{"gene":"NUP153","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1994,"finding":"Human NUP153 (hnup153) encodes a nucleoporin with 33 copies of the XFXFG pentapeptide repeat, O-linked N-acetylglucosamine modifications, and four zinc finger motifs related to those in mdm-2 and Drosophila small optic lobes, defining its primary structure and domain architecture.","method":"cDNA sequence analysis","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 1 structural/sequence characterization; single study, foundational domain mapping","pmids":["8110839"],"is_preprint":false},{"year":1996,"finding":"Nup153 localizes to the nucleoplasmic face of the nuclear pore complex (NPC) basket via its N-terminal domain, while its C-terminal XFXFG-repeat domain is required for mRNA export; overexpression of Nup153 causes dramatic nuclear accumulation of poly(A)+ RNA without affecting protein import.","method":"Overexpression of deletion constructs in BHK cells, fluorescence microscopy of poly(A)+ RNA distribution","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — domain dissection with specific phenotypic readout, replicated in multiple constructs","pmids":["8794857"],"is_preprint":false},{"year":1998,"finding":"The N-terminal domain of Nup153 contains two distinct targeting regions: one mediates assembly into the NPC and the other targets proteins to the inner face of the nuclear envelope, while the zinc finger and C-terminal domains have no targeting role.","method":"Deletion mutagenesis with reporter (pyruvate kinase) fusion constructs expressed in cells","journal":"Chromosoma","confidence":"High","confidence_rationale":"Tier 2 — systematic deletion analysis with orthogonal reporter, multiple constructs","pmids":["9745047"],"is_preprint":false},{"year":1998,"finding":"Nup153 is a major physiological binding site for importin β at the nuclear face of the NPC; importin β binds directly to multiple sites within the Nup153 FXFG repeat region, and Nup153 can bind a complete import complex containing importin α, importin β, and an NLS substrate, consistent with a role in the terminal step of nuclear import.","method":"Immunoprecipitation from Xenopus egg extracts and isolated nuclei; in vitro binding with purified recombinant proteins","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding demonstrated with purified proteins and confirmed in physiological extract context","pmids":["9531546"],"is_preprint":false},{"year":1998,"finding":"Nup153 contains separate binding sites for importin α/β (classical NLS pathway) and transportin (M9 pathway); dominant-negative Nup153 fragments containing each site selectively block the corresponding import pathway without affecting the other.","method":"In vitro nuclear import assays in Xenopus oocyte extracts with dominant-negative Nup153 fragments","journal":"Current biology","confidence":"High","confidence_rationale":"Tier 1–2 — reconstituted import assays with pathway-specific dominant-negative fragments, strong functional dissection","pmids":["9889100"],"is_preprint":false},{"year":1999,"finding":"Nup153 contains an M9 nuclear localization sequence in its N-terminus that binds transportin 1 (TRN1); Nup153 also contains a zinc finger Ran-binding domain that binds RanGDP; Nup153 interacts with both import and export receptors in a RanGTP-regulated fashion (RanGTP dissociates import receptor complexes but is required for export receptor interactions); Nup153 shuttles between nuclear and cytoplasmic faces of the NPC.","method":"Phage display screen for TRN1 interactors; co-immunoprecipitation; RanGTP-regulated binding assays; in vitro transport assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods identifying novel Ran-binding domain and M9 NLS, highly cited","pmids":["10202161"],"is_preprint":false},{"year":1999,"finding":"Nup153 is required for nuclear export of snRNA, mRNA, 5S rRNA, and NES-protein (HIV Rev) export pathways but not for tRNA export or importin β recycling; Nup153 can directly associate with poly(G) and poly(U) RNA in vitro, suggesting an RNA-binding capacity unique among tested nucleoporins.","method":"Anti-Nup153 antibody microinjection into Xenopus oocytes; RNA export assays; homoribopolymer binding assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — antibody perturbation in oocytes combined with in vitro RNA binding; multiple RNA export classes tested","pmids":["10069809"],"is_preprint":false},{"year":2000,"finding":"Nup153 incorporation into the nuclear envelope requires prior lamina assembly; lamin B3 specifically co-immunoprecipitates with Nup153 via the C-terminal domain of Nup153; preventing lamina assembly blocks Nup153 recruitment while other nucleoporins assemble normally.","method":"Co-immunoprecipitation of in vitro translated proteins; Xenopus cell-free nuclear assembly with dominant-negative lamin mutant; immunofluorescence","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 — cell-free reconstitution plus direct binding, multiple orthogonal approaches","pmids":["10921874"],"is_preprint":false},{"year":2000,"finding":"Nup153 localizes to the nuclear ring of the NPC (basket base); NPCs assembled without Nup153 lack nuclear basket components, are unevenly distributed and mobile within the nuclear envelope (not anchored), and show strongly reduced importin α/β-mediated import while transportin-mediated import is unaffected.","method":"Immunogold electron microscopy; Xenopus egg extract nuclear reconstitution with Nup153 immunodepletion; nuclear transport assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 — reconstituted in vitro NPC assembly with depletion; multiple structural and functional readouts","pmids":["11598013"],"is_preprint":false},{"year":2000,"finding":"During telophase in living HeLa cells, Nup153 is recruited to reforming nuclear envelopes very early (along with emerin, LBR, and RanBP2), prior to recovery of nuclear import function, establishing the temporal order of NPC reassembly.","method":"Live fluorescence imaging of GFP-tagged nuclear envelope proteins in HeLa cells; immunofluorescence at precise mitotic time points","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — direct live-cell imaging with precise temporal resolution, single