Affinage

NUP205

Nuclear pore complex protein Nup205 · UniProt Q92621

Round 2 corrected
Length
2012 aa
Mass
227.9 kDa
Annotated
2026-04-29
41 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP205 is a scaffold nucleoporin of the inner ring (Nup93 sub-complex) of the nuclear pore complex, essential for NPC size-exclusion gating, long-term NPC maintenance, and regulated nuclear transport. It resides in the core NPC scaffold between the two coaxial rings, where it is reciprocally interdependent with NUP93 for NPC assembly; disease-causing mutations that disrupt NUP93 binding cause steroid-resistant nephrotic syndrome (PMID:26878725, PMID:15229283). NUP205 participates in gene regulation by tethering the HOXA gene cluster at the nuclear periphery with NUP93/NUP188 to maintain a repressive chromatin state, and it mediates nuclear import of the Hippo pathway effectors YAP and TAZ, coupling NPC function to transcriptional signaling in podocytes (PMID:27980680, PMID:37565816). At mitotic onset, NUP205 is removed from the nuclear envelope near centrosomes in an Aurora-A kinase–dependent manner, acting as a negative modulator of mitotic entry timing (PMID:22740626).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2003 High

    The first functional characterization of Nup205 revealed that, beyond structural scaffolding, it is specifically required for the NPC's passive diffusion barrier — resolving whether individual inner-ring nucleoporins have discrete transport roles.

    Evidence RNAi depletion in C. elegans embryos with fluorescent size-exclusion and nuclear import assays

    PMID:12937276

    Open questions at the time
    • Mechanism by which Nup205 establishes size exclusion not defined
    • Vertebrate validation of size-exclusion role not performed
  2. 2004 High

    Immunoelectron microscopy placed Nup205 at the core scaffold between the NPC's coaxial rings and RNAi showed it is dispensable for initial NPC assembly but required for long-term NPC maintenance, distinguishing its role from early-acting assembly factors.

    Evidence Postembedding immunoelectron microscopy and RNAi knockdown in HeLa cells

    PMID:15229283

    Open questions at the time
    • Structural contacts with neighboring nucleoporins not resolved at molecular level
    • Mechanism of NPC destabilization upon Nup205 loss not identified
  3. 2012 High

    Discovery that Nup205 is selectively removed from the nuclear envelope near centrosomes at mitotic onset via Aurora-A kinase revealed an unexpected cell-cycle regulatory function — Nup205 negatively modulates mitotic entry timing.

    Evidence Live imaging, centrosome ablation/addition, Aurora-A inhibition, and RNAi modifier screen in C. elegans embryos

    PMID:22740626

    Open questions at the time
    • Direct phosphorylation sites on Nup205 by Aurora-A not identified
    • Whether this mitotic role is conserved in vertebrates not tested
  4. 2014 Medium

    BioID proximity labeling in living human cells confirmed Nup205's spatial position within the Nup93 sub-complex at the inner ring, providing an in vivo interaction map complementing earlier EM data.

    Evidence BioID-mass spectrometry of NPC constituents in human cells

    PMID:24927568

    Open questions at the time
    • Proximity does not prove direct binding; stoichiometry of interactions not resolved
    • NUP205-specific contacts versus shared inner-ring contacts not distinguished
  5. 2016 High

    Human genetic studies established NUP205 as a disease gene: mutations causing steroid-resistant nephrotic syndrome abrogate the NUP93–NUP205 interaction, and reciprocal knockdown demonstrated mutual dependence for NPC assembly, linking NPC structural integrity to podocyte function.

    Evidence Exome sequencing of SRNS families, co-immunoprecipitation, and NUP93 knockdown in podocytes

    PMID:26878725

    Open questions at the time
    • Which specific NPC transport pathways are disrupted in patient podocytes not defined
    • Whether other organ phenotypes arise from NUP205 mutations not systematically assessed
  6. 2016 Medium

    A gene-regulatory role was established: NUP205, together with NUP93 and NUP188, associates with HOXA promoters and tethers the HOXA locus to the nuclear periphery to maintain a repressive chromatin state, showing inner-ring nucleoporins directly participate in transcriptional regulation.

