exoc3l2b (exocyst complex component 3-like 2b) is one of two zebrafish co-orthologs of vertebrate EXOC3L2, retained from the teleost-specific genome duplication; its paralog is exoc3l2a, to which it is about 51% identical. It encodes a 917-aa member of the EXOC3/Sec6 family with an N-terminal region and a C-terminal Sec6 helical-bundle domain. It is the slower-evolving copy, closer to the single gar gene. Mammalian EXOC3L2 associates with the exocyst subunit EXOC4. It is needed for VEGFA-induced VEGFR2 phosphorylation and directional migration of endothelial cells, and for cardiovascular development in mouse; human biallelic mutations cause a hindbrain, kidney and bone-marrow syndrome. In zebrafish, a probe that ZFIN assigns to exoc3l2b ("sec6" in the original paper) detects expression in premigratory neural crest at 12 hpf and later in the dorsal hindbrain and pharyngeal arches. Public RNA-seq detects the gene in many adult tissues, including intestine, spleen, gill and kidney. No loss-of-function or biochemical study of exoc3l2b has been published.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000145 exocyst | IEA GO_REF:0000002 | ACCEPT | Summary: Exocyst from the InterPro EXOC3/Sec6 entry (IPR010326) mapping. Reason: exoc3l2b keeps a complete Sec6 domain and is an EXOC3L2 co-ortholog. Mammalian EXOC3L2 co-precipitates with EXOC4 and colocalises with EXOC4 and EXOC7, which supports association with the exocyst. Whether it is a stoichiometric subunit or a separate partner has not been settled, so the term is kept at the complex level. The same call is made for exoc3l2a, which also carries this term as an IBA. Supporting Evidence: PMID:21566143 Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. file:DANRE/exoc3l2a/exoc3l2a-bioinformatics/RESULTS.md Both copies keep a full-length Sec6 domain and the N-terminal region; neither is truncated. |
| GO:0006887 exocytosis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Exocytosis from the InterPro EXOC3/Sec6 mapping. Reason: Plausible for an exocyst-associated protein, and the proposed model for EXOC3L2 is exocyst-dependent delivery of VEGFR2 to the cell surface. But no secretion or exocytosis assay has been done for EXOC3L2 in any species. The zebrafish "sec6" study that detected this gene in neural crest did not test its function in trafficking. Supporting Evidence: PMID:21566143 We hypothesized that EXOC3L2 may be involved in the exocytosis of VEGFR2, and that a down-regulation of EXOC3L2 expression thus could have an effect on VEGFR2 phosphorylation. |
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Download this section (compressed HTML)Q: Is the probe ZFIN assigns to exoc3l2b ("sec6" in PMID:20463035) specific for exoc3l2b, rather than for exoc3 or exoc3l2a? The neural-crest and pharyngeal-arch pattern should be confirmed with a gene-specific probe.
Q: Is exoc3l2b expressed in endothelium, as exoc3l2a and mouse Exoc3l2 are, or has the endothelial domain been lost from this copy?
Experiment: Do HCR in situ hybridization for exoc3l2b alongside exoc3l2a, kdrl and sox10 at 12-72 hpf to map shared and copy-specific domains.
Experiment: Generate exoc3l2b single and exoc3l2a;exoc3l2b double mutants, including an RNA-less allele, and score neural-crest migration, craniofacial cartilage and vascular integrity.
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