study","pmids":["10671368"],"is_preprint":false},{"year":2001,"finding":"Nup153 contains a novel RNA binding domain mapping to amino acids 250–400 that directly binds RNA; this domain is functionally conserved across Drosophila, Xenopus, and human Nup153, and recombinant Nup153 fragments interact with endogenous RNA targets.","method":"In vitro RNA binding assays with recombinant Nup153 fragments; cross-species domain analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with direct binding assays; cross-species conservation confirmed","pmids":["11567018"],"is_preprint":false},{"year":2002,"finding":"Smad2 directly interacts with nucleoporins CAN/Nup214 and Nup153; these interactions mediate constitutive nucleocytoplasmic shuttling of Smad2 and compete with binding to the cytoplasmic retention factor SARA and nuclear partner FAST-1 via a hydrophobic corridor on Smad2 MH2 domain; TGFβ receptor phosphorylation does not affect Smad2 affinity for Nup153 but alters its interactions with SARA and Smad4.","method":"Direct protein interaction assays; competition binding experiments; nuclear accumulation assays in TGFβ-stimulated cells","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding with competition assays and functional transport readout; highly cited","pmids":["12191473"],"is_preprint":false},{"year":2003,"finding":"Nup153 directly binds Tpr (a nuclear filament protein) and is required for Tpr localization to the NPC periphery; in the absence of Nup153 (via RNAi), Tpr mislocalizes to the nuclear interior; depletion of Nup153 also causes mislocalization of Nup50; the specificity of the Nup153–Tpr interaction is confirmed by Tpr mutations that abolish NPC binding and eliminate direct Nup153 binding.","method":"RNAi depletion; affinity chromatography; yeast two-hybrid interaction studies; immunofluorescence","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (RNAi, affinity chromatography, yeast two-hybrid, mutagenesis) identifying direct interaction and dependency","pmids":["12802065"],"is_preprint":false},{"year":2003,"finding":"Nup153 recruits the COPI coatomer complex to the nuclear membrane at mitosis via its zinc finger domain, thereby directing nuclear envelope breakdown; this involves vesiculation as an important step and COPI recruitment provides feedback to other aspects of nuclear disassembly.","method":"Xenopus egg extract nuclear envelope breakdown assay; immunodepletion; functional rescue experiments","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1–2 — reconstituted Xenopus extract system with immunodepletion and rescue; specific domain mapped","pmids":["12967567"],"is_preprint":false},{"year":2004,"finding":"Nup153 is a dynamic (mobile) nucleoporin that exchanges on and off the NPC in a transcription-dependent manner; its exchange is inhibited when RNA Pol I and Pol II transcription is blocked; distinct domains control NPC localization versus transcription-coupled mobility.","method":"Fluorescence recovery after photobleaching (FRAP) of GFP-Nup153 in live cells; transcription inhibitors; deletion analysis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — direct live-cell FRAP with domain mapping and pharmacological perturbation","pmids":["14718558"],"is_preprint":false},{"year":2004,"finding":"The Nup153 RNA binding domain (amino acids 250–400) associates preferentially with single-stranded RNA with little sequence preference.","method":"In vitro RNA binding assays testing diverse RNA substrates with purified recombinant Nup153 RBD fragment","journal":"RNA","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution, single study","pmids":["14681581"],"is_preprint":false},{"year":2005,"finding":"PU.1 undergoes carrier-independent nuclear import requiring energy and direct interaction with Nup153; RanGTP dramatically increases PU.1 binding to Nup153 (forming a PU.1·RanGTP·Nup153 complex), suggesting RanGTP propels PU.1 toward the nuclear basket; gold-labeled PU.1 accumulates at the nuclear side of the pore in permeabilized cells.","method":"GFP-PU.1 transport assays; direct binding assays with purified Nup153 and Nup62; immunoelectron microscopy","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro binding plus ultrastructural localization, RanGTP stimulation provides mechanistic detail","pmids":["15632149"],"is_preprint":false},{"year":2005,"finding":"Nup153 zinc finger domain binds the COPI complex and is required for nuclear envelope breakdown; both Nup153 and Nup358/RanBP2 zinc finger domains independently recruit COPI to the NPC and play non-redundant roles (cytoplasmic and nuclear faces) in coordinating nuclear envelope disassembly.","method":"Xenopus extract nuclear envelope breakdown assay; dominant-negative zinc finger domain expression; COPI binding assays; antibody inhibition","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 — reconstituted in vitro system with domain-specific dominant negatives and antibody inhibition","pmids":["16314393"],"is_preprint":false},{"year":2007,"finding":"The Nup153 RNA binding domain discriminates between RNA targets via recognition of a loose sequence motif, preferentially binding specific subregions of mRNA over structured RNAs (tRNA, snRNA, dsRNA), indicating sequence-dependent rather than purely general single-stranded RNA recognition.","method":"Systematic in vitro binding assays with synthetic RNA oligonucleotides; mapping binding determinants within cellular mRNA fragments","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro binding with systematic mutagenesis of RNA, single study","pmids":["17242408"],"is_preprint":false},{"year":2007,"finding":"In Drosophila, the FG repeats of Nup153 are necessary for its function in importin α/β-mediated nuclear import, while the non-FG portion of Nup153 maintains pore integrity; Nup153 is selectively required for import but not CRM1-dependent export.","method":"RNAi knockdown of nucleoporins in Drosophila S2 cells; quantitative import and export assays; domain rescue experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — systematic RNAi screen with domain rescue, clear functional dissection","pmids":["17682050"],"is_preprint":false},{"year":2009,"finding":"HIV-1 integrase (IN) directly binds the FxFG-rich C-terminal