Nip7 (SPCC320.11c) is a small (180 aa) conserved trans-acting factor of large ribosomal subunit biogenesis. It consists of an N-terminal pre-PUA domain and a C-terminal PUA domain, the RNA-binding module that in Nip7 orthologs mediates preferential binding to polyuridine RNA. In fission yeast Nip7 is a component of early nucleolar pre-60S particles whose cryo-EM structures have been determined (PDB 8ESQ/8ESR), and a GFP-tagged protein is found in the nucleolus with an additional cytoplasmic pool. By orthology with budding-yeast Nip7 (same PANTHER subfamily), which is essential, cosediments with free 60S particles but not with 80S ribosomes or polysomes, and is required for efficient 27S pre-rRNA processing, fission-yeast Nip7 is an RNA-binding assembly factor of the large-subunit precursor rather than a structural protein of the mature ribosome. No catalytic activity is known.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003723 RNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: RNA binding via the conserved PUA domain, consistent with direct RNA-binding assays on Nip7 orthologs. Reason: Q1MTQ9 carries the Nip7-type PUA domain (InterPro PUA, Pfam UPF0113) and sits in the NIP7 branch of PANTHER PTHR23415 (subfamily SF4, with S. cerevisiae NIP7). RNA binding mediated by the Nip7 PUA domain was shown experimentally for budding-yeast and archaeal Nip7 orthologs, so the activity is ancestral to the Nip7 lineage and transfers to the fission-yeast protein. The orthologs' polyuridine preference has not been tested for Q1MTQ9, so RNA binding is the appropriate precision here. The CKS proteins grouped in the same PANTHER family play no part in this inference. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt DR InterPro; IPR002478; PUA. PMID:18001138 This work provides experimental verification that the PUA domain mediates Nip7 interaction with RNA and reveals that the preference for interaction with polyuridine sequences is conserved in Archaea and eukaryotic Nip7 proteins. |
| GO:0003723 RNA binding | NAS GO_REF:0000051 | ACCEPT | Summary: RNA binding via the conserved PUA domain; same claim as the InterPro row. Reason: This row makes the same claim as the IEA row and is consistent with it. Ortholog assays show that the Nip7 PUA domain binds RNA, and Q1MTQ9 has the same domain architecture and lies in the same PANTHER NIP7 subfamily. Supporting Evidence: PMID:18001138 Both proteins can bind specifically to polyuridine, and RNA interaction requires specific residues of the PUA domain as determined by site-directed mutagenesis. file:SCHPO/nip7/nip7-uniprot.txt DR InterPro; IPR002478; PUA. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | MODIFY | Summary: Nuclear localization is correct, but the localization survey also places the protein in the nucleolus, which is the more precise site of action. Reason: The same ORFeome localization study gives a nucleolar assignment (GO:0005730, already annotated to this gene by HDA), and the structurally defined pre-60S particles that contain Nip7 are nucleolar assembly intermediates. Nucleus is correct but less specific than the evidence supports. Proposed replacements: nucleolus Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, |
| GO:0005634 nucleus | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general; nucleolus is the supported refinement. Reason: The InterPro NIP7 family mapping gives nucleus. The target's own nucleolar localization and its presence in nucleolar pre-60S particles support the more specific term, which the gene already carries. Proposed replacements: nucleolus Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt DR InterPro; IPR016686; Ribosomal_synth_fac_NIP7. PMID:9271378 in vivo localization of a Nip7p-green fluorescent protein fusion protein revealed that a significant amount of Nip7p is present inside the nucleus, most probably in the nucleolus |
| GO:0005730 nucleolus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Nucleolar localization from the genome-wide GFP localization survey. Reason: Large-subunit assembly starts in the nucleolus, which is where Nip7 acts. The HDA assignment matches budding-yeast Nip7-GFP localization and the nucleolar pre-60S particles that contain Q1MTQ9. The localization paper is cached as abstract only, so the per-gene image call is accepted as the curator recorded it. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, |
| GO:0005730 nucleolus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleolar location inherited from the eukaryotic NIP7 ancestral node. Reason: The PAINT IBD at PTN000602113 (taxon Eukaryota) covers the NIP7 clade that contains Q1MTQ9. It was placed on nucleolar evidence from human NIP7 and Trypanosoma Q389E3, and fission-yeast HDA localization independently agrees with it. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, PMID:20798176 The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S-80S, suggesting an association to nucleolar pre-ribosomal particles. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping of the experimentally determined nucleolar localization. Reason: This mapping comes from the curated UniProt subcellular location, which is backed by the PMID:16823372 localization data. It agrees with the HDA and IBA rows. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A cytoplasmic pool was observed, but the cytoplasm is not where Nip7 is known to act. Reason: The localization survey reports cytoplasmic signal, and budding-yeast Nip7 is also partly cytoplasmic and cosediments with free 60S particles. No cytoplasmic function has been shown, and Nip7 is absent from 80S ribosomes and polysomes, so this is retained as a genuine but peripheral localization. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, PMID:9271378 A fraction of Nip7p cosedimented through sucrose gradients with free 60S ribosomal subunits but not with 80S monosomes or polysomal ribosomes, indicating that it is not a ribosomal protein. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Cytosolic signal in the genome-wide localization survey; peripheral to the nucleolar role. Reason: This is the experimental observation behind the cytoplasm row. It is kept as recorded, but the characterized activity of Nip7 is in nucleolar pre-60S particles, and no cytosolic activity is known. Supporting Evidence: file:SCHPO/nip7/nip7-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus, |
