with FRH (FRQ-interacting RNA helicase, Q873J5), the partner with which FRQ forms the FFC repressor complex of the clock negative arm. Reason: The WITH/FROM partner is FRH. The FRQ-FRH interaction is real and central to clock negative feedback (FRQ binds FRH via its FFD domain and positions it near CK1 in the FFC), but 'protein binding' names no activity. The informative statement about FRQ's molecular role is captured by the condensate-scaffold annotation; this row is retained as non-core interaction evidence. Supporting Evidence: PMID:20807745 FREQUENCY-interacting RNA helicase (FRH), a component that complexes with FRQ to mediate negative feedback control in Neurospora PMID:38526948 Translated FRQ binds to FRH via its FFD domain and to CK1 via its two FCD domains (1 and 2) to form the repressive FFC |
| 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. |
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