Affinage

NUP155

Nuclear pore complex protein Nup155 · UniProt O75694

Round 2 corrected
Length
1391 aa
Mass
155.2 kDa
Annotated
2026-04-29
52 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP155 is a symmetrically distributed structural nucleoporin essential for nuclear pore complex (NPC) assembly, nuclear envelope formation, and selective nucleocytoplasmic transport. Its β-propeller domain anchors to the NPC via Nup53 and Nup93, while its α-solenoid domain independently organizes inner nuclear membrane proteins and binds chromatin at the end of mitosis (PMID:22718353, PMID:24363447). NUP155 mediates mRNA export—including Hsp70 and INO80 mRNAs—through its C-terminal interaction with the export factor Gle1, and maintains nuclear envelope integrity via physical interaction with lamin A/C (PMID:14645504, PMID:30488537, PMID:39111625). Loss-of-function mutations in NUP155 cause familial atrial fibrillation by disrupting Hsp70 mRNA export and protein import, and homozygous loss is embryonic lethal in mice (PMID:19070573).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 High

    Establishing NUP155 as a novel, non-FG-repeat nucleoporin symmetrically distributed on both NPC faces resolved its identity among the growing catalog of pore constituents and implied a structural rather than transport-signal-dependent role.

    Evidence Molecular cloning, immunoelectron microscopy, and biochemical fractionation of rat liver nuclear envelopes

    PMID:8458861

    Open questions at the time
    • No interaction partners identified
    • No functional loss-of-function data
    • Structural role inferred but not demonstrated
  2. 2003 Medium

    Identification of the Gle1–NUP155 interaction placed NUP155 directly in the mRNA export pathway, showing that Gle1 docks at the NPC through the C-terminal domain of NUP155.

    Evidence Yeast two-hybrid screen, in vitro binding with deletion constructs, and HeLa cell localization assays

    PMID:14645504

    Open questions at the time
    • No in vivo functional validation of mRNA export dependence on this interaction
    • Stoichiometry and affinity not determined
    • Whether other nucleoporins contribute to Gle1 docking was not addressed
  3. 2005 High

    Demonstrating that NUP155 depletion blocks both NPC assembly and nuclear envelope membrane formation in two model organisms established it as an essential late-recruited scaffold whose incorporation gates the transition from pore assembly to membrane closure.

    Evidence RNAi in C. elegans embryos and immunodepletion in Xenopus egg extracts with EM and live imaging

    PMID:16193066

    Open questions at the time
    • Molecular mechanism by which NUP155 promotes membrane sealing not defined
    • Position in the temporal hierarchy relative to all other scaffold nups not fully resolved
  4. 2008 High

    The discovery that a homozygous NUP155 R391H mutation causes familial atrial fibrillation—by impairing Hsp70 mRNA export and Hsp70 protein import—provided the first causal link between a structural nucleoporin and human cardiovascular disease.

    Evidence Human genetic mapping, co-segregation analysis, Nup155-knockout and heterozygous mice, mRNA export and protein import assays

    PMID:19070573

    Open questions at the time
    • Whether additional cargo mRNAs or proteins are affected was not systematically assessed
    • Mechanism by which reduced Hsp70 leads to atrial fibrillation not elucidated
    • Whether the R391H mutation disrupts NPC structure globally or affects a specific transport route unclear
  5. 2012 High

    Domain dissection revealed that NUP155's NPC-anchoring function (β-propeller) and its role in organizing inner nuclear membrane proteins (α-solenoid) are separable, establishing NUP155 as a multifunctional scaffold that bridges the pore and the nuclear lamina/membrane compartment.

    Evidence RNAi with domain-specific rescue constructs in Drosophila cells, chromatin fractionation, and immunofluorescence

    PMID:22718353

    Open questions at the time
    • Direct binding partners of the α-solenoid domain for INM protein tethering not identified
    • Whether this dual function is conserved in vertebrates not tested
  6. 2013 High

    Mapping the Nup53→NUP155 recruitment step during NPC assembly, alongside the Nup53–Ndc1 membrane interaction, defined the molecular hierarchy by which inner-ring nucleoporins integrate membrane and scaffold assembly.

    Evidence In vitro binding, co-immunoprecipitation, depletion/reconstitution in Xenopus egg extracts, membrane-bending assays

    PMID:24363447

    Open questions at the time
    • Structural basis of the Nup53–NUP155 interface not resolved at atomic resolution
    • Whether post-translational modifications regulate this recruitment in vivo unknown
  7. 2018 High

    Showing that a lamin A/C AF-linked mutation disrupts the physical lamin A/C–NUP155 interaction, with downstream effects on Hsp70 transport and Nav1.5 surface expression, established the nuclear lamina–NPC interface as a functional unit required for cardiac ion channel biogenesis.

