Affinage

NUP160

Nuclear pore complex protein Nup160 · UniProt Q12769

Round 2 corrected
Length
1436 aa
Mass
162.1 kDa
Annotated
2026-04-29
48 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP160 is a core scaffold nucleoporin of the Nup107-160 outer-ring subcomplex of the nuclear pore complex, essential for NPC architecture, mRNA export, and kinetochore targeting during mitosis. It forms a stable complex with Nup107, Nup133, Nup96, Sec13, Nup37, Nup43, and Seh1, with 32 copies of this subcomplex assembling into two reticulated rings at the cytoplasmic and nuclear faces of the NPC (PMID:11684705, PMID:11564755, PMID:24315095). NUP160 is required for poly(A)+ RNA export but dispensable for protein import/export, and its loss in podocytes post-transcriptionally reduces CDC42 protein levels and activity, disrupting cytoskeletal architecture and glomerular filtration (PMID:11684705, PMID:40298220). Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome, validated by rescue experiments in Drosophila nephrocytes and recapitulated in podocyte-specific knockout mice (PMID:30910934, PMID:38224683).

Mechanistic history

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

    Identification of NUP160 as a novel vertebrate nucleoporin within a defined NPC subcomplex (with Nup107, Nup133, Nup96, Sec13) resolved the composition of a major outer-ring module and established that NUP160 fragments selectively block mRNA export without affecting protein transport.

    Evidence Pulldown from Xenopus egg extracts, co-IP, immunofluorescence, in vivo transport assays in mammalian cells; independently, yeast two-hybrid and reciprocal co-IP in human cells

    PMID:11564755 PMID:11684705

    Open questions at the time
    • Precise contact surfaces between NUP160 and other subcomplex members not mapped
    • Mechanism by which NUP160 selectively facilitates mRNA but not protein export unresolved
  2. 2004 High

    Demonstration that the entire Nup107-160 complex (now including Nup37, Nup43, Seh1) relocates as a unit to kinetochores during mitosis, with individual subunit depletions phenocopying each other, established functional interdependence and a dual interphase/mitotic role for NUP160.

    Evidence GFP-tagging, immunofluorescence, RNAi knockdown, biochemical fractionation in human cells

    PMID:15146057

    Open questions at the time
    • Direct contribution of NUP160 to kinetochore function versus passive co-recruitment not distinguished
    • Whether mitotic targeting requires NUP160 specifically or any intact subcomplex member unknown
  3. 2013 High

    High-resolution structural analysis revealed that 32 copies of the Nup107 subcomplex assemble into two reticulated rings at the NPC, defining the stoichiometry and spatial arrangement of NUP160 within the intact human pore scaffold.

    Evidence Electron tomography, single-particle EM, crosslinking mass spectrometry of human NPCs

    PMID:24315095

    Open questions at the time
    • Atomic-resolution contacts of NUP160 within the ring not resolved
    • Conformational dynamics of NUP160 during cargo translocation unknown
  4. 2014 Medium

    BioID proximity labeling using NUP160 fusions as a molecular ruler mapped in vivo spatial relationships within the Nup107-160 complex, confirming its extreme stability and delineating subunit proximity in living cells.

    Evidence BioID proximity biotinylation with mass spectrometry in HEK293 cells

    PMID:24927568

    Open questions at the time
    • Proximity data do not distinguish direct from indirect contacts
    • Single study without orthogonal structural validation of the inferred distances
  5. 2015 Medium

    Discovery of the NUP160-SLC43A3 fusion oncogene in angiosarcomas and its ability to drive endothelial proliferation and tumor formation in vivo revealed that truncation of NUP160 can be oncogenic, raising the question of whether NPC scaffold disruption contributes to tumorigenesis.

    Evidence Transcriptome sequencing of angiosarcomas, stable cell line expression, xenograft tumor assay

    PMID:26527604

    Open questions at the time
    • Which domains of NUP160 are required for oncogenic activity not determined
    • Whether the fusion alters NPC-dependent transport or acts through a gain-of-function mechanism unknown
  6. 2015 Medium

    Genetic analysis in Drosophila showed that Nup160 interacts epistatically with Nup96 to cause hybrid lethality and evolves under recurrent positive selection, linking NPC outer-ring components to speciation barriers.

