Affinage

NIP7

60S ribosome subunit biogenesis protein NIP7 homolog · UniProt Q9Y221

Round 2 corrected
Length
180 aa
Mass
20.5 kDa
Annotated
2026-04-29
40 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NIP7 is a conserved nucleolar trans-acting factor required for ribosome biogenesis, functioning in pre-rRNA processing and ribosomal subunit maturation. Its two-domain architecture—an N-terminal alpha-beta domain and a C-terminal PUA domain—mediates specific RNA binding with preference for polyuridine sequences, as demonstrated by crystallography and mutagenesis of the archaeal ortholog and confirmed for the eukaryotic protein (PMID:18001138, PMID:15522784). In human cells, NIP7 localizes to the nucleus, co-sediments with pre-ribosomal particles, and is required for accurate processing at site 2 in the pre-rRNA maturation pathway leading to 18S rRNA production; it physically and functionally cooperates with the methyltransferase FTSJ3 in this process (PMID:20798176, PMID:22195017). NIP7 additionally promotes translation of the cell-cycle regulator UBE2C, linking ribosome biogenesis to cell proliferation in cancer contexts (PMID:40461291).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2004 Medium

    Determining the three-dimensional structure of human NIP7 revealed a two-domain fold with a C-terminal PUA domain, establishing the first structural framework for predicting an RNA-binding function.

    Evidence X-ray crystallography at 1.9 Å resolution (MAD phasing) of recombinant human NIP7 (KD93/HSPC031), with DALI structural comparison to known PUA domains

    PMID:15522784

    Open questions at the time
    • RNA binding was inferred from structural homology but not experimentally tested in this study
    • No functional assays linking the structure to ribosome biogenesis were performed
  2. 2007 High

    Direct RNA-binding activity was demonstrated and mapped to the PUA domain, resolving which domain mediates substrate recognition and establishing polyuridine as a preferred ligand.

    Evidence Crystal structure of archaeal Nip7 (P. abyssi), site-directed mutagenesis of PUA domain residues, EMSA and filter-binding assays with yeast and archaeal orthologs

    PMID:18001138

    Open questions at the time
    • The specific in vivo rRNA targets of NIP7 PUA domain binding were not identified
    • Functional consequence of RNA-binding mutants on ribosome biogenesis was not tested
  3. 2010 High

    NIP7 was shown to be required for pre-rRNA processing at site 2, directly linking its function to 18S rRNA maturation and 40S subunit production in human cells.

    Evidence Conditional siRNA knockdown of NIP7 in HEK293 cells, Northern blotting of pre-rRNA intermediates, sucrose gradient sedimentation, subcellular fractionation, and proliferation assays

    PMID:20798176

    Open questions at the time
    • The precise mechanism by which NIP7 facilitates cleavage at site 2 remains undefined
    • Whether NIP7 acts catalytically or as a structural scaffold on the pre-ribosome is unknown
  4. 2011 High

    Identification of FTSJ3 as a direct physical and functional partner established NIP7 as part of a biogenesis module, with parallel knockdown phenotypes confirming their cooperation in the same pre-rRNA processing pathway.

    Evidence Yeast two-hybrid, co-immunoprecipitation, co-localization by immunofluorescence, and conditional siRNA knockdown of FTSJ3 with Northern blot analysis in human cells

    PMID:22195017

    Open questions at the time
    • Whether NIP7 modulates FTSJ3 methyltransferase activity or vice versa is not determined
    • The pre-ribosomal particle on which the NIP7–FTSJ3 complex acts has not been structurally resolved
  5. 2024 Medium

    Cross-species complementation in Chlamydomonas confirmed that NIP7's role in 60S subunit biogenesis is functionally conserved across deep evolutionary distances and identified novel candidate interaction partners.

    Evidence Yeast NIP7-deletion complementation by CrNip7, yeast two-hybrid identification of UNC-p and G-patch domain protein partners, nucleic acid interaction assays

    PMID:39216654

    Open questions at the time
    • Novel partners (UNC-p, G-patch protein) await co-IP confirmation and functional validation
    • Whether the dual-domain rRNA binding observed in Chlamydomonas NIP7 reflects the mammalian protein is untested
  6. 2025 Medium

    A cancer-specific function was uncovered in which NIP7 promotes translation of the cell-cycle ubiquitin-conjugating enzyme UBE2C, linking ribosome biogenesis factor activity to oncogenic proliferation.

    Evidence siRNA knockdown in anaplastic thyroid cancer cells, SUnSET translation assay, UBE2C rescue experiment, xenograft tumor model, Western blotting

    PMID:40461291

    Open questions at the time
    • Whether NIP7 regulates UBE2C translation via general ribosome biogenesis or a specific mRNA-level mechanism is unresolved
    • Findings from a single lab in one cancer type; generalizability is untested
    • Direct NIP7–UBE2C mRNA interaction has not been demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise catalytic or structural mechanism by which NIP7 facilitates pre-rRNA cleavage at site 2, and whether its RNA-binding activity is required in cis on the pre-ribosome, remain open questions.
  • No cryo-EM or crosslinking data resolve NIP7's binding site on the human pre-ribosomal particle
  • Separation-of-function mutants distinguishing RNA binding from protein–protein interaction roles are lacking
  • Structural basis for NIP7–FTSJ3 complex formation is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-392499 Metabolism of proteins 2
Partners
FTSJ3

