Affinage

NUP133

Nuclear pore complex protein Nup133 · UniProt Q8WUM0

Round 2 corrected
Length
1156 aa
Mass
129.0 kDa
Annotated
2026-04-29
46 papers in source corpus 14 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP133 is a scaffold nucleoporin of the Nup107-160 (Y-complex) that is essential for nuclear pore complex biogenesis, proper NPC distribution across the nuclear envelope, mRNA export, and nuclear basket assembly. Its C-terminal domain anchors to Nup107 in a tail-to-tail arrangement positioning Nup133 at the NPC periphery (PMID:18570875), while its N-terminal β-propeller contains an ALPS motif that mediates direct membrane binding to tether the NPC to the nuclear envelope (PMID:25139911, PMID:33247142). Beyond interphase NPC function, the N-terminal domain recruits dynein/dynactin to the nuclear envelope during prophase via a CENP-F/NudE/NudEL chain, thereby maintaining centrosome–NE association at mitotic entry (PMID:21383080), and the central domain is required for assembling Tpr and Nup153 into the nuclear basket (PMID:29791854). Homozygous loss-of-function mutations in NUP133 cause Galloway-Mowat syndrome featuring microcephaly, brain anomalies, and nephrotic syndrome (PMID:30427554).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1995 High

    The first functional characterization established that Nup133 is required for two fundamental NPC-associated processes—mRNA export and the even distribution of pores across the nuclear envelope—answering whether this nucleoporin has roles beyond structural scaffolding.

    Evidence Yeast gene disruption and temperature-sensitive mutants with poly(A)+ RNA FISH, immunofluorescence, and EM

    PMID:7626806 PMID:7862658

    Open questions at the time
    • Mechanism of NPC clustering upon Nup133 loss not resolved
    • Direct versus indirect role in mRNA export undefined
  2. 2001 High

    Identification of vertebrate Nup133 as a subunit of a Nup107-containing complex (with Nup96 and Sec13) and demonstration that specific Nup133 fragments block poly(A)+ RNA export established the biochemical context of Nup133 within a larger NPC subcomplex.

    Evidence Pulldowns from Xenopus egg extracts, co-IP, dominant-negative fragment transport assays in vivo

    PMID:11684705

    Open questions at the time
    • Stoichiometry and architectural position within the complex not determined
    • Binding interface between Nup133 and Nup107 not structurally resolved
  3. 2003 High

    Depletion experiments demonstrated that the Nup107-160 complex (including Nup133) is essential for postmitotic NPC assembly, and must be incorporated before nuclear envelope closure, resolving the temporal requirement for this subcomplex in pore biogenesis.

    Evidence RNAi in HeLa cells combined with in vitro nuclear assembly in Xenopus egg extracts, immunodepletion and EM

    PMID:12705868

    Open questions at the time
    • Individual contribution of Nup133 versus other Y-complex subunits to assembly not separated
    • Mechanism by which the complex seeds NPC insertion into membranes unknown
  4. 2004 High

    Structural and biochemical dissection of human Nup133 revealed a two-domain architecture—an N-terminal β-propeller and a C-terminal region that directly binds Nup107—providing the first molecular framework for understanding how Nup133 is anchored to its subcomplex while presenting an interaction surface for additional partners.

    Evidence X-ray crystallography of the N-terminal β-propeller, domain deletions and co-IP

    PMID:15557116

    Open questions at the time
    • Function of the N-terminal β-propeller surface unknown
    • Atomic details of the Nup107-binding interface not yet resolved
  5. 2008 High

    The crystal structure of the Nup107–Nup133 C-terminal complex revealed a tail-to-tail elongated interface and confirmed via mutagenesis that Nup107 is the critical anchor positioning Nup133 at the NPC periphery, resolving the architecture of this dimer.

    Evidence X-ray crystallography and structure-guided mutagenesis

    PMID:18570875

    Open questions at the time
    • How the Nup107–Nup133 dimer integrates into the full Y-complex ring not structurally resolved
    • Conformational dynamics in vivo unknown
  6. 2009 High

    Structural comparison of Nup133 with Nup157/170 demonstrated that NPC scaffold nucleoporins share an ancestral coatomer-like element (ACE), establishing the evolutionary origin of the NPC scaffold from protocoatomer building blocks.

