oaz

id: Q9NHZ4
gene_symbol: oaz
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:54126
  label: Pristionchus pacificus
description: >-
  Ornithine decarboxylase antizyme (ODC-Az) is a small (142 aa) regulatory
  protein and the master negative regulator of cellular polyamine homeostasis.
  It binds to monomers of ornithine decarboxylase (ODC), the rate-limiting
  enzyme of polyamine biosynthesis, sterically preventing assembly of the
  catalytically active ODC homodimer and thereby inhibiting ODC enzymatic
  activity. In addition to inhibiting ODC, antizyme targets the bound ODC
  monomer for ubiquitin-independent degradation by the 26S proteasome, providing
  a second, irreversible layer of down-regulation. Through these activities
  antizyme lowers intracellular putrescine, spermidine and spermine levels and
  also suppresses cellular polyamine uptake, coupling polyamine biosynthesis and
  transport to feedback control. Antizyme synthesis is itself controlled by an
  autoregulatory, polyamine-stimulated +1 ribosomal frameshifting event required
  to translate the full-length protein from two overlapping open reading frames,
  so that high polyamine levels increase antizyme production and thereby
  reinforce the negative feedback loop. The protein acts predominantly in the
  cytoplasm but can also localize to the nucleus. This regulatory mechanism is
  deeply conserved across eukaryotes, from yeast to nematodes to mammals.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Nuclear localization is inferred by phylogenetic propagation from the
      antizyme ortholog family (PANTHER PTN001616256), where mammalian antizymes
      have been observed to shuttle between cytoplasm and nucleus. This is a
      plausible but peripheral localization for the P. pacificus protein; the
      defining, growth-regulatory action of antizyme (ODC binding, inhibition
      and proteasomal targeting) occurs predominantly in the cytoplasm. Retained
      as a valid but non-core cellular component.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Cytoplasm is the principal site where antizyme binds ODC monomers,
      inhibits ODC activity and delivers ODC to the 26S proteasome, consistent
      with the well-established antizyme ortholog family. The localization is
      correct, but "cytoplasm" is a broad cellular-component term that does not
      itself describe the molecular function; retained as a valid non-core
      location.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008073
    label: ornithine decarboxylase inhibitor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      This is the core molecular function of antizyme and is strongly supported.
      The annotation is propagated phylogenetically from an antizyme ortholog
      family with direct experimental evidence (e.g. human and mouse antizymes,
      UniProtKB:P54368, O95190, Q9UMX2). The P. pacificus protein belongs to the
      ODC antizyme family (Pfam PF02100, InterPro IPR002993) and is documented
      to negatively regulate ODC and polyamine biosynthesis, including the
      conserved polyamine-induced ribosomal frameshifting that controls its own
      expression. Accept as the central function of this gene.
    action: ACCEPT
- term:
    id: GO:0008073
    label: ornithine decarboxylase inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Electronic InterPro2GO annotation assigning the same core molecular
      function based on the diagnostic ODC antizyme domain (InterPro
      IPR002993 / Pfam PF02100 / PROSITE PS01337) present in this protein. This
      corroborates the IBA annotation for the same term and is consistent with
      the antizyme family. Accept as supporting the core function.
    action: ACCEPT
core_functions:
- description: >-
    Ornithine decarboxylase inhibitor activity: binds ODC monomers to block
    formation of the active ODC homodimer, inhibiting the rate-limiting enzyme of
    polyamine biosynthesis and targeting ODC for ubiquitin-independent
    proteasomal degradation. This drives negative regulation of polyamine
    biosynthesis.
  molecular_function:
    id: GO:0008073
    label: ornithine decarboxylase inhibitor activity
  supported_by:
  - reference_id: GO_REF:0000033
  - reference_id: GO_REF:0000002
  directly_involved_in:
  - id: GO:0170066
    label: negative regulation of polyamine biosynthetic process
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: []