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 The C-terminal PUA domain of Nip7 mediates specific RNA binding, with preference for polyuridine sequences. Crystal structure of archaeal Pyrococcus abyssi Nip7 revealed a two-domain architecture: an N-terminal alpha-beta domain and a C-terminal PUA domain. Structural alignment and site-directed mutagenesis identified key residues in the PUA domain required for RNA interaction (R151, R152, K155, K158 in archaeal protein; corresponding hydrophobic residues in eukaryotic orthologs). Both archaeal and yeast Nip7 orthologs bind polyuridine specifically, and this preference is conserved. X-ray crystallography, site-directed mutagenesis, RNA interaction assays (EMSA/filter binding), structural alignment Biochemistry High 18001138
2004 The crystal structure of KD93 (human NIP7 homologue encoded by HSPC031/UPF0113 family) was solved at 1.9 Å resolution by MAD, revealing two interlinked alpha/beta domains. The C-terminal domain matches the PUA domain of RNA modification enzymes (notably ArcTGT), suggesting a role in RNA binding. The N-terminal domain is structurally unique with no known homologs. X-ray crystallography (MAD phasing at 1.9 Å), structural homology analysis (DALI) Journal of structural biology Medium 15522784
2010 Human NIP7 is required for accurate pre-rRNA processing and 18S rRNA maturation. Conditional knockdown of NIP7 in HEK293 cells caused decreased 34S pre-rRNA and accumulation of 26S and 21S pre-rRNA intermediates, indicating slower processing at site 2. NIP7 depletion also caused an imbalance in the 40S/60S subunit ratio and inhibited cell proliferation. NIP7 protein localizes exclusively to the nuclear compartment and co-sediments with 40S–80S complexes, consistent with association with nucleolar pre-ribosomal particles. Conditional siRNA knockdown, Northern blotting (pre-rRNA analysis), sucrose gradient sedimentation, subcellular fractionation, cell proliferation assay Nucleic acids research High 20798176
2011 Human NIP7 physically interacts with FTSJ3 (putative ortholog of yeast Spb1p methyltransferase) in human cells, as demonstrated by yeast two-hybrid, co-localization, and co-immunoprecipitation. Conditional knockdown of FTSJ3 causes pre-rRNA processing defects including accumulation of 34S pre-rRNA (spanning A' to site 2b), indicating slower processing at sites A0, 1, and 2, phenocopying NIP7 depletion. Both NIP7 and FTSJ3 are thus functionally linked in the pathway leading to 18S rRNA maturation. Yeast two-hybrid, co-immunoprecipitation, co-localization (immunofluorescence), conditional siRNA knockdown, Northern blotting PloS one High 22195017
2024 Chlamydomonas reinhardtii NIP7 (CrNip7) functionally complements yeast NIP7 deletion, implicating it in 60S ribosomal subunit biogenesis. Protein interaction studies via yeast two-hybrid identified two potential CrNip7 partners: UNC-p and G-patch domain protein. Nucleic acid interaction assays showed that both the N- and C-terminal domains of CrNip7 participate in rRNA binding. Yeast complementation assay, paromomycin resistance test, yeast two-hybrid, nucleic acid interaction assay, in silico structural analysis Biochimica et biophysica acta. Proteins and proteomics Medium 39216654
2025 NIP7 promotes tumor growth in anaplastic thyroid cancer by upregulating UBE2C (ubiquitin-conjugating enzyme E2C) at the translational level. NIP7 silencing reduced UBE2C protein but not mRNA levels; the SUnSET assay combined with co-immunoprecipitation indicated NIP7 affects UBE2C translation. UBE2C overexpression rescued the proliferation defect caused by NIP7 knockdown. Both NIP7 and UBE2C regulate DNA replication pathway genes (POLE2, RFC4). NIP7 protein localizes predominantly to the nucleus in ATC cells. siRNA knockdown, CCK-8 proliferation assay, colony formation assay, xenograft tumor model, SUnSET translation assay, co-immunoprecipitation, qRT-PCR, Western blotting, GSEA Zhejiang da xue xue bao. Yi xue ban Medium 40461291

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2005 Nucleolar proteome dynamics. Nature 934 15635413
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2000 Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome research 392 10810093
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2016 FOXA1 Directs H3K4 Monomethylation at Enhancers via Recruitment of the Methyltransferase MLL3. Cell reports 137 27926873
2022 Human transcription factor protein interaction networks. Nature communications 123 35140242
2011 Arabidopsis thaliana NIP7;1: an anther-specific boric acid transporter of the aquaporin superfamily regulated by an unusual tyrosine in helix 2 of the transport pore. Biochemistry 54 21710975
2011 The human nucleolar protein FTSJ3 associates with NIP7 and functions in pre-rRNA processing. PloS one 32 22195017
2010 The NIP7 protein is required for accurate pre-rRNA processing in human cells. Nucleic acids research 30 20798176
2007 Structural insights into the interaction of the Nip7 PUA domain with polyuridine RNA. Biochemistry 12 18001138
2004 Crystal structure of KD93, a novel protein expressed in human hematopoietic stem/progenitor cells. Journal of structural biology 7 15522784
2014 Molecular dynamics simulations of the Nip7 proteins from the marine deep- and shallow-water Pyrococcus species. BMC structural biology 4 25315147
2017 High temperature and pressure influence the interdomain orientation of Nip7 proteins from P. abyssi and P. furiosus: MD simulations. Journal of biomolecular structure & dynamics 3 27924686
2016 Identification of residues of the archaeal RNA-binding Nip7 proteins specific to environmental conditions. Journal of bioinformatics and computational biology 3 27832721
2025 [NIP7 upregulates the expression of ubiquitin-conjugating enzyme E2 C to promote tumor growth in anaplastic thyroid cancer]. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 0 40461291
2024 Assigning roles in Chlamydomonas ribosome biogenesis: The conserved factor NIP7. Biochimica et biophysica acta. Proteins and proteomics 0 39216654