id: Q67XX3 gene_symbol: JMJ22 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:3702 label: Arabidopsis thaliana description: >- JMJ22 (JUMONJI 22, At5g06550) is a nuclear Fe(II)/2-oxoglutarate-dependent JmjC-domain protein with an N-terminal F-box, belonging to the JMJD6/JMJD8-related PANTHER family PTHR12480 (subfamily SF21). It acts as a histone arginine demethylase that removes the repressive H4R3me2 mark. Its expression is repressed in darkness or far-red light by the zinc-finger protein SOMNUS and released when phytochrome B is activated by red light. Together with its paralog JMJ20, with which it is genetically redundant, JMJ22 then demethylates histone arginines at the gibberellin biosynthesis genes GA3ox1 and GA3ox2. This raises bioactive gibberellin levels and promotes light-induced seed germination. JMJ22 also has a role that JMJ20 does not share: loss-of-function alleles partially suppress the dwarf phenotype of the thermospermine-deficient acl5 mutant and stabilise mRNAs of the SAC51 family. The mechanism of that role is unknown. No DNA-binding domain is present, and the F-box has not been shown to work in an SCF ubiquitin ligase. alternative_products: - name: '1' id: Q67XX3-1 - name: '2' id: Q67XX3-2 sequence_note: VSP_024322 existing_annotations: - term: id: GO:0000976 label: transcription cis-regulatory region binding evidence_type: IPI original_reference_id: PMID:25533953 qualifier: enables supporting_entities: - AGI_LocusCode:AT5G49720 review: summary: >- This comes from a high-throughput yeast one-hybrid (Y1H) screen of secondary cell wall gene promoters against a library of transcription factor clones. JMJ22 was recovered as binding the KOR1 (AT5G49720) promoter. JMJ22 is not discussed in the main text, and the interaction was not validated. action: MARK_AS_OVER_ANNOTATED reason: >- JMJ22 has only an F-box and a JmjC/cupin demethylase domain, with no recognisable DNA-binding domain. Its characterised function is enzymatic, at chromatin (H4R3me2 removal at GA3ox1/GA3ox2). A single unvalidated Y1H hit from a screen that is prone to false positives is weak support for cis-regulatory DNA binding as an enabled molecular function. I do not REMOVE it, because the Y1H readout is real data, but it should not be read as evidence that JMJ22 is a transcription factor. supported_by: - reference_id: PMID:25533953 supporting_text: against a library of 1,664 full-length Arabidopsis transcription factors - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Histone demethylase that demethylates 'Arg-3' (H4R3me) of histone H4 with a specific activity for H4R3me2 - term: id: GO:0000987 label: cis-regulatory region sequence-specific DNA binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - AGI_LocusCode:AT5G06550 - PANTHER:PTN001753861 review: summary: >- PAINT IBD at PTN001753861 (PTHR12480). The only seed is JMJ22's own IDA from Cho et al. 2012. action: MARK_AS_OVER_ANNOTATED reason: >- JMJ22 appearing as the donor of its own IBA is expected, not circular. The problem is the underlying claim. JMJ22 lacks a DNA-binding domain, and the demethylase action at GA3ox1/GA3ox2 described by Cho et al. ("at GA3ox1/GA3ox2") is chromatin occupancy, not sequence-specific DNA recognition. This row matches the IDA row it was propagated from (MARK_AS_OVER_ANNOTATED). Because the term is the only MF that PAINT placed at this node, transfers to SF21 orthologs (for example wheat) should not be read as evidence of TF-like DNA binding. propagation_review: root_cause: TERM_SCOPING_PROBLEM failure_modes: - ROLE_CONFLATION source_entities: - source_id: PANTHER:PTN001753861 source_label: PTN001753861 source_status: SOURCE_WEAK_OR_INFERRED comment: >- The IBD for GO:0000987 is seeded only by the JMJ22 (AT5G06550) IDA from Cho et al. 2012. The underlying observation is chromatin-level action at GA3ox1/GA3ox2 by a JmjC demethylase that has no DNA-binding domain, and the sequence-specific DNA-binding MF over-states it. The histone demethylase activity from the same donor was not placed at this node. supported_by: - reference_id: PMID:22483719 supporting_text: removal of repressive histone arginine methylations at GA3ox1/GA3ox2 - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Histone demethylase that demethylates 'Arg-3' (H4R3me) of histone H4 with a specific activity for H4R3me2 - term: id: GO:0000987 label: cis-regulatory region sequence-specific DNA binding evidence_type: IDA original_reference_id: PMID:22483719 qualifier: enables review: summary: >- TAIR IDA from Cho et al. 2012. The cached record is abstract-only, and the abstract places JMJ22's action at the GA3ox1/GA3ox2 loci; the paper's MeSH terms list chromatin immunoprecipitation and EMSA. The assay behind this annotation could not be inspected. action: MARK_AS_OVER_ANNOTATED