cep-1

id: A8WW61
gene_symbol: cep-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6238
  label: Caenorhabditis briggsae
description: >-
  Cbr-CEP-1 is the Caenorhabditis briggsae ortholog of the nematode p53/p63/p73-family
  transcription factor CEP-1, the sole representative of the p53 superfamily in
  Caenorhabditis. It is a sequence-specific, zinc-dependent DNA-binding transcription
  factor that recognizes a p53-like DNA consensus element and acts predominantly as a
  transcriptional activator. Its central, conserved role is to trigger germline apoptosis
  in response to genotoxic stress (ionizing radiation and other DNA-damaging insults),
  acting downstream of DNA-damage signaling by directly inducing transcription of the
  BH3-only pro-apoptotic activators egl-1 and ced-13. It also contributes to physiological
  roles outside DNA-damage apoptosis, including ensuring proper meiotic chromosome
  segregation, modulating responses to additional stresses such as hypoxia, oxidative
  stress and starvation, regulating germline proliferation (via phg-1), and negatively
  influencing adult lifespan. The protein binds one zinc ion per subunit through its
  p53-like DNA-binding domain, functions as a homodimer, and its pro-apoptotic activity is
  modulated by interacting partners (for example inhibition by ape-1 and by methylated
  cbp-1 in the prmt-5/cbp-1 complex). Like vertebrate p53, it functions in the nucleus.
existing_annotations:
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      CEP-1 is a bona fide DNA-binding protein, so this is not wrong, but DNA binding is a
      generic parent term. The more specific and informative molecular functions
      (sequence-specific DNA binding and DNA-binding transcription factor activity) are
      separately annotated and better capture the function.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      CEP-1 is the worm p53-family transcription factor and binds a p53-like DNA consensus
      to activate transcription of target genes. This is a core molecular function. I
      propose a more specific RNA polymerase II-specific term as the core function, but the
      general term is correct.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase II-specific
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      As a transcription factor, CEP-1 acts in the nucleus; UniProt records nuclear
      localization by similarity to the C. elegans ortholog. Core cellular component for a
      transcription factor.
    action: ACCEPT
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 regulates transcription of target genes. This is correct but very general; the
      RNA polymerase II-specific positive-regulation term better reflects its activator
      role. Retained as a non-core, broader process annotation.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 promotes apoptosis under hypoxic and other stress conditions (UniProt
      FUNCTION). This is a peripheral stress-response process for a pleiotropic
      transcription factor, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: >-
      Consistent with nuclear localization of a transcription factor. Reasonable but more
      granular than needed; subsumed by the nucleus annotation, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: >-
      Nucleolar localization is not part of the established function of worm p53/CEP-1,
      which acts as a sequence-specific transcription factor in the nucleoplasm. This
      electronically propagated component looks like an over-reach not supported by CEP-1
      biology.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 promotes apoptosis under conditions of cellular and genotoxic stress,
      consistent with a role in oxidative-stress responses. Peripheral process for this
      pleiotropic TF, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      The p53-like DNA-binding domain coordinates one zinc ion per subunit (UniProt
      COFACTOR and BINDING sites at residues 319, 322, 375, 379). Correct and structurally
      supported, though it is an accessory binding function supporting DNA binding rather
      than the core function.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 negatively regulates lifespan (UniProt FUNCTION). A genuine but peripheral
      organismal-level role for this pleiotropic transcription factor, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 is the central mediator of DNA-damage-induced germline apoptosis, acting
      downstream of DNA-damage signaling to induce egl-1 and ced-13. This is a core
      biological process. The p53-class-mediator child term is the most specific
      representation.
    action: ACCEPT
- term:
    id: GO:0017053
    label: transcription repressor complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: >-
      CEP-1 functions predominantly as a transcriptional activator of pro-apoptotic
      targets. While it interacts with the prmt-5/cbp-1 complex (which can inhibit its
      activity), placement in a transcription repressor complex mischaracterizes its
      primary role and is an over-reach of an electronically propagated component
      annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0042594
    label: response to starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 promotes apoptosis under starvation among other stress conditions (UniProt
      FUNCTION). Peripheral stress-response process for this pleiotropic TF, kept as
      non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0042770
    label: signal transduction in response to DNA damage
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 acts in the DNA-damage response and is itself induced and phosphorylated
      following DNA damage. It functions as the transcriptional effector at the end of the
      pathway; the DNA-damage apoptotic-signaling terms capture this best. Kept as a
      non-core supporting process.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class
      mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      This is the single most specific and accurate process term for CEP-1, the worm
      p53-class mediator of DNA-damage-induced germline apoptosis (inducing egl-1/ced-13).
