id: Q8RYC8
gene_symbol: ARF19
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:3702
  label: Arabidopsis thaliana
description: >-
  ARF19 is an A-class Auxin Response Factor transcription factor that binds to
  auxin-responsive promoter elements (AuxREs; consensus TGTCTC) and activates
  transcription of downstream target genes including LBD16 and LBD29. It functions
  redundantly with ARF7 in lateral root formation, gravitropism, leaf expansion,
  and callus formation. ARF19 activity is regulated by AUX/IAA repressor proteins
  that are degraded via the SCFTIR1/AFB ubiquitin ligase complex upon auxin
  perception, releasing ARFs to activate transcription. ARF19 also integrates
  ethylene signaling in roots. The protein contains an N-terminal B3-type DNA
  binding domain, a glutamine-rich middle activation domain, and a C-terminal
  PB1 domain for homo/heterodimerization and interaction with AUX/IAA proteins.
existing_annotations:
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 binds specifically to auxin response elements (AuxREs) containing the
      TGTCTC motif in promoters of target genes. This is a core molecular function
      well supported by phylogenetic inference and experimental data from the ARF
      family [PMID:15659631, PMID:17259263].
    action: ACCEPT
    reason: >-
      ARF transcription factors bind to cis-regulatory AuxRE sequences. This is the
      fundamental molecular function of the ARF family and has been directly demonstrated
      for ARF7/ARF19. IBA annotation is appropriate given the conserved function
      across the ARF family.
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "ARF7 and ARF19 directly regulate the auxin-mediated transcription of LATERAL ORGAN BOUNDARIES-DOMAIN16/ASYMMETRIC LEAVES2-LIKE18 (LBD16/ASL18) and/or LBD29/ASL16 in roots"
      - reference_id: PMID:15659631
        supporting_text: "The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 is a nuclear transcription factor. Nuclear localization is conserved
      across the ARF family and has been directly demonstrated for ARF19
      [PMID:9342315, PMID:29184030].
    action: ACCEPT
    reason: >-
      Nuclear localization is the expected and verified location for a DNA-binding
      transcription factor. Multiple experimental studies confirm ARF19 nuclear
      localization.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
      - reference_id: PMID:9342315
        supporting_text: "The Aux/IAA family of early genes encodes proteins that are short-lived and nuclear-localized"
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 is a transcription factor that regulates transcription by binding to
      AuxREs. This is the core function of ARF proteins [PMID:15659631].
    action: ACCEPT
    reason: >-
      This is the primary biological process function of ARF19. As a transcription
      factor, regulation of transcription is its fundamental role. The IBA
      annotation reflects conserved function across the ARF family.
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression"
- term:
    id: GO:0009733
    label: response to auxin
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 mediates cellular responses to auxin by activating transcription of
      auxin-responsive genes upon release from AUX/IAA repression. This is a
      core function shared across ARF family members [PMID:15659631, PMID:16461383].
    action: ACCEPT
    reason: >-
      ARF19 is a key effector of auxin responses. Its transcriptional activity is
      released when auxin triggers degradation of AUX/IAA repressors. This is a
      core biological process annotation.
    supported_by:
      - reference_id: PMID:16461383
        supporting_text: "Both arf19 and arf7 mutants isolated from our forward genetic screens are auxin resistant"
      - reference_id: PMID:15659631
        supporting_text: "Global gene expression analysis revealed that auxin-induced gene expression is severely impaired in the arf7 single and arf7 arf19 double mutants"
- term:
    id: GO:0010311
    label: lateral root formation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 together with ARF7 is essential for lateral root formation in
      Arabidopsis. The arf7 arf19 double mutant is severely impaired in lateral
      root formation [PMID:15659631, PMID:17259263].
    action: ACCEPT
    reason: >-
      Lateral root formation is a well-established core function of ARF19. This
      is supported by extensive genetic evidence showing the arf7 arf19 double
      mutant phenotype.
