id: A0A8N7UT25 gene_symbol: olfm3b product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: olfm3b (olfactomedin 3b) is one of two zebrafish co-orthologs of vertebrate OLFM3 (optimedin, noelin-3), retained from the teleost-specific genome duplication; its paralog is olfm3a. It encodes a secreted glycoprotein with a signal peptide, an N-terminal coiled-coil region and a C-terminal olfactomedin (beta-propeller) domain, and belongs to the noelin subfamily with OLFM1 and OLFM2. In mammals OLFM3 is expressed in retina, brain and the anterior eye, forms homo- and hetero-oligomers with other noelins and binds myocilin, and the noelins together are extracellular constituents of AMPA-type glutamate receptor complexes that anchor the receptors at synapses. The zebrafish protein keeps the coiled coil, the olfactomedin domain and the cysteines of human OLFM3. olfm3b is expressed at low levels throughout embryonic and larval development; public RNA-seq detects it in adult brain, intestine and ovary. No functional study of this gene has been published. existing_annotations: - term: id: GO:0005576 label: extracellular region evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - MGI:MGI:1202864 - MGI:MGI:1860437 - MGI:MGI:2387329 - MGI:MGI:2388361 - MGI:MGI:2443310 - MGI:MGI:2444741 - MGI:MGI:2685142 - PANTHER:PTN000573635 - RGD:727879 - UniProtKB:O95897 - UniProtKB:Q6UX06 - UniProtKB:Q99972 - UniProtKB:Q9IAK4 - UniProtKB:Q9XTA3 review: summary: Extracellular region (IBA) from the olfactomedin family node PTN000573635. action: ACCEPT reason: Olfactomedin-domain proteins are secreted, and OLFM3 is secreted in transfected cells. olfm3b has a predicted signal peptide and keeps the olfactomedin domain and cysteines of human OLFM3, so it is inside the secreted clade. supported_by: - reference_id: PMID:12019210 supporting_text: Both optimedin and myocilin are localized in Golgi and are secreted proteins. - reference_id: file:DANRE/olfm3a/olfm3a-bioinformatics/RESULTS.md supporting_text: Both copies keep the coiled coil, the olfactomedin domain, all six human cysteines and the calcium-site residues. - term: id: GO:0005576 label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0243 review: summary: Extracellular region from the UniProt 'Secreted' subcellular location (ARBA rule). action: ACCEPT reason: Consistent with the signal peptide and with secretion of mammalian OLFM3. supported_by: - reference_id: PMID:12019210 supporting_text: Both optimedin and myocilin are localized in Golgi and are secreted proteins. - term: id: GO:0007165 label: signal transduction evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:1202864 - MGI:MGI:1860437 - PANTHER:PTN000573635 - UniProtKB:Q99972 review: summary: Signal transduction propagated from the olfactomedin family node, seeded by myocilin (mouse Myoc, human MYOC) and mouse Olfm1. action: MARK_AS_OVER_ANNOTATED reason: The node sits at the base of a large and functionally varied family (noelins, myocilin, gliomedin, OLFM4 and others), and its donors are myocilin and Olfm1, not an OLFM3. The best-supported mammalian role of the noelins, OLFM3 included, is extracellular organization of AMPA-receptor complexes, which is not signal transduction in the GO sense; OLFM3-specific data are limited to binding partners and overexpression effects on adhesion. For a secreted protein of unknown mechanism this very general process term says more than the evidence does. The same call is made for olfm3a. supported_by: - reference_id: PMID:37591201 supporting_text: Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration with a variety of secreted and membrane-anchored proteins including Neurexin1, Neuritin1, and Seizure 6-like. - reference_id: PMID:16115881 supporting_text: Although the function of optimedin is still not clear, it is suggested to be involved in cell-cell adhesion and cell attachment to the extracellular matrix. - term: id: GO:0045202 label: synapse evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0258 review: summary: Synapse from the UniProt subcellular-location mapping (ARBA rule). action: KEEP_AS_NON_CORE reason: Noelins 1-3, including noelin-3 (OLFM3), co-purify with AMPA receptor complexes from all mouse brain regions, and the olfm3b protein keeps every feature of OLFM3 examined, so the location is plausible. It is kept as non-core for this copy because olfm3b is barely expressed in the developing nervous system and has only a modest adult brain call, so whether it contributes to synapses in vivo is unknown. supported_by: - reference_id: PMID:37591201 supporting_text: Both, Noe1-3 and Nrn1, were effectively co-purified with the AMPAR complexes in all brain regions (even under high stringency conditions) and correlated well with each other - reference_id: file:DANRE/olfm3a/olfm3a-bioinformatics/RESULTS.md supporting_text: olfm3a is the predominant larval copy; olfm3b is barely detected in whole embryos and larvae. core_functions: - description: Secreted noelin-family olfactomedin glycoprotein; protein features are shared with olfm3a, but olfm3b is weakly expressed during development (adult brain, intestine and ovary calls). No molecular activity or process has been measured for this copy. locations: - id: GO:0005576 label: extracellular region supported_by: - reference_id: PMID:12019210 supporting_text: Both optimedin and myocilin are localized in Golgi and are secreted proteins. - reference_id: file:DANRE/olfm3a/olfm3a-bioinformatics/RESULTS.md supporting_text: Both copies keep the coiled coil, the olfactomedin domain, all six human cysteines and the calcium-site residues. references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: PMID:12019210 title: 'Optimedin: a novel olfactomedin-related protein that interacts with myocilin.' findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract only; identification of human/rat OLFM3 (optimedin), secretion, myocilin binding. - id: PMID:16115881 title: The Optimedin gene is a downstream target of Pax6. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; two promoters/splice variants; Pax6 regulation; states function unclear. - id: PMID:37591201 title: A Noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Mouse Olfm1-3 knockouts; noelins as extracellular AMPAR-complex constituents; Olfm3 single KO mild. - id: file:DANRE/olfm3a/olfm3a-bioinformatics/RESULTS.md title: olfm3a / olfm3b protein, expression and synteny comparison reference_review: relevance: HIGH correctness: VERIFIED review_notes: Manual audit verified the sidecar supports both OLFM3 copies retaining coiled-coil and olfactomedin features; the expression differences are suggestive of partitioning but not definitive. findings: [] suggested_questions: - question: Is olfm3b a low-expressed copy on the way to loss, or does it have a restricted adult domain (intestine, ovary, specific brain nuclei) that olfm3a lacks? - question: Which medaka OLFM3 copy is orthologous to olfm3b, and is its expression pattern similar? suggested_experiments: - hypothesis: olfm3b has an adult-restricted expression domain complementary to olfm3a. description: Paralog-specific HCR in situ hybridization for olfm3a and olfm3b in adult brain, retina, intestine and ovary. experiment_type: expression analysis - hypothesis: olfm3b protein is functionally equivalent to olfm3a. description: Test whether olfm3b coding sequence expressed from the olfm3a locus restores any olfm3a mutant phenotype, or whether both proteins co-purify with GluA complexes when tagged. experiment_type: cross-rescue