    Evidence Co-IP, GST pull-down, nuclear envelope extractability assays, mRNA export assays, patch-clamp electrophysiology

    PMID:30488537

    Open questions at the time
    • Direct binding interface between lamin A/C and NUP155 not structurally defined
    • Whether other NPC components compensate in lamin A/C mutant backgrounds not tested
  8. 2019 Medium

    Discovery that NUP155 controls p21 translation via transcriptional regulation of the methyltransferase FTSJ1 revealed an unexpected gene-regulatory circuit linking a structural nucleoporin to the p53 tumor-suppressor pathway.

    Evidence Proteomics, polysome fractionation, RNAi knockdown, transcriptional reporters in hepatocellular carcinoma models

    PMID:31089132

    Open questions at the time
    • Whether NUP155 regulates FTSJ1 transcription directly (e.g. at the gene locus) or indirectly is unresolved
    • Generalizability beyond liver cancer cells not demonstrated
    • FTSJ1's RNA substrate specificity in this context undefined
  9. 2024 Medium

    Identification of INO80 mRNA as a second NUP155-dependent nuclear export cargo, whose loss induces podocyte senescence, extended the selective transport function of NUP155 to renal biology and cellular aging.

    Evidence siRNA knockdown and overexpression in rat podocytes, SA-β-gal staining, qRT-PCR, immunofluorescence, comet assay