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "arf7 arf19 has a strong auxin-related phenotype not observed in the arf7 and arf19 single mutants, including severely impaired lateral root formation"
      - reference_id: PMID:17259263
        supporting_text: "The arf7 arf19 double knockout mutant is severely impaired in lateral root formation"
- term:
    id: GO:0048366
    label: leaf development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF7 and ARF19 together promote leaf cell expansion. The arf7 arf19 double
      mutant shows decreased leaf cell expansion [PMID:15960621].
    action: KEEP_AS_NON_CORE
    reason: >-
      While ARF7/ARF19 do contribute to leaf development, this is a secondary
      pleiotropic effect. The primary core function is in lateral root formation
      and auxin-mediated transcription. Leaf development is a downstream
      consequence of their transcriptional activity.
    supported_by:
      - reference_id: PMID:15960621
        supporting_text: "in combination with mutations in NPH4/ARF7, encoding the most closely related ARF, they cause several phenotypes including a drastic decrease in lateral and adventitious root formation and a decrease in leaf cell expansion"
- term:
    id: GO:1990110
    label: callus formation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ARF19 together with ARF7 is required for callus formation during cellular
      dedifferentiation. They recruit ATXR2 to deposit H3K36me3 at LBD gene
      promoters [PMID:29184030].
    action: KEEP_AS_NON_CORE
    reason: >-
      Callus formation is a specialized developmental process that occurs in tissue
      culture conditions. While ARF19 plays a role, this is not a core physiological
      function under normal growth conditions.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "Leaf explants from arf7-1arf19-2 double mutants were defective in callus formation and showed reduced H3K36me3 accumulation at LBD promoters"
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      ARF19 contains a B3-type DNA binding domain and binds to AuxRE sequences.
      This IEA annotation is correct but overly general [PMID:15659631].
    action: MODIFY
    reason: >-
      While correct, "DNA binding" is too general for a transcription factor.
      More specific terms like "cis-regulatory region sequence-specific DNA binding"
      (GO:0000987) or "transcription cis-regulatory region binding" (GO:0000976)
      better capture the specific function.
    proposed_replacement_terms:
      - id: GO:0000987
        label: cis-regulatory region sequence-specific DNA binding
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for nuclear localization based on sequence features. This
      duplicates the IBA annotation but is independently valid.
    action: ACCEPT
    reason: >-
      Nuclear localization is correct and consistent with experimental evidence.
      The duplicate with IBA is acceptable as they represent independent evidence
      paths.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation based on InterPro mapping. Correct and consistent with ARF19's
      role as a transcription factor.
    action: ACCEPT
    reason: >-
      This annotation is accurate and reflects the core molecular function of ARF19.
      The IEA evidence appropriately captures the conserved domain-based inference.
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression"
- term:
    id: GO:0009725
    label: response to hormone
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      This is a parent term of "response to auxin". The annotation is correct but
      less specific than the available specific term.
    action: ACCEPT
    reason: >-
      While "response to auxin" (GO:0009733) is more specific, the broader "response
      to hormone" is not incorrect. ARF19 also integrates ethylene signaling, so
      the broader term captures this additional hormone response role.
    supported_by:
      - reference_id: PMID:16461383
        supporting_text: "Here we show that ARF19 and ARF7 not only participate in auxin signaling, but also play a critical role in ethylene responses in Arabidopsis (Arabidopsis thaliana) roots, indicating that the ARFs serve as a cross talk point between the two hormones"
- term:
    id: GO:0009734
    label: auxin-activated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      GO:0009734 is defined as "The series of molecular signals generated by the
      binding of the plant hormone auxin to a receptor, and ending with modulation
      of a downstream cellular process, e.g. transcription." ARF19 is a transcriptional
      effector downstream of auxin perception, not the receptor itself. TIR1/AFB
      proteins are the auxin receptors [PMID:15659631].
    action: MODIFY
    reason: >-
      ARF19 does not bind auxin directly - it is released from AUX/IAA repression
      after auxin binds to TIR1/AFB receptors. ARF19 is the endpoint effector of
      the signaling pathway, executing the transcriptional response. The term
      "response to auxin" (GO:0009733) more accurately describes ARF19's role as
      the transcriptional output of auxin perception. This is a subtle but important
      distinction - ARF19 RESPONDS to the signaling pathway rather than being
      part of the signal transduction cascade itself.
