Existing Annotations Review

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

Core Functions

Acts as a box C/D small nucleolar ribonucleoprotein (snoRNP) assembly factor, serving as a protein-macromolecule adaptor/scaffold that bridges interactions between core box C/D proteins within the R2TP-associated pre-snoRNP complex (with ZNHIT3 and the RUVBL1/RUVBL2 ATPases), thereby facilitating snoRNP biogenesis for rRNA processing and modification.

Molecular Function:

protein-macromolecule adaptor activity

Directly Involved In:

box C/D snoRNP assembly

Cellular Locations:

nucleolus

Supporting Evidence:

PMID:17636026
NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP

Functions as the selective-autophagy (ribophagy) receptor for ribosomes during starvation/mTORC1 inhibition, binding ribosomes (with ZNHIT3) and the ATG8-family protein LC3B via a LIR motif to deliver ribosomes to autophagosomes for degradation, supporting cell survival. This function is not yet represented in the current GOA.

Molecular Function:

autophagy cargo adaptor activity

Directly Involved In:

ribophagy

Supporting Evidence:

PMID:29700228
depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10556305

A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein.

NUFIP1 is a novel RNA-binding nuclear protein that interacts with the fragile X mental retardation protein FMR1/FMRP.

PMID:12941608

NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes.

PMID:15107825

BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II.

NUFIP interacts with BRCA1 and associates with P-TEFb (via Cyclin T1), stimulating activator-independent RNA polymerase II transcription; immunodepletion of NUFIP decreases pol II transcription.

PMID:17636026

A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly.

NUFIP, with BCD1, NOP17, TAF9 and the ATPases TIP48/TIP49, is a pre-snoRNP assembly factor; NUFIP bridges interactions between core box C/D proteins in a partially reconstituted pre-snoRNP.

PMID:25170085

Protein Hit1, a novel box C/D snoRNP assembly factor, controls cellular concentration of the scaffolding protein Rsa1 by direct interaction.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:28335020

ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:29700228

NUFIP1 is a ribosome receptor for starvation-induced ribophagy.

Upon mTORC1 inhibition/starvation, NUFIP1 redistributes from the nucleus to autophagosomes, binds ribosomes (with ZNHIT3), and delivers them to autophagosomes by directly binding LC3B; a NUFIP1 mutant unable to bind LC3B cannot support ribosome degradation. NUFIP1 is the selective-autophagy receptor for ribosomes (ribophagy), promoting cell survival under starvation.

Suggested Experiments

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.

📚 Additional Documentation

Notes

(NUFIP1-notes.md)

NUFIP1 (nuclear FMR1-interacting protein 1) — review notes

UniProt: Q9UHK0. Gene: NUFIP1. Human.

Function overview (synthesized)

NUFIP1 is a small zinc-finger nucleocytoplasmic shuttling protein with two distinct, well-supported roles plus historical transcription/FMRP associations:

1. Ribophagy receptor (headline cytoplasmic function; NOT yet in current GOA)

Upon mTORC1 inhibition/starvation, NUFIP1 redistributes from the nucleus to the cytoplasm/autophagosomes, binds ribosomes (with its partner ZNHIT3), and delivers them to autophagosomes by directly binding LC3B via a LIR motif, acting as the selective-autophagy receptor for ribosomes (ribophagy). A NUFIP1 LC3B-binding mutant cannot support ribosome degradation. Ribophagy provides metabolites supporting cell survival under starvation.
[PMID:29700228 "NUFIP1 is a ribosome receptor for starvation-induced ribophagy" — Wyant et al., Science 2018: "Upon mTORC1 inhibition, NUFIP1 redistributes from the nucleus to autophagosomes and lysosomes, where it interacts with ribosomes and delivers them to autophagosomes by directly binding to LC3B"; "a NUFIP1 mutant that does not bind LC3B cannot support ribosomal degradation"]

