peb-1

id: A8XJ98
gene_symbol: peb-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6238
  label: Caenorhabditis briggsae
description: >-
  Cbr-PEB-1 is a FLYWCH-type zinc finger protein and sequence-specific DNA-binding
  transcriptional regulator. Its N-terminal DNA-binding domain contains a Cys/His-rich
  FLYWCH motif (related to Drosophila Mod(mdg4)) that is required for DNA binding and
  in vivo activity, while a conserved C-terminal domain of otherwise unknown function
  is required for full activity; both regions contribute to efficient nuclear
  localization. PEB-1 binds a YDTGCCRW consensus site found in cis-regulatory elements
  of pharyngeal target genes such as myo-2, and it can modulate their transcription. In
  the pharynx PEB-1 is co-expressed with the activating transcription factor PHA-4 at
  overlapping binding sites and can interfere with PHA-4 function, contributing to
  control of pharyngeal gene expression. PEB-1 is expressed in most pharyngeal cell
  types (muscle, epithelial, marginal and gland cells) and at lower levels in hypodermis
  and hindgut, and is required for normal morphogenesis of the pharynx, vulva and
  hindgut as well as for normal molting and feeding.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization is well supported: PEB-1 is a DNA-binding transcription factor
      and its C. elegans ortholog localizes to nuclei (dependent in part on the FLYWCH
      domain). This electronic annotation is concordant with the experimental IDA
      annotation below and is accepted as a core localization.
    action: ACCEPT
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Consistent with the ortholog's documented ability to interfere with/repress
      activity of the PHA-4 transcriptional activator at overlapping cis-regulatory
      sites. This electronic ortholog-transfer annotation is biologically plausible but
      captures only one direction of PEB-1's context-dependent regulatory activity; it
      is retained as a non-core process annotation since the directionality is
      context-specific rather than a defining function.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      Strongly supported: PEB-1 binds a defined YDTGCCRW consensus sequence in
      cis-regulatory regions of RNA polymerase II target genes (e.g. the myo-2 C183
      element), and DNA binding requires the FLYWCH motif. This sequence-specific
      cis-regulatory DNA binding is a core molecular function of the protein.
    action: ACCEPT
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      PEB-1's regulatory output is context-dependent and has been described both as
      cooperative/activating and as interfering with PHA-4 at the myo-2 element, so a
      positive-regulation role is plausible by ortholog transfer. As with the negative
      regulation term, the specific direction is context-dependent rather than a defining
      function, so it is retained as a non-core process annotation.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15165844
  qualifier: located_in
  review:
    summary: >-
      Experimental (IDA) evidence supports nuclear localization; the curators report that
      efficient nuclear localization requires both the FLYWCH motif and the C-terminal
      domain. Consistent with PEB-1 function as a nuclear DNA-binding transcription
      factor. Accepted as a core localization.
    action: ACCEPT
core_functions:
- description: >-
    Sequence-specific DNA-binding transcription factor that binds a YDTGCCRW consensus
    in RNA polymerase II cis-regulatory elements of pharyngeal target genes and modulates
    their transcription.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  supported_by:
  - reference_id: PMID:15165844
    supporting_text: >-
      Analysis of binding sites revealed a YDTGCCRW PEB-1 consensus-binding site, and
      matches to this consensus are widespread in the C.elegans genome.
- description: >-
    FLYWCH-motif-dependent sequence-specific binding to cis-regulatory regions of RNA
    polymerase II-transcribed target genes (e.g. the myo-2 C183 element).
  molecular_function:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:15165844
    supporting_text: >-
      The PEB-1 FLYWCH motif is essential for DNA-binding and in vivo function; however,
      it does not bind detectable metal.
references:
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15165844
  title: DNA binding and in vivo function of C.elegans PEB-1 require a conserved FLYWCH
    motif.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary research on PEB-1; the C. briggsae sequence is characterized
      here and the FLYWCH motif is shown to be required for DNA binding and in vivo
      function. Establishes the YDTGCCRW consensus and nuclear localization requirements.
      Cached entry is abstract-only (full_text_available: false); quotes used are verbatim
      from the abstract.