      Core biological process.
    action: ACCEPT
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      CEP-1 functions as a homodimer (UniProt SUBUNIT), consistent with p53-family DNA
      binding. Correct accessory molecular function supporting DNA binding; kept as
      non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      CEP-1 binds the same DNA consensus sequence as p53 (UniProt FUNCTION) via its
      p53-like DNA-binding domain. This is a core molecular function underpinning its
      activity as a sequence-specific transcription factor.
    action: ACCEPT
- term:
    id: GO:0045132
    label: meiotic chromosome segregation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      CEP-1 has a normal developmental role ensuring proper meiotic chromosome segregation
      (UniProt FUNCTION). A genuine but non-core developmental process distinct from its
      DNA-damage apoptotic role.
    action: KEEP_AS_NON_CORE
- 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: >-
      CEP-1 is primarily a transcriptional activator, directly inducing target genes
      (egl-1, ced-13, phg-1) via RNA polymerase II. This accurately captures its mode of
      action as an activator and is treated as core together with the DNA-damage apoptosis
      role.
    action: ACCEPT
- term:
    id: GO:0072332
    label: intrinsic apoptotic signaling pathway by p53 class mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Correct parent term describing CEP-1 as a p53-class mediator of intrinsic apoptosis.
      The DNA-damage-specific child (GO:0042771) is more precise and treated as core; this
      broader term is retained as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Duplicate of the nucleus localization (here by ISS from the C. elegans ortholog).
      CEP-1 acts in the nucleus; core component for a transcription factor.
    action: ACCEPT
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS duplicate of the hypoxia-response annotation. CEP-1 promotes apoptosis under
      hypoxic stress; peripheral process, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS transfer of the core transcription factor activity from the C. elegans ortholog.
      Correct; the RNA polymerase II-specific term is proposed as the most precise core
      molecular function.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase II-specific
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS duplicate. Correct but very general regulation-of-transcription term; retained as
      non-core in favor of the RNA polymerase II-specific positive regulation term.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS duplicate of the oxidative-stress response. Peripheral stress process for this
      pleiotropic TF, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS duplicate. The DNA-binding domain coordinates one zinc ion per subunit; accessory
      binding function supporting DNA binding, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS duplicate. CEP-1 negatively regulates lifespan; peripheral organismal role, kept
      as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class
      mediator
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS transfer of the most specific and accurate process term: CEP-1 as the worm
      p53-class mediator of DNA-damage-induced germline apoptosis. Core biological process.
    action: ACCEPT
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS duplicate. CEP-1 acts as a homodimer; accessory molecular function supporting DNA
      binding, kept as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS transfer of sequence-specific DNA binding, a core molecular function. CEP-1 binds
      a p53-like consensus via its DNA-binding domain.
    action: ACCEPT
- term:
    id: GO:0045132
    label: meiotic chromosome segregation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS duplicate. Genuine developmental role ensuring proper meiotic chromosome
      segregation, distinct from the core DNA-damage apoptosis function; kept as non-core.
    action: KEEP_AS_NON_CORE
core_functions:
- description: >-
    Sequence-specific RNA polymerase II DNA-binding transcription factor that binds a
    p53-like DNA consensus element and activates transcription of target genes.
  supported_by:
  - reference_id: GO_REF:0000024
    supporting_text: >-
      Transcriptional activator that binds the same DNA consensus sequence as p53.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
- description: >-
    As the worm p53-class mediator, drives the intrinsic apoptotic response to DNA damage
    by transactivating pro-apoptotic BH3-only target genes (egl-1, ced-13) to trigger
    germline apoptosis after genotoxic stress.
  supported_by:
  - reference_id: GO_REF:0000024
    supporting_text: >-
      Regulates DNA damage-induced apoptosis by inducing transcription of the programmed
      cell death activator egl-1.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  locations:
  - id: GO:0005634
    label: nucleus
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      ISS transfer from the experimentally characterized C. elegans ortholog cep-1
      (UniProtKB Q20646). Appropriate for transcription factor activity, DNA binding,
      nuclear localization, and DNA-damage apoptosis given strong orthology and conserved
      p53-family DNA-binding domain.
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Automated Compara-based transfer from the C. elegans ortholog. Most transferred terms
      are appropriate, but some electronically propagated component terms (nucleolus,
      transcription repressor complex) over-reach relative to the established activator
      biology of CEP-1.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Combined IEA (InterPro2GO and related) annotations. Consistent with the p53-like
      DNA-binding domain (IPR008967, IPR012346); the generic DNA binding term is subsumed
      by the more specific sequence-specific DNA binding annotation.