2. Box C/D snoRNP assembly factor (nuclear)

NUFIP (with ZNHIT3/NHP2L1, BCD1/ZNHIT6, and the R2TP/AAA+ ATPases TIP48/RUVBL2 and TIP49/RUVBL1) is a pre-snoRNP scaffold/assembly factor. NUFIP bridges interactions between core box C/D proteins in the pre-snoRNP, facilitating box C/D snoRNP biogenesis (rRNA processing/modification machinery).
[PMID:17636026 "we show that NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP"; "four novel human biogenesis factors (BCD1, NOP17, NUFIP, and TAF9) which, along with the ATPases TIP48 and TIP49, are likely to be involved in the formation of the pre-snoRNP"]
- Interacts with ZNHIT3 (defective in PEHO syndrome). PMID:28335020

3. FMRP interaction / transcription (historical)

NUFIP1 was identified as a nuclear FMR1 (FMRP)-interacting protein, an RNA-binding nucleocytoplasmic shuttling protein associated with active synaptoneurosomes; also reported to cooperate with BRCA1 and P-TEFb (Cyclin T1) to stimulate RNA polymerase II transcription. It does NOT itself bind DNA directly (acts via protein interactions and stimulates pol II transcription).
[PMID:10556305 NUFIP identified as nuclear FMRP-interacting RNA-binding protein]
PMID:12941608
[PMID:15107825 "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II" — yeast two-hybrid with BRCA1; stimulates activator-independent pol II transcription; associates with P-TEFb via Cyclin T1]

Domain / binding

Zinc-finger-containing protein. Binds RNA (and snoRNA). LIR motif mediates LC3B binding (ribophagy).
[file:human/NUFIP1/NUFIP1-uniprot.txt "FUNCTION: Binds RNA"; "Interacts with FMR1 ... Interacts with ZNHIT3"]

Localization

Predominantly nucleus (nucleoplasm, nucleolus, perichromatin fibrils, nuclear matrix); shuttles to cytoplasm/autophagosomes upon starvation. Synapse/presynaptic active zone annotations are by IEA/ISS (Ensembl Compara ortholog transfer; synaptoneurosome association).

Annotation judgments

Core ACCEPT: box C/D snoRNP assembly (GO:0000492 IBA and IMP), protein-macromolecule adaptor activity (GO:0030674 IBA/IPI — scaffold/bridging role), pre-snoRNP complex (GO:0070761), snoRNA binding (GO:0030515 contributes_to), RNA binding (GO:0003723), ATPase binding (GO:0051117 — TIP48/49), nucleus/nucleolus/nucleoplasm localization, identical protein binding.
The headline ribophagy receptor function (LC3B binding, ribosome cargo receptor) is NOT in the current GOA -> propose as NEW terms (GO:0034517 ribophagy; GO:0160247 autophagy cargo adaptor activity). Reviewer should add these.
KEEP_AS_NON_CORE: transcription elongation factor complex (GO:0008023), positive regulation of transcription by pol II (GO:0045944), RNA processing (GO:0006396 TAS), perichromatin fibrils, nuclear matrix, protein-containing complex (generic).
DNA binding NEGATED (GO:0003677 NOT, IDA, PMID:15107825): ACCEPT the negation — NUFIP stimulates pol II transcription via protein interactions, not direct DNA binding. Keep as-is (negated true).
synapse / presynaptic active zone (IEA/ISS GO_REF:0000107, PMID:12941608): KEEP_AS_NON_CORE — based on synaptoneurosome association / ortholog transfer; plausible but peripheral.
protein binding (GO:0005515) — KEEP_AS_NON_CORE (uninformative bare; many high-throughput interactome PMIDs; 28335020=ZNHIT3, 17636026=snoRNP, 25170085=Rsa1/Hit1 yeast homolog context).

Pn Notes

(NUFIP1-pn-notes.md)

NUFIP1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UHK0
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-14
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/NUFIP1/NUFIP1-ai-review.yaml
AIGR review HTML: missing - genes/human/NUFIP1/NUFIP1-ai-review.html
Gene notes: present - genes/human/NUFIP1/NUFIP1-notes.md
GOA TSV: present - genes/human/NUFIP1/NUFIP1-goa.tsv
UniProt record: present - genes/human/NUFIP1/NUFIP1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/NUFIP1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/NUFIP1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 13; KEEP_AS_NON_CORE: 21; NEW: 2