    proposed_replacement_terms:
      - id: GO:0009733
        label: response to auxin
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "Global gene expression analysis revealed that auxin-induced gene expression is severely impaired in the arf7 single and arf7 arf19 double mutants"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15889151
  review:
    summary: >-
      "Protein binding" is a low-information term. ARF19 interacts specifically
      with AUX/IAA proteins via its PB1 domain. This interaction is functionally
      important for auxin signaling.
    action: UNDECIDED
    reason: >-
      Unable to access the specific details of PMID:15889151 to determine the
      exact interaction partner and context. "Protein binding" is generally
      too vague but may be acceptable if the interaction partner is unknown.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16236149
  review:
    summary: >-
      "Protein binding" is too general. ARF19 interacts with specific partners
      like AUX/IAA proteins. This paper likely documents IAA14 interactions.
    action: UNDECIDED
    reason: >-
      Unable to access PMID:16236149 to determine the specific interaction partner.
      The term should ideally be more specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18505759
  review:
    summary: >-
      Paper documents IAA18 mutations. ARF19 likely interacts with IAA18.
    action: UNDECIDED
    reason: >-
      Unable to access full text of PMID:18505759. "Protein binding" is too vague
      but may reflect documented ARF-AUX/IAA interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21734647
  review:
    summary: >-
      Paper on auxin signaling network at shoot apex. Likely documents ARF interactions.
    action: UNDECIDED
    reason: >-
      Unable to access PMID:21734647 to evaluate specific interaction context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28650476
  review:
    summary: >-
      CrY2H-seq is a high-throughput interactome mapping method. Interactions may
      be of lower confidence than targeted studies.
    action: UNDECIDED
    reason: >-
      Unable to access PMID:28650476. High-throughput interaction data requires
      careful evaluation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32612234
  review:
    summary: >-
      Paper on phytohormone protein network. ARF19 interactions with hormone
      signaling components likely documented.
    action: UNDECIDED
    reason: >-
      Unable to access PMID:32612234 to evaluate specific interaction context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36088536
  review:
    summary: >-
      Paper on TF protein-protein interactions during gynoecium development.
    action: UNDECIDED
    reason: >-
      Unable to access PMID:36088536 to evaluate specific interaction context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9342315
  review:
    summary: >-
      This foundational paper demonstrates ARF19 (then called IAA22/IAA24)
      interacts with AUX/IAA proteins via dimerization domains. The interactions
      are homo- and heterotypic [PMID:9342315].
    action: ACCEPT
    reason: >-
      While "protein binding" is vague, this paper documents biologically relevant
      ARF-AUX/IAA interactions that are central to auxin signaling. The IPI evidence
      is valid for documenting this interaction capability.
    supported_by:
      - reference_id: PMID:9342315
        supporting_text: "Screening an Arabidopsis lambda-ACT cDNA library using IAA1 as a bait reveals heterotypic interactions of IAA1 with known and newly discovered members of the Arabidopsis Aux/IAA gene family"
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:29681137
  review:
    summary: >-
      This paper demonstrates LBD18 binds to ARF19 promoter to regulate its
      expression. ARF7/ARF19 directly bind AuxRE in LBD18 promoter. This supports
      ARF19's sequence-specific DNA binding activity [PMID:29681137].
    action: ACCEPT
    reason: >-
      Excellent, specific annotation for ARF19's molecular function. The IDA evidence
      from this paper demonstrates direct DNA binding to cis-regulatory sequences.
    supported_by:
      - reference_id: PMID:29681137
        supporting_text: "We showed that ARF7 and ARF19 directly bind AuxRE in the LBD18 promoter"
- term:
    id: GO:1990110
    label: callus formation
  evidence_type: IMP
  original_reference_id: PMID:29184030
  review:
    summary: >-
      The arf7-1 arf19-2 double mutant is defective in callus formation. ARF19
      with ARF7 recruits ATXR2 to LBD promoters to facilitate cellular
      dedifferentiation [PMID:29184030].
