60S ribosomal export protein NMD3 is an essential protein required for cytoplasmic assembly and nuclear export of the 60S ribosomal subunit. Functions as a Crm1-dependent export adapter that binds nascent 60S particles and mediates their transport through nuclear pore complexes. Essential for ribosome biogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Correctly identifies nuclear localization. IBA annotation is based on phylogenetic inference and is supported by experimental evidence showing NMD3 shuttles between nucleus and cytoplasm. Reason: NMD3 is explicitly documented in the literature as a shuttling protein that mediates nuclear export processes. The primary mapping places the functional nuclear localization signal (NLS) at aa 387-435 and the leucine-rich nuclear export signal (NES; INIDELLDEL) at aa 491-500. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000297338 Β· PTN000297338 SUPPORTS TRANSFER The eukaryotic NMD3 ancestral node correctly captures conserved nuclear localization for a shuttling 60S-export adaptor. Supporting Evidence: PMID:11086007 We show here that Nmd3p shuttles PMID:11313466 Nmd3p shuttles between the nucleus and cytoplasm and is exported by the nuclear export receptor Xpo1p |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Correctly identifies cytoplasmic localization. NMD3 is present in both nucleus and cytoplasm, shuttling between compartments. Reason: NMD3 is a cytoplasmic protein that fractionates as a cytoplasmic factor and sediments in the position of free 60S subunits in sucrose gradients. Essential cytoplasmic role in stabilizing mature 60S subunits post-export. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000978434 Β· PTN000978434 SUPPORTS TRANSFER This NMD3-family node correctly propagates cytoplasmic localization to yeast Nmd3, whose direct evidence shows cytoplasmic 60S association. Supporting Evidence: PMID:10022925 Nmd3p fractionated as a cytoplasmic protein and sedimented in the position of free 60S subunits in sucrose gradients PMID:11086007 We show here that Nmd3p shuttles and that it is an essential adapter protein that provides the NES to direct nuclear export of nascent 60S subunits via the Crm1p pathway |
| GO:0000055 ribosomal large subunit export from nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Correct identification of core biological process. NMD3 is a key adapter protein for 60S subunit nuclear export, recruiting Crm1 export receptor. Reason: This is a central function of NMD3. Extensive experimental evidence demonstrates NMD3 is required for nuclear export of 60S subunits. Functions as Crm1-dependent adapter that directly binds to 60S subunits through rRNA contacts and provides nuclear export signal (NES) that is recognized by export receptor Crm1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000297338 Β· PTN000297338 SUPPORTS TRANSFER The eukaryotic node is placed on the conserved NMD3 60S-export adaptor clade and includes direct yeast and human descendant evidence. Supporting Evidence: PMID:11086007 Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit PMID:11313466 Nuclear export of 60s ribosomal subunits depends on Xpo1p and requires a nuclear export sequence-containing factor, Nmd3p PMID:17347149 Nuclear export of the large (60S) ribosomal subunit depends on the adapter protein Nmd3 to provide a nuclear export signal (NES) file:yeast/NMD3/NMD3-deep-research-falcon.md Falcon synthesis supports Nmd3 as the conserved Crm1/Xpo1-dependent 60S ribosomal export adaptor. |
| GO:0043023 ribosomal large subunit binding | IBA GO_REF:0000033 | ACCEPT | Summary: Correct identification of protein-rRNA interaction. NMD3 directly binds the 60S subunit through multiple rRNA contact sites. Reason: NMD3 physically interacts with 60S subunits through direct binding to 25S rRNA helices. Nascent 60S subunits enter the free pool bound by Nmd3p. Coimmunoprecipitation experiments demonstrate specific interaction with 60S (not 40S) subunits. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000978434 Β· PTN000978434 SUPPORTS TRANSFER The NMD3-family node correctly propagates the large-ribosomal-subunit-binding function; yeast has direct coimmunoprecipitation and rRNA-crosslink support. Supporting Evidence: PMID:11105761 The interaction was specific for 60S subunits; 40S subunits were not coimmunoprecipitated PMID:24240281 binding sites, which were found to lie in H38, H69 and H89 of 25S rRNA |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Correct identification of nucleoplasmic localization. NMD3 functions in nucleoplasm during pre-60S maturation and export preparation. Reason: UniProt-based IEA annotation is supported by functional studies showing NMD3 associates with nucleoplasmic pre-60S particles and is required for late nucleoplasmic maturation steps. Sequential late pre-60S work places Nmd3 after the Nog2 checkpoint and used Nmd3-TAP to isolate late assembly intermediates. Supporting Evidence: PMID:27251291 This enables release of Nog2 and replacement by the key export factor Nmd3 PMID:11086007 We show here that Nmd3p shuttles |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate IEA annotation for cytoplasm location. Acceptable as both annotations are correct. Reason: Redundant with IBA annotation to same term but both are correct. UniProt-based annotation confirms cytoplasmic localization. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | MODIFY | Summary: Very broad annotation. NMD3 is specifically involved in ribosomal subunit transport, not general protein transport. Reason: While technically correct that NMD3 is involved in "protein transport" (as 60S is a protein complex), this term is too general and loses the critical specificity of the function. NMD3 is specifically involved in ribosomal subunit export, not general protein transport. Should be replaced with more specific term for 60S export. Proposed replacements: ribosomal large subunit export from nucleus |
