NUFIP1 (nuclear fragile X mental retardation-interacting protein 1) is a small zinc-finger, RNA-binding nucleocytoplasmic shuttling protein with two well-supported, distinct roles. In the nucleus/nucleolus it acts as a box C/D small nucleolar ribonucleoprotein (snoRNP) biogenesis/assembly factor: as part of the R2TP-associated pre-snoRNP machinery (with ZNHIT3, BCD1/ZNHIT6 and the AAA+ ATPases RUVBL1/TIP49 and RUVBL2/TIP48), NUFIP1 serves as a scaffold that bridges interactions between the core box C/D proteins, facilitating assembly of the snoRNPs that process and modify rRNA. In the cytoplasm, upon mTORC1 inhibition/nutrient starvation, NUFIP1 relocalizes from the nucleus to autophagosomes and functions as the selective-autophagy receptor for ribosomes (ribophagy): together with its partner ZNHIT3 it binds ribosomes and delivers them to the autophagosome by directly binding the ATG8-family protein LC3B through a LIR motif, providing metabolites that support cell survival under starvation. NUFIP1 was originally identified as a nuclear interactor of the fragile X protein FMR1/FMRP and is associated with active synaptoneurosomes; it has also been reported to cooperate with BRCA1 and the elongation factor P-TEFb (via Cyclin T1) to stimulate RNA polymerase II transcription, although it does not bind DNA directly. NUFIP1 localizes mainly to the nucleoplasm, nucleolus, perichromatin fibrils and nuclear matrix, redistributing to the cytoplasm during starvation-induced ribophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of protein-macromolecule adaptor activity, consistent with NUFIP1's scaffold/bridging role in pre-snoRNP assembly. Reason: Core molecular function; NUFIP1 bridges interactions between core box C/D proteins during snoRNP assembly, an adaptor/scaffold activity. Supported experimentally (PMID:17636026). Supporting Evidence: PMID:17636026 NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP |
| GO:0000492 box C/D snoRNP assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of involvement in box C/D snoRNP assembly. Core nuclear process for NUFIP1. Reason: Core biological process; NUFIP1 is a conserved pre-snoRNP assembly factor. Redundant with the experimental IMP evidence (PMID:17636026). Supporting Evidence: PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly |
| GO:0003723 RNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of RNA binding; experimentally supported (NUFIP1 binds RNA, including snoRNA). Reason: Correct molecular function; NUFIP1 is an RNA-binding protein, relevant to both snoRNP assembly (snoRNA binding) and its FMRP-associated role. Redundant with experimental IDA evidence (PMID:10556305). Supporting Evidence: file:human/NUFIP1/NUFIP1-uniprot.txt FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305} |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of nuclear localization; the predominant compartment for NUFIP1's snoRNP-assembly role. Reason: Correct primary localization; NUFIP1 is predominantly nuclear/nucleolar. Redundant with experimental IDA nucleoplasm/nucleolus annotations. Supporting Evidence: PMID:12941608 NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein |
| GO:0005515 protein binding | IPI PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | KEEP AS NON CORE | Summary: IPI interactions with core box C/D proteins and pre-snoRNP factors (TIP48/TIP49, etc.) from the snoRNP-assembly study. Bare protein binding is uninformative. Reason: Records the functionally central snoRNP-assembly interactions but the bare term is uninformative; the adaptor-activity and snoRNP-assembly annotations capture the function. Supporting Evidence: PMID:17636026 the novel biogenesis factors and TIP48 and TIP49 interacted with one or more of the core box C/D proteins |
| GO:0005515 protein binding | IPI PMID:25170085 Protein Hit1, a novel box C/D snoRNP assembly factor, contro... | KEEP AS NON CORE | Summary: Interaction reported in a study of the box C/D snoRNP assembly factor Hit1/Rsa1 (yeast homologs of ZNHIT3/NUFIP), relevant to snoRNP assembly. Bare protein binding is uninformative. Reason: Records an interaction relevant to the conserved snoRNP-assembly machinery, but the bare term is uninformative. Supporting Evidence: PMID:25170085 Protein Hit1, a novel box C/D snoRNP assembly factor, controls cellular concentration of the scaffolding protein Rsa1 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: High-throughput quantitative interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: High-throughput interactome-community interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary interactome reference map interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Cell-specific proteome-scale interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell endogenous-tagging interactome interaction. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic ortholog-transfer (Ensembl Compara) of synapse localization; consistent with NUFIP1's reported association with active synaptoneurosomes (FMRP context). Reason: Plausible but peripheral localization based on ortholog transfer and synaptoneurosome association (FMRP-related); not the core snoRNP-assembly/ribophagy function. Supporting Evidence: PMID:12941608 a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes |
| GO:0048786 presynaptic active zone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic ortholog-transfer of presynaptic active zone localization; based on synaptoneurosome association. Reason: Peripheral, ortholog-transferred localization (synaptoneurosome/FMRP context); not the core function. Supporting Evidence: PMID:12941608 associated with active synaptoneurosomes |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based nucleoplasm localization; consistent with NUFIP1's predominant nuclear localization. Reason: Correct nuclear localization where NUFIP1 functions in snoRNP assembly. Supporting Evidence: PMID:12941608 nuclear FMRP interacting protein 1 |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based nucleolus localization; consistent with NUFIP1's role in snoRNP biogenesis (nucleolar). Reason: Correct nucleolar localization, the site of box C/D snoRNP assembly and rRNA processing where NUFIP1 acts. Supporting Evidence: PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly |
| GO:0003677 DNA binding | IDA NOT PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | ACCEPT | Summary: NOT annotation — NUFIP1 does not directly bind DNA; it stimulates RNA polymerase II transcription via protein-protein interactions (BRCA1, P-TEFb/Cyclin T1) rather than direct DNA binding. Reason: The negation is correct and informative; NUFIP1 acts through protein interactions, not direct DNA binding. Retain as a NOT annotation. Supporting Evidence: PMID:15107825 NUFIP specifically stimulates activator-independent pol II transcription in vitro and in vivo |
| GO:0005515 protein binding | IPI PMID:28335020 ZNHIT3 is defective in PEHO syndrome, a severe encephalopath... | KEEP AS NON CORE | Summary: IPI interaction with ZNHIT3 (defective in PEHO syndrome), NUFIP1's partner in snoRNP assembly and ribophagy. Bare protein binding is uninformative. Reason: Records the functionally important NUFIP1-ZNHIT3 interaction but the bare term is uninformative; the snoRNP-assembly annotations capture the function. Supporting Evidence: PMID:28335020 ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss |
| GO:0048786 presynaptic active zone | ISS PMID:12941608 NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytop... | KEEP AS NON CORE | Summary: Sequence/orthology-based presynaptic active zone localization, derived from the synaptoneurosome association of NUFIP1. Reason: Peripheral localization based on synaptoneurosome association (FMRP context); not the core function. Supporting Evidence: PMID:12941608 associated with active synaptoneurosomes |
| GO:0051117 ATPase binding | IPI PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | KEEP AS NON CORE | Summary: IPI evidence that NUFIP1 binds the AAA+ ATPases TIP48/RUVBL2 and TIP49/RUVBL1 within the R2TP/pre-snoRNP machinery. Functionally meaningful interaction. Reason: Real and functionally relevant (interaction with the RUVBL1/2 ATPases of the snoRNP-assembly machinery), but a binding descriptor supporting the core adaptor/assembly function rather than a core function itself. Supporting Evidence: PMID:17636026 along with the ATPases TIP48 and TIP49, are likely to be involved in the formation of the pre-snoRNP |
| GO:0032991 protein-containing complex | IDA PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | KEEP AS NON CORE | Summary: Direct evidence that NUFIP1 is part of a protein-containing (pre-snoRNP) complex. Generic parent of the specific pre-snoRNP complex. Reason: Correct but generic; the specific pre-snoRNP complex annotation captures the relevant assembly. Supporting Evidence: PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly |
| GO:0070761 pre-snoRNP complex | IDA PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | ACCEPT | Summary: Direct evidence that NUFIP1 is part of the pre-snoRNP complex. Core cellular component for its assembly-factor role. Reason: Core cellular component; NUFIP1 is a constituent of the pre-snoRNP assembly complex where it bridges core box C/D proteins. Supporting Evidence: PMID:17636026 NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP |
| GO:0000492 box C/D snoRNP assembly | IMP PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | ACCEPT | Summary: Mutant-phenotype/functional evidence that NUFIP1 facilitates box C/D snoRNP assembly by bridging core proteins in the pre-snoRNP. Core biological process. Reason: Core biological process directly supported; NUFIP1 is required as a bridging assembly factor for box C/D snoRNP biogenesis. Supporting Evidence: PMID:17636026 NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP |
| GO:0030515 snoRNA binding | IDA PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | ACCEPT | Summary: Direct evidence that NUFIP1 (within the pre-snoRNP) contributes to snoRNA binding during assembly. Core molecular function in the snoRNP-assembly context. Reason: Core molecular function relevant to snoRNP assembly; contributes_to qualifier appropriately reflects its role within the assembly complex. Supporting Evidence: PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | ACCEPT | Summary: IPI evidence that NUFIP1 bridges/adapts interactions between core box C/D proteins during pre-snoRNP assembly. Core molecular function. Reason: Core molecular function; NUFIP1's scaffold/adaptor activity bridging core snoRNP proteins is directly supported. Supporting Evidence: PMID:17636026 NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP |
| GO:0042802 identical protein binding | IPI PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human b... | KEEP AS NON CORE | Summary: IPI self-interaction reported in the snoRNP-assembly study; NUFIP1 self-association. Reason: Self-association is a descriptive binding property rather than a core function. Supporting Evidence: PMID:17636026 A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly |
| GO:0005515 protein binding | IPI PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | KEEP AS NON CORE | Summary: IPI interactions with BRCA1 and P-TEFb (Cyclin T1) from the transcription-activation study. Bare protein binding is uninformative. Reason: Records real interactions (BRCA1, Cyclin T1) supporting the reported transcription role, but the bare term is uninformative. Supporting Evidence: PMID:15107825 NUFIP not only interacts with BRCA1 but also associates with the positive elongation factor P-TEFb through interaction with the regulatory Cyclin T1 subunit |
| GO:0008023 transcription elongation factor complex | IDA PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | KEEP AS NON CORE | Summary: Direct evidence that NUFIP associates with the P-TEFb transcription elongation factor (via Cyclin T1) in a transcription-activating complex. Reason: Real interaction with P-TEFb in a reported transcription role, but secondary/less-characterized relative to NUFIP1's core snoRNP-assembly and ribophagy functions. Supporting Evidence: PMID:15107825 associates with the positive elongation factor P-TEFb through interaction with the regulatory Cyclin T1 subunit |
| GO:0005515 protein binding | IPI PMID:10556305 A novel RNA-binding nuclear protein that interacts with the ... | KEEP AS NON CORE | Summary: IPI interaction with FMR1/FMRP from the original NUFIP1 identification. Bare protein binding is uninformative. Reason: Records the original NUFIP1-FMRP interaction but the bare term is uninformative. Supporting Evidence: file:human/NUFIP1/NUFIP1-uniprot.txt Interacts with FMR1 (PubMed:10556305) |
| GO:0003723 RNA binding | IDA PMID:10556305 A novel RNA-binding nuclear protein that interacts with the ... | ACCEPT | Summary: Direct experimental evidence that NUFIP1 binds RNA. Core molecular property. Reason: Directly demonstrated RNA binding, relevant to NUFIP1's snoRNP-assembly (snoRNA) and FMRP-associated roles. Supporting Evidence: file:human/NUFIP1/NUFIP1-uniprot.txt FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305} |
