CG46301 is the single Drosophila melanogaster member of the NOL4/NOL4L (nucleolar protein 4) family. The gene model merges the former CG17341 and CG16879 annotations. A0A1W5PXH3 is its longest product (1237 residues). It has an N-terminal region that aligns with the N-terminal part of vertebrate NOL4 and a C-terminal NOL4 helical (HTH_NOL4) domain at residues 789-886, which is about 80% identical to the corresponding domain of human NOL4 and NOL4L. Much of the rest of the protein is predicted disordered and low-complexity, and a coiled coil lies near the C terminus. PANTHER places it in its own subfamily, separate from the vertebrate NOL4 and NOL4L subfamilies. By family inference it is a nuclear (nucleoplasmic) protein. Mammalian NOL4 splice variants bind Mblk-1-related transcription factors and modulate their transactivation, but no molecular activity, partner or biological process has been tested for the fly protein, and neither nucleolar residence nor a role in ribosome biogenesis is established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No molecular activity has been demonstrated for CG46301, so the ND root annotation stands. Reason: No experiment on the fly protein is found in the literature search (deep research, PubMed-cached leads). The only experimental work on the family is on mouse NOL4 splice variants. They bind the transcription factors Mlr1/Mlr2 and suppress or enhance their transactivation (PMID:25366156). The fly protein is in a different PANTHER subfamily (SF22) from vertebrate NOL4 (SF17). Mlr-modulating activity is a variant-dependent result for a single subfamily and is not shown as a conserved family activity, so it is not transferred. The HTH_NOL4 domain is a structural classification and does not by itself establish DNA binding. Supporting Evidence: file:DROME/CG46301/CG46301-deep-research-falcon.md It should **not** presently be called an enzyme, transporter, DNA-binding protein, ribosome-biogenesis factor, or confirmed nucleolar protein. PMID:25366156 transactivation activity of Mlr1 was significantly suppressed by both NOL4-S and NOL4-SΞ, with almost complete suppression by NOL4-SΞ file:DROME/CG46301/CG46301-bioinformatics/RESULTS-rereview.md PANTHER places the fly protein in its own subfamily (SF22), separate from vertebrate NOL4 (SF17 |
| GO:0005654 nucleoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: FlyBase transferred nucleoplasmic localization from human NOL4L by curator judgement. Family placement supports this. Reason: The donor, human NOL4L (Q96MY1), is in PANTHER subfamily SF19 and the fly protein is in SF22, so this is a family-level transfer rather than a transfer within one subfamily. Nuclear localization is reported in both vertebrate subfamilies. Human NOL4 (SF17) and human NOL4L (SF19) both have nucleoplasm localization from HPA immunofluorescence, so this is a shared family property, not a feature of one paralog. The fly HTH_NOL4 domain is about 80% identical to both human proteins. Nucleoplasm is a broad location claim. It does not imply nucleolar residence, which is not established for the fly protein. No target-specific evidence contradicts the transfer. The term is no more specific than the evidence allows. Supporting Evidence: file:DROME/CG46301/CG46301-uniprot.txt DR InterPro; IPR039788; NOL4/NOL4L. file:DROME/CG46301/CG46301-uniprot.txt FT DOMAIN 789..886 FT /note="Nucleolar protein 4 helical" FT /evidence="ECO:0000259|Pfam:PF23079" file:DROME/CG46301/CG46301-bioinformatics/RESULTS-rereview.md The helical domain is equally similar to NOL4 and NOL4L, so it does not discriminate between them. PMID:25366156 NOL4-SΞ, which lacks nuclear localization signal (NLS)-containing domain of NOL4-S |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: No biological process has been established for CG46301, so the ND root annotation stands. Reason: No genetic, developmental or biochemical study of CG46301 was found. The family name does not show participation in ribosome biogenesis or any nucleolar process. The mammalian transcriptional-modulation data come from a different PANTHER subfamily and from heterologous reporter assays, so they do not support a process annotation here. Supporting Evidence: file:DROME/CG46301/CG46301-deep-research-falcon.md No experimentally supported biological process or signaling or biochemical pathway can be assigned. |
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Download this section (compressed HTML)Q: Is CG46301 the single invertebrate co-ortholog of vertebrate NOL4 and NOL4L, and is PANTHER SF22 a sister clade to both vertebrate subfamilies?
Q: Does the fly protein bind and modulate the Mblk-1 family transcription factor E93 (Eip93F), the insect counterpart of the mouse Mlr1/Mlr2 partners of NOL4?
Q: Do the short products of CG46301 that lack the HTH_NOL4 domain (A0A1W5PVN5, A0A1W5PW03) have functions separate from the full-length 1237-residue product?
Experiment: Endogenously tag CG46301 with CRISPR (separately on the N- and C-terminal exons) and determine its nuclear and nucleolar distribution relative to fibrillarin in neurons and other tissues where it is expressed.
Experiment: Test interaction of full-length CG46301 and its HTH_NOL4 region with E93 by co-immunoprecipitation, and measure E93-dependent reporter activity with and without CG46301.
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