id: A0A8B8L1Z3
gene_symbol: A0A8B8L1Z3
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:3816
  label: Abrus precatorius
description: >-
  A0A8B8L1Z3 (LOC113860185) is a 474-amino-acid protein from Abrus precatorius (Indian
  licorice). It has an N-terminal J domain (residues 70-135) followed by long low-complexity
  and disordered regions. It belongs to the plant-specific PTHR45496 family, subfamily SF19.
  The only Arabidopsis thaliana member of SF19 is At5g64360, which is known as SDJ1, DNAJ1 or
  EIP9. The Abrus protein is most similar to SDJ1 among Arabidopsis proteins (about 46%
  identity over its length) and the two have similar lengths. The J domain lacks the
  His-Pro-Asp (HPD) motif needed to stimulate Hsp70 ATPase activity. SDJ1 also lacks this
  motif, which argues against a canonical Hsp70 cochaperone role. In Arabidopsis, SDJ1 and
  its paralogs SDJ2 and SDJ3 are nuclear proteins. They lack DNA-binding domains. The SU(VAR)3-9
  homologs SUVH1 and SUVH3, which read DNA methylation, recruit them to methylated
  euchromatic sites near transposons. There they enhance transcription of nearby genes,
  counteracting the silencing effect of transposon methylation. By descent, A0A8B8L1Z3 is
  predicted to be a nuclear transcriptional coactivator of this SUVH-SDJ type. The Abrus
  protein itself has not been characterized experimentally.
references:
  - id: PMID:31775284
    title: "Detection of Abrin-Like and Prepropulchellin-Like Toxin Genes and Transcripts Using Whole Genome Sequencing and Full-Length Transcript Sequencing of Abrus precatorius"
    reference_review:
      relevance: LOW
      correctness: VERIFIED
      review_notes: >-
        Genome-sequencing paper that is the source of the Abrus precatorius gene model, as
        cited in the UniProt record. It contains no functional information about this protein.
        Kept as provenance for the sequence.
  - id: PMID:30523112
    title: "A DNA methylation reader complex that enhances gene transcription."
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Harris et al. 2018 (full text cached). Shows that SUVH1 and SUVH3 recruit DNAJ1
        (At5g64360, the Arabidopsis PTHR45496:SF19 member and the closest relative of
        A0A8B8L1Z3) and DNAJ2 to methylated DNA. Tethering DNAJ1 to DNA activated
        transcription in plants, yeast and mammals. Basis for the predicted coactivator
        function of A0A8B8L1Z3.
  - id: PMID:30589221
    title: "A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes."
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Zhao et al. 2019 (abstract only in the cache). Defines the SUVH-SDJ complex
        (SDJ1, SDJ2, SDJ3), shows that its components have transcriptional activation
        activity, and that they are needed to express promoter-methylated genes.
  - id: PMID:21700722
    title: "EMF1 interacts with EIP1, EIP6 or EIP9 involved in the regulation of flowering time in Arabidopsis."
    reference_review:
      relevance: MEDIUM
      correctness: VERIFIED
      review_notes: >-
        Park et al. 2011 (abstract only). EIP9 is the same gene as SDJ1 (At5g64360). The
        abstract places the EMF1-EIP9 heterodimer in the nucleus and reports altered
        flowering time in eip9 mutants. The flowering-time result is an organismal
        phenotype and is not transferred to Abrus.
  - id: PMID:34185870
    title: "Roles of IDM3 and SDJ1/2/3 in Establishment and/or Maintenance of DNA Methylation in Arabidopsis."
    reference_review:
      relevance: MEDIUM
      correctness: VERIFIED
      review_notes: >-
        Miao et al. 2021 (abstract only). The sdj1/2/3 triple mutant has reduced DNA
        methylation at a subset of RdDM targets, and SDJ1 and SDJ3 interact with RDM1 and
        DMS3. This shows the SDJs are needed for methylation there, but not how they take
        part, so no RdDM process term is transferred.
  - id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
    title: "A0A8B8L1Z3 re-review: placement among PTHR45496 relatives"
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Reproducible re-review analysis. Covers PANTHER 19.0 subfamily membership, the
        PAINT node PTN002896004 seed set, global alignment identities to the Arabidopsis
        and Populus relatives, and the absence of the HPD motif.
  - id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-deep-research-falcon.md
    title: "Deep research report (falcon) on LOC113860185"
    reference_review:
      relevance: LOW
      correctness: MISCITED
      review_notes: >-
        Generic summary of J-domain proteins. It assumes a canonical HPD-dependent Hsp70
        cochaperone role and never identifies the SUVH-SDJ relatives. It is no longer
        used as support for the core function; kept for provenance.
existing_annotations:
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: ISS
    original_reference_id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
    review:
      summary: >-
        Proposed nuclear location, inherited from PAINT node PTN002896004 and supported by
        experimental nuclear localization of the closest Arabidopsis relative EIP9/SDJ1.
      action: NEW
      reason: >-
        GOA has no annotations for A0A8B8L1Z3. Abrus is not one of the PANTHER reference
        genomes, so it cannot receive IBA rows. PAINT placed nucleus (IBD) at
        PTN002896004, a flowering-plant node whose descendants include SDJ1 (SF19), SDJ2
        (SF1), SDJ3 (SF10) and ADMETOS (SF32). A0A8B8L1Z3 is a flowering-plant SF19
        member, so it descends from this node. EIP9/SDJ1 (At5g64360) has a direct nuclear
        localization result, and the SUVH-SDJ complex works on chromatin.
