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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm (IEA) from InterPro BAR domain / UniProt subcellular location mapping. 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). Supporting Evidence: PMID:11161816 Furthermore, SH3GLB members colocalize to the cytoplasmic compartment of the cell together with Bax and are excluded from the nucleus. file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md Both copies keep the N-terminal amphipathic helix, the full BAR domain and the SH3 domain of endophilin-B2. |
| GO:0016020 membrane | ISS file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md | NEW | Summary: Membrane, proposed from sequence: sh3glb2a keeps the membrane-binding amphipathic helix and N-BAR domain of endophilin-B2. 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. Supporting Evidence: file:DANRE/sh3glb2b/sh3glb2b-bioinformatics/RESULTS.md Both copies keep the N-terminal amphipathic helix, the full BAR domain and the SH3 domain of endophilin-B2. PMID:28455444 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. |
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Download this section (compressed HTML)Q: 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.
Q: 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.
Experiment: 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.
Hypothesis: sh3glb2a and sh3glb2b are functionally redundant in endosome maturation.
Type: genetic interaction
Experiment: Quantify both transcripts across tissues and single-cell atlases, and compare with gar SH3GLB2 expression to test for quantitative subfunctionalization.
Hypothesis: The copies differ only in expression level.
Type: expression analysis
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