id: A0A8M9Q5H9 gene_symbol: exoc3l2b product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: 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. existing_annotations: - term: id: GO:0000145 label: exocyst evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of supporting_entities: - InterPro:IPR010326 review: summary: Exocyst from the InterPro EXOC3/Sec6 entry (IPR010326) mapping. action: ACCEPT 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. supported_by: - reference_id: PMID:21566143 supporting_text: Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. - reference_id: file:DANRE/exoc3l2a/exoc3l2a-bioinformatics/RESULTS.md supporting_text: Both copies keep a full-length Sec6 domain and the N-terminal region; neither is truncated. - term: id: GO:0006887 label: exocytosis evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in supporting_entities: - InterPro:IPR010326 review: summary: Exocytosis from the InterPro EXOC3/Sec6 mapping. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:21566143 supporting_text: 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. core_functions: - description: EXOC3/Sec6-family protein and EXOC3L2 co-ortholog. By analogy with mammalian EXOC3L2 it probably associates with the exocyst. In the embryo it is reported in premigratory neural crest, dorsal hindbrain and pharyngeal arches, and in adults in many tissues. No activity or process has been tested for this copy, and whether it is expressed in endothelium like exoc3l2a is unknown. in_complex: id: GO:0000145 label: exocyst supported_by: - reference_id: PMID:21566143 supporting_text: Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. - reference_id: PMID:20463035 supporting_text: At earlier stages, expression of all four genes was ubiquitous throughout the embryo but later became enriched in the NC at 12 hpf and in the dorsal hindbrain and pharyngeal arches at 24-72 hpf (data not shown). - reference_id: file:DANRE/exoc3l2a/exoc3l2a-bioinformatics/RESULTS.md supporting_text: At bulk-tissue level the adult profiles of the two copies overlap broadly and both resemble gar. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: PMID:20463035 title: Ovo1 links Wnt signaling with N-cadherin localization during neural crest migration. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Full text. The gene is called "sec6" throughout; ZFIN (ZDB-PUB-100518-8) curates the in situ and RT-PCR data to exoc3l2b. Expression only; sec6 was up-regulated in Ovo1 morphants and after dnTcf3 induction, but its function was not tested (the overexpression phenocopy used rab11fip2). - id: PMID:21566143 title: Exocyst complex component 3-like 2 (EXOC3L2) associates with the exocyst complex and mediates directional migration of endothelial cells. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; founding functional study of human EXOC3L2. Human and mouse cells, not zebrafish. - id: PMID:36362885 title: Essential Roles of Exocyst Complex Component 3-like 2 on Cardiovascular Development in Mice. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; mouse Exoc3l2 knockout. Also reports Exoc3l2 reporter expression in probable cranial neural crest, relevant to the zebrafish neural-crest domain of this copy. - id: PMID:30327448 title: Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; human patients with biallelic EXOC3L2 variants. - id: file:DANRE/exoc3l2a/exoc3l2a-bioinformatics/RESULTS.md title: exoc3l2a / exoc3l2b orthology, protein, expression and synteny comparison reference_review: relevance: HIGH correctness: VERIFIED review_notes: Manual audit verified the sidecar supports both copies as EXOC3L2 co-orthologs retaining the full Sec6 domain; its expression comparison is compatible with subfunctionalization but is not a functional assay. findings: [] suggested_questions: - question: 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. - question: Is exoc3l2b expressed in endothelium, as exoc3l2a and mouse Exoc3l2 are, or has the endothelial domain been lost from this copy? suggested_experiments: - description: Do HCR in situ hybridization for exoc3l2b alongside exoc3l2a, kdrl and sox10 at 12-72 hpf to map shared and copy-specific domains. - description: Generate exoc3l2b single and exoc3l2a;exoc3l2b double mutants, including an RNA-less allele, and score neural-crest migration, craniofacial cartilage and vascular integrity.