Affinage

NUP43

Nucleoporin Nup43 · UniProt Q8NFH3

Round 2 corrected
Length
380 aa
Mass
42.2 kDa
Annotated
2026-04-29
53 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP43 is a WD-repeat nucleoporin and stable subunit of the Nup107-160 (Y-complex) of the nuclear pore complex, with roles spanning nucleocytoplasmic transport, mitotic chromosome segregation, and DNA damage-induced transcriptional silencing. Within the Y-complex it directly contacts NUP85 and is required for normal NPC density and cell viability upon differentiation, though it is dispensable for pluripotency in mouse embryonic stem cells (PMID:15146057, PMID:24927568, PMID:34037234). During mitosis, NUP43 localizes to kinetochores where the Nup107-160 complex interacts with CENP-F and the Ndc80 complex to support chromosome congression, kinetochore–microtubule attachment, and recruitment of Crm1 and RanGAP1–RanBP2 (PMID:17363900). At DNA double-strand breaks, NUP43 cooperates with Polycomb repressive complex 1 subunit PHC2 to enforce damage-induced transcriptional gene silencing, and in colorectal cancer it facilitates PD-L1 nuclear translocation through regulation of the karyopherin IPO5, feeding a JAK/STAT3-dependent PD-L1 amplification loop that promotes metastasis (PMID:40440073, PMID:38762481).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2004 High

    Identification of NUP43 as a new WD-repeat nucleoporin within the Nup107-160 complex and its mitotic targeting to kinetochores established the gene's dual nuclear pore and cell-division functions.

    Evidence Biochemical co-purification, GFP-tagging, RNAi, and immunofluorescence in human cells

    PMID:15146057

    Open questions at the time
    • Direct binding partner within the Y-complex not yet mapped
    • Functional consequence of kinetochore targeting not determined
  2. 2007 High

    Defining the mitotic phenotype of Nup107-160 depletion — impaired chromosome congression, reduced kinetochore tension, and loss of Crm1/RanGAP1–RanBP2 recruitment — showed that the complex (including NUP43) is essential for kinetochore–microtubule attachment fidelity.

    Evidence siRNA knockdown of multiple Y-complex subunits, Co-IP, live-cell imaging, kinetochore tension assays

    PMID:17363900

    Open questions at the time
    • Specific contribution of NUP43 versus other Y-complex subunits to kinetochore function not individually resolved
    • Mechanism by which the complex recruits Crm1 and RanBP2 unclear
  3. 2014 High

    BioID proximity labeling in living cells mapped a direct NUP43–NUP85 interaction, refining the molecular architecture of the Y-complex and positioning NUP43 within the subcomplex.

    Evidence BioID proximity-dependent biotinylation with mass spectrometry

    PMID:24927568

    Open questions at the time
    • Structural details of the NUP43–NUP85 interface unresolved
    • Whether NUP43 contacts other Y-complex members beyond NUP85 not addressed
  4. 2017 Medium

    Morpholino knockdown in zebrafish linked NUP43 loss-of-function to cardiac defects, connecting Y-complex integrity to cardiovascular development in vivo.

    Evidence Morpholino knockdown in zebrafish embryos, corroborated by a truncating human variant from whole-exome sequencing

    PMID:28611029

    Open questions at the time
    • Single morpholino study without genetic mutant confirmation
    • Mechanism connecting NPC function to cardiac morphogenesis unknown
    • Human variant causality not formally proven by segregation or rescue
  5. 2021 High

    CRISPR knockout in mouse ESCs showed NUP43 is dispensable for pluripotency but required for normal NPC density, growth rate, and viability upon differentiation, separating Y-complex integrity from NPC number in controlling cell fate.

    Evidence CRISPR/Cas9 knockout in mouse ESCs with flow cytometry, immunofluorescence for NPC density, and differentiation assays

    PMID:34037234

    Open questions at the time
    • Whether NUP43 loss alters specific transport pathways during differentiation unknown
    • Contribution of reduced NPC density versus altered gene expression not separated
  6. 2024 Medium

    A genome-wide CRISPR screen in colorectal cancer uncovered a non-canonical role for NUP43 in promoting PD-L1 nuclear translocation via regulation of the karyopherin IPO5, establishing a PD-L1/nPD-L1/JAK-STAT3 feedback loop that drives metastasis.

    Evidence CRISPR-Cas9 screen combined with RNA-seq, nuclear fractionation, rescue experiments, and in vivo metastasis models in CRC cells

    PMID:38762481

    Open questions at the time
    • Whether NUP43 regulates IPO5 transcriptionally or post-transcriptionally not resolved
    • Generalizability beyond colorectal cancer not tested
    • Whether this function depends on Y-complex membership unclear
  7. 2025 Medium

    Discovery that NUP43 localizes to DNA double-strand break sites interdependently with PRC1 subunit PHC2 and is required for DSB-induced transcriptional silencing extended the gene's function to genome stability maintenance.

