id: A0A8M1N8K5
gene_symbol: sh3glb2a
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: sh3glb2a (SH3-domain GRB2-like endophilin B2a) is one of two zebrafish co-orthologs of vertebrate SH3GLB2 (endophilin-B2),
  retained from the teleost genome duplication; its paralog is sh3glb2b. It encodes a cytoplasmic protein with an N-terminal
  membrane-binding amphipathic helix, an N-BAR domain that senses and induces membrane curvature and mediates homo- and heterodimerization,
  and a C-terminal SH3 domain. In mammals endophilin-B2 promotes trafficking of endocytic vesicles and autophagosomes to late
  endosomes and lysosomes and, together with endophilin-B1, mitophagy; the knockout mouse is viable. The zebrafish protein
  keeps all these domains. sh3glb2a transcripts peak at blastula stages and are low but present later; adult RNA-seq detects
  it broadly. No functional study of the zebrafish gene has been published.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  supporting_entities:
  - InterPro:IPR004148
  - UniProtKB-SubCell:SL-0086
  review:
    summary: Cytoplasm (IEA) from InterPro BAR domain / UniProt subcellular location mapping.
    action: ACCEPT
    reason: Mammalian SH3GLB proteins are cytoplasmic and excluded from the nucleus; sh3glb2a keeps the endophilin-B2 architecture.
      Correct, if general; the protein acts on cytoplasmic membranes (endosomes, autophagosomes).
    supported_by:
    - reference_id: PMID:11161816
      supporting_text: Furthermore, SH3GLB members colocalize to the cytoplasmic compartment of the cell together with Bax
        and are excluded from the nucleus.
    - reference_id: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md
      supporting_text: Both copies keep the N-terminal amphipathic helix, the full BAR domain and the SH3 domain of endophilin-B2.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISS
  original_reference_id: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md
  review:
    summary: 'Membrane, proposed from sequence: sh3glb2a keeps the membrane-binding amphipathic helix and N-BAR domain of
      endophilin-B2.'
    action: NEW
    reason: sh3glb2b receives membrane (IBA) from the endophilin node PTN009017136, but sh3glb2a receives no IBA rows because
      PANTHER places every sh3glb2a UniProt entry in subfamily SF68 ('DREBRIN-LIKE PROTEIN-RELATED') rather than the endophilin-B2
      subfamily. sh3glb2a is 85% identical to human SH3GLB2 in the amphipathic helix and 77% in the BAR domain, and its SH3
      domain ends in the same sequence as human SH3GLB2, so the membrane-binding function is expected to be shared. Proposed
      as a location only; the paired process terms are left to a corrected PANTHER placement.
    supported_by:
    - reference_id: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md
      supporting_text: Both copies keep the N-terminal amphipathic helix, the full BAR domain and the SH3 domain of endophilin-B2.
    - reference_id: PMID:28455444
      supporting_text: The endophilin B family of proteins contains an N-terminal Bin/amphiphysin/Rvs (N-BAR) domain that
        induces membrane curvature to regulate intracellular membrane dynamics.
references:
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11161816
  title: SH3GLB, a new endophilin-related protein family featuring an SH3 domain.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Abstract only; identification of human SH3GLB1/2, dimerization via coiled coil, cytoplasmic localization.
- id: PMID:27112121
  title: Endophilin B2 promotes inner mitochondrial membrane degradation by forming heterodimers with Endophilin B1 during
    mitophagy.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Human cell lines; EB2 (endophilin-B2) in mitophagy as heterodimer with endophilin-B1.
- id: PMID:28455444
  title: Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and
    influenza A virus infection.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Mouse knockout viable; endophilin-B2 needed for endosome-to-lysosome trafficking in cells; N-BAR required,
      SH3 dispensable for EGFR degradation.
- id: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md
  title: sh3glb2a / sh3glb2b protein, expression and synteny comparison
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Manual audit verified the sidecar supports both copies as SH3GLB2 ohnologs retaining endophilin-B2
      BAR and SH3 architecture, with broad overlapping expression and no copy-specific functional assay.
  findings: []
core_functions:
- description: 'Endophilin-B2 orthologue (N-terminal amphipathic helix plus N-BAR domain and C-terminal SH3 domain): by homology
    with mammalian endophilin-B2 a cytoplasmic membrane-remodelling protein that binds and curves membranes and promotes trafficking
    of endocytic vesicles and autophagosomes to late endosomes and lysosomes. Inferred from conserved domains (no process
    terms are recorded here because this copy carries no process annotations, owing to its PANTHER subfamily placement); no
    zebrafish measurement. Protein features shared with sh3glb2b.'
  locations:
  - id: GO:0016020
    label: membrane
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:28455444
    supporting_text: The endophilin B family of proteins contains an N-terminal Bin/amphiphysin/Rvs (N-BAR) domain that induces
      membrane curvature to regulate intracellular membrane dynamics.
  - reference_id: PMID:28455444
    supporting_text: Mechanistically, although the loss of endophilin B2 did not affect endocytic internalization and lysosomal
      function, endophilin B2 appeared to regulate the trafficking of endocytic vesicles and autophagosomes to late endosomes
      or lysosomes.
  - reference_id: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md
    supporting_text: Both copies keep the N-terminal amphipathic helix, the full BAR domain and the SH3 domain of endophilin-B2.
suggested_questions:
- question: Is the PANTHER subfamily split (sh3glb2a in PTHR14167:SF68 'DREBRIN-LIKE PROTEIN-RELATED', sh3glb2b in SF106 'ENDOPHILIN-B2')
    a classification artefact? The sh3glb2a protein keeps the full endophilin-B2 architecture, and its misplacement removes
    all IBA rows from it.
- question: Does the strong maternal load of sh3glb2b and the blastula-only peak of sh3glb2a reflect a temporal split of an
    ancestral early-embryo expression, or independent drift? Gar embryo time-course data would test this.
suggested_experiments:
- hypothesis: sh3glb2a and sh3glb2b are functionally redundant in endosome maturation.
  description: Make single and double mutants (including RNA-less alleles to avoid transcriptional adaptation) and measure
    endosome acidification, EGFR or dextran trafficking to lysosomes, and autophagic flux in larval tissues; cross-rescue
    each mutant with the other copy's mRNA.
  experiment_type: genetic interaction
- hypothesis: The copies differ only in expression level.
  description: Quantify both transcripts across tissues and single-cell atlases, and compare with gar SH3GLB2 expression to
    test for quantitative subfunctionalization.
  experiment_type: expression analysis