prom1a (prominin 1a) is one of two zebrafish co-orthologs of vertebrate PROM1 (prominin-1, CD133), retained from the teleost-specific genome duplication; its paralog is prom1b. It encodes a pentaspan membrane glycoprotein with two large glycosylated extracellular loops. Prominins sit in cholesterol-rich plasma-membrane protrusions such as microvilli and primary cilia and in extracellular vesicles derived from them; mammalian PROM1 is also required for photoreceptor outer-segment disc morphogenesis. prom1a is the more broadly expressed copy. It is maternally supplied, is expressed in embryonic proliferative zones of the central nervous system and sensory organs, in the lens and otic vesicle, in adult brain germinative zones of the forebrain and dorsal midbrain, on the vitreal side of the retinal inner nuclear layer and at low level in rods and cones, and in several adult organs including gill, intestine, kidney and gonads. A prom1a knockout was reported to leave photoreceptors intact, in contrast to prom1b mutants, so its specific functions remain unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Endoplasmic reticulum, mapped from a UniProt by-similarity subcellular location. Reason: Prominins are plasma-membrane proteins of protrusions and extracellular vesicles; the ER is a biosynthetic transit compartment for any glycosylated membrane protein. No zebrafish data place Prom1a in the ER, and the term does not describe where the protein acts. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Endoplasmic reticulum, transferred from human PROM1 by sequence similarity. Reason: Transit compartment; the functional locations of prominins are the apical plasma membrane, its protrusions and derived vesicles. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: ER-Golgi intermediate compartment, mapped from a UniProt by-similarity subcellular location. Reason: Secretory transit compartment; not where Prom1a is thought to act, and not observed in zebrafish. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ER-Golgi intermediate compartment, transferred from human PROM1. Reason: Secretory transit compartment, as for the ER rows. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma membrane, transferred from human PROM1. Reason: Correct for a prominin; Prom1a keeps the five transmembrane segments and the extracellular loops of the family (bioinformatics RESULTS.md), and the paralog's GFP fusion localizes to the apical plasma membrane. Supporting Evidence: file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md All five transmembrane segments of human PROM1 align without gaps in both copies PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0005902 microvillus | IBA GO_REF:0000033 | ACCEPT | Summary: Microvillus, from the PANTHER prominin node (mouse and rat Prom1). Reason: Microvilli are a defining location of prominins across animals; no zebrafish-specific evidence argues against it for the broadly expressed epithelial copy. Supporting Evidence: PMID:21407811 microvillus, cilium, filopodium) [3], [18], [20], [29] might be the underlying reason of such phenomenon as demonstrated in mature photoreceptors. |
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: Cilium, from the PANTHER prominin node. Reason: Prominins localize to primary cilia and regulate ciliary length in human cells and zebrafish (prom3); the location is ancestral to the family. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. PMID:32201384 These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane, from the prominin InterPro signature. Reason: Correct; multi-pass membrane protein. Supporting Evidence: file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md All five transmembrane segments of human PROM1 align without gaps in both copies |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Apical plasma membrane, from the PANTHER prominin node (fly and mouse donors). Reason: Apical enrichment is a conserved prominin property; the zebrafish paralog Prom1b-GFP is apical in retinal neuroepithelia. Supporting Evidence: PMID:22492354 We also generated a transgenic line in which GFP is fused with Prominin1b (Prom1b-GFP), a cholesterol-interacting pentaspan membrane protein that is enriched at the apical region of polarized cells, including retinal neuroepithelia |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Apical plasma membrane, from UniProt subcellular location. Reason: As for the IBA row. Supporting Evidence: PMID:22492354 We also generated a transgenic line in which GFP is fused with Prominin1b (Prom1b-GFP), a cholesterol-interacting pentaspan membrane protein that is enriched at the apical region of polarized cells, including retinal neuroepithelia |
| GO:0031528 microvillus membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Microvillus membrane, from UniProt subcellular location. Reason: Consistent with the family's location in microvilli. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0032528 microvillus organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Microvillus organization, from the PANTHER prominin node (Drosophila prominin-like donor). Reason: Plausible for a prominin that shapes membrane protrusions, but no zebrafish data address it and the copy's knockout phenotype is not described beyond the retina. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
| GO:0060219 camera-type eye photoreceptor cell differentiation | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Camera-type eye photoreceptor cell differentiation, from the PANTHER PROM1 node (mouse Prom1 and human PROM1). Reason: The photoreceptor role of the ancestral gene has gone to prom1b in zebrafish. prom1b loss disrupts outer-segment morphogenesis and causes cone degeneration, whereas the same study concluded that prom1a is not the copy that matters in photoreceptors. prom1a transcripts are present in rods and cones, but at about a third to a quarter of the prom1b level (scRNA-seq reanalysis). The row is marked rather than removed because a minor, masked contribution cannot be excluded without a double mutant. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002733197 SUPPORTS SOURCE BUT NOT TARGET The PROM1 node rightly carries the photoreceptor role of mammalian PROM1, but after the teleost duplication the photoreceptor requirement is carried by prom1b; a same-node IBA cannot see this split. MGI:MGI:1100886 · Prom1 (mouse) SUPPORTS SOURCE BUT NOT TARGET Mouse Prom1 is required for outer-segment disc morphogenesis; that role maps to prom1b in zebrafish. Supporting Evidence: PMID:31362982 The Prom1 orthologs in zebrafish include prom1a and prom1b, and our results showed that prom1b, rather than prom1a, plays an important role in zebrafish photoreceptors. file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md Both copies are detected in rods and in every cone type, with prom1b three to four times more abundant than prom1a |
| GO:0071914 prominosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Prominosome (prominin-containing extracellular vesicle), from the PANTHER prominin node. Reason: Release of prominin-containing vesicles from protrusions is a family property shown in mammals; not examined in zebrafish. Supporting Evidence: PMID:32201384 They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. |
Loading supporting content…
Download this section (compressed HTML)Q: Does prom1a contribute to outer-segment morphogenesis when prom1b is absent (prom1a; prom1b double mutants), and is prom1a upregulated in prom1b mutants?
Q: What does prom1a do in the maternal embryo and in adult epithelial organs (intestine, kidney, gill) where prom1b is not detected?
Q: Do Prom1a splice variants reach the photoreceptor outer segment?
Experiment: Express Prom1a from the prom1b promoter (or a photoreceptor promoter) in prom1b mutants and score outer-segment morphology and cone survival.
Hypothesis: The photoreceptor split between the copies is due to expression level, not protein function.
Type: cross-rescue
Experiment: Compare prom1b single and prom1a; prom1b double mutants for outer-segment defects and rod survival, and measure prom1a mRNA in prom1b mutants.
Hypothesis: prom1a and prom1b are partly redundant in photoreceptors.
Type: double mutant
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)