    Evidence PHC2 interactome pulldown, siRNA knockdown, ChIP-based DSB localization, and reporter-based transcriptional silencing assays

    PMID:40440073

    Open questions at the time
    • Mechanism of NUP43 recruitment to DSBs not defined
    • Whether other Y-complex subunits co-localize at DSBs not fully addressed
    • Relationship between NPC-associated and DSB-associated NUP43 pools unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: how NUP43 is partitioned among its NPC, kinetochore, and DSB-associated pools; whether the cancer-associated functions (PD-L1 translocation, proliferation control) are mechanistically linked to its Y-complex role; and whether the cardiac phenotype seen in zebrafish reflects a conserved developmental function in mammals.
  • No high-resolution structure of NUP43 in the context of the human Y-complex
  • Separation-of-function alleles distinguishing NPC from non-NPC roles not generated
  • No mammalian in vivo knockout model phenotyped comprehensively

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005634 nucleus 3 GO:0005635 nuclear envelope 3 GO:0005694 chromosome 3
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 2 R-HSA-73894 DNA Repair 1
Partners
CENP-FIPO5NUP107NUP85PHC2SEH1L
Complex memberships
Nup107-160 complex (Y-complex)

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 NUP43 was identified as a new WD-repeat nucleoporin and member of the Nup107-160 complex, specific to higher eukaryotes. All constituents of the Nup107-160 complex, including NUP43, are targeted to kinetochores from prophase to anaphase of mitosis. Biochemical co-purification, GFP-tagging, RNAi knockdown, immunofluorescence microscopy Molecular biology of the cell High 15146057
2007 The Nup107-160 complex (of which NUP43 is a constituent) interacts with CENP-F and the Ndc80 complex for kinetochore targeting; efficient depletion of the complex induces mitotic delay, impaired chromosome congression, reduced kinetochore tension, and kinetochore-microtubule attachment defects, and the complex is required for recruitment of Crm1 and RanGAP1-RanBP2 to kinetochores. siRNA knockdown of multiple Nup107-160 subunits including NUP43 components, co-immunoprecipitation, live-cell imaging, kinetochore tension assays The EMBO journal High 17363900
2014 BioID proximity labeling demonstrated a direct interaction of NUP43 with NUP85 within the Nup107-160 subcomplex, refining the molecular architecture of this conserved NPC subcomplex. BioID (proximity-dependent biotin identification) in living cells, streptavidin affinity purification, mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 24927568
2017 Morpholino-mediated knockdown of NUP43 in zebrafish caused cardiac abnormalities including pericardial edema and heart failure, identifying NUP43 as a candidate gene for cardiovascular disease. Morpholino knockdown in zebrafish embryos, whole exome sequencing (truncating variant identified in patient) Circulation. Cardiovascular genetics Medium 28611029
2017 Adenosine-to-inosine RNA editing of the NUP43 transcript occurs at constant levels between single mammalian cells, and editing is uncorrelated with nuclear localization or paraspeckle association of the transcript. inoFISH (single-molecule RNA FISH for edited transcripts), single-cell quantification Nature methods Medium 28604724
2021 NUP43 and SEH1 are dispensable for pluripotency in mouse embryonic stem cells but are required for normal cell growth rates, viability upon differentiation, and maintenance of proper NPC density. An N-terminally truncated NUP85 mutation (impairing interaction with SEH1) also reduces NPC density but does not affect proliferation or differentiation, indicating that Y-complex integrity rather than NPC number per se is critical for these processes. CRISPR/Cas9 genome editing in mouse ESCs, flow cytometry, immunofluorescence for NPC density, differentiation assays Journal of cell science High 34037234
2019 NUP43 is a direct target gene of miR-409-5p; miR-409-5p negatively regulates NUP43 expression, and NUP43 knockdown inhibits CML cell proliferation and arrests the cell cycle in G0/G1, implicating NUP43 in cell cycle progression in leukemia cells. Dual-luciferase reporter assay (3′-UTR binding), qRT-PCR, Western blot, CCK-8 proliferation assay, flow cytometry cell cycle analysis European review for medical and pharmacological sciences Medium 31646577
2020 In gastric cancer cells, the lncRNA NCK1-AS1 acts as a sponge for miR-137, thereby upregulating NUP43 expression; elevated NUP43 promotes gastric cancer cell proliferation, migration, and invasion, and tumor growth in vivo. Luciferase reporter assay, RNA immunoprecipitation (RIP), siRNA knockdown, rescue experiments, xenograft mouse model OncoTargets and therapy Medium 33116577
2024 NUP43 promotes PD-L1 nuclear translocation in colorectal cancer by regulating the expression of the PD-L1 chaperone protein IPO5; nuclear PD-L1 then stimulates TM4SF1 expression, activates the JAK/STAT3 signaling pathway, and transcriptionally enhances PD-L1 expression, establishing a PD-L1–nPD-L1–PD-L1 feedback loop that promotes CRC progression and liver metastasis. CRISPR-Cas9 genome-wide screening combined with RNA-seq, loss-of-function experiments, rescue experiments, nuclear fractionation, western blot, in vivo metastasis models Cell death discovery Medium 38762481
2025 NUP43 and NUP107, as members of the NPC Y-complex, localize to DNA double-strand break (DSB) sites in a manner interdependent with PHC2 (a PRC1 subunit); depletion of NUP43 disrupts DSB-induced transcriptional gene silencing, revealing a cooperative role between nucleoporins and Polycomb repressive complex 1 in DNA damage-induced transcriptional repression and genome stability. Interactome analysis (PHC2 pulldown), siRNA knockdown, ChIP/DSB localization assays, reporter-based transcriptional silencing assays Proceedings of the National Academy of Sciences of the United States of America Medium 40440073
2025 In Drosophila, Nup43 is essential for fertility in both sexes; in males, loss of Nup43 arrests spermiogenesis at the canoe stage, impairing nuclear elongation, nuclear shaping, and actin cone assembly during individualization complex formation. Myosin VI (jar) interacts physically with Nup43 and rescues actin cone assembly (but not sterility) in Nup43 null mutants, revealing a non-canonical role for Nup43 in actin-based sperm individualization. Drosophila null mutant generation, transgene rescue, co-immunoprecipitation (Nup43–Myosin VI interaction), fluorescence imaging of actin cones and nuclei bioRxivpreprint Medium bio_10.1101_2025.09.29.679220

