Affinage

NUP160

Nuclear pore complex protein Nup160 · UniProt Q12769

Length
1436 aa
Mass
162.1 kDa
Annotated
2026-06-10
16 papers in source corpus 9 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP160 is a structural nucleoporin of the nuclear pore complex (NPC) that assembles into the Nup160 outer-ring complex together with Nup133, Nup107, Nup96, and Sec13 (PMID:11684705). This complex is tethered to the pore through interactions with Nup98 and Nup153, and these contacts are required to target Nup98 and Nup153 to the nucleus and the pore respectively (PMID:11684705). Functionally, dominant-negative fragments of Nup160 selectively block poly[A]+ mRNA export without affecting protein import or export, establishing a dedicated role in mRNA export (PMID:11684705). Beyond its core NPC function, NUP160 is essential for podocyte biology: loss of NUP160 in podocytes disrupts expression and subcellular localization of slit diaphragm proteins nephrin, podocin, and CD2AP, perturbs cell-cycle progression through cyclin D1/CDK4/p27, and post-transcriptionally lowers CDC42 protein and activity despite elevated mRNA (PMID:29704630, PMID:40298220). Allele-specific rescue in Drosophila nephrocytes and a podocyte-specific knockout mouse that develops proteinuria, hypoalbuminemia, and glomerulosclerosis demonstrate that NUP160 loss-of-function causes steroid-resistant nephrotic syndrome (PMID:30910934, PMID:38224683). NUP160 additionally modulates autophagic flux in disease contexts, and its mRNA is stabilized by the circRAPGEF5/IGF2BP2 axis in lung adenocarcinoma (PMID:40629330).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Whether vertebrate Nup160 was a discrete nucleoporin with a defined complex and transport function was unknown; this work defined the Nup160 outer-ring complex and assigned it a direct role in mRNA export.

    Evidence Pulldown, co-IP, and reconstitution from Xenopus egg extracts with dominant-negative fragment transport assays

    PMID:11684705

    Open questions at the time
    • Atomic structure of the complex not resolved
    • Mechanism by which the complex selects mRNA versus protein cargo not defined
  2. 2001 Medium

    How peripheral nucleoporins are anchored to the pore was unclear; mapping showed the Nup160 complex provides the binding sites that tether Nup98 to the nucleus and target Nup153 to the pore.

    Evidence Domain-mapping pulldowns with Nup98/Nup153 fragments and immunofluorescence in Xenopus extracts

    PMID:11684705

    Open questions at the time
    • Single-study domain mapping
    • Stoichiometry and structural interface not determined
  3. 2018 Medium

    The cellular consequence of NUP160 loss in podocytes was unknown; knockdown linked NUP160 to slit-diaphragm protein expression/localization, cell-cycle control, and survival.

    Evidence shRNA knockdown in immortalized mouse podocytes with Western blot, flow cytometry, immunofluorescence

    PMID:29704630

    Open questions at the time
    • Whether effects are direct or secondary to NPC dysfunction unknown
    • Single cell-line model
  4. 2019 Medium

    Whether patient NUP160 mutations are pathogenic was untested; nephrocyte-specific rescue showed wild-type but not the mutant allele restores function, establishing loss-of-function disease causation.

    Evidence Drosophila nephrocyte RNAi with allele-specific human NUP160 rescue and functional/structural assays

    PMID:30910934

    Open questions at the time
    • Molecular defect of the mutant protein not defined
    • Single lab
  5. 2024 High

    Whether podocyte NUP160 loss alone is sufficient for disease was open; conditional knockout mice developed proteinuria, hypoalbuminemia, and glomerulosclerosis, proving sufficiency.

    Evidence Podocyte-specific Nup160 knockout mouse (CRISPR/Cre-loxP) with albumin/creatinine, serum albumin, and histology

    PMID:38224683

    Open questions at the time
    • Downstream effector cascade not fully mapped in this study
  6. 2025 Medium

    The molecular driver of NUP160-associated nephrotic syndrome was unresolved; KO mice revealed post-transcriptional CDC42 downregulation as a candidate effector.

    Evidence Podocyte-specific KO mouse with single-cell omics, primary podocyte culture, and Cdc42 activity assay

    PMID:40298220

    Open questions at the time
    • Mechanism coupling NPC function to CDC42 protein stability unknown
    • Causality of CDC42 loss for the full phenotype not formally tested
  7. 2021 Medium

    A role for NUP160 in autophagy and inflammation was untested; knockdown in diabetic-nephropathy models restored autophagic flux and reduced NF-kB-driven inflammation/fibrosis.

    Evidence shRNA knockdown in NRK-52E cells and STZ diabetic mice with autophagy/NF-kB markers and histology

    PMID:34533106

    Open questions at the time
    • Direct vs indirect link to autophagy machinery unresolved
    • Whether NPC transport role mediates the effect unknown
  8. 2023 Low

    The signaling route for NUP160's autophagy effect was unknown; knockdown in high-glucose podocytes implicated the JAK2/STAT3 pathway.