domain of NUP153 (NUP153C); this interaction mediates nuclear import of IN independently of classical Ran-dependent pathways; excess NUP153C inhibits IN nuclear import and reduces HIV-1 vector infectivity by interfering with viral cDNA nuclear translocation.","method":"Semi-permeabilized cell nuclear import assay; direct binding assay between purified IN and NUP153C; overexpression competition experiment","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding with purified proteins combined with functional nuclear import assay and viral infectivity readout","pmids":["19369352"],"is_preprint":false},{"year":2009,"finding":"Nup153 depletion by RNAi delays the late stages of mitosis and increases unresolved midbodies; more severe depletion causes multilobed nuclei accumulation early in mitosis; the FG-rich domain of Nup153 is specifically required to rescue late mitotic defects, while rescue of multilobed nuclei is FG-domain-independent, revealing two separable mitotic roles.","method":"siRNA knockdown in HeLa cells; live cell imaging; domain rescue with Nup153 deletion constructs","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — RNAi with domain-specific rescue and quantitative phenotypic analysis","pmids":["19158386"],"is_preprint":false},{"year":2010,"finding":"In Drosophila, Nup153 and Megator bind continuously to 25% of the genome in large domains (10 kb–500 kb, called NARs) enriched for active transcription marks (high RNA Pol II, H4K16ac); RNAi knockdown of Nup153 alters expression of ~5,700 genes with pronounced downregulation within NARs; Nup153 depletion abolishes dosage compensation complex function on the male X chromosome, and this regulation occurs independent of nuclear periphery localization.","method":"ChIP-chip (chromatin immunoprecipitation + microarray); RNAi knockdown; expression profiling; 3D imaging","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — genome-wide ChIP combined with RNAi and expression analysis; multiple orthogonal approaches","pmids":["20174442"],"is_preprint":false},{"year":2010,"finding":"Nup153 directly binds Mad1 (spindle assembly checkpoint protein) via its N-terminal domain; overexpression of Nup153 induces multinucleated cells, multipolar spindles, and spindle checkpoint inactivation through Mad1 hypophosphorylation; depletion of Nup153 causes Mad1 loss from nuclear pores during interphase and delayed Mad1 dissociation from kinetochores in metaphase, keeping the checkpoint active.","method":"In vitro binding assay (direct Mad1-Nup153 binding); RNAi knockdown; overexpression in HeLa cells; immunofluorescence","journal":"Nucleus","confidence":"High","confidence_rationale":"Tier 1–2 — direct in vitro binding combined with RNAi and overexpression phenotypes","pmids":["21327106"],"is_preprint":false},{"year":2010,"finding":"Nup153 depletion by RNAi disrupts nuclear lamina organization, mislocalizes Sun1, and causes dramatic cytoskeletal rearrangement that impairs cell migration in human breast carcinoma cells.","method":"RNAi knockdown; immunofluorescence for lamins and Sun1; cell migration assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2–3 — RNAi with defined cellular phenotype but limited molecular mechanism detail","pmids":["20561986"],"is_preprint":false},{"year":2011,"finding":"HIV-1 capsid (CA) protein determines the requirement for NUP153 during infection; CA mutants N74D and P90A are largely insensitive to NUP153 depletion; cyclophilin A depletion or cyclosporine A treatment also relieves NUP153 dependency; NUP153 knockdown causes a reduction in 2-LTR circles and large reduction in integrated proviruses, suggesting NUP153 function is at the nuclear import step of the viral preintegration complex.","method":"siRNA knockdown; HIV-1/MLV chimera viruses; CA missense mutants; quantitative PCR for viral integration intermediates","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 — genetic dissection with capsid mutants and chimeric viruses plus quantitative molecular readouts","pmids":["21593146"],"is_preprint":false},{"year":2011,"finding":"Nup153 interacts with A-type (lamin A/C) and B-type lamins through multiple binding sites: both its N-terminal domain and C-terminal domain associate with the Ig-fold domain of lamins; mutations in the lamin A Ig-fold selectively abolish Nup153 binding.","method":"GST pull-down assays; blot overlay assays with purified proteins; lamin mutant binding analysis","journal":"Nucleus","confidence":"High","confidence_rationale":"Tier 1 — direct binding with purified proteins, multiple domain interactions mapped","pmids":["21983083"],"is_preprint":false},{"year":2011,"finding":"NUP153 knockdown specifically prevents 53BP1 nuclear import in newly forming daughter cells without blocking nuclear import of other DNA damage response factors; the C-terminal part of NUP153 is required for 53BP1 nuclear import; 53BP1 import involves an NUP153–importin-β interplay.","method":"siRNA screen; live-cell imaging; cell and molecular biology approaches including fractionation; domain mapping","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 — functional siRNA screen with live-cell imaging, domain mapping, and specific cargo dependency","pmids":["22075984"],"is_preprint":false},{"year":2011,"finding":"β-catenin Arm repeats R3-8 and R10-12 directly interact in vitro with FG repeats of Nup153 (as well as Nup62 and Nup98), enabling Ran/transport receptor-independent NPC traversal; knockdown of Nup153 (and Nup62/Nup358) impedes β-catenin nuclear import/export rate.","method":"FRAP in living cells; in vitro binding with purified components; proteomics screen (RanBP2/Nup358 identification); siRNA knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro binding with purified proteins combined with FRAP and siRNA functional assays","pmids":["22110128"],"is_preprint":false},{"year":2012,"finding":"Nup153 scaffolds Nup50 at the NPC via a dual interface: (1) the unique N-terminal domain of Nup153 is critical for Nup50 pore localization; (2) a second site in the Nup153 C-terminal FG region is importin α-dependent; disruption of the Nup153–Nup50 interface decreases nuclear import efficiency.","method":"Deletion mutagenesis; co-immunoprecipitation; nuclear import assays; rescue experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — domain mapping with functional import readout and rescue experiments","pmids":["23007389"],"is_preprint":false},{"year":2012,"finding":"Nup153 interacts with SUMO proteases SENP1 and SENP2 at two distinct sites (N-terminal domain and C-terminal FG region); Nup153 itself is a substrate for sumoylation and this modification is kept in check by SENP1/SENP2; SENP1 levels are regulated by Nup153 abundance, while SENP2 is not sensitive to Nup153 levels.","method":"Co-immunoprecipitation; RNAi depletion; dominant-negative SENP expression; sumoylation assays for endogenous Nup153","journal":"Nucleus","confidence":"High","confidence_rationale":"Tier 2 — multiple binding site mapping plus post-translational modification of Nup153 established","pmids":["22688647"],"is_preprint":false},{"year":2013,"finding":"The FG-repeat-enriched C-terminal domain of NUP153 directly binds the N-terminal domain of HIV-1 capsid (CA) protein; this interaction maps to the CA α-helix 3/4 hydrophobic pocket also targeted by CPSF6 and PF74; different FG motifs mediate HIV-1 versus EIAV capsid binding; PF74 and CPSF6 compete with NUP153(C) for the same CA pocket; the NUP153(C)–CA interaction underlies HIV-1 infection of non-dividing cells.","method":"Trim-NUP153(C) restriction assay (intracellular binding readout); direct binding assays with purified proteins; mutagenesis of NUP153(C) and CA; competition assays; cell-cycle dependency experiments","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding with purified proteins, mutagenesis, competition assays, and functional viral infectivity readout; highly cited","pmids":["24130490"],"is_preprint":false},{"year":2015,"finding":"Nup153 depletion in mouse embryonic stem cells causes derepression of developmental genes and induction of differentiation; Nup153 binds around the transcriptional start site of developmental genes and mediates recruitment of Polycomb Repressive Complex 1 (PRC1) to a subset of its target loci; this epigenetic silencing function is not mediated through nuclear import of pluripotency factors.","method":"RNAi knockdown; ChIP-seq; gene expression analysis; PRC1 recruitment assays","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 — genome-wide ChIP-seq with functional RNAi and mechanistic exclusion of alternative (transport) mechanisms","pmids":["26080816"],"is_preprint":false},{"year":2015,"finding":"Nup153 is required for NPC assembly during interphase but not during mitotic exit; it functions in interphasic NPC formation by binding directly to the inner nuclear membrane via an N-terminal amphipathic helix; this membrane binding facilitates recruitment of the Nup107-160 complex to assembly sites; transportin and Ran regulate the Nup153–membrane interaction to direct NPC assembly during interphase.","method":"siRNA knockdown; in vitro membrane binding assay; domain mutagenesis; co-immunoprecipitation; live-cell imaging","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro membrane binding with domain mutagenesis plus cell-based functional assays","pmids":["26051542"],"is_preprint":false},{"year":2016,"finding":"Prelamin A accumulation mislocalizes NUP153, disrupts the Ran gradient (NUP153 is required for nuclear Ran localization), and thereby impairs nuclear import of 53BP1, causing defective DNA damage response in vascular smooth muscle cells.","method":"Immunofluorescence; nuclear fractionation; siRNA and overexpression in cells expressing prelamin A; small molecule rescue (Remodelin)","journal":"Aging cell","confidence":"Medium","confidence_rationale":"Tier 2–3 — mechanistic chain established but single lab, partially based on localization studies","pmids":["27464478"],"is_preprint":false},{"year":2017,"finding":"Nup153 interacts directly with Sox2 in adult neural progenitor cells; genome-wide binding shows Nup153 and Sox2 co-regulate hundreds of genes; Nup153 binding at gene promoters correlates with increased expression while binding at transcriptional end sites correlates with decreased expression; Nup153 depletion disrupts Sox2 genomic localization and promotes differentiation in vitro and a gliogenic fate switch in vivo.","method":"Co-immunoprecipitation; ChIP-seq; ATAC-seq (open chromatin); shRNA knockdown; in vitro and in vivo differentiation assays","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 — direct binding combined with genome-wide analyses and in vivo functional readout","pmids":["28919367"],"is_preprint":false},{"year":2017,"finding":"Nup153 (with Nup50) promotes 53BP1 recruitment to DNA double-strand break foci independently of its role in 53BP1 nuclear import; this recruitment function requires antagonism of BRCA1/BARD1-mediated events and places Nup153 and Nup50 in the molecular pathway regulating NHEJ vs. HR pathway choice.","method":"siRNA knockdown; DSB focus formation assays (etoposide, olaparib); epistasis with BRCA1/BARD1/BRCA2 knockdown","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis with defined pathway placement; single study","pmids":["28751496"],"is_preprint":false},{"year":2017,"finding":"Nup153 localizes SENP1 to nuclear pores; loss of Nup153 displaces SENP1, reduces 53BP1 sumoylation (a prerequisite for efficient 53BP1 accumulation at DSBs), and impairs NHEJ; artificial tethering of SENP1 to NPCs in the absence of Nup153 restores NHEJ and 53BP1 sumoylation.","method":"siRNA knockdown; artificial SENP1 tethering; NHEJ reporter assay; SUMO modification assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — mechanistic rescue experiment linking Nup153 to SENP1 localization, 53BP1 sumoylation, and NHEJ","pmids":["28576968"],"is_preprint":false},{"year":2018,"finding":"Crystal structures of hexameric HIV-1 capsid in complex with NUP153-derived FG-repeat peptides guided mutagenesis; HIV-1 capsid N57 residue is critical for interaction with both NUP153 and CPSF6; N57 mutant HIV-1 infects dividing but not non-dividing cells, undergoes reverse transcription but not nuclear translocation, and shows diminished integration into transcriptionally active genes resembling CPSF6 knockout patterns.","method":"X-ray crystallography; structure-based mutagenesis; infectivity assays in dividing