reason: >- Occupancy of the GA3ox1/GA3ox2 regulatory regions by JMJ22 is consistent with its role as a histone arginine demethylase acting there. However, the protein (F-box plus JmjC) has no sequence-specific DNA-binding domain, and the abstract says JMJ22 acts by removing histone methylation, not by recognising a DNA sequence. Most likely JMJ22 is recruited to these loci, so "sequence-specific DNA binding" over-states the molecular function. The full text was not readable, so I flag the row as an over-annotation rather than removing it. supported_by: - reference_id: PMID:22483719 supporting_text: removal of repressive histone arginine methylations at GA3ox1/GA3ox2 - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - AGI_LocusCode:AT5G06550 - PANTHER:PTN001753861 - UniProtKB:Q386V9 - UniProtKB:Q96S16 review: summary: >- PAINT IBD at PTN001753861, seeded by JMJ22 itself and two other family members. action: ACCEPT reason: >- This agrees with the experimental nuclear localisation of JMJ22 and with its chromatin function as a histone demethylase. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22483719}.' - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:22483719 qualifier: located_in review: summary: Experimental nuclear localisation of JMJ22 (Cho et al. 2012, curated by UniProt and TAIR). action: ACCEPT reason: Nuclear localisation is required for its role in demethylating histone H4R3me2 at target loci. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22483719}.' - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0191 review: summary: UniProt subcellular location mapping, which rests on the experimental IDA. action: ACCEPT reason: This is consistent with the experimental nuclear localisation. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22483719}.' - term: id: GO:0005634 label: nucleus evidence_type: ISM original_reference_id: GO_REF:0000122 qualifier: located_in review: summary: AtSubP sequence-based localisation prediction. action: ACCEPT reason: The prediction agrees with the experimental nuclear localisation. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22483719}.' - term: id: GO:0010030 label: positive regulation of seed germination evidence_type: IGI original_reference_id: PMID:22483719 qualifier: acts_upstream_of_or_within supporting_entities: - AGI_LocusCode:AT5G63080 review: summary: >- This genetic interaction with JMJ20 (AT5G63080) rests on the jmj20 jmj22 double mutant, which has reduced germination after phyB activation by a red-light pulse. action: ACCEPT reason: >- This is the best-established biological role of JMJ22. JMJ20 and JMJ22 act redundantly, so the phenotype is seen in the double mutant. JMJ22 contributes directly by demethylating H4R3me2 at GA3ox1/GA3ox2, which raises GA levels that promote germination. supported_by: - reference_id: PMID:22483719 supporting_text: JMJ22, act redundantly as positive regulators of seed germination - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:DISRUPTION PHENOTYPE"] supporting_text: Plants missing both JMJ20 and JMJ22 exhibit reduced seed germination efficiency during PHYB activation after red light (R)-pulse treatment - term: id: GO:0010030 label: positive regulation of seed germination evidence_type: IMP original_reference_id: PMID:22483719 qualifier: involved_in review: summary: Mutant analysis showing that JMJ22 promotes light-induced seed germination (Cho et al. 2012). action: ACCEPT reason: >- This is consistent with the IGI row. JMJ22 promotes germination downstream of phyB by derepressing the GA biosynthesis genes GA3ox1/GA3ox2. supported_by: - reference_id: PMID:22483719 supporting_text: JMJ22, act redundantly as positive regulators of seed germination - term: id: GO:0010099 label: regulation of photomorphogenesis evidence_type: IMP original_reference_id: PMID:22483719 qualifier: involved_in review: summary: >- TAIR IMP from Cho et al. 2012. The abstract describes only phyB-dependent seed germination. Any seedling photomorphogenesis assay would be in the full text, which was not readable. action: KEEP_AS_NON_CORE reason: >- Light-induced germination downstream of phyB is a light-controlled developmental response, so the curator's annotation is plausible. I defer to the curator, who read the full text. The term is peripheral to the core chromatin and germination function and is better captured by positive regulation of seed germination. supported_by: - reference_id: PMID:22483719 supporting_text: upon PHYB activation, JMJ20/JMJ22 are derepressed - term: id: GO:0010114 label: response to red light evidence_type: IEP original_reference_id: PMID:22483719 qualifier: involved_in review: summary: >- JMJ22 expression is induced by red light: SOMNUS represses it when phyB is inactive, and the repression is lifted when phyB is activated. action: KEEP_AS_NON_CORE reason: >- The red-light induction is well documented, but it describes how JMJ22 is regulated rather than what JMJ22 does. Non-core. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:INDUCTION"] supporting_text: Repressed by the zinc-finger protein SOMNUS when PHYB is inactive in far-red (FR) conditions, but derepressed upon PHYB activation by red light (R). - term: id: GO:0010114 label: response to red light evidence_type: IMP original_reference_id: PMID:22483719 qualifier: involved_in review: summary: The jmj20 jmj22 double mutant has reduced germination after a red-light pulse. action: KEEP_AS_NON_CORE reason: >- JMJ22 links red-light/phyB perception to GA biosynthesis in seeds, so the term is true. The specific output is captured by positive regulation of seed germination. supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:DISRUPTION PHENOTYPE"] supporting_text: Plants missing both JMJ20 and JMJ22 exhibit reduced seed germination efficiency during PHYB activation after red light (R)-pulse treatment - term: id: GO:0010476 label: gibberellin mediated signaling pathway evidence_type: IMP original_reference_id: PMID:22483719 qualifier: acts_upstream_of_or_within_positive_effect review: summary: >- Cho et al. show that JMJ20/JMJ22 raise gibberellin levels by derepressing the GA biosynthetic genes GA3ox1 and GA3ox2. action: MODIFY reason: >- The evidence places JMJ22 upstream of gibberellin biosynthesis (GA3ox1/GA3ox2 expression and endogenous GA levels), not within GA signal transduction (GA perception, DELLA degradation). The precise process is positive regulation of gibberellin biosynthetic process. Any effect on GA signalling is indirect, through hormone levels. proposed_replacement_terms: - id: GO:0010372 label: positive regulation of gibberellin biosynthetic process supported_by: - reference_id: PMID:22483719 supporting_text: increased gibberellic acid levels through the removal of repressive histone arginine methylations at GA3ox1/GA3ox2 - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:DISRUPTION PHENOTYPE"] supporting_text: impaired H4R3me2 removal-dependent derepression of GA3ox1 and GA3ox2 causing lower endogenous gibberellic acid (GA) biosynthesis - term: id: GO:0032452 label: histone demethylase activity evidence_type: IGI original_reference_id: PMID:22483719 qualifier: enables supporting_entities: - AGI_LocusCode:AT5G63080 review: summary: >- Cho et al. 2012 identify JMJ20/JMJ22 as histone arginine demethylases. UniProt curates H4R3me2-specific demethylation and the RHEA:58352 reaction (dimethyl-Arg to monomethyl-Arg) as experimental (ECO:0000269) from this paper. action: MODIFY reason: >- The activity is right, but the experimentally supported specificity is for histone H4 Arg3 (H4R3me2), so the more specific child term GO:0033749 histone H4R3 demethylase activity is warranted. The JmjC domain keeps the Fe(II)-binding triad (H324, D326, H407), consistent with catalytic competence. PAINT did not propagate this term from JMJ22 at PTN001753861, although it propagated nucleus and DNA binding from the same donor. I take that as a deliberate decision not to treat histone demethylase activity as an inherited SF21-wide function. It is established for JMJ22 itself. proposed_replacement_terms: - id: GO:0033749 label: histone H4R3 demethylase activity supported_by: - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Histone demethylase that demethylates 'Arg-3' (H4R3me) of histone H4 with a specific activity for H4R3me2 - reference_id: PMID:22483719 supporting_text: the histone arginine demethylases, JMJ20 and JMJ22 - term: id: GO:0040029 label: epigenetic regulation of gene expression evidence_type: IDA original_reference_id: PMID:22483719 qualifier: involved_in review: summary: >- JMJ22 removes repressive histone arginine methylation (H4R3me2) at GA3ox1/GA3ox2 chromatin, which derepresses these genes. action: ACCEPT reason: >- Removing a repressive histone mark to switch on target genes is a direct chromatin mechanism of gene regulation and is the core process in which JMJ22 acts. supported_by: - reference_id: PMID:22483719 supporting_text: removal of repressive histone arginine methylations at GA3ox1/GA3ox2 core_functions: - description: >- Nuclear Fe(II)/2-oxoglutarate-dependent histone arginine demethylase that removes repressive H4R3me2 at the GA biosynthesis genes GA3ox1 and GA3ox2 after phyB activation. Acting redundantly with JMJ20, it raises gibberellin levels and promotes light-induced seed germination. The activity and the germination role are experimentally established in Arabidopsis (Cho et al. 2012). supported_by: - reference_id: PMID:22483719 supporting_text: increased gibberellic acid levels through the removal of repressive histone