    Evidence Genetic crosses, introgression lines, population genetics in D. simulans/D. melanogaster

    PMID:26022241

    Open questions at the time
    • Molecular basis of Nup160-Nup96 hybrid incompatibility not identified
    • Whether the rapid evolution affects NPC transport function or another activity unclear
  7. 2019 High

    Identification of compound-heterozygous NUP160 mutations in steroid-resistant nephrotic syndrome patients, with functional validation showing that wild-type but not mutant NUP160 rescues nephrocyte defects in Drosophila, established NUP160 as a causative SRNS gene.

    Evidence Whole-exome sequencing, Drosophila nephrocyte RNAi with human NUP160 rescue

    PMID:30910934

    Open questions at the time
    • How specific NUP160 mutations impair NPC function at the molecular level unknown
    • Whether SRNS-associated mutations affect mRNA export, CDC42 regulation, or both not resolved
  8. 2018 Medium

    Knockdown of NUP160 in mouse podocytes revealed downstream cell-cycle arrest, apoptosis, autophagy induction, and mislocalization of slit-diaphragm proteins, establishing that NUP160 loss has broad effects on podocyte homeostasis beyond NPC function.

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

    PMID:29704630

    Open questions at the time
    • Whether effects on slit-diaphragm proteins are direct or secondary to NPC dysfunction not distinguished
    • Single cell-line study without in vivo validation at the time
  9. 2024 High

    Generation of podocyte-specific Nup160 knockout mice confirmed the causal role of NUP160 in glomerular disease by recapitulating progressive proteinuria and glomerulosclerosis in a mammalian model, bridging human genetics and Drosophila studies.

    Evidence CRISPR/Cas9 and Cre/loxP conditional knockout mouse, histology, urine ACR, serum albumin

    PMID:38224683

    Open questions at the time
    • Temporal requirement for NUP160 in mature versus developing podocytes not defined
    • Whether the phenotype is fully cell-autonomous or involves paracrine effects not tested
  10. 2025 High

    Multi-omic profiling of Nup160-knockout podocytes revealed that NUP160 loss post-transcriptionally decreases CDC42 protein and activity despite elevated CDC42 mRNA, identifying a shared mechanism with other outer-ring nucleoporin knockouts (NUP85, NUP107, NUP133) and linking NPC scaffold integrity to Rho GTPase-dependent cytoskeletal regulation.

    Evidence Conditional KO mouse, dual-fluorescent reporter, single-cell transcriptomics, proteomics, CDC42 activity assay

