TMA16 (Translation machinery-associated protein 16) is a conserved nuclear assembly factor involved in the biogenesis of the 60S ribosomal subunit. Cryo-EM structural studies (PMID:32669547) reveal that TMA16 associates with pre-60S ribosomal particles, localizing between the 5S RNA and the P0 stalk. The protein functions as a ribosome-associated factor (RAF) in the late stages of pre-60S maturation and nuclear export, acting as an adaptor between the preribosome and other assembly machinery components. TMA16 belongs to the TMA16 family (PF11176) and is present throughout eukaryotes with conserved function in ribosome biogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: TMA16 nuclear localization is well-supported by cryo-EM structural studies showing TMA16 associates with pre-60S ribosomal particles in the nucleus, and by immunofluorescence data from the Human Protein Atlas (HPA). The IBA annotation based on phylogenetic inference is consistent with experimental evidence. Reason: Nuclear localization is strongly supported by PMID:32669547 which describes TMA16 as a "nuclear assembly factor" and shows its structural association with pre-60S particles. HPA immunofluorescence data (GO_REF:0000052) also confirms nucleoplasm and nucleolus localization. This is a core cellular compartment for TMA16 function. Supporting Evidence: PMID:32669547 human factors, including an uncharacterized factor TMA16 localized between the 5S RNA and the P0 stalk file:human/TMA16/TMA16-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProt subcellular location mapping. This is consistent with experimental evidence from cryo-EM studies and HPA immunofluorescence data confirming nuclear localization. Reason: While this is a computationally inferred annotation, it is fully consistent with the experimentally validated nuclear localization of TMA16. The IBA annotation above provides higher-confidence phylogenetic evidence, and IDA evidence from HPA confirms nucleoplasm/nucleolus localization. Supporting Evidence: PMID:32669547 TMA16 is an uncharacterized nuclear assembly factor |
| GO:0042254 ribosome biogenesis | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation based on UniProt keyword mapping. TMA16 is indeed involved in ribosome biogenesis, but more specifically in ribosomal large subunit (60S) biogenesis. The general term is acceptable but a more specific IDA annotation exists (GO:0042273). Reason: This annotation captures the core biological process of TMA16. While GO:0042273 (ribosomal large subunit biogenesis) is more specific and is annotated with IDA evidence, the parent term GO:0042254 remains valid. The annotation correctly reflects TMA16's role in ribosome assembly. Supporting Evidence: PMID:32669547 we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding annotation from high-throughput interactome mapping study. The interactors reported (KLHL2/O95198, KRTAP10-7/P60409) are from large-scale screens and do not directly relate to TMA16's core function in ribosome biogenesis. Reason: GO:0005515 (protein binding) is an uninformative molecular function term that does not specify the functional context of the interaction. TMA16 has a more specific molecular function annotation (GO:0030674, protein-macromolecule adaptor activity) and (GO:1990275, preribosome binding) that better describes its activity. The interactions from high-throughput screens may not reflect biologically relevant functional interactions. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding annotation from study examining disruption of protein interactions by genetic variants. The interaction with KLHL2 is reported but without functional context related to ribosome biogenesis. Reason: GO:0005515 (protein binding) is uninformative and should be replaced by more specific functional terms. TMA16's core molecular function is preribosome binding (GO:1990275) and protein-macromolecule adaptor activity (GO:0030674). Generic protein binding annotations from interactome studies do not add meaningful functional information. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding annotation from "A reference map of the human binary protein interactome network" high-throughput study. Multiple interactors reported (KLHL2, CASTOR1, AP2M1, TSPYL2) from systematic yeast two-hybrid screening. Reason: GO:0005515 (protein binding) is uninformative and does not capture TMA16's specific functional role. The interactors identified in this high-throughput screen may represent true physical interactions but the biological relevance to TMA16's core function in pre-60S ribosome biogenesis is unclear. More informative annotations (GO:1990275, GO:0030674) already capture TMA16's molecular function. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding annotation from "Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins" study. Reports interaction with HTT (huntingtin) from systematic interactome mapping. Reason: GO:0005515 (protein binding) is uninformative. The reported interaction with huntingtin (HTT) from a neurodegenerative disease interactome study is unlikely to represent a core functional interaction for TMA16, which functions primarily in ribosome biogenesis. More specific molecular function terms (GO:1990275, GO:0030674) already capture TMA16's function. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on Human Protein Atlas immunofluorescence data showing TMA16 localization to the nucleoplasm. This is consistent with TMA16's role in pre-60S ribosomal subunit biogenesis in the nucleus. Reason: The nucleoplasm localization is appropriate for TMA16's function in ribosome biogenesis. Pre-60S particles are assembled in the nucleolus and then transit through the nucleoplasm for export. TMA16 associates with pre-60S particles at stages before and after nuclear export (PMID:32669547), consistent with nucleoplasm localization. Supporting Evidence: PMID:32669547 Here we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on Human Protein Atlas immunofluorescence data showing TMA16 localization to the nucleolus. The nucleolus is where ribosomal subunit assembly initiates, consistent with TMA16's role as a ribosome assembly factor. Reason: Nucleolar localization is expected for a protein involved in ribosome biogenesis. The nucleolus is the site of rRNA transcription and early steps of ribosomal subunit assembly. TMA16 likely associates with pre-60S particles in the nucleolus before they transit to the nucleoplasm for export. Deep research confirms TMA16 is "nuclear/nucleolar and ribosome-associated." Supporting Evidence: PMID:32669547 TMA16 is an uncharacterized nuclear assembly factor |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:32669547 Structural snapshots of human pre-60S ribosomal particles be... | ACCEPT | Summary: IDA annotation from cryo-EM structural study showing TMA16 localized on pre-60S particles between the 5S RNA and P0 stalk. TMA16 functions as an adaptor between the preribosome complex and other assembly/export machinery components. Reason: This is a core molecular function annotation for TMA16. The cryo-EM structure (PMID:32669547) shows TMA16 positioned between the 5S RNA and P0 stalk on pre-60S particles, consistent with an adaptor function bridging different components of the preribosome. Deep research describes TMA16 as an "export adapter" in the pre-60S pathway. This is more informative than generic "protein binding." Supporting Evidence: PMID:32669547 human factors, including an uncharacterized factor TMA16 localized between the 5S RNA and the P0 stalk |
| GO:0042273 ribosomal large subunit biogenesis | IDA PMID:32669547 Structural snapshots of human pre-60S ribosomal particles be... | ACCEPT | Summary: IDA annotation from cryo-EM structural study demonstrating TMA16 association with pre-60S ribosomal particles at stages immediately before and after nuclear export. This is the core biological process for TMA16. Reason: This is the primary biological process annotation for TMA16. PMID:32669547 provides direct structural evidence showing TMA16 on pre-60S particles in four sequential assembly states. UniProt annotation confirms "Involved in the biogenesis of the 60S ribosomal subunit in the nucleus." This is more specific than the parent term GO:0042254 (ribosome biogenesis). Supporting Evidence: PMID:32669547 we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export |
| GO:1990275 preribosome binding | IDA PMID:32669547 Structural snapshots of human pre-60S ribosomal particles be... | ACCEPT | Summary: IDA annotation from cryo-EM structural study demonstrating direct binding of TMA16 to pre-60S ribosomal particles. TMA16 is localized between the 5S RNA and P0 stalk on the preribosome. Reason: This is a core molecular function annotation for TMA16, supported by high-resolution cryo-EM structures (3.1 Angstrom resolution) showing TMA16 bound to pre-60S particles in multiple assembly states. UniProt states "Associates with pre-60S ribosomal particles." This specific binding activity distinguishes TMA16's function from generic protein binding. Supporting Evidence: PMID:32669547 human factors, including an uncharacterized factor TMA16 localized between the 5S RNA and the P0 stalk |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: HDA (high-throughput direct assay) annotation from proteomic characterization of the human sperm nucleus. Detection of TMA16 in the sperm nuclear proteome is consistent with its nuclear localization. Reason: This annotation from sperm nuclear proteomics is consistent with TMA16's nuclear localization. While derived from a tissue-specific proteomics study, it confirms the nuclear localization that is also supported by IBA and IDA evidence. Nuclear localization is a core aspect of TMA16 function in ribosome biogenesis. Supporting Evidence: PMID:21630459 Jun 1. Proteomic characterization of the human sperm nucleus. |
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