    PMID:39111625

    Open questions at the time
    • Mechanism by which NUP155 selects INO80 mRNA for export not defined
    • Whether the ferulic acid stabilization of NUP155 is direct and specific requires independent confirmation
    • In vivo renal phenotype not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of NUP155 within the inner ring, the mechanism by which NUP155 selectively promotes export of specific mRNAs (Hsp70, INO80), the structural basis of the lamin A/C–NUP155 interface, and whether NUP155's gene-regulatory functions (FTSJ1/p21 axis) operate through chromatin-proximal or transport-dependent mechanisms.
  • No high-resolution structure of full-length NUP155 in the NPC context
  • Cargo selectivity mechanism unknown
  • Chromatin-proximal versus transport-dependent gene regulation not disentangled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005635 nuclear envelope 5 GO:0005634 nucleus 3 GO:0005694 chromosome 1
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
GLE1LMNANDC1NUP53NUP93
Complex memberships
Nuclear pore complex (NPC)Nup93 subcomplex (inner ring)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Nup155 was identified as a novel ~155 kDa nuclear pore complex (NPC) protein lacking repetitive sequence motifs and WGA reactivity. By immunoelectron microscopy, Nup155 localizes to both the nucleoplasmic and cytoplasmic faces of the NPC (symmetric distribution), and redistributes to a diffuse cytoplasmic localization in mitotic cells. It was extracted from rat liver nuclear envelopes by 2M urea/1mM EDTA and separated from WGA-reactive nucleoporins. Molecular cloning, immunoelectron microscopy, biochemical fractionation (urea/EDTA extraction, WGA-Sepharose, SDS-hydroxylapatite) The Journal of cell biology High 8458861
2003 Human Gle1 (hGle1) physically interacts with hNup155. Yeast two-hybrid and in vitro binding assays identified the C-terminal 177 amino acids of hNup155 as the hGle1-binding domain, and the N-terminal 29 residues of hGle1 as the hNup155-binding domain. Deletion of this 29-residue domain abolishes nuclear rim localization of hGle1B in HeLa cells, indicating that hGle1 docks to the NPC via hNup155, placing this interaction as a step in the mRNA export pathway. Genome-wide yeast two-hybrid screen, in vitro binding (deletion analysis), HeLa cell localization assays Molecular & cellular proteomics : MCP Medium 14645504
2005 Nup155 is essential for nuclear envelope (NE) formation during cell division in metazoans. In C. elegans embryos, depletion of Nup155 caused failure of nuclear lamina formation, chromosome segregation defects at anaphase, and inhibition of nucleoporin accumulation at the nuclear periphery (including early-recruited nucleoporins). In Xenopus egg extracts, Nup155 depletion blocked formation of a continuous nuclear membrane. Time-course experiments showed Nup155 is recruited to chromatin at the time of NE sealing, indicating NPC assembly must progress to a late stage before NE membrane assembly. RNAi depletion in C. elegans embryos (in vivo), immunodepletion in Xenopus egg extracts (in vitro), electron microscopy, live imaging The EMBO journal High 16193066
2008 A homozygous R391H missense mutation in NUP155 was identified in a family with atrial fibrillation (AF) and early sudden cardiac death. The mutation affects nuclear localization of NUP155 and reduces nuclear envelope permeability. Homozygous Nup155−/− mice die before E8.5; heterozygous Nup155+/− mice exhibit AF. R391H and NUP155 reduction are associated with inhibited export of Hsp70 mRNA from the nucleus and impaired nuclear import of Hsp70 protein, linking NPC function to cardiovascular disease. Human genetic mapping, co-segregation analysis, mouse knockout/heterozygous models, nuclear envelope permeability assays, mRNA export assays (Hsp70 mRNA), protein import assays (Hsp70 protein), localization studies Cell High 19070573
2010 HIV-1 nuclear import is sensitive to NUP155 depletion in a capsid-dependent manner. Wild-type HIV-1 primarily requires NUP153, whereas a CA N74D mutant that cannot interact with CPSF6 becomes more sensitive to NUP155 depletion, revealing that alternative NPC entry routes differentially depend on NUP155. siRNA knockdown of NUP155 in cells, HIV-1 infection assays with wild-type and CA N74D mutant virus Cell host & microbe Medium 20227665
2012 In Drosophila, the Nup155 β-propeller domain anchors the protein to the NPC (via interactions with Nup93 and Nup53), whereas the α-solenoid domain is essential for correct localization of inner nuclear membrane (INM) proteins lamin-B receptor (LBR) and otefin. The α-solenoid also exhibits chromatin-binding activity that is stronger at the end of mitosis. Thus, Nup155's role in INM protein organization is independent of its NPC-anchoring function. RNAi knockdown in Drosophila cells, protein binding assays, rescue assays with domain mutants, chromatin fractionation from semi-synchronized cells, immunofluorescence Journal of cell science High 22718353
2013 Nup53 recruits Nup155 to the assembling NPC via direct interaction, and this Nup53–Nup155 interaction is required for NPC formation in vertebrates. Additionally, Nup53's interaction with the integral pore membrane protein Ndc1 is essential for NPC assembly; the Ndc1-binding site on Nup53 overlaps with its membrane-bending region, suggesting Ndc1 binding modulates Nup53's membrane-deforming activity during assembly. In vitro binding assays, co-immunoprecipitation, siRNA knockdown in Xenopus egg extracts and vertebrate cells, membrane-bending assays, NPC assembly reconstitution Journal of cell science High 24363447
2018 A lamin A/C mutation p.Arg399Cys associated with AF impairs the physical interaction between lamin A/C and NUP155 (demonstrated by co-IP and GST pull-down), increases NUP155 extractability from the nuclear envelope, causes lamin A/C aggregation, inhibits Hsp70 mRNA export and Hsp70 protein nuclear import, and reduces cell-surface expression of the cardiac sodium channel Nav1.5 (decreasing peak sodium current). These data establish that nuclear lamina–NPC (lamin A/C–NUP155) interaction integrity is required for proper nucleocytoplasmic transport. Co-immunoprecipitation, GST pull-down, nuclear envelope extractability assay, mRNA export assay, protein import assay, electrophysiology (patch clamp), flow cytometry (Nav1.5 surface expression) Human mutation High 30488537
2019 Nup155 controls mRNA translation of p21 (CDKN1A), a key mediator of the p53 response, through transcriptional regulation of the putative tRNA/rRNA methyltransferase FTSJ1. Nup155 and FTSJ1 are themselves targets of p53-mediated repression, establishing a regulatory feedback network in liver cancer where a structural NPC component modulates the p53 pathway via translational control. Large-scale proteomics, polysome fractionation, focused RNAi knockdown, transcriptional reporter assays; validated in murine and human hepatocellular carcinoma models Nature communications Medium 31089132
2024 Loss of Nup155 in podocytes inhibits nuclear export of INO80 mRNA, leading to decreased INO80 protein levels and induction of cellular senescence. Overexpression of Nup155 or INO80 reverses high fructose-induced podocyte senescence. Ferulic acid stabilizes Nup155 protein by direct binding and enhances its transcription, thereby promoting INO80 mRNA nuclear export. siRNA knockdown and overexpression in rat podocytes, SA-β-gal staining, Western blot, qRT-PCR, immunofluorescence, comet assay, transmission electron microscopy of NPCs, virtual screening/binding assay for ferulic acid Journal of advanced research Medium 39111625
2024 NUP155 knockdown in NSCLC cells reduces cell viability, migration, and invasion, and increases apoptosis. Mechanistically, NUP155 knockdown upregulates PTEN and downregulates phosphorylated AKT (p-AKT) without altering total AKT, placing NUP155 upstream of the PTEN/AKT signaling axis. Addition of the PTEN inhibitor SF1670 partially reverses the effects of NUP155 knockdown, confirming pathway involvement. siRNA knockdown, Western blot, CCK-8 proliferation assay, Transwell migration/invasion assay, PTEN inhibitor rescue experiment Translational cancer research Low 39697746
2024 Small-molecule ligands to E3 ligase TRIM21 identified via DNA-Encoded Library technology induce proteasome-dependent degradation of NUP155 (primary target) and GLE1 (passenger target, secondary to NUP155 loss). Degradation of NUP155 and GLE1 impairs nuclear envelope integrity and leads to cell death, demonstrating that NUP155 is required for nuclear envelope integrity in living cells. DEL-based ligand discovery, crystallography (TRIM21–ligand), quantitative proteomics, immunofluorescence, proteasome inhibitor rescue, TRIM21 knockdown rescue bioRxivpreprint Medium bio_10.1101_2024.12.03.626577