    action: KEEP_AS_NON_CORE
    reason: >-
      Valid IMP evidence for ARF19 involvement in callus formation. However, this
      is a tissue culture phenotype, not a normal physiological function. Keep
      as non-core annotation.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "Leaf explants from arf7-1arf19-2 double mutants were defective in callus formation and showed reduced H3K36me3 accumulation at LBD promoters"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29184030
  review:
    summary: >-
      ARF19 interacts with ATXR2 histone methyltransferase in the nucleus to
      facilitate H3K36me3 deposition at LBD promoters [PMID:29184030].
    action: ACCEPT
    reason: >-
      While "protein binding" is general, the IPI evidence for ATXR2 interaction
      is valid. This is a functionally important interaction for chromatin
      modification at target genes.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:29184030
  review:
    summary: >-
      Direct experimental evidence for ARF19 nuclear localization, consistent
      with its function as a transcription factor [PMID:29184030].
    action: ACCEPT
    reason: >-
      IDA evidence for nuclear localization is the strongest evidence type for
      this cellular component annotation.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29923261
  review:
    summary: >-
      ARF19 interacts with JMJ30 histone demethylase to promote H3K9me3
      demethylation at LBD promoters during callus formation [PMID:29923261].
    action: ACCEPT
    reason: >-
      Valid IPI evidence for ARF19-JMJ30 interaction. This interaction is
      functionally important for epigenetic regulation of target genes.
    supported_by:
      - reference_id: PMID:29923261
        supporting_text: "The JMJ30 protein binds to promoters of the LBD16 and LBD29 genes along with AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 and activates LBD expression"
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:25533953
  review:
    summary: >-
      This Nature paper mapped a gene regulatory network for secondary cell wall
      synthesis using enhanced yeast one-hybrid. ARF19 was identified as binding
      to cis-regulatory regions of target genes [PMID:25533953].
    action: ACCEPT
    reason: >-
      Valid annotation for ARF19's DNA binding activity. The eY1H approach provides
      direct evidence for regulatory DNA binding.
    supported_by:
      - reference_id: PMID:25533953
        supporting_text: "Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes"
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:27650334
  review:
    summary: >-
      Enhanced yeast one-hybrid study identified ARF19 binding to PRC2 gene
      promoters [PMID:27650334].
    action: ACCEPT
    reason: >-
      Valid IPI evidence for ARF19 binding to cis-regulatory regions. Consistent
      with its role as a transcription factor.
    supported_by:
      - reference_id: PMID:27650334
        supporting_text: "Using enhanced yeast one-hybrid analysis, upstream regulators of the PRC2 member genes are identified"
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:30356219
  review:
    summary: >-
      ARF19 identified as regulating nitrogen-associated metabolism genes via
      binding to their cis-regulatory regions [PMID:30356219].
    action: ACCEPT
    reason: >-
      Valid evidence for ARF19 cis-regulatory binding function. Extends our
      understanding of ARF19 target gene repertoire.
    supported_by:
      - reference_id: PMID:30356219
        supporting_text: "Here we present a transcriptional regulatory network and twenty-one transcription factors that regulate the architecture of root and shoot systems in response to changes in nitrogen availability"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISM
  original_reference_id: GO_REF:0000122
  review:
    summary: >-
      Computational prediction of nuclear localization based on AtSubP analysis.
      Consistent with experimental data.
    action: ACCEPT
    reason: >-
      ISM prediction is validated by experimental IDA evidence for nuclear
      localization.
    supported_by:
      - reference_id: PMID:29184030
        supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:23020607
  review:
    summary: >-
      This paper is about BAT1 brassinosteroid acyltransferase. ARF19 DNA binding
      may have been demonstrated as part of promoter analysis studies, but the
      primary focus is not on ARF19.
    action: UNDECIDED
    reason: >-
      The paper's primary focus is BAT1, not ARF19. Unable to verify how ARF19
      DNA binding was demonstrated in this context without full text access.