| GO:0043023 ribosomal large subunit binding | IEA GO_REF:0000002 | ACCEPT | Summary: Correct but redundant with IDA annotations for same term. InterPro-based annotation is consistent with protein domain analysis. Reason: InterPro annotation IPR039768 correctly identifies NMD3 domain and its role in 60S binding. This is supported by experimental data showing direct rRNA binding. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | REMOVE | Summary: Generic "protein binding" annotation derived from protein complex data. Annotation is too general; specific protein-interaction data should be used instead. Reason: The reported interaction need not be false, but the generic "protein binding" term is uninformative. NMD3's relevant binding function is already captured by "ribosomal large subunit binding" (GO:0043023) and direct IDA support; PMID:16554755 is a global protein-complex map rather than a mechanistic NMD3 study. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae |
| GO:0005515 protein binding | IPI PMID:21852791 The mRNA export factor Npl3 mediates the nuclear export of l... | REMOVE | Summary: Generic "protein binding" annotation. While NMD3 does interact with Npl3 and ribosomal proteins, the term is uninformative. Reason: The Npl3/Rpl25 interaction evidence belongs in ribosomal-export context, but as a molecular-function assertion GO:0005515 is generic and uninformative. More specific, experimentally supported terms already capture NMD3 as a 60S-subunit binder and Crm1/export adaptor. Supporting Evidence: PMID:21852791 The mRNA export factor Npl3 mediates the nuclear export of large ribosomal subunits |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic "protein binding" annotation from recent protein interactome study. Reason: PMID:37968396 provides global interactome evidence, not a mechanistic NMD3 molecular-function study. GO:0005515 is generic and should be removed in favor of the already annotated, specific 60S-subunit-binding and adaptor activities. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:11086007 Nmd3p is a Crm1p-dependent adapter protein for nuclear expor... | ACCEPT | Summary: Excellent molecular function annotation. NMD3 directly functions as an adapter protein that bridges the 60S subunit to the Crm1 export receptor. Reason: NMD3 is functionally a protein-macromolecule adaptor that recruits the Crm1 export receptor to 60S subunits. The protein contains a functional nuclear export signal (NES) that directly recruits Crm1 while simultaneously bound to the 60S subunit. This is the defining characteristic of an adapter activity. Supporting Evidence: PMID:11086007 Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit PMID:17347149 the adapter protein Nmd3 to provide a nuclear export signal (NES). The leucine-rich NES is recognized by the export receptor Crm1 |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:11313466 Nuclear export of 60s ribosomal subunits depends on Xpo1p an... | ACCEPT | Summary: Duplicate IDA annotation for adapter activity. Correctly identifies the molecular function. Reason: Second experimental source confirming adapter function. PMID:11313466 demonstrates NMD3 physically associates with ribosomal protein Rpl10p while functioning as an export adapter. Supporting Evidence: PMID:11313466 that associates with the large subunit protein Rpl10p...nuclear export sequence-containing factor |
| GO:0070180 large ribosomal subunit rRNA binding | IDA PMID:24240281 Coupled GTPase and remodelling ATPase activities form a chec... | ACCEPT | Summary: Excellent annotation specifying direct rRNA binding. CRAC and cross-linking data identify multiple specific binding sites. Reason: PMID:24240281 provides direct UV cross-linking (CRAC) evidence showing NMD3 contacts 25S rRNA at specific helix positions (H38, H69, H89). This is more specific and informative than generic protein binding and represents core structural contacts essential for function. Supporting Evidence: PMID:24240281 binding sites, which were found to lie in H38, H69 and H89 of 25S rRNA |
| GO:0000055 ribosomal large subunit export from nucleus | IMP PMID:11086007 Nmd3p is a Crm1p-dependent adapter protein for nuclear expor... | ACCEPT | Summary: Correct experimental evidence for nuclear export function. IMP (Inferred from Mutant Phenotype) is appropriate evidence code. Reason: Temperature-sensitive nmd3 mutants are impaired in large subunit export, providing direct evidence for the functional requirement. This is a core biological process for NMD3. Supporting Evidence: PMID:11086007 We showed previously that a temperature sensitive nmd3 mutant failed to accumulate 60S subunits at nonpermissive temperature |
