id: Q6P0J1
gene_symbol: hes6
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
status: COMPLETE
description: DNA binding, transcriptional regulation and dimerization are experimentally grounded in zebrafish
  Hes6. Their broad labels omit partner dependence and the specific negative transcriptional role.
source_documents:
- genes/DANRE/hes6/hes6-protnlm-source.json
- genes/DANRE/hes6/hes6-notes.md
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:0000104
  title: Electronic Gene Ontology annotations created by transferring manual GO annotations between related
    proteins based on shared sequence features
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15905406
  title: Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the
    periodic segmentation of somites.
  findings:
  - statement: The primary reporter and interaction experiments establish transcriptional repression and
      Her1 association for Her13.2/Hes6.
    supporting_text: Her13.2 augments autorepression of her1 in association with Her1 protein.
  - statement: Primary zebrafish perturbation links Hes6 to the segmentation clock and somite formation.
    supporting_text: 'her13.2 is required for periodic repression of the

      Notch-regulated genes her1 and her7, and for proper somite segmentation.'
  full_text_unavailable: false
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary report checked against the cached abstract/full text; the evidence scope is
      stated in the finding.
- id: PMID:16545363
  title: her1 and her13.2 are jointly required for somitic border specification along the entire axis
    of the fish embryo.
  findings:
  - statement: The primary abstract explicitly reports combined Her1/Her13.2 loss-of-function effects
      on somitic borders.
    supporting_text: 'joint inactivation of her1 and her13.2 leads to a complete loss of all somitic

      borders'
  full_text_unavailable: true
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary report checked against the cached abstract/full text; the evidence scope is
      stated in the finding.
- id: PMID:20637625
  title: Segment number and axial identity in a segmentation clock period mutant.
  findings:
  - statement: The period-mutant study supports clock-dependent segment number; target identity is independently
      corroborated by the full 2018 report.
    supporting_text: 'precise control of segmentation

      clock period in relation to axial growth ensures a species-specific segment

      number'
  - statement: The period-mutant study distinguishes segment number from Hox-associated regional identity.
    supporting_text: 'arguing

      against an instructive role of the segmentation clock in determining axial

      identities.'
  full_text_unavailable: true
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary report checked against the cached abstract/full text; the evidence scope is
      stated in the finding.
- id: PMID:22911291
  title: Topology and dynamics of the zebrafish segmentation clock core circuit.
  findings:
  - statement: Direct zebrafish biochemistry establishes partner-dependent DNA binding by Hes6 in the
      Her7:Hes6 heterodimer.
    supporting_text: only Her1 homodimers and Her7:Hes6 heterodimers have strong DNA binding activity
      and target similar DNA sites.
  - statement: Hes6 forms heterodimers and homodimers; their DNA-binding capabilities differ.
    supporting_text: all of the possible dimers between Her1, Her7 and Hes6 form
  - statement: MyoD association is experimentally measured but is used to demonstrate promiscuous bHLH
      interactions, not a physiological Hes6 myogenesis mechanism.
    supporting_text: even the bHLH containing factor MyoD, but not the negative control non-bHLH protein
      PPARγ, was co-purified by Her1, Her7, and Hes6 to a similar extent
  full_text_unavailable: false
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary report checked against the cached abstract/full text; the evidence scope is
      stated in the finding.
- id: PMID:29624170
  title: Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the
    segmentation clock.
  findings:
  - statement: The full primary report directly generates and analyzes a hes6 mutant; its focus on notochord-derived
      centra does not make the Hes6 annotation a wrong-gene citation.
    supporting_text: The novel hes6 mutation was created by injection of a TALEN targeted against hes6
      in wild type.
  - statement: The full figure caption reports disordered myotome boundaries in her1;hes6 mutants and
      compares multiple segmentation-clock mutant combinations.
    supporting_text: her1;hes6 mutants (n=15)
  full_text_unavailable: false
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary report checked against the cached abstract/full text; the evidence scope is
      stated in the finding.
- id: file:DANRE/hes6/hes6-interaction-partners.json
  title: UniProt identities of the three experimental GOA interaction partners
- id: file:DANRE/hes6/hes6-protnlm-source.json
  title: Frozen exact-input ProtNLM output and UniProt sequence for Q6P0J1
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-10
  source_reference_id: file:DANRE/hes6/hes6-protnlm-source.json
  predicted_term:
    id: GO:0003677
    label: DNA binding
  predicted_term_type: GO_MF
  review:
    assessment: LSP
    confidence_score: 2
    summary: Direct assays establish sequence-specific promoter binding by Her7:Hes6, already covered
      by the more specific GOA term. Generic DNA binding is valid for the complex contribution but must
      not be interpreted as autonomous Hes6 homodimer binding.
    supported_by:
    - &id001
      reference_id: PMID:22911291
      supporting_text: only Her1 homodimers and Her7:Hes6 heterodimers have strong DNA binding activity
        and target similar DNA sites.
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-10
  source_reference_id: file:DANRE/hes6/hes6-protnlm-source.json
  predicted_term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  predicted_term_type: GO_BP
  review:
    assessment: LSP
    confidence_score: 2
    summary: Hes6-dependent negative transcriptional regulation is established by reporter, genetic and
      biochemical experiments and already represented more specifically in GOA.
    supported_by:
    - reference_id: PMID:15905406
      supporting_text: Her13.2 augments autorepression of her1 in association with Her1 protein.
    - reference_id: PMID:15905406
      supporting_text: 'her13.2 is required for periodic repression of the

        Notch-regulated genes her1 and her7, and for proper somite segmentation.'
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-10
  source_reference_id: file:DANRE/hes6/hes6-protnlm-source.json
  predicted_term:
    id: GO:0046983
    label: protein dimerization activity
  predicted_term_type: GO_MF
  review:
    assessment: CNN
    confidence_score: 2
    summary: Both homo- and heterodimerization are directly demonstrated and the same broad term is already
      present in GOA. Different dimer combinations have different DNA-binding capabilities.
    supported_by:
    - reference_id: PMID:22911291
      supporting_text: all of the possible dimers between Her1, Her7 and Hes6 form
    - *id001