- term:
    id: GO:0010311
    label: lateral root formation
  evidence_type: IGI
  original_reference_id: PMID:17259263
  review:
    summary: >-
      The arf7 arf19 double mutant is severely impaired in lateral root formation,
      demonstrating genetic interaction between these functionally redundant
      transcription factors [PMID:17259263].
    action: ACCEPT
    reason: >-
      Excellent IGI evidence for ARF19 role in lateral root formation. This is
      the primary paper establishing ARF7/ARF19 function in lateral root
      development via LBD gene activation.
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "The arf7 arf19 double knockout mutant is severely impaired in lateral root formation"
- term:
    id: GO:0048366
    label: leaf development
  evidence_type: IGI
  original_reference_id: PMID:15960621
  review:
    summary: >-
      The arf7 arf19 double mutant shows decreased leaf cell expansion, indicating
      redundant roles in leaf development [PMID:15960621].
    action: KEEP_AS_NON_CORE
    reason: >-
      Valid IGI evidence for ARF19 contribution to leaf development. However,
      this is a secondary pleiotropic effect compared to the primary lateral
      root function.
    supported_by:
      - reference_id: PMID:15960621
        supporting_text: "in combination with mutations in NPH4/ARF7, encoding the most closely related ARF, they cause several phenotypes including a drastic decrease in lateral and adventitious root formation and a decrease in leaf cell expansion"
- term:
    id: GO:0048527
    label: lateral root development
  evidence_type: IGI
  original_reference_id: PMID:15960621
  review:
    summary: >-
      The arf7 arf19 double mutant shows drastic decrease in lateral root
      formation [PMID:15960621].
    action: ACCEPT
    reason: >-
      Valid IGI evidence for a core function. "Lateral root development" is
      closely related to "lateral root formation" (GO:0010311) - both capture
      ARF19's essential role. Having both is acceptable as they represent
      complementary aspects of the same biological process.
    supported_by:
      - reference_id: PMID:15960621
        supporting_text: "in combination with mutations in NPH4/ARF7, encoding the most closely related ARF, they cause several phenotypes including a drastic decrease in lateral and adventitious root formation"
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:17259263
  review:
    summary: >-
      Direct experimental evidence for ARF19 DNA binding from the foundational
      paper on ARF7/ARF19 function [PMID:17259263].
    action: MODIFY
    reason: >-
      While DNA binding is correct, this is too general. The paper demonstrates
      binding to specific AuxRE sequences in LBD gene promoters. More specific
      terms should be used.
    proposed_replacement_terms:
      - id: GO:0000987
        label: cis-regulatory region sequence-specific DNA binding
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "ARF7 and ARF19 directly regulate the auxin-mediated transcription of LATERAL ORGAN BOUNDARIES-DOMAIN16/ASYMMETRIC LEAVES2-LIKE18 (LBD16/ASL18) and/or LBD29/ASL16 in roots"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17259263
  review:
    summary: >-
      Nuclear localization demonstrated in the context of ARF7/ARF19 functional
      studies [PMID:17259263].
    action: ACCEPT
    reason: >-
      IDA evidence for nuclear localization is consistent with ARF19's function
      as a transcription factor.
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "These LBD/ASL proteins are localized in the nucleus"
- term:
    id: GO:0009733
    label: response to auxin
  evidence_type: IMP
  original_reference_id: PMID:15659631
  review:
    summary: >-
      arf19 mutant (and especially arf7 arf19 double mutant) shows impaired
      auxin-induced gene expression, demonstrating ARF19's role in auxin response
      [PMID:15659631].
    action: ACCEPT
    reason: >-
      Strong IMP evidence from mutant phenotype analysis. This is a core annotation
      for ARF19 function.
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "Global gene expression analysis revealed that auxin-induced gene expression is severely impaired in the arf7 single and arf7 arf19 double mutants"
- term:
    id: GO:0009733
    label: response to auxin
  evidence_type: IMP
  original_reference_id: PMID:17259263
  review:
    summary: >-
      arf7 arf19 double mutant shows severely impaired auxin-mediated responses
      including lateral root formation [PMID:17259263].
    action: ACCEPT
    reason: >-
      Additional IMP evidence confirming ARF19's essential role in auxin response.
      Duplicate GO term with different reference is acceptable.