    Evidence siRNA knockdown in podocytes with phospho-JAK2/STAT3 and LC3B Westerns, apoptosis flow cytometry

    PMID:38043110

    Open questions at the time
    • Pathway inferred from phospho-Westerns only
    • No epistasis or rescue to confirm JAK2/STAT3 dependence
  9. 2019 Low

    Whether NUP160 is regulated by non-coding RNA was unaddressed; miR-577 was shown to directly target NUP160 mRNA, linking it to imatinib sensitivity in CML.

    Evidence Dual-luciferase reporter, qRT-PCR, proliferation and drug-sensitivity assays in CML cells

    PMID:31486501

    Open questions at the time
    • Limited mechanistic depth for NUP160 itself
    • Single lab, single reporter validation
  10. 2025 Medium

    Post-transcriptional control of NUP160 in cancer was uncharacterized; circRAPGEF5/IGF2BP2 was found to stabilize NUP160 mRNA, with elevated NUP160 suppressing autophagy and promoting lung adenocarcinoma malignancy.

    Evidence RNA pulldown/MS/RIP, m6A-RIP, autophagy flux reporter, siRNA knockdown, and xenografts

    PMID:40629330

    Open questions at the time
    • Mechanism by which NUP160 suppresses autophagy not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NUP160's core NPC/mRNA-export function mechanistically connects to its tissue-specific roles in podocyte CDC42 regulation, autophagy, and cancer remains unresolved.
  • No molecular link established between mRNA-export function and CDC42 protein stability
  • Mechanism of autophagy regulation undefined
  • Structural basis of disease mutations not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005634 nucleus 2 GO:0005635 nuclear envelope 2
Pathway
R-HSA-9612973 Autophagy 2 R-HSA-8953854 Metabolism of RNA 1
Partners
NUP107NUP133NUP153NUP96NUP98SEC13
Complex memberships
Nup160 complex (Nup107-160 outer ring)nuclear pore complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Nup160 and Nup133 are novel vertebrate nucleoporins that exist as a complex (Nup160 complex) together with Nup107, Nup96, and Sec13 in Xenopus egg extracts and in assembled nuclear pores. Nup98 and Nup153 each bind this complex, and specific fragments of Nup160 and Nup133 block poly[A]+ RNA (mRNA) export but not protein import or export, establishing a direct role in mRNA export. Pulldown from Xenopus egg extracts, co-immunoprecipitation, immunofluorescence, protein purification and sequencing, transfection with in vivo transport assays The Journal of cell biology High 11684705
2001 The binding site on Nup98 for the Nup160 subcomplex is used to tether Nup98 to the nucleus; the binding site on Nup153 for the Nup160 subcomplex targets Nup153 to the nuclear pore. Domain mapping via pulldown experiments with fragments of Nup98 and Nup153 from Xenopus egg extracts, immunofluorescence The Journal of cell biology Medium 11684705
2018 Knockdown of NUP160 in mouse podocytes inhibits cell proliferation by decreasing cyclin D1 and CDK4 expression, increasing p27, and inducing S-phase arrest; it also promotes apoptosis and autophagy, enhances cell migration, decreases expression of nephrin, podocin, and CD2AP, increases α-actinin-4, and alters subcellular localization of nephrin, podocin, and CD2AP. shRNA-mediated knockdown in conditionally immortalized mouse podocytes; Western blot, flow cytometry, immunofluorescence Gene Medium 29704630
2019 Silencing of Drosophila NUP160 specifically in nephrocytes leads to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure; these defects are completely rescued by wild-type human NUP160, but not by the NUP160 disease-associated mutant allele, establishing loss-of-function phenotypes for two compound-heterozygous mutations identified in a patient with steroid-resistant nephrotic syndrome. Drosophila nephrocyte-specific RNAi knockdown; rescue by wild-type and mutant human NUP160 expression; functional assays for nephrocyte function, cell size, nuclear volume, nuclear membrane structure Journal of the American Society of Nephrology : JASN Medium 30910934
2024 Podocyte-specific knockout of Nup160 in mice causes progressive proteinuria, reduced serum albumin, and glomerulosclerosis, directly demonstrating that loss of Nup160 in podocytes is sufficient to produce nephrotic syndrome phenotypes. Podocyte-specific Nup160 knockout mice generated by CRISPR/Cas9 and Cre/loxP; protein and DNA level verification; urinary albumin/creatinine ratio, serum albumin, histology Human molecular genetics High 38224683
2025 Loss of Nup160 in podocytes of podocyte-specific knockout mice decreases Cdc42 protein levels and reduces Cdc42 activity (despite elevated Cdc42 mRNA), linking NUP160 to post-transcriptional regulation of Cdc42 and suggesting that CDC42 dysregulation contributes to NUP160-associated steroid-resistant nephrotic syndrome pathogenesis. Podocyte-specific Nup160 KO mouse with double-fluorescent Cre reporter; single-cell transcriptomics and proteomics of glomerular cells; primary podocyte culture; Cdc42 activity assay; Western blot; RT-qPCR Human molecular genetics Medium 40298220
2021 Knockdown of NUP160 in high glucose-treated kidney tubular cells and STZ-induced diabetic nephropathy mice restores autophagic flux (increased LC3II/LC3I ratio, decreased p62) and reduces NF-κB-dependent inflammation and fibrosis, identifying NUP160 as a regulator of autophagy in diabetic nephropathy. shRNA knockdown in NRK-52E cells; STZ mouse model; Western blot for autophagy markers, NF-κB pathway components, and inflammatory cytokines; histological staining in vivo Bioengineered Medium 34533106
2023 NUP160 knockdown in high glucose-treated podocytes activates the JAK2/STAT3 signaling pathway (increased p-JAK2/JAK2 and p-STAT3/STAT3 ratios) and reduces autophagic flux (decreased LC3B-II/LC3B-I), indicating that NUP160 regulates cellular autophagy through the JAK2/STAT3 pathway. siRNA knockdown in podocytes; Western blot for JAK2/STAT3 phosphorylation and LC3B; flow cytometry for apoptosis Iranian journal of kidney diseases Low 38043110
2019 microRNA-577 directly targets NUP160 mRNA (validated by dual-luciferase reporter assay), and upregulation of miR-577 reduces NUP160 expression in CML cells, linking NUP160 to imatinib sensitivity in chronic myeloid leukemia. Dual-luciferase reporter assay; qRT-PCR; cell proliferation and cycle assays; cell reverse test for drug sensitivity European review for medical and pharmacological sciences Low 31486501
2025 circRAPGEF5 interacts with the KH3-4 domain of IGF2BP2, which then stabilizes NUP160 mRNA; elevated NUP160 suppresses autophagic flux in lung adenocarcinoma cells, and RNAi-mediated knockdown of NUP160 restores autophagy and attenuates malignant behaviors in vitro and in vivo. RNA pulldown, mass spectrometry, RNA immunoprecipitation; m6A-RIP-PCR; immunofluorescence; FISH; mRFP-GFP-LC3 lentiviral labeling for autophagy flux; xenograft mouse model; siRNA knockdown Molecular cancer Medium 40629330