| GO:0030684 preribosome | IDA PMID:36423630 Chromatin localization of nucleophosmin organizes ribosome b... | MODIFY | Summary: Q1MTQ9 is a modelled component (entity 43, chain l) of the fission-yeast pre-60S particle structure 8ESQ, deposited with this study. Reason: The article text centres on Fkbp39 (nucleophosmin) and does not name Nip7, but the deposited structure from this study maps chain l to accession Q1MTQ9. The particle is a large-subunit precursor containing 60S ribosomal proteins and LSU assembly factors, so the specific term GO:0030687, which the gene already carries by IBA, is supported. The curator's IDA is accepted in substance. Proposed replacements: preribosome, large subunit precursor Supporting Evidence: file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" PMID:36423630 Chromatin localization of nucleophosmin organizes ribosome biogenesis. |
| GO:0030687 preribosome, large subunit precursor | IBA GO_REF:0000033 | ACCEPT | Summary: Membership of the pre-60S particle, inherited from the eukaryotic NIP7 node and confirmed directly for Q1MTQ9. Reason: The IBD at PTN000602113 is seeded by S. cerevisiae NIP7, which is in the same PANTHER subfamily (PTHR23415:SF4) as Q1MTQ9 and cosediments with free 60S particles. The fission-yeast protein is itself a modelled component of the pre-60S cryo-EM structure 8ESQ. Supporting Evidence: file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" PMID:9271378 A fraction of Nip7p cosedimented through sucrose gradients with free 60S ribosomal subunits but not with 80S monosomes or polysomal ribosomes, indicating that it is not a ribosomal protein. |
| GO:0042255 ribosome assembly | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general; Nip7 acts in assembly of the large-subunit precursor. Reason: GO:1902626 (assembly of large subunit precursor of preribosome) is an is_a descendant of ribosome assembly, and the gene already carries it by EXP. Ortholog depletion (budding yeast, same PANTHER subfamily) specifically reduces 60S subunits through delayed 27S pre-rRNA processing. Proposed replacements: assembly of large subunit precursor of preribosome Supporting Evidence: PMID:9271378 Delayed processing of 27S pre-rRNA appeared to be the cause of reduced synthesis of 25S rRNA relative to 18S rRNA, which may be responsible for the deficit of 60S subunits in these cells. file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" |
| GO:0042273 ribosomal large subunit biogenesis | IBA GO_REF:0000033 | MODIFY | Summary: Large-subunit biogenesis is correct and well grounded phylogenetically; the specific assembly term is supported. Reason: The IBD at the eukaryotic NIP7 node is sound. Q1MTQ9 appears among its own donors, which reflects the target's experimental annotation rather than circularity. GO:1902626 is an is_a descendant (via ribosomal large subunit assembly) that the gene already carries by EXP, so it is the precise term. PAINT curators did not propagate the budding-yeast rRNA-processing terms, and no rRNA-processing term is proposed here either. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000602113 SUPPORTS TRANSFER Eukaryote-level NIP7 node. Q1MTQ9 descends from it (PTHR23415:SF4, together with S. cerevisiae NIP7); the CKS subfamilies of PTHR23415 are outside this clade. The term is correct but broader than the gene's own EXP-supported assembly term. SGD:S000006132 SUPPORTS TRANSFER Budding-yeast NIP7 depletion and 60S cosedimentation (PMID:9271378) ground the node. PomBase:SPCC320.11c SUPPORTS TRANSFER The target's own experimental annotation, used as descendant evidence for the IBD; this is expected and not circular. Proposed replacements: assembly of large subunit precursor of preribosome Supporting Evidence: PMID:9271378 Delayed processing of 27S pre-rRNA appeared to be the cause of reduced synthesis of 25S rRNA relative to 18S rRNA, which may be responsible for the deficit of 60S subunits in these cells. file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" |
| GO:1902626 assembly of large subunit precursor of preribosome | EXP PMID:36423630 Chromatin localization of nucleophosmin organizes ribosome b... | ACCEPT | Summary: Nip7 is a component of the structurally resolved early pre-60S assembly intermediate. Reason: The curator attributed this to the pre-60S structures from PMID:36423630, in which Q1MTQ9 is modelled as chain l. A protein bound within the assembling particle does part of the assembly work, as an RNA-binding assembly factor, and is not merely required for the process. Budding-yeast Nip7 (same PANTHER subfamily) is likewise required for 60S assembly and is released before the mature subunit forms. Supporting Evidence: file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" PMID:9271378 Depletion of Nip7-1p resulted in a decrease in protein synthesis rates, accumulation of halfmers, reduced levels of 60S subunits, and, ultimately, cessation of growth. |
| GO:1902626 assembly of large subunit precursor of preribosome | IEA GO_REF:0000117 | ACCEPT | Summary: Same claim as the EXP row; correct. Reason: The ARBA prediction agrees with the experimental structural evidence on the target and with the PANTHER/PAINT placement of Q1MTQ9 in the NIP7 LSU-assembly clade. The support cited here is independent of the ARBA rule. Supporting Evidence: file:SCHPO/nip7/nip7-8ESQ-entities.json "database_accession": "Q1MTQ9" |
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Download this section (compressed HTML)Q: Which pre-rRNA segment does the fission-yeast Nip7 PUA domain contact in the 8ESQ/8ESR pre-60S structures, and does it coincide with a uridine-rich region as the ortholog binding preference predicts?
Q: Human NIP7 knockdown mainly impairs ITS1/18S processing, whereas budding-yeast Nip7 loss impairs 27S/60S processing. Which phenotype does S. pombe Nip7 depletion produce?
Experiment: Conditional depletion of S. pombe nip7 followed by northern blotting of pre-rRNA intermediates and polysome profiling, to test whether the budding-yeast 27S-processing and 60S-deficit phenotype is conserved.
Experiment: CRAC or UV crosslinking of tagged Nip7 in fission yeast, with PUA-domain point mutants, to map its RNA contacts in the pre-60S particle.
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