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "ARF7 and ARF19 directly regulate the auxin-mediated transcription of LATERAL ORGAN BOUNDARIES-DOMAIN16/ASYMMETRIC LEAVES2-LIKE18 (LBD16/ASL18) and/or LBD29/ASL16 in roots"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:9342315
  review:
    summary: >-
      Nuclear localization supported by traceable author statement in this
      foundational paper on Aux/IAA protein interactions [PMID:9342315].
    action: ACCEPT
    reason: >-
      TAS evidence for nuclear localization is consistent with other evidence
      types for this annotation.
    supported_by:
      - reference_id: PMID:9342315
        supporting_text: "The Aux/IAA family of early genes encodes proteins that are short-lived and nuclear-localized"
- term:
    id: GO:0009723
    label: response to ethylene
  evidence_type: IMP
  original_reference_id: PMID:16461383
  review:
    summary: >-
      arf19 mutant shows ethylene-insensitive roots, demonstrating ARF19's role
      in ethylene response integration. ARF19 expression is induced by ethylene
      [PMID:16461383].
    action: ACCEPT
    reason: >-
      Valid IMP evidence for ARF19 role in ethylene response. This represents
      hormone crosstalk function and is a legitimate annotation.
    supported_by:
      - reference_id: PMID:16461383
        supporting_text: "In addition to being auxin resistant, arf19 has also ethylene-insensitive roots and ARF19 expression is induced by ethylene treatment"
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISS
  original_reference_id: PMID:11118137
  review:
    summary: >-
      ARF19 is classified as a transcription factor based on sequence similarity
      to characterized ARF family members [PMID:11118137].
    action: MODIFY
    reason: >-
      The annotation is correct but could be more specific. ARF19 is an activator,
      and more specific terms are available. However, ISS evidence appropriately
      captures the inference from sequence similarity.
    proposed_replacement_terms:
      - id: GO:0001228
        label: DNA-binding transcription activator activity, RNA polymerase II-specific
    supported_by:
      - reference_id: PMID:15659631
        supporting_text: "The AUXIN RESPONSE FACTOR (ARF) gene family products, together with the AUXIN/INDOLE-3-ACETIC ACID proteins, regulate auxin-mediated transcriptional activation/repression"
      - reference_id: PMID:15960621
        supporting_text: "We show that ARF19, the fifth Q-rich ARF, also activates transcription"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: GO_REF:0000122
  title: AtSubP analysis
  findings: []
- id: PMID:11118137
  title: 'Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.'
  findings: []
- id: PMID:15659631
  title: 'Functional genomic analysis of the AUXIN RESPONSE FACTOR gene family members in Arabidopsis thaliana: unique and overlapping functions of ARF7 and ARF19.'
  findings:
    - statement: arf7 arf19 double mutant has severely impaired lateral root formation
      supporting_text: "arf7 arf19 has a strong auxin-related phenotype not observed in the arf7 and arf19 single mutants, including severely impaired lateral root formation"
    - statement: Auxin-induced gene expression is severely impaired in arf7 arf19
      supporting_text: "Global gene expression analysis revealed that auxin-induced gene expression is severely impaired in the arf7 single and arf7 arf19 double mutants"
    - statement: ARF7 and ARF19 regulate overlapping sets of target genes
      supporting_text: "The data suggest that the ARF7 and ARF19 proteins play essential roles in auxin-mediated plant development by regulating both unique and partially overlapping sets of target genes"
- id: PMID:15889151
  title: Developmental specificity of auxin response by pairs of ARF and Aux/IAA transcriptional regulators.
  findings: []
- id: PMID:15960621
  title: NPH4/ARF7 and ARF19 promote leaf expansion and auxin-induced lateral root formation.
  findings:
    - statement: ARF19 activates transcription
      supporting_text: "We show that ARF19, the fifth Q-rich ARF, also activates transcription"
    - statement: arf7 arf19 double mutant has decreased lateral root formation and leaf cell expansion
      supporting_text: "in combination with mutations in NPH4/ARF7, encoding the most closely related ARF, they cause several phenotypes including a drastic decrease in lateral and adventitious root formation and a decrease in leaf cell expansion"
- id: PMID:16236149
  title: Tissue-specific expression of stabilized SOLITARY-ROOT/IAA14 alters lateral root development in Arabidopsis.