vs. non-dividing cells; integration site analysis","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1 — crystal structure with mutagenesis and functional viral assays","pmids":["29997211"],"is_preprint":false},{"year":2018,"finding":"Seh1 is required for the association of Nup153 (and GATOR2) with mitotic chromosomes but is not needed for Nup107 complex chromosome association, revealing a Seh1-dependent pathway for Nup153 mitotic chromosome targeting.","method":"Chemical genetics (auxin-inducible degron); quantitative chromosome proteomics; immunofluorescence","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — chemical genetics with quantitative proteomics; single study","pmids":["29618633"],"is_preprint":false},{"year":2020,"finding":"Mad1 depletion delays recruitment of Nup153 to anaphase chromatin and prolongs anaphase; the Nup153–Mad1 association requires a nuclear envelope to be present; both Nup153 and Mad1 depletion alter NPC architecture (membrane curvature and inner/outer nuclear membrane spacing); Nup153 depletion also causes interphase NPC assembly defects independent of Mad1.","method":"siRNA depletion; in situ proximity ligation assay; time-lapse microscopy; electron microscopy; 3D-SIM","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal approaches including ultrastructural analysis and live imaging","pmids":["33023979"],"is_preprint":false},{"year":2022,"finding":"Disrupting Nup153 function during telophase impairs ongoing addition of B-type lamins, lamin B receptor, and SUN1 to the expanding nuclear envelope after initial chromatin enclosure, while lamin A and SUN2 recruitment is minimally affected; this reveals two functionally separable phases of nuclear envelope formation in mammalian cells with Nup153 acting in the expansion phase.","method":"siRNA knockdown; dominant-negative Nup153 constructs; live-cell imaging; immunofluorescence during telophase","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — mechanistic temporal dissection of NE assembly with specific protein-level readouts","pmids":["36044344"],"is_preprint":false},{"year":2023,"finding":"NUP153 engages assembled HIV-1 CA lattice through a bipartite motif: a canonical FG motif that binds the CA hexamer, and a newly identified triple-arginine (RRR) motif that targets the CA tri-hexamer interface; both motifs are required for HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies in vitro.","method":"Cryo-EM structure of CA assemblies with NUP153 peptides; mutagenesis; HIV-1 infection assays; in vitro CA assembly stabilization assay","journal":"Proceedings of the National Academy of Sciences","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure with mutagenesis and functional infection assays","pmids":["36943880"],"is_preprint":false},{"year":2023,"finding":"RTEL1 interacts with NUP153 through a distinct C-terminal domain; this interaction contributes to nuclear internalization of peptides; RTEL1 overexpression protects against nuclear envelope anomalies caused by protein import inhibition in an S-phase-specific manner.","method":"Co-immunoprecipitation; domain deletion mapping; nuclear transport assays with peptides; live-cell high-resolution microscopy","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2–3 — direct interaction mapping and functional rescue, single study","pmids":["38132118"],"is_preprint":false},{"year":2024,"finding":"Nup153 is the nucleoporin anchor for the kinesin Kif1a at the nuclear envelope, required for G1-specific basal nuclear migration (interkinetic nuclear migration) in radial glial progenitor cells; this interaction is specific to G1 phase basal migration.","method":"Co-immunoprecipitation; siRNA/shRNA knockdown; live-cell imaging of nuclear migration in brain progenitors","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — direct binding identified with functional cell biological readout in vivo-relevant progenitor system","pmids":["39666457"],"is_preprint":false},{"year":2025,"finding":"SPOP (a Cul3 E3 ligase substrate adaptor) directly binds Nup153 in a multivalent manner and targets it for ubiquitylation and proteasomal degradation; SPOP depletion stabilizes Nup153; loss of SPOP activity increases Mad1 localization at the nuclear envelope (which depends on Nup153 tethering); SPOP-F102C (substrate-binding-deficient mutant) cannot degrade Nup153.","method":"Co-immunoprecipitation; colocalization; ubiquitylation assay; RNAi stabilization; domain mutagenesis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — direct binding with substrate-binding mutant control, ubiquitylation assay, and RNAi stabilization","pmids":["39785820"],"is_preprint":false}],"current_model":"NUP153 is a multifunctional nucleoporin residing at the nuclear basket of the NPC that: (1) mediates nuclear import of diverse cargos (including classical NLS substrates via importin α/β, M9-containing proteins via transportin, PU.1, 53BP1, and β-catenin) by providing direct docking sites for import receptors and cargo; (2) facilitates nuclear export of mRNA, snRNA, rRNA, and NES-proteins via its FG-repeat C-terminal domain; (3) directly engages HIV-1 and other lentiviral capsid FG-binding pockets (via FG motifs and an RRR motif) to enable nuclear import of the viral preintegration complex in non-dividing cells; (4) is required for interphasic NPC assembly through its N-terminal amphipathic helix that anchors it to the inner nuclear membrane and recruits the Nup107-160 complex; (5) scaffolds Tpr, Nup50, SENP1, SENP2, and Mad1 at the nuclear basket, regulating DNA damage repair (via 53BP1 sumoylation and NHEJ) and the spindle checkpoint; (6) undergoes constitutive RanGTP-regulated mobility and transcription-coupled exchange on and off the NPC; (7) interacts with A- and B-type lamins via both its N- and C-terminal domains, linking NPC anchoring to nuclear architecture; (8) binds chromatin and recruits PRC1 to silence developmental genes in stem cells, and interacts with Sox2 to bimodally regulate neural progenitor gene expression; and (9) is targeted for proteasomal degradation by the Cul3-SPOP E3 ligase complex."