    PMID:40298220

    Open questions at the time
    • Mechanism of post-transcriptional CDC42 downregulation (translation, stability, or export defect) not determined
    • Whether restoring CDC42 activity is sufficient to rescue the podocyte phenotype not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise molecular mechanism by which NUP160 (and the Nup107-160 complex) post-transcriptionally controls CDC42 levels in podocytes remains to be determined — whether through selective mRNA export, translational regulation, or protein stability — and whether this mechanism operates in non-podocyte contexts is unknown.
  • No reconstitution of the CDC42 regulatory mechanism in vitro
  • Atomic-resolution structure of NUP160 within the intact human NPC not available
  • Whether NUP160's role in mRNA export and its CDC42-regulatory function are mechanistically linked is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005635 nuclear envelope 4 GO:0005694 chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 2 R-HSA-8953854 Metabolism of RNA 1
Partners
CDC42NUP107NUP133NUP37NUP43NUP96SEC13SEH1L
Complex memberships
Nuclear pore complexNup107-160 complex (Y-complex / outer ring complex)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NUP160 and NUP133 are novel vertebrate nucleoporins that form a complex (the Nup160 complex) with Nup107, Nup96, and Sec13 in Xenopus egg extracts and assembled pores. They are accessible on the basket side of the nuclear pore and were identified through pulldown experiments using Nup98 and Nup153 fragments. Specific Nup160 and Nup133 fragments block poly[A]+ RNA export but not protein import or export, establishing a direct role for NUP160 in mRNA export. Pulldown from Xenopus egg extracts, immunofluorescence, co-immunoprecipitation, in vivo transport assays with transfected fragments The Journal of cell biology High 11684705
2001 Human Nup107 and Nup133 form a nuclear pore subcomplex that also contains Nup96 and a novel nucleoporin designated hNup120 (later referred to as Nup160). This Nup107-160 subcomplex localizes stably to both faces of the NPC at interphase and redistributes to kinetochores during mitosis, revealing a connection between NPC scaffold components and kinetochore function. Two-hybrid screens, immunoprecipitation, immunofluorescence, photobleaching (FRAP) The Journal of cell biology High 11564755
2004 The entire Nup107-160 complex, including NUP160 and three newly identified members (Nup37, Nup43, Seh1), is targeted as one entity to kinetochores from prophase to anaphase during mitosis. Depletion of individual members by RNAi phenocopies each other, indicating functional interdependence within the complex. GFP-tagging, immunofluorescence with specific antibodies, RNA interference knockdown, biochemical fractionation Molecular biology of the cell High 15146057
2013 Electron tomography, single-particle EM, and crosslinking mass spectrometry show that 32 copies of the Nup107 subcomplex (which includes NUP160) assemble into two reticulated rings at the cytoplasmic and nuclear faces of the human NPC, defining how the scaffold accommodates large cargo transport. Electron tomography, single-particle electron microscopy, crosslinking mass spectrometry Cell High 24315095
2014 BioID proximity-dependent biotinylation applied to constituents of the Nup107-160 complex (including NUP160) in living human cells defined the spatial organization of the NPC subcomplex and demonstrated a direct interaction of Nup43 with Nup85 within the extremely stable Nup107-160 structure, using NUP160-BioID fusions as a molecular ruler to define the labeling radius. Proximity-dependent biotin identification (BioID), mass spectrometry Proceedings of the National Academy of Sciences of the United States of America Medium 24927568
2015 The NUP160-SLC43A3 fusion oncogene, arising from NUP160 truncation, is expressed in a subset of human angiosarcomas. Stable expression of the fusion in endothelial cells increases cell proliferation and induces an angiosarcoma-like gene expression pattern; subcutaneous implantation of fusion-expressing fibroblasts produces angiosarcoma-like tumors in vivo, implicating NUP160 truncation as oncogenic. Transcriptome sequencing, stable cell line expression, RNAi knockdown, xenograft tumor assay Cancer research Medium 26527604
2015 Drosophila Nup160 (D. simulans allele) interacts genetically with Nup96 and additional autosomal factors to cause hybrid lethality in crosses with D. melanogaster; population genetic analysis reveals recurrent positive selection at Nup160 before and after speciation of the D. simulans clade, consistent with NUP160 evolving rapidly under natural selection at the species interface. Genetic crosses, introgression lines, population genetics analysis, complementation tests Genetics Medium 26022241
2019 Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome (SRNS). In a Drosophila nephrocyte model, silencing of Nup160 caused functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure; these defects were rescued by wild-type human NUP160 but not by one of the disease-associated mutant alleles, establishing NUP160 mutations as causative for SRNS. Whole-exome/Sanger sequencing, Drosophila nephrocyte RNAi model, rescue experiments with wild-type and mutant human NUP160 Journal of the American Society of Nephrology : JASN High 30910934
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, autophagy, and cell migration, and decreases expression and alters subcellular localization of slit-diaphragm proteins nephrin, podocin, and CD2AP while increasing α-actinin-4. shRNA knockdown in immortalized mouse podocytes, flow cytometry, Western blot, immunofluorescence Gene Medium 29704630
2024 Podocyte-specific Nup160 knockout (Nup160podKO) mice generated by CRISPR/Cas9 and Cre/loxP develop progressive proteinuria and glomerulosclerosis, recapitulating the nephrotic syndrome phenotype of human NUP160 mutations and establishing NUP160 as causally required for podocyte integrity in a mammalian model. CRISPR/Cas9 and Cre/loxP conditional knockout mouse model, urine ACR measurement, serum albumin, histology Human molecular genetics High 38224683
2025 Loss of Nup160 in podocyte-specific knockout mice decreases CDC42 protein levels and activity (despite elevated CDC42 mRNA), causing progressive proteinuria and foot-process fusion. This post-transcriptional dysregulation of CDC42 parallels findings from knockout of other outer-ring NPC components (NUP85, NUP107, NUP133), implicating CDC42 downregulation as a shared mechanism in NUP160-associated SRNS. CRISPR/Cas9 Cre/loxP knockout mouse with dual-fluorescent reporter, single-cell transcriptomics, proteomics of primary podocytes, CDC42 activity assay Human molecular genetics High 40298220
2021 NUP160 knockdown in high-glucose-treated kidney tubular cells and STZ-induced diabetic nephropathy mice restores autophagic flux (increased LC3II/LC3I ratio, decreased p62) and inhibits NF-κB signaling, inflammation, and fibrosis, suggesting NUP160 negatively regulates autophagy in the diabetic kidney context. shRNA knockdown in NRK-52E cells, STZ mouse model, Western blot, immunofluorescence, histological staining Bioengineered Medium 34533106
2019 MicroRNA-577 directly targets NUP160 mRNA (validated by dual-luciferase reporter assay); up-regulation of miR-577 reduces NUP160 expression in CML cells, inhibits cell proliferation and cycle progression, and enhances imatinib sensitivity, placing NUP160 downstream of miR-577 in CML drug resistance. qRT-PCR, dual-luciferase reporter assay, CCK-8 proliferation assay, flow cytometry, cell reverse experiment European review for medical and pharmacological sciences Medium 31486501
2022 lncRNA HCG18 upregulates NUP160 by sponging miR-495-3p (a ceRNA mechanism); miR-495-3p directly targets NUP160 (confirmed by luciferase reporter). NUP160 overexpression reverses the protective effects of HCG18 knockdown in high-glucose-treated podocytes, placing NUP160 as a downstream effector in the HCG18/miR-495-3p axis regulating podocyte apoptosis and inflammation. Luciferase reporter assay, Western blot, RT-qPCR, flow cytometry, ELISA, in vivo STZ rat model Regenerative therapy Medium 35785044