| GO:0005726 perichromatin fibrils | IDA PMID:12941608 NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytop... | KEEP AS NON CORE | Summary: Direct evidence of NUFIP1 localization to perichromatin fibrils (sites of active transcription/RNA processing). Reason: A specific nuclear sub-localization; correct but secondary to the broader nucleoplasm/nucleolus localization most relevant to function. Supporting Evidence: PMID:12941608 a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes |
| GO:0005730 nucleolus | IDA PMID:12941608 NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytop... | ACCEPT | Summary: Direct evidence of nucleolar localization of NUFIP1, consistent with its snoRNP-biogenesis role. Reason: Correct nucleolar localization, the site of box C/D snoRNP assembly where NUFIP1 acts. Supporting Evidence: PMID:12941608 nuclear FMRP interacting protein 1 |
| GO:0016363 nuclear matrix | IDA PMID:12941608 NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytop... | KEEP AS NON CORE | Summary: Direct evidence of NUFIP1 association with the nuclear matrix. Reason: A specific nuclear sub-compartment; correct but secondary to the nucleoplasm/nucleolus localization most relevant to function. Supporting Evidence: PMID:12941608 a nucleocytoplasmic shuttling protein |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence (immunodepletion/restoration) that NUFIP stimulates RNA polymerase II transcription, cooperating with BRCA1 and P-TEFb. Reason: Real reported transcription-stimulatory role, but secondary and less-corroborated relative to NUFIP1's core snoRNP-assembly and ribophagy functions; acts indirectly (not via DNA binding). Supporting Evidence: PMID:15107825 Immunodepletion of the endogenous NUFIP causes a marked decrease of pol II transcription |
| GO:0006396 RNA processing | TAS PMID:10556305 A novel RNA-binding nuclear protein that interacts with the ... | KEEP AS NON CORE | Summary: Author-statement involvement in RNA processing; generic term consistent with NUFIP1's snoRNP-assembly role (snoRNPs process/modify rRNA). Reason: Correct but generic; the specific box C/D snoRNP assembly annotation better captures NUFIP1's contribution to RNA processing. Supporting Evidence: file:human/NUFIP1/NUFIP1-uniprot.txt FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305} |
| GO:0160247 autophagy cargo adaptor activity | IDA PMID:29700228 NUFIP1 is a ribosome receptor for starvation-induced ribopha... | NEW | Summary: NUFIP1 acts as the selective-autophagy cargo receptor for ribosomes by binding ribosomes and LC3B under starvation/mTORC1-inhibited conditions. Reason: The review already captured this in core_functions, and PN confirmed the existing GO MF term is appropriate. This converts the redundant proposed-new-term request into an explicit recommendation for GO:0160247. Supporting Evidence: PMID:29700228 NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to microtubule-associated proteins 1A/1B light chain 3B |
| GO:0034517 ribophagy | IMP PMID:29700228 NUFIP1 is a ribosome receptor for starvation-induced ribopha... | NEW | Summary: NUFIP1 is required for starvation-induced autophagic degradation of ribosomes. Reason: The PN pass confirmed ribophagy is an existing GO process term and is absent from the current GOA. It should be recommended directly rather than as part of an NTR-style proposal. Supporting Evidence: PMID:29700228 The starvation-induced degradation of ribosomes via autophagy (ribophagy) depends on the capacity of NUFIP1 to bind LC3B |
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Download this section (compressed HTML)Q: How is NUFIP1's partitioning between its nuclear snoRNP-assembly role and its cytoplasmic ribophagy-receptor role regulated beyond mTORC1 signaling, and does ZNHIT3 coordinate both functions?
Q: Is NUFIP1-mediated ribophagy selective for particular ribosome subpopulations (e.g. 60S vs 40S, or stalled/damaged ribosomes), and what determines cargo selectivity?
Experiment: Map the NUFIP1 LIR motif by mutagenesis and test LC3B-binding-deficient NUFIP1 for ribosome delivery to autophagosomes and starvation survival, while separately assaying snoRNP assembly to determine whether the two functions are genetically separable.
Experiment: Use proximity labeling and ribosome-profiling in nucleus- versus autophagosome-localized NUFIP1 pools under fed and starved conditions to define the in vivo cargo (ribosomes/snoRNPs) and partner repertoire of each functional state.
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