sh3glb2b

Gene 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 Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IEA GO_REF:0000002	ACCEPT	Summary: Cytoplasm (IEA) from InterPro BAR domain / UniProt subcellular location mapping. 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). 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:0006897 endocytosis	IBA GO_REF:0000033	MODIFY	Summary: Endocytosis (IBA) from the endophilin node PTN009017136; donors include endophilin-A and endophilin-B proteins of mouse, rat, fly and worm. 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. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN009017136 SUPPORTS SOURCE BUT NOT TARGET 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. Proposed replacements: endosome to lysosome transport Supporting Evidence: PMID:28455444 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. PMID:28455444 endophilin B2 is not required for embryonic development in vivo but that endophilin B2 deficiency impairs endosomal trafficking in vitro
GO:0016020 membrane	IBA GO_REF:0000033	ACCEPT	Summary: Membrane (IBA) from the endophilin node PTN009017136. Reason: Endophilin-B proteins bind membranes through the N-terminal amphipathic helix and N-BAR domain, both conserved in sh3glb2b. Correct general location. Supporting Evidence: 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. 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:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Protein-macromolecule adaptor activity (IBA) from the deeper node PTN009017043, donors human SORBS1 and two mouse genes. 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. Supporting Evidence: PMID:28455444 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 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:0061024 membrane organization	IBA GO_REF:0000033	ACCEPT	Summary: Membrane organization (IBA) from the endophilin node PTN009017136. 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. Supporting Evidence: 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. 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.

Core Functions

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:

membrane organization endosome to lysosome transport

Cellular Locations:

membrane cytoplasm

Supporting Evidence:

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.
PMID:28455444
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.
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.

References

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Suggested Experiments

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

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

Bioinformatics Results

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