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. The Journal of cell biology 154 11684705
2015 NUP160-SLC43A3 is a novel recurrent fusion oncogene in angiosarcoma. Cancer research 44 26527604
2019 Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic Syndrome. Journal of the American Society of Nephrology : JASN 34 30910934
2018 Knockdown of NUP160 inhibits cell proliferation, induces apoptosis, autophagy and cell migration, and alters the expression and localization of podocyte associated molecules in mouse podocytes. Gene 15 29704630
2021 Nucleoporin 160 (NUP160) inhibition alleviates diabetic nephropathy by activating autophagy. Bioengineered 13 34533106
2019 MicroRNA-577 promotes the sensitivity of chronic myeloid leukemia cells to imatinib by targeting NUP160. European review for medical and pharmacological sciences 13 31486501
2015 Lineage-Specific Evolution of the Complex Nup160 Hybrid Incompatibility Between Drosophila melanogaster and Its Sister Species. Genetics 12 26022241
2024 Podocyte-specific Nup160 knockout mice develop nephrotic syndrome and glomerulosclerosis. Human molecular genetics 8 38224683
2024 Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children. Italian journal of pediatrics 7 38650033
2025 M6A-Methylated circRAPGEF5 drives lung adenocarcinoma progression and metastasis via IGF2BP2/NUP160-mediated autophagy suppression. Molecular cancer 6 40629330
2012 Genetic dissection of Nucleoporin 160 (Nup160), a gene involved in multiple phenotypes of reproductive isolation in Drosophila. Genes & genetic systems 6 22820383
2022 NUP160 knockdown inhibits the progression of diabetic nephropathy in vitro and in vivo. Regenerative therapy 4 35785044
2025 Loss of Nup160 dysregulates Cdc42 in the podocytes of podocyte-specific Nup160 knockout mice. Human molecular genetics 3 40298220
2023 Novel LAGE3 Pathogenic Variants Combined with TRPC6 and NUP160 Variants in Galloway-Mowat Syndrome: A Case Report. Case reports in nephrology and dialysis 2 37900929
2023 Role and Mechanism of NUP160-regulated Autophagy in Pathogenesis of Diabetic Nephropathy. Iranian journal of kidney diseases 2 38043110
2025 Identification of Aging-Related Hub Genes (ATP11B, RBBP7, DOCK10, and NUP160) as Potential Biomarkers and Therapeutic Targets in Sepsis. Human mutation 1 41394771

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