      supported_by:
        - reference_id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
          supporting_text: >-
            PAINT asserts nucleus (GO:0005634) and GO:0001228 "DNA-binding transcription activator
        - reference_id: PMID:21700722
          supporting_text: >-
            EMF1-EIP1, EMF1-EIP6 and
            EMF1-EIP9 heterodimers were localized in the nucleus
  - term:
      id: GO:0003713
      label: transcription coactivator activity
    evidence_type: ISS
    original_reference_id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
    review:
      summary: >-
        Proposed transcription coactivator activity, by descent from the SUVH-SDJ J-domain
        proteins. These proteins activate transcription when methyl-DNA readers recruit
        them to DNA.
      action: NEW
      reason: >-
        At PTN002896004, PAINT asserts that SDJ-family proteins activate transcription,
        using GO:0001228 (DNA-binding transcription activator activity, RNA polymerase
        II-specific). This review keeps that function but uses the coactivator term instead
        of the DNA-binding transcription factor term, because the evidence points to a
        recruited coregulator. SDJ1 and SDJ2 have no DNA-binding domain. SUVH1 and SUVH3,
        which bind methylated DNA, recruit them to DNA, and activation was shown by
        tethering DNAJ1 artificially to DNA. SDJ2 already carries a direct experimental
        GO:0003713 annotation (PMID:30589221). This is a refinement of the term that PAINT
        assigned, not a function that PAINT left out. A0A8B8L1Z3 shares the subfamily of
        SDJ1/DNAJ1, the protein whose recruitment-dependent activation Harris et al.
        demonstrated. Confidence is moderate: no Abrus experiment exists.
      supported_by:
        - reference_id: PMID:30523112
          supporting_text: >-
            Ectopic
            recruitment of DNAJ1 enhanced gene transcription in plants, yeast, and mammals.
        - reference_id: PMID:30523112
          supporting_text: >-
            DNAJ1 and DNAJ2 lack any discernible methyl-binding domain, but they are robustly
            associated with SUVH1 and SUVH3
        - reference_id: PMID:30589221
          supporting_text: >-
            We
            demonstrate that the SUVH-SDJ complex components have transcriptional activation
            activity.
        - reference_id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
          supporting_text: >-
            The only Arabidopsis thaliana member of PTHR45496:SF19 is Q9FMF3 (At5g64360)
core_functions:
  - description: >-
      Predicted nuclear transcriptional coactivator of the SUVH-SDJ type. In Arabidopsis,
      the closest relative SDJ1/DNAJ1 (same PANTHER subfamily, SF19) has no DNA-binding
      domain. The methyl-DNA readers SUVH1 and SUVH3 recruit it to methylated euchromatin
      and transposon-proximal sites, where it enhances transcription of nearby genes. The
      J domain of A0A8B8L1Z3 lacks the HPD motif, so it may not act as a canonical Hsp70
      cochaperone. How these proteins activate transcription is unknown. The earlier
      core function ("protein folding chaperone" in the cytoplasm) was based only on the
      generic J-domain signature and is withdrawn.
    molecular_function:
      id: GO:0003713
      label: transcription coactivator activity
    locations:
      - id: GO:0005634
        label: nucleus
    directly_involved_in:
      - id: GO:0045893
        label: positive regulation of DNA-templated transcription
    supported_by:
      - reference_id: PMID:30523112
        supporting_text: >-
          Thus, the SUVH proteins bind to methylated DNA and recruit the DNAJ proteins to
          enhance proximal gene expression, thereby counteracting the repressive effects
          of transposon insertion near genes.
      - reference_id: file:ABRPR/A0A8B8L1Z3/A0A8B8L1Z3-bioinformatics/RESULTS-rereview.md
        supporting_text: >-
          The query's J domain (residues 70-135) has no His-Pro-Asp tripeptide.
suggested_questions:
  - question: >-
      The PAINT node PTN002896004 is annotated with GO:0001228 (DNA-binding transcription
      activator activity, RNA polymerase II-specific). SDJ proteins have no DNA-binding
      domain and are recruited by SUVH1 and SUVH3. Should the node term be transcription
      coactivator activity (GO:0003713) instead?
  - question: >-
      The J domain of SDJ1-type proteins has no HPD motif. Does it still bind any Hsp70?
      Or has it been repurposed to recruit transcriptional machinery?
  - question: >-
      Does the Abrus SF19 protein interact with Abrus SUVH1/SUVH3 orthologs, and does it
      localize to methylated promoters?
suggested_experiments:
  - hypothesis: >-
      A0A8B8L1Z3 activates transcription when it is recruited to DNA.
    description: >-
      Fuse A0A8B8L1Z3 to the GAL4 DNA-binding domain or a programmable zinc finger, and
      measure reporter activation in yeast and in Nicotiana benthamiana leaves. Include
      J-domain deletions as controls.
    experiment_type: reporter assay
  - hypothesis: >-
      A0A8B8L1Z3 is nuclear and forms a complex with Abrus SUVH1/SUVH3 orthologs.
    description: >-
      Co-express GFP-tagged A0A8B8L1Z3 with tagged Abrus SUVH1/SUVH3 orthologs in
      N. benthamiana. Image the proteins by confocal microscopy with a nuclear marker,
      then perform co-immunoprecipitation.
    experiment_type: fluorescence microscopy and co-immunoprecipitation
