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.