    Evidence Crystal structures and structural homology analysis of yeast Nup170 and human Nup107·Nup133

    PMID:19674973

    Open questions at the time
    • Functional consequences of the ACE-fold conservation not tested directly
  7. 2011 High

    Discovery that the Nup133 N-terminal domain recruits dynein/dynactin to the nuclear envelope during prophase via a CENP-F–NudE/NudEL chain revealed a mitotic function for this nucleoporin in centrosome tethering and bipolar spindle assembly, independent of its NPC scaffolding role.

    Evidence RNAi, dominant-negative domains, co-IP, live-cell imaging, epistasis with the RanBP2–BICD2 pathway in HeLa cells

    PMID:21383080

    Open questions at the time
    • Whether the ALPS motif and dynein-recruitment function overlap spatially on the N-terminal domain not resolved
    • Regulation of the Nup133–CENP-F interaction across the cell cycle unclear
  8. 2014 High

    Identification and validation of an ArfGAP1 lipid packing sensor (ALPS) motif within the Nup133 N-terminal domain resolved how the NPC is anchored to the curved pore membrane, providing a direct membrane-sensing mechanism for scaffold nucleoporins.

    Evidence Integrative structural modeling (SAXS, EM, crosslinking MS, crystallography), mutagenesis of ALPS motif

    PMID:25139911

    Open questions at the time
    • Quantitative contribution of the ALPS motif to NPC stability in vivo not measured
    • Lipid specificity of the ALPS motif not characterized
  9. 2018 High

    Two parallel advances resolved: (1) Nup133's central domain specifically assembles the nuclear basket by recruiting Tpr and stabilizing Nup153, distinguishing basket assembly from scaffold assembly; and (2) a NUP133 splicing mutation causes Galloway-Mowat syndrome by disrupting NUP107 interaction, linking Nup133 loss-of-function to human neurodevelopmental and renal disease.

    Evidence Nup133-null mESCs with super-resolution microscopy and FRAP (basket assembly); human WES, co-IP, and zebrafish morphant rescue (disease)

    PMID:29791854 PMID:30427554

    Open questions at the time
    • How the central domain contacts Tpr and Nup153 at the molecular level is unknown
    • Genotype-phenotype spectrum across different NUP133 mutations remains incomplete
    • Whether basket deficiency or general NPC dysfunction drives Galloway-Mowat pathology not distinguished
  10. 2022 Medium

    CRISPR knockout of NUP133 in human podocytes confirmed that NPC scaffold assembly, the podocyte transcriptome, and cellular protrusion formation all depend on NUP133, while disease-associated point mutations cause partial loss-of-function through reduced Y-complex interaction and lower protein levels.

    Evidence CRISPR/Cas9 KO and point-mutation knock-in in human podocytes, RNA-seq, co-IP, protrusion assays

    PMID:35455939

    Open questions at the time
    • Results from a single lab; independent replication pending
    • Molecular basis for protrusion defects downstream of NPC disruption not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of Nup133's central-domain interaction with Tpr/Nup153 for basket assembly, the mechanistic relationship between NPC basket deficiency and Galloway-Mowat syndrome pathology, and how the three distinct functional surfaces (ALPS, dynein-recruitment, basket-assembly) are coordinately regulated across the cell cycle.
  • No structural model of Nup133–Tpr or Nup133–Nup153 interaction
  • Cell-cycle regulation of Nup133 N-terminal domain functions (ALPS vs dynein) unknown
  • Tissue-specific consequences of partial NUP133 loss not systematically studied

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 6 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005635 nuclear envelope 7 GO:0005634 nucleus 3
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-1643685 Disease 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-1640170 Cell Cycle 1
Partners
CENPFNUP107NUP153NUP160NUP96NUP98SEC13TPR
Complex memberships
Nuclear pore complex (NPC)Nup107-160 complex (Y-complex)

