id: P0DH90 gene_symbol: FRI product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:3702 label: Arabidopsis thaliana description: >- 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. alternative_records: - id: Q67Z93 relationship: REFERENCE_PROTEOME_LOCUS_COUNTERPART reference_proteome: UP000006548 reviewed_on: '2026-10-19' reason: 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. evidence: - type: PROTEOME_SEARCH description: 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. supported_by: - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: 'target_sequence_count: 39272' - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: 'candidate_count: 6' - type: SEQUENCE_COMPARISON description: '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.' supported_by: - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: |- 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 - type: PROTEOME_MEMBERSHIP description: 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. supported_by: - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: 'primary_in_any_reference_proteome: false' - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: 'alternative_in_reference_proteome: true' - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: 'same_taxon: true' - type: RECORD_HISTORY description: '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.' supported_by: - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: |- entry_date: 11-NOV-2015, entry version 21. proteomes: [] - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: |- entry_date: 12-AUG-2020, entry version 36. proteomes: [] - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: |- entry_date: 24-JAN-2024, entry version 43. proteomes: [] - type: CURATION_CONTEXT description: UniProt directly identifies the inactive Columbia FRI allele and cross-references the complete H51 sequence. supported_by: - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: loss-of-function mutations lead to inactive FRI protein - reference_id: file:ARATH/FRI/FRI-record-evidence.yaml supporting_text: cv. H51 (AC P0DH90) existing_annotations: - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19429606 qualifier: enables supporting_entities: - UniProtKB:O23550 review: summary: >- FRI interacts with FIP2 (FRIGIDA-interacting protein 2) in yeast two-hybrid screens. action: REMOVE 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. supported_by: - reference_id: PMID:19429606 supporting_text: >- 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19429606 qualifier: enables supporting_entities: - UniProtKB:Q8S8K9 review: summary: FRI interacts with FIP1 in yeast two-hybrid screens. action: REMOVE 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. supported_by: - reference_id: PMID:19429606 supporting_text: >- 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. - term: id: GO:0016607 label: nuclear speck evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0186 review: summary: >- Nuclear speckle localization, mapped from the UniProt subcellular location based on YFP:FRI imaging. action: ACCEPT reason: >- Experimentally supported: YFP-FRI forms evenly distributed nuclear speckles, and cold further promotes FRI nuclear condensates. supported_by: - reference_id: PMID:17138694 supporting_text: >- YFP:FRI was dispersed throughout the nucleus, and fluorescence was observed as evenly distributed speckles - reference_id: PMID:34732891 supporting_text: >- Here we show that cold rapidly promotes the formation of FRI nuclear condensates that do not colocalize with an active FLC locus. - term: id: GO:0003713 label: transcription coactivator activity evidence_type: IDA original_reference_id: PMID:21282526 review: 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. action: NEW 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. supported_by: - reference_id: PMID:21282526 supporting_text: >- 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). - reference_id: PMID:21282526 supporting_text: >- SUF4 binds to a cis-element of the FLC promoter, FLX and FES1 have transcriptional activation potential, and FRL1 and FES1 stabilize the complex. - reference_id: PMID:21282526 supporting_text: >- FRI-C recruits a general transcription factor, a TAF14 homolog, and chromatin modification factors, the SWR1 complex and SET2 homolog. - reference_id: PMID:19567704 supporting_text: >- FRI mediates WDR5a enrichment at the FLC locus, leading to increased H3K4me3 and FLC upregulation. - term: id: GO:0045893 label: positive regulation of DNA-templated transcription evidence_type: IMP original_reference_id: PMID:19567704 review: summary: >- FRI up-regulates FLC transcription; fri null alleles in rapid-cycling accessions give low FLC. action: NEW reason: >- FRI participates directly as the scaffold of the FLC activator complex at the promoter. It is not simply required upstream. supported_by: - reference_id: PMID:19567704 supporting_text: >- Here, we show that FRI promotes histone H3 lysine-4 trimethylation (H3K4me3) in FLC to upregulate its expression. - reference_id: PMID:14973192 supporting_text: >- In winter-annual accessions of Arabidopsis, FRI activity blocks flowering through the up-regulation of the floral inhibitor FLOWERING LOCUS C (FLC). - reference_id: PMID:21282526 supporting_text: >- 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). - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:17138694 review: summary: FRI is a nuclear protein. action: NEW reason: Supports the parent compartment of the speckle annotation directly. supported_by: - reference_id: PMID:17138694 supporting_text: >- YFP:FRI was dispersed throughout the nucleus, and fluorescence was observed as evenly distributed speckles references: - id: file:ARATH/FRI/FRI-record-evidence.yaml title: Compact archived record and sequence evidence for P0DH90 - id: GO_REF:0000044 title: >- Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: PMID:19429606 title: >- FRIGIDA delays flowering in Arabidopsis via a cotranscriptional mechanism involving direct interaction with the nuclear cap-binding complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; FRI-CBP20 interaction; FIP1/FIP2 Y2H interactors. - id: PMID:11030654 title: >- Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time. reference_review: relevance: HIGH correctness: VERIFIED review_notes: FRI cloning (Johanson et al. 2000); abstract only. - id: PMID:14973192 title: FRIGIDA-related genes are required for the winter-annual habit in Arabidopsis. reference_review: relevance: HIGH correctness: VERIFIED review_notes: FRL1; FRI up-regulates FLC. - id: PMID:17138694 title: >- SUPPRESSOR OF FRIGIDA4, encoding a C2H2-Type zinc finger protein, represses flowering by transcriptional activation of Arabidopsis FLOWERING LOCUS C. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; FRI-SUF4 interaction and FRI nuclear speckles. - id: PMID:19567704 title: >- Establishment of the winter-annual growth habit via FRIGIDA-mediated histone methylation at FLOWERING LOCUS C in Arabidopsis. reference_review: relevance: HIGH correctness: VERIFIED review_notes: FRI recruits WDR5a/COMPASS-like H3K4me3 to FLC. - id: PMID:21282526 title: >- The FRIGIDA complex activates transcription of FLC, a strong flowering repressor in Arabidopsis, by recruiting chromatin modification factors. reference_review: relevance: HIGH correctness: VERIFIED review_notes: FRI-C scaffold; abstract only. - id: PMID:34732891 title: Cold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression. reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Full text. The paper was the subject of a Matters Arising exchange (Nature 2023, 619:E27-E32; author reply PMID:37438593) and an author correction. The comment was not reviewed here, so the condensate interpretation is used cautiously. core_functions: - description: >- Scaffold/coactivator of the FRI-C transcription activator complex (with SUF4, FLX, FES1, FRL1). It recruits chromatin modifiers and the cap-binding complex to up-regulate FLC, establishing the winter-annual vernalization requirement. molecular_function: id: GO:0003713 label: transcription coactivator activity directly_involved_in: - id: GO:0045893 label: positive regulation of DNA-templated transcription locations: - id: GO:0016607 label: nuclear speck supported_by: - reference_id: PMID:21282526 supporting_text: >- 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). - reference_id: PMID:21282526 supporting_text: >- SUF4 binds to a cis-element of the FLC promoter, FLX and FES1 have transcriptional activation potential, and FRL1 and FES1 stabilize the complex. - reference_id: PMID:21282526 supporting_text: >- FRI-C recruits a general transcription factor, a TAF14 homolog, and chromatin modification factors, the SWR1 complex and SET2 homolog. - reference_id: PMID:19567704 supporting_text: >- FRI mediates WDR5a enrichment at the FLC locus, leading to increased H3K4me3 and FLC upregulation. - reference_id: PMID:19429606 supporting_text: >- Our data suggest that FRI up-regulates FLC expression through a cotranscriptional mechanism involving direct physical interaction with the nuclear CBC with concomitant effects on FLC transcription and splicing. - reference_id: PMID:17138694 supporting_text: >- YFP:FRI was dispersed throughout the nucleus, and fluorescence was observed as evenly distributed speckles suggested_questions: - question: >- 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? - question: >- How does cold-induced partitioning of FRI into condensates relate mechanistically to COOLAIR induction and to the later VIN3-dependent Polycomb nucleation? suggested_experiments: - hypothesis: FRI scaffolding of SUF4 and FLX is necessary and sufficient to activate FLC. description: >- 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.