| GO:0000055 ribosomal large subunit export from nucleus | IGI PMID:23212245 Targeted proteomics reveals compositional dynamics of 60S pr... | ACCEPT | Summary: Duplicate annotation with IGI evidence from proteomics study of post-export particles. Appropriate evidence for genetic interaction data. Reason: PMID:23212245 supports the IGI annotation because the bud20Ξ strain was synthetic lethal or synthetic enhanced with nmd3ΞNES1 and other known pre-60S export-factor mutants. Supporting Evidence: PMID:23212245 Indeed, the bud20Ξ strain exhibits synthetic lethal (sl) or synthetic enhanced (se) growth defects when combined with mutants of known pre-60S subunit export factors |
| GO:0005829 cytosol | IDA PMID:10022925 NMD3 encodes an essential cytoplasmic protein required for s... | ACCEPT | Summary: Correct identification of cytosolic localization. NMD3 fractionates with free 60S subunits in the cytosol. Reason: PMID:10022925 demonstrates by fractionation that Nmd3p sediments in sucrose gradients at the position of free 60S subunits in the cytosol, confirming cytosolic localization and association with mature subunits. Supporting Evidence: PMID:10022925 Nmd3p fractionated as a cytoplasmic protein and sedimented in the position of free 60S subunits in sucrose gradients |
| GO:0043023 ribosomal large subunit binding | IDA PMID:11105761 Nascent 60S ribosomal subunits enter the free pool bound by ... | ACCEPT | Summary: Correct identification of 60S binding. IDA evidence from coimmunoprecipitation experiments. Reason: PMID:11105761 demonstrates by coimmunoprecipitation that Nmd3p forms stable complex with free 60S subunits, with specific interaction for 60S (not 40S). Interaction occurs both with nascent and mature subunits. Supporting Evidence: PMID:11105761 Nmd3p forms a stable complex with free 60S subunits. Using an epitope-tagged Nmd3p, we show that free 60S subunits can be coimmunoprecipitated with Nmd3p |
| GO:0043023 ribosomal large subunit binding | IDA PMID:17347149 Novel interaction of the 60S ribosomal subunit export adapte... | ACCEPT | Summary: Duplicate IDA annotation for 60S binding from study of NPC interactions. Both confirm binding is core function. Reason: PMID:17347149 provides complementary evidence showing NMD3 binding to 60S subunit at nuclear pore complex, demonstrating binding occurs throughout the export process (nucleoplasm and at NPC). Supporting Evidence: PMID:17347149 Certain mutant Nmd3 proteins that are impaired for binding to the 60S subunit accumulate at the nuclear envelope |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: Generic protein-binding annotation from an in vivo yeast interactome screen. Reason: PMID:18467557 is a genome-wide protein-fragment-complementation interactome map rather than a mechanistic NMD3 functional study. The IntAct Tif6 interaction does not change the GO conclusion that GO:0005515 is an uninformative molecular function for Nmd3, whose specific activities are already captured by 60S-subunit binding and Crm1/export adaptor annotations. Supporting Evidence: PMID:18467557 genome-wide in vivo screen for protein-protein interactions in Saccharomyces cerevisiae by means of a protein-fragment complementation assay |
| GO:0005515 protein binding | IPI PMID:27251291 Diverse roles of assembly factors revealed by structures of ... | REMOVE | Summary: Generic protein-binding annotation from a structural late nuclear pre-60S ribosome study. Reason: PMID:27251291 used tagged Nmd3 as one of several baits to isolate and compare late pre-60S intermediates, but the resulting IntAct Tif6 row is still a generic GO:0005515 assertion. It should be removed in favor of Nmd3's specific 60S-subunit-binding and export-adaptor activities. Supporting Evidence: PMID:27251291 TAP-tagged Nsa1, Nog2 and Nmd3 were used as baits to isolate ribosome assembly intermediates |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Generic Tif6 protein-binding annotation from the high-throughput 2023 yeast interactome. Reason: PMID:37968396 is a comprehensive affinity-enrichment mass-spectrometry interactome, not a study that establishes a new NMD3 molecular activity. As with the Rpl25 row from the same paper, the Tif6 interaction row is generic and redundant with the precise large-ribosomal-subunit-binding and adaptor activities already annotated for Nmd3. Supporting Evidence: PMID:37968396 affinity purification coupled to mass spectrometry is an ideal tool for such mapping |
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Download this section (compressed HTML)Q: Should NMD3's rRNA-binding and adaptor activities both be retained as core molecular functions, or should the annotation emphasize adaptor activity as the primary function?
Experiment: Separate rRNA-binding from Crm1 recruitment by targeted Nmd3 NES and rRNA-contact mutants, then quantify effects on pre-60S export and cytosolic maturation.
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Download this section (compressed HTML)Protein involved in nuclear export of the large ribosomal subunit; acts as a Crm1p-dependent adapter protein for export of nascent ribosomal subunits through the nuclear pore complex
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