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
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
1996 Nucleocytoplasmic transport. Science (New York, N.Y.) 1062 8599106
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
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
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
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
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
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2010 Flexible use of nuclear import pathways by HIV-1. Cell host & microbe 396 20227665
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
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
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2008 Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell 224 19070573
2005 Nup155 regulates nuclear envelope and nuclear pore complex formation in nematodes and vertebrates. The EMBO journal 91 16193066
1993 Nup155 is a novel nuclear pore complex protein that contains neither repetitive sequence motifs nor reacts with WGA. The Journal of cell biology 76 8458861
2013 Interaction of Nup53 with Ndc1 and Nup155 is required for nuclear pore complex assembly. Journal of cell science 64 24363447
1998 Nup154, a new Drosophila gene essential for male and female gametogenesis is related to the nup155 vertebrate nucleoporin gene. The Journal of cell biology 62 9732281
2003 The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155. Molecular & cellular proteomics : MCP 54 14645504
2009 Whole genome characterization of reassortant G10P[11] strain (N155) from a neonate with symptomatic rotavirus infection: identification of genes of human and animal rotavirus origin. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 42 19505846
2019 Nucleoporin Nup155 is part of the p53 network in liver cancer. Nature communications 37 31089132
2018 Lamin A mutation impairs interaction with nucleoporin NUP155 and disrupts nucleocytoplasmic transport in atrial fibrillation. Human mutation 31 30488537
2018 Host Interaction Analysis of PA-N155 and PA-N182 in Chicken Cells Reveals an Essential Role of UBA52 for Replication of H5N1 Avian Influenza Virus. Frontiers in microbiology 17 29867845
1999 Localization of a human nucleoporin 155 gene (NUP155) to the 5p13 region and cloning of its cDNA. Genomics 16 10191094
2018 NUP155 insufficiency recalibrates a pluripotent transcriptome with network remodeling of a cardiogenic signaling module. BMC systems biology 13 29848314
2012 The Nup155-mediated organisation of inner nuclear membrane proteins is independent of Nup155 anchoring to the metazoan nuclear pore complex. Journal of cell science 13 22718353
2002 Genomic organization, transcript variants and comparative analysis of the human nucleoporin 155 (NUP155) gene. Gene 9 12034489
2024 Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis. BMC cancer 6 38504158
2024 Loss of Nup155 promotes high fructose-driven podocyte senescence by inhibiting INO80 mRNA nuclear export. Journal of advanced research 5 39111625
2024 NUP155 and NDC1 interaction in NSCLC: a promising target for tumor progression. Frontiers in pharmacology 3 39720592
2020 Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot. Frontiers in cardiovascular medicine 3 32118046
2024 Siwu tablet attenuates high fructose-induced glomerular podocyte senescence in rats through increasing Nup155 to promote INO80 mRNA nuclear export. Journal of ethnopharmacology 2 39362331
2025 MALAT1 elevates the secretion of Th2 cytokines via miR-422a/NUP155 axis in allergic rhinitis mice. Archives of biochemistry and biophysics 0 40885462
2024 Postexercise downregulation of NUP155 in regulating non-small cell lung cancer progression via the PTEN/AKT signaling pathway. Translational cancer research 0 39697746
2020 Corrigendum: Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot. Frontiers in cardiovascular medicine 0 33381532