Affinage

NUP205

Nuclear pore complex protein Nup205 · UniProt Q92621

Length
2012 aa
Mass
227.9 kDa
Annotated
2026-06-10
13 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP205 is a scaffold nucleoporin of the nuclear pore complex (NPC) inner ring required for proper NPC distribution and for the size-exclusion barrier that restricts passive diffusion of large macromolecules, with its loss producing chromatin condensation defects and embryonic lethality in C. elegans (PMID:12937276). It functions as an obligate, interdependent partner of NUP93: NUP205 and NUP93 physically associate, NUP93 depletion reduces NUP205 at the NPC, and a disease-associated NUP205 alteration abolishes the interaction (PMID:26878725); reciprocally, NUP205 loss destabilizes NUP93 and NUP62 protein, causing NPC structural defects (PMID:42049205). Beyond its structural role, NUP205 acts in gene regulation by tethering the HOXA locus to the nuclear periphery, where the NUP93 sub-complex maintains repressive chromatin and silences HOXA genes (PMID:27980680), and it controls nuclear import and activity of transcriptional regulators: NUP205 mediates YAP/TAZ nuclear entry and their TEAD1-dependent transcriptional output (PMID:37565816), stabilizes YAP1 via the ubiquitin-proteasome pathway to promote proliferation (PMID:41868261), and facilitates Gli-1 nuclear translocation to drive Hedgehog signaling downstream of a FOXO6 transcriptional axis (PMID:42231458). At mitotic onset, NUP205 (NPP-3 in C. elegans) is locally removed from the nuclear envelope near centrosomes in an Aurora-A (AIR-1)-dependent manner, and it negatively modulates the timing of mitotic entry (PMID:22740626). These activities give NUP205 roles in oogenesis and fertility (PMID:42049205) and in supporting influenza A virus replication (PMID:35339191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 High

    Established that NUP205 is required for the NPC's passive size-exclusion barrier specifically, distinguishing this scaffold function from active nuclear import and from nuclear envelope assembly itself.

    Evidence RNAi depletion in C. elegans embryos with in vivo size-exclusion and import assays and fluorescence microscopy

    PMID:12937276

    Open questions at the time
    • Did not define the molecular interactions that position NUP205 within the inner ring
    • Link between size-exclusion failure and the observed chromatin condensation/lethality not mechanistically resolved
  2. 2012 High

    Revealed that NUP205 is not statically incorporated but is locally and dynamically removed from the nuclear envelope at mitotic onset, connecting a nucleoporin to mitotic timing control.

    Evidence RNAi modifier screen, live imaging, centrosome manipulation, and Aurora-A kinase perturbation in C. elegans embryos

    PMID:22740626

    Open questions at the time
    • Whether Aurora-A acts directly on NUP205 or on an intermediary is unknown
    • Mechanism by which NUP205 removal modulates mitotic entry timing not defined
  3. 2016 High

    Defined NUP205 and NUP93 as mutually interdependent scaffold subunits and tied this interaction directly to human disease through a mutation that abrogates binding.

    Evidence Patient mutation analysis, reciprocal co-immunoprecipitation, and siRNA knockdown with NPC localization readout

    PMID:26878725

    Open questions at the time
    • Stoichiometry and structural basis of the NUP205–NUP93 interface not resolved
    • Did not address roles for NUP205 beyond NPC scaffolding
  4. 2016 Medium

    Extended NUP205 function from structural scaffolding to chromatin regulation, showing the NUP93 sub-complex tethers the HOXA locus to the periphery to enforce repression.

    Evidence ChIP, siRNA knockdown, 3D-FISH, histone mark analysis, and RT-qPCR in DLD1 colorectal cancer cells

    PMID:27980680

    Open questions at the time
    • NUP205-specific contribution is secondary to NUP93 and not separable in this study
    • Single cell line; generality across loci/cell types untested
  5. 2023 Medium

    Identified NUP205 as a selective import/activity regulator for the YAP/TAZ transcriptional program, moving beyond bulk transport to pathway-specific control.

    Evidence Quantitative label-free MS interactome, siRNA knockdown, nuclear fractionation, co-IP, and reporter assays in podocytes

    PMID:37565816

    Open questions at the time
    • Whether YAP/TAZ import is direct or via the general transport machinery is unclear
    • Single lab and cell type
  6. 2026 Medium

    Connected NUP205 to YAP1 protein stability through the ubiquitin-proteasome pathway, linking it to tumor cell proliferation and survival in vivo.

    Evidence siRNA knockdown/overexpression, proliferation and apoptosis assays, proteasome pathway analysis, and xenograft model in HCC cells

    PMID:41868261

    Open questions at the time
    • Molecular mechanism by which NUP205 protects YAP1 from degradation not defined
    • Limited mechanistic depth available
  7. 2026 Medium

    Demonstrated that NUP205 maintains the protein stability of partner nucleoporins NUP93 and NUP62 and is required for normal oogenesis and fertility.

    Evidence siRNA knockdown and western blot in COV434 cells, CRISPR/Cas9 zebrafish nup205 truncation model, and transmission electron microscopy

    PMID:42049205

    Open questions at the time
    • Whether NUP62 destabilization is direct or a downstream consequence of NPC collapse is unresolved
    • Mechanistic link from NPC defects to oogenesis failure not detailed
  8. 2026 Medium

    Placed NUP205 within a FOXO6→NUP205→Gli-1 axis, showing it facilitates Hedgehog effector nuclear translocation to drive cancer stemness downstream of PI3K/AKT signaling.

    Evidence Luciferase reporter and ChIP assays, pathway inhibitors, siRNA knockdown, and xenograft model

    PMID:42231458

    Open questions at the time
    • Whether NUP205 directly transports Gli-1 or acts indirectly is unknown
    • Single lab
  9. 2022 Low

    Implicated NUP205 as a host factor required for efficient influenza A virus replication.