},"narrative":{"teleology":[{"year":1994,"claim":"Cloning of human NUP153 defined the domain architecture—33 XFXFG repeats, four zinc fingers, and O-GlcNAc modification—establishing the molecular framework for all subsequent functional dissection.","evidence":"cDNA sequencing and domain prediction","pmids":["8110839"],"confidence":"Medium","gaps":["No functional data for individual domains","Zinc finger ligands unknown","Post-translational modification roles untested"]},{"year":1998,"claim":"Systematic domain mapping revealed that the N-terminal domain targets NUP153 to the NPC and nuclear envelope, while the C-terminal FG domain serves as a direct binding platform for importin β and transportin, with separate sites mediating the classical NLS and M9 import pathways.","evidence":"Deletion-reporter fusions in cells; in vitro binding with purified importin β and dominant-negative fragment import assays in Xenopus","pmids":["9745047","9531546","9889100"],"confidence":"High","gaps":["How NUP153 coordinates simultaneous binding of multiple import receptors in vivo","Structural basis of pathway-specific binding sites unresolved"]},{"year":1999,"claim":"Discovery that NUP153 contains a zinc-finger Ran-binding domain and an M9 NLS for transportin, and that RanGTP differentially regulates import vs. export receptor interactions, established NUP153 as a Ran-regulated, bidirectional transport platform; simultaneously, antibody-blocking experiments showed NUP153 is required for export of mRNA, snRNA, rRNA, and NES proteins.","evidence":"Phage display; co-IP; RanGTP-regulated binding assays; antibody microinjection in Xenopus oocytes; RNA export assays","pmids":["10202161","10069809"],"confidence":"High","gaps":["RNA binding domain not yet mapped","Mechanism of NUP153 shuttling between NPC faces unclear"]},{"year":2000,"claim":"Reconstitution experiments demonstrated that NUP153 is essential for nuclear basket assembly and NPC anchoring; NPCs assembled without NUP153 lack basket components, are mobile in the envelope, and are selectively deficient in importin α/β-mediated import; NUP153 incorporation itself requires prior lamin assembly, linking it to the lamina.","evidence":"Immunodepletion from Xenopus egg extracts; immunogold EM; co-IP showing lamin B3 binding; nuclear transport assays","pmids":["11598013","10921874"],"confidence":"High","gaps":["Which lamin interaction domain is critical for NPC anchoring","Whether lamin dependency applies in somatic cells"]},{"year":2001,"claim":"Identification of a conserved RNA-binding domain (aa 250–400) revealed that NUP153 directly engages RNA substrates, with subsequent studies showing loose sequence selectivity favoring single-stranded mRNA over structured RNAs.","evidence":"In vitro RNA binding with recombinant fragments; cross-species comparison; systematic RNA substrate panel","pmids":["11567018","14681581","17242408"],"confidence":"High","gaps":["In vivo RNA targets not identified","Functional consequence of RNA binding on specific transcript export unclear"]},{"year":2003,"claim":"NUP153 was shown to scaffold Tpr and Nup50 at the nuclear basket (their localization depends on NUP153), and to recruit the COPI coatomer complex via its zinc finger domain to direct nuclear envelope breakdown at mitosis.","evidence":"RNAi; affinity chromatography; yeast two-hybrid; Xenopus NE breakdown assay with immunodepletion and rescue","pmids":["12802065","12967567"],"confidence":"High","gaps":["Whether Tpr contributes reciprocally to NUP153 stability","COPI-mediated vesiculation mechanism not fully resolved"]},{"year":2004,"claim":"FRAP studies established that NUP153 is a constitutively mobile nucleoporin whose exchange on/off the NPC depends on active RNA Pol I/II transcription, distinguishing it from stable scaffold nucleoporins and linking it to ongoing gene expression.","evidence":"FRAP of GFP-NUP153 in live HeLa cells with transcription inhibitors; domain deletion analysis","pmids":["14718558"],"confidence":"High","gaps":["Molecular signal coupling transcription to NUP153 mobility unknown","Whether RNA binding domain mediates transcription-coupled exchange"]},{"year":2009,"claim":"The FG-repeat C-terminal domain was identified as a direct binding partner for HIV-1 integrase and capsid, establishing NUP153 as a host factor for HIV-1 nuclear entry; capsid mutant analysis showed that this dependency is CA-determined and linked to the nuclear import step of the preintegration complex.","evidence":"Semi-permeabilized cell import assays; direct binding with purified proteins; CA mutant panel; qPCR for viral intermediates","pmids":["19369352","21593146"],"confidence":"High","gaps":["Structural basis of NUP153–CA interaction not yet resolved","Whether NUP153 guides integration site selection"]},{"year":2010,"claim":"Genome-wide ChIP in Drosophila revealed NUP153 binds large chromatin domains enriched for active transcription marks and regulates thousands of genes including dosage compensation targets, establishing a transport-independent gene-regulatory role; separately, direct binding to Mad1 linked NUP153 to spindle assembly checkpoint regulation.","evidence":"ChIP-chip; RNAi expression profiling in S2 cells; direct in vitro Mad1–NUP153 binding; RNAi and overexpression phenotypes","pmids":["20174442","21327106"],"confidence":"High","gaps":["How NUP153 chromatin binding is distinguished from NPC-tethered vs. intranuclear pools","Whether Mad1 regulation is conserved across species"]},{"year":2011,"claim":"NUP153 was shown to interact with both A- and B-type lamins through N- and C-terminal domains, to mediate cargo-specific nuclear import of 53BP1 via importin β, and to facilitate β-catenin NPC traversal through direct FG-repeat engagement, broadening its known transport substrates.","evidence":"GST pull-downs with purified lamins; siRNA screen for 53BP1 import; FRAP and in vitro binding for β-catenin","pmids":["21983083","22075984","22110128"],"confidence":"High","gaps":["Structural details of lamin Ig-fold–NUP153 interface lacking","Whether 53BP1 import function is separable from 53BP1 DSB recruitment"]},{"year":2012,"claim":"Mapping of NUP153–Nup50 and NUP153–SENP1/SENP2 interactions revealed a dual-interface scaffolding system at the basket that controls import efficiency and SUMO protease localization; NUP153 itself is sumoylated and kept in check by