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
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
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2002 Proteomic analysis of the mammalian nuclear pore complex. The Journal of cell biology 785 12196509
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
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
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
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
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
2014 Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America 432 24927568
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2005 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proceedings of the National Academy of Sciences of the United States of America 383 16009940
2011 Global identification of modular cullin-RING ligase substrates. Cell 354 21963094
2006 DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes & development 287 17079684
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
2010 Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Molecular & cellular proteomics : MCP 262 21139048
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
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
2021 N6-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation. Cancer cell 207 34048709
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2007 The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. The EMBO journal 171 17363900
2013 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. Nature methods 170 23455922
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2008 Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. Journal of proteome research 162 18781797
2017 Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease. Circulation. Cardiovascular genetics 35 28611029
2017 Visualizing adenosine-to-inosine RNA editing in single mammalian cells. Nature methods 30 28604724
2021 A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer. Frontiers in genetics 20 33584825
2021 Identification of novel cell glycolysis related gene signature predicting survival in patients with breast cancer. Scientific reports 19 33597614
2019 MiRNA-409-5p dysregulation promotes imatinib resistance and disease progression in children with chronic myeloid leukemia. European review for medical and pharmacological sciences 16 31646577
2020 Long Non-Coding RNA NCK1-AS1 Serves an Oncogenic Role in Gastric Cancer by Regulating miR-137/NUP43 Axis. OncoTargets and therapy 14 33116577
2024 NUP43 promotes PD-L1/nPD-L1/PD-L1 feedback loop via TM4SF1/JAK/STAT3 pathway in colorectal cancer progression and metastatsis. Cell death discovery 11 38762481
2022 In silico development and validation of a novel glucose and lipid metabolism-related gene signature in gastric cancer. Translational cancer research 11 35966316
2021 Integrity of the short arm of the nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation. Journal of cell science 6 34037234
2019 Network-based transcriptomic analysis reveals novel melatonin-sensitive genes in cardiovascular system. Endocrine 6 30989468
2018 Triazophos-induced toxicity in zebrafish: miRNA-217 inhibits nup43. Toxicology research 6 30310668
2023 Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS. Frontiers in endocrinology 5 37547318
2021 Identification of keygenes, miRNAs and miRNA-mRNA regulatory pathways for chemotherapy resistance in ovarian cancer. PeerJ 4 34820170
2025 Identifying periphery biomarkers of first-episode drug-naïve patients with schizophrenia using machine-learning-based strategies. Progress in neuro-psychopharmacology & biological psychiatry 3 40015618
2024 Mutations in nuclear pore complex promote osmotolerance in Arabidopsis by suppressing the nuclear translocation of ACQOS and its osmotically induced immunity. Frontiers in plant science 3 38318497
2024 Integrative approaches to m6A and m5C RNA modifications in autism spectrum disorder revealing potential causal variants. Mammalian genome : official journal of the International Mammalian Genome Society 3 39738578
2026 Machine Learning-Based Integrative Analysis Identifies SUMOylation-Related Genes Underlying the Immune Heterogeneity of Sepsis. IET systems biology 1 41616376
2025 Transcriptomic insights into developmental arrest in fluorescent labeling transgenic Asian elephant (Elephas maximus) embryos via inter-order cloning. Frontiers in cell and developmental biology 1 40092629
2025 Transcriptomics-based analysis of key genes and potential mechanism and therapeutic agents in cadmium-induced esophageal squamous cell carcinoma progression. Scientific reports 1 41449178
2025 Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double-strand breaks. Proceedings of the National Academy of Sciences of the United States of America 0 40440073
2024 Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double strand breaks. Research square 0 39070640