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Disruption or mutation of yeast NUP133 (RAT3) causes temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive clustering of nuclear pore complexes into one or a few regions of the nuclear envelope, establishing Nup133 as a nucleoporin required for mRNA export and proper NPC distribution. Yeast genetics (temperature-sensitive mutants, gene disruption), fluorescent in situ hybridization for poly(A)+ RNA, indirect immunofluorescence, electron microscopy, epitope tagging and co-localization with NPC markers Molecular biology of the cell High 7626806 7862658
2001 Vertebrate Nup133 and Nup160 were identified as novel nucleoporins that bind Nup98 and Nup153 (via pulldowns from Xenopus egg extracts), form a complex with Nup107, Nup96, and Sec13 (the Nup160 complex), are accessible on the basket side of the pore, and specific Nup133/Nup160 fragments block poly(A)+ RNA export but not protein import or export. Pulldown from Xenopus egg extracts, protein purification and sequencing, co-immunoprecipitation, immunofluorescence, in vivo transport assays (transfection of dominant-negative fragments) The Journal of cell biology High 11684705
2003 The conserved Nup107-160 complex (containing Nup133) is critical for postmitotic NPC assembly: RNAi depletion of Nup133 or Nup107 in HeLa cells reduced nucleoporin levels and NPC density; immunodepletion of the entire complex from in vitro nuclear assembly reactions produced nuclei with a continuous NE but no NPCs, reversible only if the complex was added before closed NE formation. RNAi knockdown in HeLa cells, in vitro nuclear assembly assay with Xenopus egg extracts, immunodepletion, immunofluorescence, electron microscopy Cell High 12705868
2004 Human Nup133 contains two distinct domains: a C-terminal domain that mediates interaction with Nup107 (anchoring Nup133 to its subcomplex), and an N-terminal domain whose crystal structure reveals a seven-bladed beta-propeller with surface properties suggesting multiple protein interactions. Crystal structure determination of the N-terminal beta-propeller domain, deletion/domain mapping, co-immunoprecipitation to define Nup107-binding region The Journal of cell biology High 15557116
2008 Crystal structure of the human Nup107–Nup133 C-terminal domain complex reveals that both proteins form elongated structures interacting tightly via a compact interface in tail-to-tail fashion; structure-guided mutagenesis confirms that Nup107 is the critical anchor positioning Nup133 at the periphery of the NPC. Crystal structure determination, structure-guided mutagenesis, functional interaction assays Molecular cell High 18570875
2009 Crystal structures of yNup170(979–1502) and hNup107(658–925)·hNup133(517–1156) reveal conserved domain arrangement and tertiary structure between Nup157/170 and Nup133, suggesting they descend from a common ancestral coatomer-like element (ACE); together with ACE1, these define the major alpha-helical building blocks of the NPC scaffold. Crystal structure determination, structural comparison, evolutionary analysis The Journal of biological chemistry High 19674973
2011 The N-terminal domain of Nup133 (though largely dispensable for NPC assembly) is required for efficient anchoring of the dynein/dynactin complex to the nuclear envelope in prophase; Nup133 acts through an interaction network involving CENP-F and NudE/NudEL, and this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to bipolar spindle assembly. RNAi knockdown, dominant-negative domain expression, co-immunoprecipitation, live-cell imaging, immunofluorescence, genetic epistasis with RanBP2-BICD2 pathway The Journal of cell biology High 21383080
2014 Integrative structural modeling of yeast Nup133 using crystal structures, SAXS, negative-stain EM, and cross-linking mass spectrometry identified an ArfGAP1 lipid packing sensor (ALPS) motif in Nup133; mutational studies confirm this motif, suggesting Nup133's ALPS mediates membrane anchoring of the NPC in the nuclear envelope. Crystal structure determination (VpNup133), SAXS (18 constructs), negative-stain EM, cross-linking mass spectrometry, mutagenesis, integrative structural modeling Molecular & cellular proteomics High 25139911
2018 Loss of Nup133 in mouse embryonic stem cells specifically perturbs nuclear basket assembly: ~50% of NPCs lack Tpr, and Nup153 dynamics are altered; the central domain of Nup133 mediates its role in assembling Tpr and Nup153 into a properly configured nuclear basket, while Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. Null mutation in mice, single-pore detection by super-resolution microscopy, average NE-fluorescence intensity measurement, FRAP (Nup153 dynamics), domain mapping via rescue experiments Cell reports High 29791854
2018 A homozygous NUP133 splicing mutation (c.3335-11T>A) causes Galloway-Mowat syndrome (microcephaly, brain anomalies, nephrotic syndrome); the mutation impairs NUP133–NUP107 interaction as shown by immunoprecipitation; nup133-knockdown zebrafish exhibit microcephaly, fewer neuronal cells, underdeveloped glomeruli, and podocyte foot process fusion, rescued by wild-type but not mutant human NUP133 mRNA. Whole exome sequencing, linkage analysis, immunoprecipitation (NUP133–NUP107 interaction), zebrafish morphant model, mRNA rescue experiments Annals of neurology High 30427554
2020 Crystal structures of full-length yeast Nup84–Nup133 C-terminal domain complex and the Nup133 N-terminal domain (nanobody-bound) reveal high flexibility of this dimeric unit; the Nup133 NTD contains a structurally conserved ALPS motif confirmed by liposome interaction studies to mediate membrane binding. Cryo-EM/X-ray crystallography with nanobody-bound complexes, liposome interaction assay Nature communications High 33247142
2020 Nup133 protein level declines in male but not female mouse oligodendrocyte progenitor cells (OPCs) following hyperoxia; Nrf1 is identified as a direct downstream transcriptional target of Nup133, and Nup133 regulates mitochondrial function and oxidative stress response through Nrf1. Cell culture (primary OPCs), hyperoxia treatment, western blotting, siRNA knockdown, reporter assays for Nrf1 transcriptional regulation Molecular and cellular pediatrics Low 32844334
2022 CRISPR/Cas9-mediated NUP133 loss-of-function in human podocytes disrupts nuclear pore scaffold assembly, alters the podocyte-specific transcriptome, and impairs cellular protrusion generation; SRNS-related NUP133 point mutations show only mild defects but impair Y-complex protein interaction and reduce NUP133 protein levels, suggesting partial loss-of-function as the disease mechanism. CRISPR/Cas9 genome editing, RNA-seq transcriptome analysis, immunofluorescence (NPC assembly), co-immunoprecipitation (Y-complex interaction), cytoskeletal/protrusion assays Cells Medium 35455939