basket-localized SENPs.","evidence":"Domain deletion; co-IP; import assays; sumoylation assays; RNAi","pmids":["23007389","22688647"],"confidence":"High","gaps":["Functional consequence of NUP153 sumoylation on its individual activities unknown","Whether SENP2 has transport-independent roles at the basket"]},{"year":2013,"claim":"Structural and biochemical dissection showed NUP153 FG motifs bind directly into the CA hexamer α-helix 3/4 hydrophobic pocket (shared with CPSF6 and PF74), with different FG motifs discriminating HIV-1 from EIAV capsids, explaining lentiviral specificity.","evidence":"Trim-NUP153(C) restriction assay; direct binding; CA and NUP153 mutagenesis; competition assays","pmids":["24130490"],"confidence":"High","gaps":["No high-resolution structure of full NUP153(C)–CA complex","Whether NUP153 engagement alters CA lattice stability in vivo"]},{"year":2015,"claim":"NUP153 was shown to recruit PRC1 to developmental gene promoters in ESCs for epigenetic silencing, and its N-terminal amphipathic helix was found to bind inner nuclear membrane directly to drive interphasic NPC assembly via Nup107-160 complex recruitment, separating its chromatin and structural functions.","evidence":"ChIP-seq; RNAi with PRC1 recruitment assays in mESCs; in vitro membrane binding; domain mutagenesis; live-cell imaging","pmids":["26080816","26051542"],"confidence":"High","gaps":["How PRC1 recruitment is coordinated with NUP153 mobility","Whether amphipathic helix–membrane interaction is regulated by phosphorylation"]},{"year":2017,"claim":"NUP153 was placed in the DNA damage repair pathway: it localizes SENP1 to NPCs, which controls 53BP1 sumoylation required for NHEJ; additionally, NUP153/Nup50 promote 53BP1 focus formation at DSBs independently of its import role, antagonizing BRCA1/BARD1 to favor NHEJ over HR; NUP153 also cooperates with Sox2 at chromatin to regulate neural progenitor gene expression.","evidence":"SENP1 artificial tethering rescue; NHEJ reporter assays; epistasis analysis with BRCA1/BARD1; co-IP with Sox2; ChIP-seq and ATAC-seq in neural progenitors","pmids":["28576968","28751496","28919367"],"confidence":"High","gaps":["Direct sumoylation sites on 53BP1 regulated by NUP153–SENP1 axis not mapped","Whether NUP153–Sox2 function is NPC-tethered or nucleoplasmic"]},{"year":2018,"claim":"Crystal structures of HIV-1 CA hexamers with NUP153-derived FG peptides identified CA-N57 as critical for NUP153 and CPSF6 binding; N57 mutant virus infects dividing but not non-dividing cells and shows altered integration site patterns, directly linking the NUP153–CA structural interface to nuclear entry and integration targeting.","evidence":"X-ray crystallography; structure-guided mutagenesis; infectivity assays in dividing vs. non-dividing cells; integration site analysis","pmids":["29997211"],"confidence":"High","gaps":["Whether NUP153 guides integration site selection independently of CPSF6","No intact capsid lattice–NUP153 structure"]},{"year":2023,"claim":"Cryo-EM resolved NUP153 engagement with assembled CA lattices via a bipartite motif: an FG motif at the hexamer pocket and an RRR motif at the tri-hexamer interface, both required for HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies, suggesting it maintains capsid integrity during nuclear entry.","evidence":"Cryo-EM of CA assemblies with NUP153 peptides; mutagenesis of FG and RRR motifs; HIV-1 infection assays; in vitro CA stabilization","pmids":["36943880"],"confidence":"High","gaps":["How bipartite binding cooperates with CPSF6 in the intact NPC context","Whether NUP153 stabilization of CA tubes occurs inside the NPC channel"]},{"year":2024,"claim":"NUP153 was identified as the nuclear envelope anchor for kinesin Kif1a, required for G1-phase basal interkinetic nuclear migration in radial glial progenitors, revealing a cell-cycle-specific cytoskeletal coupling function.","evidence":"Co-immunoprecipitation; siRNA/shRNA knockdown; live-cell imaging of nuclear migration in brain progenitors","pmids":["39666457"],"confidence":"High","gaps":["Whether this function extends to other progenitor types","Structural basis of NUP153–Kif1a interaction unknown"]},{"year":2025,"claim":"The Cul3–SPOP E3 ubiquitin ligase was identified as a direct regulator of NUP153 turnover, with SPOP binding NUP153 in a multivalent manner to target it for proteasomal degradation; SPOP loss stabilizes NUP153 and increases Mad1 at the nuclear envelope, linking NUP153 protein levels to checkpoint control.","evidence":"Co-IP; ubiquitylation assays; SPOP substrate-binding mutant control; RNAi stabilization","pmids":["39785820"],"confidence":"High","gaps":["SPOP binding sites on NUP153 not mapped","Whether SPOP-mediated degradation is cell-cycle regulated","Functional consequence for spindle checkpoint fidelity not quantified"]},{"year":null,"claim":"Key open questions include: how NUP153's transport, chromatin-regulatory, and scaffolding functions are coordinated in space and time; the structural basis of full-length NUP153 interactions with its numerous partners; and whether NUP153 sumoylation, SPOP-mediated turnover, and transcription-coupled mobility are mechanistically linked.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No full-length NUP153 structure","Functional interplay between sumoylation and ubiquitylation of NUP153 uncharacterized","In vivo RNA targets of the NUP153 RNA-binding domain not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[10,15,18]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4,29,37]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[8,12,33]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[23,32,45]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[1,2,8,33]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,22,32,35]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[22,39]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,4,8,19,27,28,29]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[1,6,10]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[21,23,40,45]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[36,37]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[22,32]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[20,25,31,38,42]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[22,32,35]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[32,35]}],"complexes":["Nuclear