FRI (FRIGIDA) is a plant-specific nuclear coiled-coil protein of Arabidopsis, the founding member of the Frigida family, and the major determinant of natural variation between the winter-annual and rapid-cycling habits. Functional FRI alleles, as in winter-annual accessions such as H51 or Sf-2, up-regulate the floral repressor FLC to levels that block flowering before winter, creating a vernalization requirement. Most rapid-cycling accessions, including Col-0 and Ler, carry independent loss-of-function deletions. FRI has no DNA-binding domain. It acts as a scaffold of the FRI-C transcription activator complex with FRL1, FES1, FLX and the FLC-promoter-binding zinc-finger protein SUF4. It recruits chromatin modifiers (SWR1/H2A.Z exchange, SDG8 H3K36 methylation and a WDR5a-containing COMPASS-like H3K4 methyltransferase) and interacts with the nuclear cap-binding complex (CBP20) to promote co-transcriptional FLC expression. In the cold, FRI quickly partitions into nuclear condensates away from the active FLC locus, lowering FRI occupancy at FLC as a first step in its shutdown.
The preferred accession for this review is P0DH90. These relationships are manually assessed.
REFERENCE PROTEOME LOCUS COUNTERPART · Reviewed 2026-10-19
Reference proteome: UP000006548
Retain P0DH90 as the primary Swiss-Prot accession. UniProt explicitly links active FRI from cv. H51 to the inactive Columbia allele Q67Z93. The reference protein covers only part of the full active sequence; curated cautions attribute inactivity to loss-of-function mutations. This is a same-locus counterpart, not functional equivalence.
MMseqs2 searched 39,272 sequences across UP000006548 at E <= 1e-5 and sensitivity 7.5, returning 6 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 6 returned candidates are retained, with 6 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity.
file:ARATH/FRI/FRI-record-evidence.yaml
target_sequence_count: 39272
file:ARATH/FRI/FRI-record-evidence.yaml
candidate_count: 6
Q67Z93: 311 identities across 609 global-alignment columns (51.0673% identity including gaps), 3 substitutions and 295 gap columns. Query coverage is 51.5599%; target coverage is 100.0%. Sequence similarity is interpreted in the manual rationale. Identity over paired residues is 99.0446% (311/314); gap columns are excluded from this denominator.
file:ARATH/FRI/FRI-record-evidence.yaml
query_length: 609 target_length: 314 alignment_columns: 609 identities: 311 mismatches: 3 gap_columns: 295 identity_percent: 51.0673 query_coverage_percent: 51.5599 target_coverage_percent: 100.0
The primary accession is outside every searched exact-taxon reference proteome. Current UniProt records place Q67Z93 in UP000006548 and give it the same taxon as the primary.
file:ARATH/FRI/FRI-record-evidence.yaml
primary_in_any_reference_proteome: false
file:ARATH/FRI/FRI-record-evidence.yaml
alternative_in_reference_proteome: true
file:ARATH/FRI/FRI-record-evidence.yaml
same_taxon: true
Sampled UniSave observations: 11-NOV-2015, entry version 21.: no Proteomes cross-reference; 12-AUG-2020, entry version 36.: no Proteomes cross-reference; 24-JAN-2024, entry version 43.: no Proteomes cross-reference. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt's motivation.
file:ARATH/FRI/FRI-record-evidence.yaml
entry_date: 11-NOV-2015, entry version 21. proteomes: []
file:ARATH/FRI/FRI-record-evidence.yaml
entry_date: 12-AUG-2020, entry version 36. proteomes: []
file:ARATH/FRI/FRI-record-evidence.yaml
entry_date: 24-JAN-2024, entry version 43. proteomes: []
UniProt directly identifies the inactive Columbia FRI allele and cross-references the complete H51 sequence.