    Evidence ChIP, 3D-FISH, histone modification analysis, and RNAi in DLD1 cells

    PMID:27980680

    Open questions at the time
    • NUP205's individual contribution versus NUP93's dominant role not cleanly separated
    • Whether other genomic loci are similarly regulated is unknown
    • Whether tethering requires NUP205's NPC-embedded state or occurs off-pore not determined
  7. 2023 High

    Unbiased interactomics in podocytes identified YAP and TAZ as NUP205 physical interactors and demonstrated that NUP205 is essential for their nuclear import and TEAD1-dependent transcriptional activity, connecting NPC function to Hippo signaling and providing a mechanistic link to the nephrotic syndrome phenotype.

    Evidence Label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, and co-IP in podocytes

    PMID:37565816

    Open questions at the time
    • Whether NUP205 acts as a direct transport receptor or facilitates FG-repeat-mediated translocation of YAP/TAZ not resolved
    • TAZ-NUP205 feedback loop mechanism not fully characterized
  8. 2026 Medium

    In hepatocellular carcinoma, NUP205 was shown to stabilize YAP1 protein through the ubiquitin-proteasome pathway, extending its Hippo-pathway connection to an oncogenic context and demonstrating NUP205 influences YAP not only through nuclear import but also through protein turnover.

    Evidence NUP205 knockdown/overexpression, proteasome pathway assays, xenograft models, proliferation and apoptosis assays in HCC cells

    PMID:41868261

    Open questions at the time
    • The E3 ubiquitin ligase involved in YAP1 destabilization upon NUP205 loss not identified
    • Whether YAP1 stabilization is direct or mediated through an intermediary not established
    • Single-lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of NUP205 within the human inner ring at atomic resolution, the direct phosphorylation events mediating its mitotic removal, and whether its selective transport and gene-regulatory functions operate through its NPC-embedded form or a soluble nucleoplasmic pool.
  • No high-resolution structure of human NUP205 in the NPC context
  • Mechanism discriminating NPC-dependent versus NPC-independent functions not established
  • Aurora-A phosphorylation sites on NUP205 not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0005215 transporter activity 2
Localization
GO:0005635 nuclear envelope 4 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2 R-HSA-1640170 Cell Cycle 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
NUP188NUP93TAZTEAD1YAP1
Complex memberships
Nuclear pore complex (NPC)Nup93 sub-complex (inner ring)

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 C. elegans Nup205 (NPP-3) is required for normal NPC distribution in the nuclear envelope and for establishing the size-exclusion limit of the NPC in vivo. Depletion of Nup205 by RNAi caused failure in nuclear exclusion of ~70 kDa macromolecules without preventing active nuclear protein import or nuclear envelope assembly, and resulted in abnormal chromatin condensation and embryonic arrest. RNAi depletion in C. elegans embryos with fluorescent size-exclusion assays and nuclear import assays Molecular biology of the cell High 12937276
2004 Nup205 localizes to the core scaffold of the vertebrate NPC (between the two coaxial rings) by immunoelectron microscopy. RNAi-mediated silencing of Nup205 in HeLa cells demonstrated it is important for long-term maintenance of NPCs but initially dispensable for anchoring of nuclear basket components Nup153 and Tpr. Postembedding immunoelectron microscopy and RNAi in HeLa cells Molecular biology of the cell High 15229283
2012 Nup205 (NPP-3) is lost from the nuclear envelope in the vicinity of centrosomes at the onset of mitosis in C. elegans embryos. Centrosomes are both necessary and sufficient for this local loss, which also requires Aurora-A kinase (AIR-1) activity. NPP-3 negatively modulates the timing of mitotic onset, and its removal by centrosomes/AIR-1 promotes timely mitotic entry. RNAi modifier screen, live imaging, centrosome ablation/addition experiments, Aurora-A kinase inhibition in C. elegans embryos Molecular biology of the cell High 22740626
2014 BioID proximity labeling applied to Nup93 complex constituents (which includes Nup205) revealed the spatial organization of Nup205 within the human NPC scaffold, consistent with its position in the inner ring/Nup93 subcomplex. Proximity-dependent biotinylation (BioID) fused to NPC constituents in living human cells, followed by mass spectrometry Proceedings of the National Academy of Sciences of the United States of America Medium 24927568
2016 Mutations in NUP205 cause steroid-resistant nephrotic syndrome (SRNS). A NUP205 alteration abrogates its interaction with NUP93, and NUP93 knockdown reduces NUP205 presence in the NPC, establishing a reciprocal interdependence between NUP93 and NUP205 for NPC assembly. Human genetics (exome sequencing), Co-IP/interaction assays, knockdown studies in podocytes Nature genetics High 26878725
2016 Nup205 assists Nup93 in repressing the HOXA gene cluster. Nup93 and its interactors Nup188 and Nup205 associate with HOXA gene promoters; depletion of this sub-complex disengages the HOXA locus from the nuclear periphery, increases active histone marks (H3K9ac), decreases repressive marks (H3K27me3), and upregulates HOXA gene expression. ChIP, RNAi knockdown, 3D-FISH, histone modification analysis in DLD1 cells Epigenetics & chromatin Medium 27980680
2020 NEK3 kinase regulates NUP205 protein levels; biallelic loss-of-function NEK3 mutations in patients significantly downregulate inner ring NPC components including NUP205, NUP188, and NUP155. NEK3 silencing in RPE cells recapitulated this downregulation, linking NUP205 abundance to NEK3 kinase activity. Whole-exome sequencing, siRNA knockdown, western blot, transcriptome analysis in RPE cells Cell death & disease Low 33230144
2023 NUP205 physically interacts with YAP and TAZ (Hippo pathway transcriptional effectors) in podocytes as identified by unbiased interactome mass spectrometry. NUP205 is essential for YAP/TAZ nuclear import; its depletion reduces nuclear YAP/TAZ interaction with TEAD1 and their transcriptional activity. A feedback loop exists whereby TAZ-mediated regulation of NUP205 expression modulates YAP activity. Quantitative label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, Co-IP in podocytes Human molecular genetics High 37565816
2026 NUP205 stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells. NUP205 knockdown inhibited cell proliferation and induced apoptosis, while overexpression had opposing effects; these phenotypes were mediated through YAP1 protein stability. NUP205 knockdown/overexpression, ubiquitin-proteasome pathway assays, xenograft mouse model, proliferation and apoptosis assays in HCC cells Journal of hepatocellular carcinoma Medium 41868261
2022 Knockdown of NUP205 in human lung (A549) cells suppresses influenza A virus (H1N1) reproduction, reducing viral titer by ~2 log units and viral RNA concentration up to 30-fold, indicating NUP205 is required for efficient influenza virus replication. siRNA knockdown, viral titer measurement, hemagglutination assay, RT-PCR quantification of viral RNA in A549 cells Infectious disorders drug targets Low 35339191

