id: A0A8M9Q303
gene_symbol: sh3glb2b
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: sh3glb2b (SH3-domain GRB2-like endophilin B2b) is one of two zebrafish co-orthologs of vertebrate SH3GLB2 (endophilin-B2),
  retained from the teleost genome duplication; its paralog is sh3glb2a. 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; several splice isoforms differ by insertions in the BAR domain and the linker. 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. sh3glb2b is strongly maternal, is
  detected in the embryonic central nervous system and eye by in situ hybridization, and is broadly expressed in adult tissues.
  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:0000002
  qualifier: located_in
  supporting_entities:
  - InterPro:IPR004148
  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; sh3glb2b 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:0006897
    label: endocytosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  supporting_entities:
  - FB:FBgn0034433
  - FB:FBgn0038659
  - MGI:MGI:700009
  - MGI:MGI:700010
  - PANTHER:PTN009017136
  - RGD:1305886
  - RGD:620276
  - WB:WBGene00006791
  review:
    summary: Endocytosis (IBA) from the endophilin node PTN009017136; donors include endophilin-A and endophilin-B proteins
      of mouse, rat, fly and worm.
    action: MODIFY
    reason: The node spans endophilin-A proteins, which act in clathrin-mediated endocytosis, and endophilin-B proteins. For
      endophilin-B2 itself, loss did not affect endocytic internalization but impaired trafficking of endocytic vesicles and
      autophagosomes to late endosomes and lysosomes. The better term for the SH3GLB2 clade is endosome to lysosome transport.
      Evidence is from mouse cells; nothing is known for zebrafish.
    proposed_replacement_terms:
    - id: GO:0008333
      label: endosome to lysosome transport
    supported_by:
    - 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: PMID:28455444
      supporting_text: endophilin B2 is not required for embryonic development in vivo but that endophilin B2 deficiency impairs
        endosomal trafficking in vitro
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - GRANULARITY_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN009017136
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: The endophilin node includes endophilin-A proteins that act in endocytic internalization; for the endophilin-B2
          clade the documented role is downstream, in endosome-to-lysosome trafficking, while internalization is unaffected
          by its loss.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  supporting_entities:
  - FB:FBgn0034433
  - FB:FBgn0038659
  - MGI:MGI:1859730
  - PANTHER:PTN009017136
  - RGD:1304859
  - RGD:620276
  - RGD:620578
  - UniProtKB:Q9UJU6
  - UniProtKB:Q9Y371
  review:
    summary: Membrane (IBA) from the endophilin node PTN009017136.
    action: ACCEPT
    reason: Endophilin-B proteins bind membranes through the N-terminal amphipathic helix and N-BAR domain, both conserved
      in sh3glb2b. Correct general location.
    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: 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:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  supporting_entities:
  - MGI:MGI:1913066
  - MGI:MGI:700014
  - PANTHER:PTN009017043
  - UniProtKB:Q9BX66
  review:
    summary: Protein-macromolecule adaptor activity (IBA) from the deeper node PTN009017043, donors human SORBS1 and two mouse
      genes.
    action: KEEP_AS_NON_CORE
    reason: The SH3 domain is conserved and endophilin-B proteins bind partners through it (endophilin-B1 is treated as a
      BAR/SH3 adaptor), but the node is placed deep in the SH3-domain superfamily, and for endophilin-B2 the SH3 domain was
      dispensable for its best-characterized cellular role (EGFR degradation), which needs the N-BAR domain. Kept as a plausible
      non-core activity.
    supported_by:
    - reference_id: PMID:28455444
      supporting_text: Interestingly, we found that the N-BAR domain of endophilin B2 is required to rescue EGFR degradation
        in endophilin B2-deficient cells, whereas the SH3 domain appears to be dispensable
    - 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:0061024
    label: membrane organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  supporting_entities:
  - FB:FBgn0034433
  - FB:FBgn0038659
  - PANTHER:PTN009017136
  - RGD:620276
  - UniProtKB:Q9Y371
  review:
    summary: Membrane organization (IBA) from the endophilin node PTN009017136.
    action: ACCEPT
    reason: The N-BAR domain of endophilin-B proteins induces membrane curvature and regulates intracellular membrane dynamics;
      sh3glb2b keeps the helix and N-BAR domain. Core process for the family, not measured in zebrafish.
    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: 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.
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: []
- 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 zebrafish
    measurement. Protein features shared with sh3glb2a.'
  directly_involved_in:
  - id: GO:0061024
    label: membrane organization
  - id: GO:0008333
    label: endosome to lysosome transport
  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