Source papers

Stage 0 corpus · 48 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
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
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
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
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
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
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
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2006 Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular psychiatry 345 17043677
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
2006 Phosphoproteome analysis of the human mitotic spindle. Proceedings of the National Academy of Sciences of the United States of America 281 16565220
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2001 An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. The Journal of cell biology 262 11564755
2004 The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Molecular biology of the cell 223 15146057
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2001 Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. The Journal of cell biology 153 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 33 30910934
2012 Nucleoporins Nup160 and Seh1 are required for disease resistance in Arabidopsis. Plant signaling & behavior 23 22902705
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 12 34533106
2019 MicroRNA-577 promotes the sensitivity of chronic myeloid leukemia cells to imatinib by targeting NUP160. European review for medical and pharmacological sciences 12 31486501
2015 Lineage-Specific Evolution of the Complex Nup160 Hybrid Incompatibility Between Drosophila melanogaster and Its Sister Species. Genetics 11 26022241
2024 Podocyte-specific Nup160 knockout mice develop nephrotic syndrome and glomerulosclerosis. Human molecular genetics 7 38224683
2024 Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children. Italian journal of pediatrics 6 38650033
2012 Genetic dissection of Nucleoporin 160 (Nup160), a gene involved in multiple phenotypes of reproductive isolation in Drosophila. Genes & genetic systems 6 22820383
2025 M6A-Methylated circRAPGEF5 drives lung adenocarcinoma progression and metastasis via IGF2BP2/NUP160-mediated autophagy suppression. Molecular cancer 5 40629330
2023 The nucleoporin NUP160 and NUP96 regulate nucleocytoplasmic export of mRNAs and participate in ethylene signaling and response in Arabidopsis. Plant cell reports 5 36598573
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 2 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