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
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
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
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
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
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
2013 Integrated structural analysis of the human nuclear pore complex scaffold. Cell 284 24315095
2000 The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. RNA (New York, N.Y.) 284 10668806
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2012 Seventy-five genetic loci influencing the human red blood cell. Nature 266 23222517
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2004 Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket. Molecular biology of the cell 194 15229283
2003 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determine the limit of nuclear pore complex size exclusion in vivo. Molecular biology of the cell 159 12937276
2016 Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nature genetics 156 26878725
2016 HOXA repression is mediated by nucleoporin Nup93 assisted by its interactors Nup188 and Nup205. Epigenetics & chromatin 44 27980680
2012 The nucleoporin Nup205/NPP-3 is lost near centrosomes at mitotic onset and can modulate the timing of this process in Caenorhabditis elegans embryos. Molecular biology of the cell 24 22740626
2020 Biallelic loss of function NEK3 mutations deacetylate α-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left-right patterning. Cell death & disease 16 33230144
2019 LncRNA SNHG1 overexpression regulates the proliferation of acute myeloid leukemia cells through miR-488-5p/NUP205 axis. European review for medical and pharmacological sciences 15 31298340
2020 LncRNA HOTAIR Influences the Growth, Migration, and Invasion of Papillary Thyroid Carcinoma via Affection on the miR-488-5p/NUP205 Axis. Technology in cancer research & treatment 14 33107391
2023 The role of the FSGS disease gene product and nuclear pore protein NUP205 in regulating nuclear localization and activity of transcriptional regulators YAP and TAZ. Human molecular genetics 11 37565816
2020 LINC00887 regulates the proliferation of nasopharyngeal carcinoma via targeting miRNA-203b-3p to upregulate NUP205. European review for medical and pharmacological sciences 9 32964975
2022 Knockdown of FLT4, Nup98, and Nup205 Cellular Genes Effectively Suppresses the Reproduction of Influenza Virus Strain A/WSN/1933 (H1N1) In vitro. Infectious disorders drug targets 3 35339191
2026 NUP205 Stabilized YAP1 Protein to Stimulate Growth of Hepatocellular Carcinoma Cells in vitro and in vivo. Journal of hepatocellular carcinoma 0 41868261