PN Consistency Summary

Consistency: Strongly consistent. PN (ribophagy receptor binding ATG8/ubiquitinated cargo), review, notes and references all agree: NUFIP1's headline cytoplasmic function is the starvation/mTORC1-induced ribophagy receptor that binds ribosomes (with ZNHIT3) and LC3B via a LIR motif (PMID:29700228, Wyant et al. Science 2018). The review also fully covers the second, nuclear box C/D snoRNP-assembly function (which PN does not address — PN is single-row, ALP-only). No contradictions; PN simply scopes only the autophagy arm.
PN story / NEW pressure: Strong, defensible ADD pressure: ribophagy is genuinely absent from GOA (confirmed — NUFIP1 GOA has no ribophagy/autophagy term). GO:0034517 ribophagy is verified real. The review ALREADY adds this as a core function (GO:0034517 ribophagy involved_in + GO:0160247 autophagy cargo adaptor activity as the MF, both supported by PMID:29700228) — fully matching the PN projection. The review additionally proposes a NEW bespoke "ribophagy receptor activity" term; per the established precedent (BNIP3L/CALCOCO1) this over-reaches — the existing GO:0160247 autophagy cargo adaptor activity already captures the ribosome-LC3B bridging MF and should be used instead of minting a new term.
Evidence alignment: Strong overlap on the autophagy arm. PN cites the LIR/cargo-receptor review and the Wyant ribophagy paper (= PMID:29700228, review HIGH, PubMed-verified). Review refs additionally span the snoRNP-assembly (PMID:17636026) and FMRP/transcription (PMID:10556305, 15107825) functions that PN omits.
Verdict: Consistent; ribophagy ADD already implemented in review; only the proposed bespoke MF term over-reaches. Recommended edits: [YAML] drop the proposed_new_terms "ribophagy receptor activity" entry — the existing GO:0034517 ribophagy (BP) + GO:0160247 autophagy cargo adaptor activity (MF), both already in the review's core_functions, fully capture the role (mirrors the BNIP3L/CALCOCO1 "use existing terms, don't mint new" precedent).

Full Consistency Review

UniProt: Q9UHK0 · batch: proteostasis-batch-2026-06-14 · review status: COMPLETE (thorough, dual-function)
PN placement: 1 row — ALP|Autophagy substrate selection|Selective autophagy receptor|Ribophagy. PN-node mapping: Ribophagy type → mapped/ok GO:0034517 ribophagy (new_to_goa); ancestors (group/class/branch) = no_mapping.
Consistency: Strongly consistent. PN (ribophagy receptor binding ATG8/ubiquitinated cargo), review, notes and references all agree: NUFIP1's headline cytoplasmic function is the starvation/mTORC1-induced ribophagy receptor that binds ribosomes (with ZNHIT3) and LC3B via a LIR motif (PMID:29700228, Wyant et al. Science 2018). The review also fully covers the second, nuclear box C/D snoRNP-assembly function (which PN does not address — PN is single-row, ALP-only). No contradictions; PN simply scopes only the autophagy arm.
PN story / NEW pressure: Strong, defensible ADD pressure: ribophagy is genuinely absent from GOA (confirmed — NUFIP1 GOA has no ribophagy/autophagy term). GO:0034517 ribophagy is verified real. The review ALREADY adds this as a core function (GO:0034517 ribophagy involved_in + GO:0160247 autophagy cargo adaptor activity as the MF, both supported by PMID:29700228) — fully matching the PN projection. The review additionally proposes a NEW bespoke "ribophagy receptor activity" term; per the established precedent (BNIP3L/CALCOCO1) this over-reaches — the existing GO:0160247 autophagy cargo adaptor activity already captures the ribosome-LC3B bridging MF and should be used instead of minting a new term.
Mapping strategy: No node change needed. Ribophagy projection (GO:0034517) is correct, specific, and new_to_goa. Cargo-adaptor MF (GO:0160247) over bare protein binding is the prescribed receptor pattern and the review already uses it. The PN node need not also project the MF — the review covers it.
Evidence alignment: Strong overlap on the autophagy arm. PN cites the LIR/cargo-receptor review and the Wyant ribophagy paper (= PMID:29700228, review HIGH, PubMed-verified). Review refs additionally span the snoRNP-assembly (PMID:17636026) and FMRP/transcription (PMID:10556305, 15107825) functions that PN omits.
Verdict: Consistent; ribophagy ADD already implemented in review; only the proposed bespoke MF term over-reaches. Recommended edits: [YAML] drop the proposed_new_terms "ribophagy receptor activity" entry — the existing GO:0034517 ribophagy (BP) + GO:0160247 autophagy cargo adaptor activity (MF), both already in the review's core_functions, fully capture the role (mirrors the BNIP3L/CALCOCO1 "use existing terms, don't mint new" precedent).
2026-06-18 follow-up: Implemented the YAML cleanup: added explicit NEW recommendations for GO:0034517 ribophagy and GO:0160247 autophagy cargo adaptor activity, and removed the redundant bespoke ribophagy-receptor NTR block.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-14
review_yaml: genes/human/NUFIP1/NUFIP1-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Ribophagy