arginine methylations at GA3ox1/GA3ox2 - reference_id: file:ARATH/JMJ22/JMJ22-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Histone demethylase that demethylates 'Arg-3' (H4R3me) of histone H4 with a specific activity for H4R3me2 molecular_function: id: GO:0033749 label: histone H4R3 demethylase activity directly_involved_in: - id: GO:0040029 label: epigenetic regulation of gene expression - id: GO:0010372 label: positive regulation of gibberellin biosynthetic process - id: GO:0010030 label: positive regulation of seed germination locations: - id: GO:0005634 label: nucleus suggested_questions: - question: >- How is JMJ22 recruited to GA3ox1/GA3ox2 chromatin, given that it lacks a DNA-binding domain? Is the TAIR "sequence-specific DNA binding" IDA based on ChIP occupancy rather than direct, sequence-specific binding? experts: - Plant chromatin biologists - TAIR curators - question: >- Does the N-terminal F-box of JMJ22 assemble into an SCF E3 ligase (binding ASK/SKP1)? If so, does that function bear on its histone demethylase or thermospermine-related roles? experts: - Plant ubiquitin-proteasome researchers - question: >- What is the molecular basis of the JMJ22-specific (not JMJ20/JMJ21) role in thermospermine signalling and SAC51-family mRNA stability? Is it histone demethylation, or a different JmjC hydroxylase/demethylase activity on RNA-associated proteins? experts: - Polyamine and vascular development researchers - question: >- Is H4R3me2 demethylase activity conserved across the F-box-containing SF21 orthologs (for example in cereals), given that PAINT did not propagate the activity from JMJ22? experts: - PAINT/PANTHER curators suggested_experiments: - hypothesis: JMJ22 demethylates H4R3me2 directly and requires its Fe(II)-binding triad. description: >- Assay recombinant wild-type JMJ22 and an H324A/D326A mutant on H4R3me2 peptides and nucleosomes by mass spectrometry, and test whether the mutant fails to complement the jmj20 jmj22 germination defect. experiment_type: in vitro enzyme assay plus genetic complementation - hypothesis: JMJ22 is recruited to GA3ox promoters through a partner protein rather than by binding DNA directly. description: >- Compare EMSA/DAP-seq of purified JMJ22 with ChIP-seq of tagged JMJ22, and identify chromatin partners by IP-MS. experiment_type: biochemistry and ChIP-seq - hypothesis: The thermospermine-related phenotype of jmj22 reflects a catalytic activity of JMJ22. description: >- Test whether catalytically dead JMJ22 complements sac59/jmj22-2 suppression of acl5, and measure SAC51 mRNA stability and translation. experiment_type: genetic complementation references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - 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: GO_REF:0000122 title: AtSubP analysis findings: [] - id: PMID:22483719 title: Control of seed germination by light-induced histone arginine demethylation activity. findings: - statement: JMJ20 and JMJ22 are histone arginine demethylases that act redundantly to promote seed germination downstream of phyB, by removing repressive arginine methylation at GA3ox1/GA3ox2. supporting_text: JMJ22, act redundantly as positive regulators of seed germination reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Primary characterisation of JMJ22 (Dev Cell 2012). Only the abstract is cached; full-text details such as the in vitro assays and ChIP come from UniProt's curated ECO:0000269 statements. - id: PMID:25533953 title: An Arabidopsis gene regulatory network for secondary cell wall synthesis. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: >- High-throughput Y1H network. JMJ22 appears only in the supplementary interaction data (KOR1 promoter) and is not discussed in the text. - id: PMID:35962471 title: Loss of function of an Arabidopsis homologue of JMJD6 suppresses the dwarf phenotype of acl5, a mutant defective in thermospermine biosynthesis. findings: - statement: jmj22 alleles (sac59, jmj22-2), but not jmj20 or jmj21, partially suppress acl5 and stabilise SAC51-family mRNAs, indicating a JMJ22-specific developmental role. supporting_text: suggesting a unique role for JMJ22 in plant development reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: >- Abstract-only. Establishes a non-redundant JMJ22 role in thermospermine signalling with no defined mechanism. Its "JMJD6" label is a class name and does not establish orthology to human JMJD6. - id: PMID:18713399 title: Comparative analysis of JmjC domain-containing proteins reveals the potential histone demethylases in Arabidopsis and rice. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Gene-family nomenclature and expression only. Background. - id: file:ARATH/JMJ22/JMJ22-uniprot.txt title: UniProtKB/Swiss-Prot entry Q67XX3 (JMJ22_ARATH) findings: []