  findings: []
- id: PMID:16461383
  title: A role for auxin response factor 19 in auxin and ethylene signaling in Arabidopsis.
  findings:
    - statement: arf19 mutant is auxin resistant
      supporting_text: "Both arf19 and arf7 mutants isolated from our forward genetic screens are auxin resistant"
    - statement: arf19 has ethylene-insensitive roots
      supporting_text: "In addition to being auxin resistant, arf19 has also ethylene-insensitive roots"
    - statement: ARF19 expression is induced by ethylene
      supporting_text: "ARF19 expression is induced by ethylene treatment"
    - statement: ARF19 can complement arf7 at the protein level
      supporting_text: "we show that a genomic fragment of ARF19 not only complements arf19, but also rescues arf7"
- id: PMID:17259263
  title: ARF7 and ARF19 regulate lateral root formation via direct activation of LBD/ASL genes in Arabidopsis.
  findings:
    - statement: ARF7 and ARF19 directly regulate LBD16/ASL18 and LBD29/ASL16 transcription
      supporting_text: "ARF7 and ARF19 directly regulate the auxin-mediated transcription of LATERAL ORGAN BOUNDARIES-DOMAIN16/ASYMMETRIC LEAVES2-LIKE18 (LBD16/ASL18) and/or LBD29/ASL16 in roots"
    - statement: arf7 arf19 double mutant is severely impaired in lateral root formation
      supporting_text: "The arf7 arf19 double knockout mutant is severely impaired in lateral root formation"
- id: PMID:18505759
  title: Domain II mutations in CRANE/IAA18 suppress lateral root formation and affect shoot development in Arabidopsis thaliana.
  findings: []
- id: PMID:21734647
  title: The auxin signalling network translates dynamic input into robust patterning at the shoot apex.
  findings: []
- id: PMID:23020607
  title: BAT1, a putative acyltransferase, modulates brassinosteroid levels in Arabidopsis.
  findings: []
- id: PMID:25533953
  title: An Arabidopsis gene regulatory network for secondary cell wall synthesis.
  findings:
    - statement: ARF19 identified in protein-DNA network regulating cell wall genes
      supporting_text: "Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes"
- id: PMID:27650334
  title: Transcriptional Regulation of Arabidopsis Polycomb Repressive Complex 2 Coordinates Cell-Type Proliferation and Differentiation.
  findings:
    - statement: ARF19 binds PRC2 gene promoters
      supporting_text: "Using enhanced yeast one-hybrid analysis, upstream regulators of the PRC2 member genes are identified"
- id: PMID:28650476
  title: 'CrY2H-seq: a massively multiplexed assay for deep-coverage interactome mapping.'
  findings: []
- id: PMID:29184030
  title: Arabidopsis ATXR2 deposits H3K36me3 at the promoters of LBD genes to facilitate cellular dedifferentiation.
  findings:
    - statement: ARF7/ARF19 recruit ATXR2 to LBD promoters
      supporting_text: "ATXR2 was recruited to LBD promoters by the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
    - statement: arf7-1 arf19-2 double mutant is defective in callus formation
      supporting_text: "Leaf explants from arf7-1arf19-2 double mutants were defective in callus formation and showed reduced H3K36me3 accumulation at LBD promoters"
- id: PMID:29681137
  title: LBD18 uses a dual mode of a positive feedback loop to regulate ARF expression and transcriptional activity in Arabidopsis.
  findings:
    - statement: ARF7 and ARF19 directly bind AuxRE in LBD18 promoter
      supporting_text: "We showed that ARF7 and ARF19 directly bind AuxRE in the LBD18 promoter"
    - statement: LBD18 interacts with ARF7 and ARF19 via PB1 domain
      supporting_text: "LBD18 interacts with ARFs including ARF7 and ARF19 via the Phox and Bem1 domain of ARF"
- id: PMID:29923261
  title: JMJ30-mediated demethylation of H3K9me3 drives tissue identity changes to promote callus formation in Arabidopsis.