UniProt: Q9UHK0
In branches: ALP
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in ribophagy
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- NUFIP1 is a ribosome receptor for starvation-induced ribophagy (science.org)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Ribophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0034517 ribophagy]
  rationale: The PN category covers receptors for autophagic turnover of ribosomes. These genes belong in the ribophagy process, but the PN label denotes a receptor role rather than the entire process class.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

GO:0034517 ribophagy | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Ribophagy

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q9UHK0
gene_symbol: NUFIP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of protein-macromolecule adaptor activity, consistent with NUFIP1's scaffold/bridging role in pre-snoRNP assembly.
    action: ACCEPT
    reason: Core molecular function; NUFIP1 bridges interactions between core box C/D proteins during snoRNP assembly, an adaptor/scaffold activity. Supported experimentally (PMID:17636026).
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP
- term:
    id: GO:0000492
    label: box C/D snoRNP assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of involvement in box C/D snoRNP assembly. Core nuclear process for NUFIP1.
    action: ACCEPT
    reason: Core biological process; NUFIP1 is a conserved pre-snoRNP assembly factor. Redundant with the experimental IMP evidence (PMID:17636026).
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment of RNA binding; experimentally supported (NUFIP1 binds RNA, including snoRNA).
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/NUFIP1/NUFIP1-uniprot.txt
      supporting_text: 'FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305}'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of nuclear localization; the predominant compartment for NUFIP1's snoRNP-assembly role.
    action: ACCEPT
    reason: Correct primary localization; NUFIP1 is predominantly nuclear/nucleolar. Redundant with experimental IDA nucleoplasm/nucleolus annotations.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17636026
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central snoRNP-assembly interactions but the bare term is uninformative; the adaptor-activity and snoRNP-assembly annotations capture the function.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: the novel biogenesis factors and TIP48 and TIP49 interacted with one or more of the core box C/D proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25170085
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records an interaction relevant to the conserved snoRNP-assembly machinery, but the bare term is uninformative.
    supported_by:
    - reference_id: PMID:25170085
      supporting_text: Protein Hit1, a novel box C/D snoRNP assembly factor, controls cellular concentration of the scaffolding protein Rsa1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: High-throughput quantitative interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome-community interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary interactome reference map interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Cell-specific proteome-scale interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Electronic ortholog-transfer (Ensembl Compara) of synapse localization; consistent with NUFIP1's reported association with active synaptoneurosomes (FMRP context).
    action: KEEP_AS_NON_CORE
    reason: Plausible but peripheral localization based on ortholog transfer and synaptoneurosome association (FMRP-related); not the core snoRNP-assembly/ribophagy function.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes
- term:
    id: GO:0048786
    label: presynaptic active zone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic ortholog-transfer of presynaptic active zone localization; based on synaptoneurosome association.
    action: KEEP_AS_NON_CORE
    reason: Peripheral, ortholog-transferred localization (synaptoneurosome/FMRP context); not the core function.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: associated with active synaptoneurosomes
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based nucleoplasm localization; consistent with NUFIP1's predominant nuclear localization.
    action: ACCEPT
    reason: Correct nuclear localization where NUFIP1 functions in snoRNP assembly.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: nuclear FMRP interacting protein 1
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based nucleolus localization; consistent with NUFIP1's role in snoRNP biogenesis (nucleolar).
    action: ACCEPT
    reason: Correct nucleolar localization, the site of box C/D snoRNP assembly and rRNA processing where NUFIP1 acts.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15107825
