olfm3a (olfactomedin 3a) is one of two zebrafish co-orthologs of vertebrate OLFM3 (optimedin, noelin-3), retained from the teleost-specific genome duplication; its paralog is olfm3b. 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 its cysteines. olfm3a is switched on during late pharyngula stages and is the predominant larval copy, expressed in brain (including tectal and hindbrain glutamatergic neurons) and retina. No functional study of this gene has been published.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root-term ND placeholder recording that no molecular function has been curated for olfm3a. Reason: Accurate. No molecular function has been measured for zebrafish olfm3a, and none is established specifically for OLFM3 in mammals beyond binding partners (myocilin, other noelins, AMPA receptor subunits). The paralog olfm3b lacks this ND row only because its record carries no MF row of any kind; the asymmetry is a bookkeeping artefact. Supporting Evidence: PMID:16115881 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. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular region (IBA) from the olfactomedin family node PTN000573635. Reason: Olfactomedin-domain proteins are secreted, and OLFM3 is secreted in transfected cells. olfm3a has a predicted signal peptide and keeps the olfactomedin domain and cysteines of human OLFM3, so it is inside the secreted clade. Supporting Evidence: PMID:12019210 Both optimedin and myocilin are localized in Golgi and are secreted proteins. file:DANRE/olfm3a/olfm3a-bioinformatics/RESULTS.md Both copies keep the coiled coil, the olfactomedin domain, all six human cysteines and the calcium-site residues. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Extracellular region from the UniProt 'Secreted' subcellular location (ARBA rule). Reason: Consistent with the signal peptide and with secretion of mammalian OLFM3. Supporting Evidence: PMID:12019210 Both optimedin and myocilin are localized in Golgi and are secreted proteins. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Signal transduction propagated from the olfactomedin family node, seeded by myocilin (mouse Myoc, human MYOC) and mouse Olfm1. 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 olfm3b. Supporting Evidence: PMID:37591201 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. PMID:16115881 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. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root-term ND placeholder for biological process. Reason: Accurate record that no process has been curated from zebrafish data. The only process row (signal transduction, IBA) is judged over-annotated, so the ND placeholder still reflects the state of knowledge. Supporting Evidence: PMID:16115881 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. |
| GO:0045202 synapse | IEA GO_REF:0000044 | ACCEPT | Summary: Synapse from the UniProt subcellular-location mapping (ARBA rule). Reason: Noelins 1-3, including noelin-3 (OLFM3), co-purify with AMPA receptor complexes from all mouse brain regions, and OLFM3 co-immunoprecipitates with GluA1 and GluA2. olfm3a is expressed in larval brain glutamatergic neurons. The location is a family-level inference but well supported for the subfamily. Supporting Evidence: PMID:37591201 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 PMID:32850838 We found that OLFM3 co-immunoprecipitation with GluA1 and GluA2. |
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Download this section (compressed HTML)Q: Where exactly are olfm3a and olfm3b expressed in larval and adult retina and brain (double in situ or single-cell data), and do they overlap in any cell type?
Q: Do zebrafish noelins (olfm1a/b, olfm2a/b, olfm3a/b) co-purify with AMPA receptor complexes, and which olfm3 copy contributes?
Experiment: Paralog-specific in situ hybridization (or HCR) for olfm3a and olfm3b in larval and adult brain, retina, intestine and ovary, with gar OLFM3 in situ as outgroup.
Hypothesis: olfm3a and olfm3b have complementary expression domains inherited from an ancestral brain/eye/ovary pattern.
Type: expression analysis
Experiment: Generate olfm3a mutants alone and combined with olfm3b and olfm1a/b; measure AMPA receptor clustering and mEPSCs in larval tectal neurons.
Hypothesis: olfm3a is dispensable alone, as Olfm3 is in mouse, and acts together with other noelins.
Type: genetic interaction
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