  findings:
    - statement: JMJ30 binds to LBD promoters along with ARF7 and ARF19
      supporting_text: "The JMJ30 protein binds to promoters of the LBD16 and LBD29 genes along with AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19"
    - statement: ARF-JMJ30 complex catalyzes H3K9me3 removal at LBD loci
      supporting_text: "The ARF-JMJ30 complex catalyzes the removal of methyl groups from H3K9me3, especially at the LBD16 and LBD29 loci"
- id: PMID:30356219
  title: Transcriptional regulation of nitrogen-associated metabolism and growth.
  findings:
    - statement: ARF19 identified as regulator of nitrogen metabolism genes
      supporting_text: "Here we present a transcriptional regulatory network and twenty-one transcription factors that regulate the architecture of root and shoot systems in response to changes in nitrogen availability"
- id: PMID:32612234
  title: Extensive signal integration by the phytohormone protein network.
  findings: []
- id: PMID:36088536
  title: The protein-protein interaction landscape of transcription factors during gynoecium development in Arabidopsis.
  findings: []
- id: PMID:9342315
  title: Protein-protein interactions among the Aux/IAA proteins.
  findings:
    - statement: ARF19 (IAA24) discovered as interacting with IAA1
      supporting_text: "Screening an Arabidopsis lambda-ACT cDNA library using IAA1 as a bait reveals heterotypic interactions of IAA1 with known and newly discovered members of the Arabidopsis Aux/IAA gene family"
    - statement: Dimerization occurs via C-terminal domains
      supporting_text: "Deletion analysis of PS-IAA4 indicates that the betaalphaalpha containing acidic C terminus of the protein is necessary for homotypic interactions"
    - statement: Aux/IAA proteins are nuclear-localized
      supporting_text: "The Aux/IAA family of early genes encodes proteins that are short-lived and nuclear-localized"
core_functions:
  - molecular_function:
      id: GO:0000987
      label: cis-regulatory region sequence-specific DNA binding
    description: >-
      ARF19 binds specifically to auxin response elements (AuxREs) containing the
      TGTCTC core motif in promoters of target genes. This has been demonstrated
      by direct DNA binding assays and transgenic complementation studies.
    directly_involved_in:
      - id: GO:0006355
        label: regulation of DNA-templated transcription
      - id: GO:0009733
        label: response to auxin
      - id: GO:0010311
        label: lateral root formation
    locations:
      - id: GO:0005634
        label: nucleus
    supported_by:
      - reference_id: PMID:17259263
        supporting_text: "ARF7 and ARF19 directly regulate the auxin-mediated transcription of LATERAL ORGAN BOUNDARIES-DOMAIN16/ASYMMETRIC LEAVES2-LIKE18 (LBD16/ASL18) and/or LBD29/ASL16 in roots"
      - reference_id: PMID:29681137
        supporting_text: "We showed that ARF7 and ARF19 directly bind AuxRE in the LBD18 promoter"
proposed_new_terms: []
suggested_questions:
  - question: >-
      What is the precise mechanism by which ARF19 recruits chromatin modifiers
      (ATXR2, JMJ30) to target promoters?
  - question: >-
      Are there ARF19-specific target genes distinct from ARF7, or do they regulate
      entirely overlapping gene sets?
  - question: >-
      What post-translational modifications regulate ARF19 activity beyond AUX/IAA
      binding?
suggested_experiments:
  - description: >-
      ChIP-seq comparing ARF19 and ARF7 binding sites genome-wide to identify
      shared vs. unique target genes
    hypothesis: ARF19 and ARF7 have largely overlapping but not identical target gene sets
  - description: >-
      Structure-function analysis of ARF19 domains to determine requirements for
      chromatin modifier recruitment
    hypothesis: Specific regions of ARF19 beyond the PB1 domain mediate ATXR2/JMJ30 recruitment
  - description: >-
      Time-resolved transcriptomics in arf19 single mutants vs. arf7 arf19 double
      mutants to dissect redundant vs. unique functions
    hypothesis: Some genes are uniquely regulated by ARF19 while others require both ARF7 and ARF19