  qualifier: enables
  negated: true
  review:
    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.
    action: ACCEPT
    reason: The negation is correct and informative; NUFIP1 acts through protein interactions, not direct DNA binding. Retain as a NOT annotation.
    supported_by:
    - reference_id: PMID:15107825
      supporting_text: NUFIP specifically stimulates activator-independent pol II transcription in vitro and in vivo
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28335020
  qualifier: enables
  review:
    summary: IPI interaction with ZNHIT3 (defective in PEHO syndrome), NUFIP1's partner in snoRNP assembly and ribophagy. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important NUFIP1-ZNHIT3 interaction but the bare term is uninformative; the snoRNP-assembly annotations capture the function.
    supported_by:
    - reference_id: PMID:28335020
      supporting_text: ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss
- term:
    id: GO:0048786
    label: presynaptic active zone
  evidence_type: ISS
  original_reference_id: PMID:12941608
  qualifier: located_in
  review:
    summary: Sequence/orthology-based presynaptic active zone localization, derived from the synaptoneurosome association of NUFIP1.
    action: KEEP_AS_NON_CORE
    reason: Peripheral localization based on synaptoneurosome association (FMRP context); not the core function.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: associated with active synaptoneurosomes
- term:
    id: GO:0051117
    label: ATPase binding
  evidence_type: IPI
  original_reference_id: PMID:17636026
  qualifier: enables
  review:
    summary: IPI evidence that NUFIP1 binds the AAA+ ATPases TIP48/RUVBL2 and TIP49/RUVBL1 within the R2TP/pre-snoRNP machinery. Functionally meaningful interaction.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: along with the ATPases TIP48 and TIP49, are likely to be involved in the formation of the pre-snoRNP
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:17636026
  qualifier: part_of
  review:
    summary: Direct evidence that NUFIP1 is part of a protein-containing (pre-snoRNP) complex. Generic parent of the specific pre-snoRNP complex.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific pre-snoRNP complex annotation captures the relevant assembly.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly
- term:
    id: GO:0070761
    label: pre-snoRNP complex
  evidence_type: IDA
  original_reference_id: PMID:17636026
  qualifier: part_of
  review:
    summary: Direct evidence that NUFIP1 is part of the pre-snoRNP complex. Core cellular component for its assembly-factor role.
    action: ACCEPT
    reason: Core cellular component; NUFIP1 is a constituent of the pre-snoRNP assembly complex where it bridges core box C/D proteins.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP
- term:
    id: GO:0000492
    label: box C/D snoRNP assembly
  evidence_type: IMP
  original_reference_id: PMID:17636026
  qualifier: involved_in
  review:
    summary: Mutant-phenotype/functional evidence that NUFIP1 facilitates box C/D snoRNP assembly by bridging core proteins in the pre-snoRNP. Core biological process.
    action: ACCEPT
    reason: Core biological process directly supported; NUFIP1 is required as a bridging assembly factor for box C/D snoRNP biogenesis.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP
- term:
    id: GO:0030515
    label: snoRNA binding
  evidence_type: IDA
  original_reference_id: PMID:17636026
  qualifier: contributes_to
  review:
    summary: Direct evidence that NUFIP1 (within the pre-snoRNP) contributes to snoRNA binding during assembly. Core molecular function in the snoRNP-assembly context.
    action: ACCEPT
    reason: Core molecular function relevant to snoRNP assembly; contributes_to qualifier appropriately reflects its role within the assembly complex.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IPI
  original_reference_id: PMID:17636026
  qualifier: enables
  review:
    summary: IPI evidence that NUFIP1 bridges/adapts interactions between core box C/D proteins during pre-snoRNP assembly. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; NUFIP1's scaffold/adaptor activity bridging core snoRNP proteins is directly supported.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17636026
  qualifier: enables
  review:
    summary: IPI self-interaction reported in the snoRNP-assembly study; NUFIP1 self-association.
    action: KEEP_AS_NON_CORE
    reason: Self-association is a descriptive binding property rather than a core function.
    supported_by:
    - reference_id: PMID:17636026
      supporting_text: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15107825
  qualifier: enables
  review:
