she-1

id: A8XDR5
gene_symbol: she-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6238
  label: Caenorhabditis briggsae
description: >-
  she-1 (Cbr-SHE-1, "spermless hermaphrodites 1") is an F-box protein of
  Caenorhabditis briggsae required for spermatogenesis in XX hermaphrodites. The
  protein contains two F-box domains (residues ~24-69 and ~523-563), the
  protein-protein interaction module through which F-box proteins are recruited,
  via Skp, into SCF (Skp1/Cullin/F-box) E3 ubiquitin-ligase complexes where they
  serve as the substrate-recognition subunit that targets specific proteins for
  ubiquitin-dependent regulation. Loss-of-function and reduction-of-function
  mutations transform XX animals from self-fertile hermaphrodites into females
  that produce only oocytes (no spermatocytes), so that they are self-sterile but
  fertile when mated to males; the alleles are temperature-sensitive, and RNAi
  knock-down yields a strongly female-biased brood. she-1 acts in the germline
  sex-determination program, with mutants failing to produce the FOG-3 protein
  that specifies the male (sperm) germ-cell fate; it thus promotes the brief burst
  of XX spermatogenesis that underlies self-fertile hermaphroditism. she-1 is a
  lineage-specific gene that arose from a recent gene duplication and has no clear
  one-to-one ortholog in C. elegans; it represents an independent recruitment of
  an F-box gene into the hermaphrodite sex-determination pathway, distinct from the
  unrelated F-box gene fog-2 used by C. elegans, exemplifying convergent evolution
  of self-fertile hermaphroditism in Caenorhabditis. Its molecular targets and the
  identity of the SCF complex it associates with have not been experimentally
  defined.
references:
- id: PMID:19836240
  title: "Independent recruitment of F box genes to regulate hermaphrodite development during nematode evolution."
  findings:
  - statement: >-
      Mutations define she-1 (spermless hermaphrodites), a novel F-box gene whose
      loss transforms C. briggsae XX hermaphrodites into self-sterile females that
      produce oocytes but no sperm; the gene is required for XX spermatogenesis.
  - statement: >-
      she-1 acts in germline sex determination; mutants fail to produce FOG-3
      protein, and she-1 arose by a recent gene duplication independent of the
      unrelated C. elegans F-box gene fog-2, demonstrating convergent recruitment
      of F-box genes to control hermaphrodite development.
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: >-
      Sole primary characterization of she-1 (Guo, Lang & Ellis, Curr. Biol. 2009).
      PMID is the reference cited by the UniProt entry (A8XDR5) for FUNCTION,
      DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, and mutagenesis of Arg-49/Gly-111.
      Full text is not available in the local publications cache, so no verbatim
      supporting_text is quoted and citation soundness is not independently verified
      here; claims are drawn from the UniProt summary and the published abstract.
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
existing_annotations: []
core_functions:
- description: >-
    Substrate-recognition subunit of an SCF (Skp1/Cullin/F-box) E3 ubiquitin-ligase
    complex. she-1 is an F-box protein (two F-box domains); F-box domains recruit the
    protein into SCF complexes via Skp1, where the F-box protein acts as the
    interchangeable adaptor that binds and presents specific substrates to the
    ubiquitin-ligase core. This molecular role is inferred from the diagnostic F-box
    domains and the canonical biology of F-box proteins; the specific substrate(s)
    of she-1 are not yet experimentally established.
  molecular_function:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  in_complex:
    id: GO:0019005
    label: SCF ubiquitin ligase complex
  supported_by:
  - reference_id: PMID:19836240
  knowledge_gaps:
  - gap_statement: >-
      The direct ubiquitylation substrate(s) presented by SHE-1 to its SCF complex,
      and the specific Skp1/Cullin partners forming that complex, are undetermined.
    boundary: >-
      SHE-1 carries two canonical F-box domains and is genetically required for XX
      spermatogenesis, but no biochemical substrate or complex composition has been
      reported.
    gap_kind:
    - BIOLOGY
- description: >-
    Germline sex-determination factor that promotes the male (sperm) germ-cell fate
    in XX hermaphrodites of C. briggsae. she-1 is required for the transient burst of
    hermaphrodite spermatogenesis: loss-of-function transforms XX animals into
    oocyte-only, self-sterile females, and mutants fail to produce the downstream
    FOG-3 protein that specifies the sperm fate. It is a lineage-specific factor
    independently recruited into the sex-determination pathway during the evolution of
    self-fertile hermaphroditism.
  molecular_function:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  directly_involved_in:
  - id: GO:0007530
    label: sex determination
  - id: GO:0048232
    label: male gamete generation
  supported_by:
  - reference_id: PMID:19836240
suggested_questions:
- question: >-
    What is the direct ubiquitylation substrate of the SHE-1 SCF complex, and how
    does targeting that substrate switch the XX germline to the sperm fate?
  experts:
  - C. elegans/Caenorhabditis germline sex-determination biologists
  - Ubiquitin-proteasome system biochemists
- question: >-
    Which Skp1 and Cullin orthologs assemble with SHE-1 into a functional SCF complex
    in the C. briggsae germline?
  experts:
  - SCF/E3 ligase structural biologists
suggested_experiments:
- experiment_type: Affinity purification / mass spectrometry
  description: >-
    Affinity-purify tagged SHE-1 from C. briggsae germline tissue and identify
    interacting Skp1/Cullin/SCF components and candidate ubiquitylation substrates by
    mass spectrometry, to confirm the SCF adaptor role and identify targets.
- experiment_type: Epistasis / genetic interaction analysis
  description: >-
    Place she-1 within the C. briggsae germline sex-determination pathway by epistasis
    with fog-3 and other sperm/oocyte-fate genes, and test whether candidate substrates
    are stabilized in she-1 loss-of-function mutants.
- experiment_type: Domain mutagenesis
  description: >-
    Mutate the F-box domains (and the Arg-49/Gly-111 residues altered in v35/v51) to
    test whether SCF recruitment is required for she-1 function in XX spermatogenesis.