    Evidence Single siRNA knockdown with viral titer, hemagglutination, and viral RNA readouts in A549 cells

    PMID:35339191

    Open questions at the time
    • No mechanistic dissection of how NUP205 supports viral replication
    • Single knockdown experiment, single lab, no orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NUP205's structural scaffolding role is mechanistically coupled to its selective cargo-import functions (YAP/TAZ, Gli-1) and to its stabilization of specific client proteins remains unresolved.
  • No structural model of NUP205 within the human inner ring in the corpus
  • Whether selective cargo effects are direct transport functions or indirect consequences of NPC integrity is undetermined
  • Mechanism of NUP205-dependent protein stabilization (YAP1, NUP93, NUP62) not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005635 nuclear envelope 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2 R-HSA-4839726 Chromatin organization 1
Partners
NUP188NUP62NUP93TAZTEAD1YAP1
Complex memberships
NUP93 sub-complexNuclear pore complex inner ring

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 C. elegans Nup205 (ortholog of vertebrate NUP205) is required for normal NPC distribution in the nuclear envelope and for NPC size-exclusion function; depletion of Nup205 by RNAi caused failure in nuclear exclusion of ~70 kDa non-nuclear macromolecules without preventing active nuclear protein import or nuclear envelope assembly, and was accompanied by abnormal chromatin condensation and embryonic arrest. RNAi depletion in C. elegans embryos, in vivo size-exclusion assay, nuclear import assay, fluorescence microscopy Molecular biology of the cell High 12937276
2012 C. elegans NPP-3 (Nup205 ortholog) is lost from the nuclear envelope near centrosomes at mitotic onset; this local loss requires centrosome activity and the Aurora-A kinase AIR-1, and NPP-3 negatively modulates the timing of mitotic onset. RNAi modifier screen, live imaging, centrosome ablation/manipulation, Aurora-A kinase perturbation in C. elegans embryos Molecular biology of the cell High 22740626
2016 NUP205 physically interacts with NUP93; a disease-causing NUP205 alteration abrogates this NUP93 interaction. Reciprocally, NUP93 knockdown reduces the presence of NUP205 at the NPC, establishing that NUP93 and NUP205 are interdependent scaffold components. Patient mutation analysis, co-immunoprecipitation, siRNA knockdown with NPC localization assay Nature genetics High 26878725
2016 Nup205, together with Nup93 and Nup188, associates with HOXA gene promoters (~1 kb upstream of TSS of HOXA1, HOXA3, HOXA5); depletion of the Nup93 sub-complex (including Nup205) upregulates HOXA gene expression, increases active histone marks (H3K9ac), decreases repressive marks (H3K27me3), and disengages the HOXA locus from the nuclear periphery, demonstrating a role for NUP205 in chromatin tethering and transcriptional repression. ChIP, siRNA knockdown, 3D-FISH, RT-qPCR, histone mark analysis in DLD1 colorectal cancer cells Epigenetics & chromatin Medium 27980680
2023 NUP205 physically interacts with YAP and TAZ in podocytes (identified by quantitative label-free mass spectrometry interactome); NUP205 is essential for YAP/TAZ nuclear import, and both nuclear interaction of YAP/TAZ with TEAD1 and their transcriptional activity depend on NUP205 expression. A regulatory feedback loop was identified whereby YAP activity is modulated in response to TAZ-mediated NUP205 expression. Quantitative label-free mass spectrometry interactome, siRNA knockdown of NUP205, nuclear fractionation, co-immunoprecipitation, transcriptional reporter assay in podocytes Human molecular genetics Medium 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, and NUP205 knockdown suppressed xenograft tumor growth. siRNA knockdown and overexpression, proliferation and apoptosis assays, ubiquitin-proteasome pathway analysis, xenograft mouse model Journal of hepatocellular carcinoma Medium 41868261
2026 NUP205 knockdown in COV434 ovarian cells impairs protein stability of NUP93 and NUP62, leading to NPC structural defects; a zebrafish model with nup205 truncation mutation shows impaired oogenesis, compromised fertility, and abnormal NPC morphology in theca cells by electron microscopy. siRNA knockdown, western blot, CRISPR/Cas9 zebrafish model, transmission electron microscopy, immunofluorescence Human reproduction Medium 42049205
2022 NUP205 knockdown by siRNA in human lung (A549) cells significantly suppresses influenza A virus (H1N1) reproduction, reducing viral titer by ~2 log units and viral RNA by up to 30-fold, without significantly decreasing cell survival, indicating NUP205 is required for efficient influenza virus replication. siRNA knockdown, viral titer by CPE titration, hemagglutination assay, RT-PCR for viral RNA quantification Infectious disorders drug targets Low 35339191
2026 FOXO6 directly activates NUP205 transcription downstream of ELYS/PI3K/AKT signaling; NUP205 in turn facilitates Gli-1 nuclear translocation to drive Hedgehog signaling and HCC stemness. FOXO6 knockdown suppressed ELYS-induced NUP205 upregulation and Gli-1 nuclear translocation. Luciferase reporter assay, ChIP assay, pathway inhibitors (GANT-61, MK-2206), siRNA knockdown, xenograft model Cell & bioscience Medium 42231458

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nature genetics 160 26878725
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 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
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 15 33107391
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
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 14 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
2026 A de novo C-terminal truncation mutation in NUP205 as a key factor in premature ovarian insufficiency. Human reproduction (Oxford, England) 0 42049205
2026 ELYS promotes hepatocellular carcinoma stemness by activating a FOXO6-NUP205 transcriptional module downstream of PI3K/AKT to drive Hedgehog signaling. Cell & bioscience 0 42231458

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