    summary: IPI interactions with BRCA1 and P-TEFb (Cyclin T1) from the transcription-activation study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (BRCA1, Cyclin T1) supporting the reported transcription role, but the bare term is uninformative.
    supported_by:
    - reference_id: PMID:15107825
      supporting_text: NUFIP not only interacts with BRCA1 but also associates with the positive elongation factor P-TEFb through interaction with the regulatory Cyclin T1 subunit
- term:
    id: GO:0008023
    label: transcription elongation factor complex
  evidence_type: IDA
  original_reference_id: PMID:15107825
  qualifier: part_of
  review:
    summary: Direct evidence that NUFIP associates with the P-TEFb transcription elongation factor (via Cyclin T1) in a transcription-activating complex.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:15107825
      supporting_text: associates with the positive elongation factor P-TEFb through interaction with the regulatory Cyclin T1 subunit
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10556305
  qualifier: enables
  review:
    summary: IPI interaction with FMR1/FMRP from the original NUFIP1 identification. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the original NUFIP1-FMRP interaction but the bare term is uninformative.
    supported_by:
    - reference_id: file:human/NUFIP1/NUFIP1-uniprot.txt
      supporting_text: Interacts with FMR1 (PubMed:10556305)
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IDA
  original_reference_id: PMID:10556305
  qualifier: enables
  review:
    summary: Direct experimental evidence that NUFIP1 binds RNA. Core molecular property.
    action: ACCEPT
    reason: Directly demonstrated RNA binding, relevant to NUFIP1's snoRNP-assembly (snoRNA) and FMRP-associated roles.
    supported_by:
    - reference_id: file:human/NUFIP1/NUFIP1-uniprot.txt
      supporting_text: 'FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305}'
- term:
    id: GO:0005726
    label: perichromatin fibrils
  evidence_type: IDA
  original_reference_id: PMID:12941608
  qualifier: located_in
  review:
    summary: Direct evidence of NUFIP1 localization to perichromatin fibrils (sites of active transcription/RNA processing).
    action: KEEP_AS_NON_CORE
    reason: A specific nuclear sub-localization; correct but secondary to the broader nucleoplasm/nucleolus localization most relevant to function.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:12941608
  qualifier: located_in
  review:
    summary: Direct evidence of nucleolar localization of NUFIP1, consistent with its snoRNP-biogenesis role.
    action: ACCEPT
    reason: Correct nucleolar localization, the site of box C/D snoRNP assembly where NUFIP1 acts.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: nuclear FMRP interacting protein 1
- term:
    id: GO:0016363
    label: nuclear matrix
  evidence_type: IDA
  original_reference_id: PMID:12941608
  qualifier: located_in
  review:
    summary: Direct evidence of NUFIP1 association with the nuclear matrix.
    action: KEEP_AS_NON_CORE
    reason: A specific nuclear sub-compartment; correct but secondary to the nucleoplasm/nucleolus localization most relevant to function.
    supported_by:
    - reference_id: PMID:12941608
      supporting_text: a nucleocytoplasmic shuttling protein
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:15107825
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence (immunodepletion/restoration) that NUFIP stimulates RNA polymerase II transcription, cooperating with BRCA1 and P-TEFb.
    action: KEEP_AS_NON_CORE
    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).
    supported_by:
    - reference_id: PMID:15107825
      supporting_text: Immunodepletion of the endogenous NUFIP causes a marked decrease of pol II transcription
- term:
    id: GO:0006396
    label: RNA processing
  evidence_type: TAS
  original_reference_id: PMID:10556305
  qualifier: involved_in
  review:
    summary: Author-statement involvement in RNA processing; generic term consistent with NUFIP1's snoRNP-assembly role (snoRNPs process/modify rRNA).
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific box C/D snoRNP assembly annotation better captures NUFIP1's contribution to RNA processing.
    supported_by:
    - reference_id: file:human/NUFIP1/NUFIP1-uniprot.txt
      supporting_text: 'FUNCTION: Binds RNA. {ECO:0000269|PubMed:10556305}'
- term:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:29700228
  qualifier: enables
  review:
    summary: NUFIP1 acts as the selective-autophagy cargo receptor for ribosomes by binding ribosomes and LC3B under starvation/mTORC1-inhibited conditions.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:29700228
      supporting_text: NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to microtubule-associated proteins 1A/1B light chain 3B
      reference_section_type: ABSTRACT
- term:
    id: GO:0034517
    label: ribophagy
  evidence_type: IMP
  original_reference_id: PMID:29700228