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. The Journal of cell biology 1850 22412018
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
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
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
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
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
2014 Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America 436 24927568
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2011 Global identification of modular cullin-RING ligase substrates. Cell 354 21963094
2003 The conserved Nup107-160 complex is critical for nuclear pore complex assembly. Cell 340 12705868
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2013 Integrated structural analysis of the human nuclear pore complex scaffold. Cell 284 24315095
2006 Phosphoproteome analysis of the human mitotic spindle. Proceedings of the National Academy of Sciences of the United States of America 281 16565220
1999 The nuclear pore complex: from molecular architecture to functional dynamics. Current opinion in cell biology 281 10395558
2011 A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase. The Journal of cell biology 153 21383080
2001 Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. The Journal of cell biology 153 11684705
2004 Structural and functional analysis of Nup133 domains reveals modular building blocks of the nuclear pore complex. The Journal of cell biology 95 15557116
1995 Mutation or deletion of the Saccharomyces cerevisiae RAT3/NUP133 gene causes temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive clustering of nuclear pore complexes. Molecular biology of the cell 88 7626806
2008 Structural and functional studies of Nup107/Nup133 interaction and its implications for the architecture of the nuclear pore complex. Molecular cell 84 18570875
1995 Disruption of the nucleoporin gene NUP133 results in clustering of nuclear pore complexes. Proceedings of the National Academy of Sciences of the United States of America 81 7862658
2009 Architectural nucleoporins Nup157/170 and Nup133 are structurally related and descend from a second ancestral element. The Journal of biological chemistry 64 19674973
2014 Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex. Molecular & cellular proteomics : MCP 54 25139911
2018 Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome. Annals of neurology 45 30427554
2020 Yeast Nup84-Nup133 complex structure details flexibility and reveals conservation of the membrane anchoring ALPS motif. Nature communications 33 33247142
2018 Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Cell reports 24 29791854
2011 Structure of the C-terminal domain of Saccharomyces cerevisiae Nup133, a component of the nuclear pore complex. Proteins 14 21365675
2020 Nup133 and ERα mediate the differential effects of hyperoxia-induced damage in male and female OPCs. Molecular and cellular pediatrics 12 32844334
2022 NUP133 Controls Nuclear Pore Assembly, Transcriptome Composition, and Cytoskeleton Regulation in Podocytes. Cells 11 35455939
2007 Purification, crystallization and preliminary X-ray analysis of a Nup107-Nup133 heterodimeric nucleoporin complex. Acta crystallographica. Section F, Structural biology and crystallization communications 6 17768364
2023 Steroid-resistant nephrotic syndrome caused by nuclear pore gene NUP133 variation. Clinical genetics 4 37041680