file:ARATH/FRI/FRI-record-evidence.yaml
loss-of-function mutations lead to inactive FRI protein
file:ARATH/FRI/FRI-record-evidence.yaml
cv. H51 (AC P0DH90)
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19429606 FRIGIDA delays flowering in Arabidopsis via a cotranscriptio... | REMOVE | Summary: FRI interacts with FIP2 (FRIGIDA-interacting protein 2) in yeast two-hybrid screens. Reason: GO:0005515 protein binding is uninformative. FIP2 has no identifiable functional domains, and fip mutants do not affect FLC, so the interaction does not point to a specific activity. Removing the generic term does not mean the interaction is false. Supporting Evidence: PMID:19429606 The additional FRI interactors identified in the yeast two-hybrid screens encode novel proteins with no clearly identifiable functional domains, so these do not help to define the biochemical function of any putative complex. |
| GO:0005515 protein binding | IPI PMID:19429606 FRIGIDA delays flowering in Arabidopsis via a cotranscriptio... | REMOVE | Summary: FRI interacts with FIP1 in yeast two-hybrid screens. Reason: Generic protein binding with no functional insight (see FIP2). FRI's informative interactions, with CBP20 and the FRI-C subunits, are captured by the coactivator/scaffold function. Supporting Evidence: PMID:19429606 The additional FRI interactors identified in the yeast two-hybrid screens encode novel proteins with no clearly identifiable functional domains, so these do not help to define the biochemical function of any putative complex. |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear speckle localization, mapped from the UniProt subcellular location based on YFP:FRI imaging. Reason: Experimentally supported: YFP-FRI forms evenly distributed nuclear speckles, and cold further promotes FRI nuclear condensates. Supporting Evidence: PMID:17138694 YFP:FRI was dispersed throughout the nucleus, and fluorescence was observed as evenly distributed speckles PMID:34732891 Here we show that cold rapidly promotes the formation of FRI nuclear condensates that do not colocalize with an active FLC locus. |
| GO:0003713 transcription coactivator activity | IDA PMID:21282526 The FRIGIDA complex activates transcription of FLC, a strong... | NEW | Summary: FRI has no DNA-binding domain. It acts as the scaffold of the FRI-C transcription activator complex, bridging the FLC-promoter-binding zinc-finger protein SUF4 with FLX/FES1, and recruits chromatin modifiers (SWR1 complex, SDG8/SET2, COMPASS-like WDR5a) and the nuclear cap-binding complex to activate FLC. Reason: This is the best-supported molecular function of FRI. FRI itself does the work of coactivation by assembling the activator complex; sequence-specific DNA binding is supplied by SUF4. Supporting Evidence: PMID:21282526 Here, we report that FRI acts as a scaffold protein interacting with FRL1, FES1, SUF4, and FLX to form a transcription activator complex (FRI-C). PMID:21282526 SUF4 binds to a cis-element of the FLC promoter, FLX and FES1 have transcriptional activation potential, and FRL1 and FES1 stabilize the complex. PMID:21282526 FRI-C recruits a general transcription factor, a TAF14 homolog, and chromatin modification factors, the SWR1 complex and SET2 homolog. PMID:19567704 FRI mediates WDR5a enrichment at the FLC locus, leading to increased H3K4me3 and FLC upregulation. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:19567704 Establishment of the winter-annual growth habit via FRIGIDA-... | NEW | Summary: FRI up-regulates FLC transcription; fri null alleles in rapid-cycling accessions give low FLC. Reason: FRI participates directly as the scaffold of the FLC activator complex at the promoter. It is not simply required upstream. Supporting Evidence: PMID:19567704 Here, we show that FRI promotes histone H3 lysine-4 trimethylation (H3K4me3) in FLC to upregulate its expression. PMID:14973192 In winter-annual accessions of Arabidopsis, FRI activity blocks flowering through the up-regulation of the floral inhibitor FLOWERING LOCUS C (FLC). PMID:21282526 Here, we report that FRI acts as a scaffold protein interacting with FRL1, FES1, SUF4, and FLX to form a transcription activator complex (FRI-C). |
| GO:0005634 nucleus | IDA PMID:17138694 SUPPRESSOR OF FRIGIDA4, encoding a C2H2-Type zinc finger pro... | NEW | Summary: FRI is a nuclear protein. Reason: Supports the parent compartment of the speckle annotation directly. Supporting Evidence: PMID:17138694 YFP:FRI was dispersed throughout the nucleus, and fluorescence was observed as evenly distributed speckles |
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Download this section (compressed HTML)Q: What is the structural basis of FRI scaffolding (coiled-coil versus disordered C-terminus), and is FRI-C a stable stoichiometric complex or a dynamic condensate?
Q: How does cold-induced partitioning of FRI into condensates relate mechanistically to COOLAIR induction and to the later VIN3-dependent Polycomb nucleation?
Experiment: Tether FRI (or FRI deletion variants) to the FLC promoter in fri suf4 backgrounds using a dCas9 fusion. Measure FLC transcription, H3K4me3/H3K36me3 and H2A.Z, and test which FRI-C partners are required.
Hypothesis: FRI scaffolding of SUF4 and FLX is necessary and sufficient to activate FLC.
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