  qualifier: involved_in
  review:
    summary: NUFIP1 is required for starvation-induced autophagic degradation of ribosomes.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:29700228
      supporting_text: The starvation-induced degradation of ribosomes via autophagy (ribophagy) depends on the capacity of NUFIP1 to bind LC3B
      reference_section_type: ABSTRACT
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10556305
  title: A novel RNA-binding nuclear protein that interacts with the fragile X mental
    retardation (FMR1) protein.
  findings:
  - statement: NUFIP1 is a novel RNA-binding nuclear protein that interacts with the fragile X mental retardation protein FMR1/FMRP.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Original identification of NUFIP1 as a nuclear FMRP-interacting RNA-binding protein. Source of the RNA binding and FMRP-interaction annotations.
- id: PMID:12941608
  title: NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling
    protein associated with active synaptoneurosomes.
  findings: []
- id: PMID:15107825
  title: BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase
    II.
  findings:
  - statement: NUFIP interacts with BRCA1 and associates with P-TEFb (via Cyclin T1), stimulating activator-independent RNA polymerase II transcription; immunodepletion of NUFIP decreases pol II transcription.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Establishes the reported (secondary) transcription-stimulatory role via BRCA1/P-TEFb; basis of the NOT DNA-binding annotation (acts via protein interactions).
- id: PMID:17636026
  title: A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP
    assembly.
  findings:
  - statement: NUFIP, with BCD1, NOP17, TAF9 and the ATPases TIP48/TIP49, is a pre-snoRNP assembly factor; NUFIP bridges interactions between core box C/D proteins in a partially reconstituted pre-snoRNP.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available. Establishes NUFIP1's core nuclear function as a box C/D snoRNP assembly scaffold/adaptor factor.
- id: PMID:25170085
  title: Protein Hit1, a novel box C/D snoRNP assembly factor, controls cellular concentration
    of the scaffolding protein Rsa1 by direct interaction.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings: []
- id: PMID:28335020
  title: ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar
    granule neuron loss.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:29700228
  title: NUFIP1 is a ribosome receptor for starvation-induced ribophagy.
  findings:
  - statement: Upon mTORC1 inhibition/starvation, NUFIP1 redistributes from the nucleus to autophagosomes, binds ribosomes (with ZNHIT3), and delivers them to autophagosomes by directly binding LC3B; a NUFIP1 mutant unable to bind LC3B cannot support ribosome degradation. NUFIP1 is the selective-autophagy receptor for ribosomes (ribophagy), promoting cell survival under starvation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Wyant et al., Science 2018 (PMID PubMed-verified). Establishes NUFIP1's headline cytoplasmic function as the ribophagy receptor binding LC3B. This function is not yet captured in the current GOA; proposed as new terms.
core_functions:
- description: Acts as a box C/D small nucleolar ribonucleoprotein (snoRNP) assembly factor, serving as a protein-macromolecule adaptor/scaffold that bridges interactions between core box C/D proteins within the R2TP-associated pre-snoRNP complex (with ZNHIT3 and the RUVBL1/RUVBL2 ATPases), thereby facilitating snoRNP biogenesis for rRNA processing and modification.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  supported_by:
  - reference_id: PMID:17636026
    supporting_text: NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP
  locations:
  - id: GO:0005730
    label: nucleolus
  directly_involved_in:
  - id: GO:0000492
    label: box C/D snoRNP assembly
- description: Functions as the selective-autophagy (ribophagy) receptor for ribosomes during starvation/mTORC1 inhibition, binding ribosomes (with ZNHIT3) and the ATG8-family protein LC3B via a LIR motif to deliver ribosomes to autophagosomes for degradation, supporting cell survival. This function is not yet represented in the current GOA.
  molecular_function:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  supported_by:
  - reference_id: PMID:29700228
    supporting_text: depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival
  directly_involved_in:
  - id: GO:0034517
    label: ribophagy
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: Is NUFIP1-mediated ribophagy selective for particular ribosome subpopulations (e.g. 60S vs 40S, or stalled/damaged ribosomes), and what determines cargo selectivity?
suggested_experiments:
- description: 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.
- description: 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.

NUFIP1

Gene Description