pore complex (nuclear basket)","Nup107-160 complex (recruiter, not subunit)"],"partners":["TPR","NUP50","SENP1","SENP2","MAD1L1","KPNB1","TNPO1","SOX2"],"other_free_text":[]},"mechanistic_narrative":"NUP153 is a dynamic FG-repeat nucleoporin of the nuclear basket that serves as a central scaffold for nucleocytoplasmic transport, NPC assembly, chromatin regulation, and mitotic checkpoint control. Its C-terminal XFXFG-repeat domain provides direct docking sites for importin α/β and transportin to mediate classical NLS and M9-dependent nuclear import, and is required for mRNA, snRNA, and rRNA export; the same FG repeats and an adjacent RRR motif engage HIV-1 capsid lattices at hexamer and tri-hexamer interfaces to enable viral preintegration complex nuclear entry in non-dividing cells [PMID:9531546, PMID:9889100, PMID:10069809, PMID:24130490, PMID:36943880]. The N-terminal domain anchors NUP153 at the inner nuclear membrane via an amphipathic helix required for interphasic NPC assembly and recruitment of the Nup107-160 complex, scaffolds Tpr, Nup50, SENP1/SENP2, and Mad1 at the basket, and interacts with A- and B-type lamins to couple NPC positioning to nuclear architecture [PMID:26051542, PMID:12802065, PMID:22688647, PMID:21327106, PMID:21983083]. Beyond transport, NUP153 binds chromatin at developmental gene promoters to recruit PRC1 for epigenetic silencing in embryonic stem cells, cooperates with Sox2 to regulate neural progenitor gene expression, localizes SENP1 to NPCs to control 53BP1 sumoylation and NHEJ pathway choice, and is itself targeted for proteasomal degradation by the Cul3–SPOP E3 ligase [PMID:26080816, PMID:28919367, PMID:28576968, PMID:39785820]."},"prefetch_data":{"uniprot":{"accession":"P49790","full_name":"Nuclear pore complex protein Nup153","aliases":["153 kDa nucleoporin","Nucleoporin Nup153"],"length_aa":1475,"mass_kda":153.9,"function":"Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC) (Microbial infection) Interacts with HIV-1 capsid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro) (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro)","subcellular_location":"Nucleus; Nucleus membrane; Nucleus, nuclear pore complex","url":"https://www.uniprot.org/uniprotkb/P49790/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP153","classification":"Common Essential","n_dependent_lines":830,"n_total_lines":1208,"dependency_fraction":0.6870860927152318},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000124789","cell_line_id":"CID000175","localizations":[{"compartment":"nuclear_membrane","grade":3}],"interactors":[{"gene":"TNPO1","stoichiometry":10.0},{"gene":"NUP50","stoichiometry":10.0},{"gene":"NOLC1","stoichiometry":4.0},{"gene":"TNPO2","stoichiometry":4.0},{"gene":"KIFC1","stoichiometry":4.0},{"gene":"DDX21","stoichiometry":0.2},{"gene":"HNRNPU","stoichiometry":0.2},{"gene":"KPNA1","stoichiometry":0.2},{"gene":"KPNA2","stoichiometry":0.2},{"gene":"KPNA4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000175","total_profiled":1310},"omim":[{"mim_id":"621057","title":"SPERMATOGENIC FAILURE 97; SPGF97","url":"https://www.omim.org/entry/621057"},{"mim_id":"621033","title":"NUP210-LIKE PROTEIN; NUP210L","url":"https://www.omim.org/entry/621033"},{"mim_id":"618785","title":"CELL DIVISION CYCLE-ASSOCIATED PROTEIN 2; CDCA2","url":"https://www.omim.org/entry/618785"},{"mim_id":"616706","title":"POLY(ADP-RIBOSE) POLYMERASE FAMILY, MEMBER 11; PARP11","url":"https://www.omim.org/entry/616706"},{"mim_id":"616496","title":"NUCLEAR ENVELOPE INTEGRAL MEMBRANE PROTEIN 1; NEMP1","url":"https://www.omim.org/entry/616496"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nuclear membrane","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP153"},"hgnc":{"alias_symbol":["HNUP153"],"prev_symbol":[]},"alphafold":{"accession":"P49790","domains":[{"cath_id":"2.20.28","chopping":"725-750","consensus_level":"medium","plddt":93.8054,"start":725,"end":750}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P49790","model_url":"https://alphafold.ebi.ac.uk/files/AF-P49790-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P49790-F1-predicted_aligned_error_v6.png","plddt_mean":43.59},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP153","jax_strain_url":"https://www.jax.org/strain/search?query=NUP153"},"sequence":{"accession":"P49790","fasta_url":"https://rest.uniprot.org/uniprotkb/P49790.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P49790/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P49790"}},"corpus_meta":[{"pmid":"24130490","id":"PMC_24130490","title":"Nucleoporin NUP153 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repeat sequences facilitate β-catenin nuclear transport in live cells via direct binding to nucleoporins Nup62, Nup153, and RanBP2/Nup358.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22110128","citation_count":65,"is_preprint":false},{"pmid":"12967567","id":"PMC_12967567","title":"The COPI complex functions in nuclear envelope breakdown and is recruited by the nucleoporin Nup153.","date":"2003","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/12967567","citation_count":65,"is_preprint":false},{"pmid":"22075984","id":"PMC_22075984","title":"Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1.","date":"2011","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/22075984","citation_count":61,"is_preprint":false},{"pmid":"23007389","id":"PMC_23007389","title":"The Nup153-Nup50 protein interface and its role in nuclear import.","date":"2012","source":"The 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Lenacapavir","date":"2024-11-25","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.25.625199","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.05.09.593438","title":"Channel width modulates the permeability of DNA origami based nuclear pore mimics","date":"2024-05-12","source":"bioRxiv","url":"https://doi.org/10.1101/2024.05.09.593438","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":35288,"output_tokens":10474,"usd":0.131487},"stage2":{"model":"claude-opus-4-6","input_tokens":14576,"output_tokens":4915,"usd":0.293633},"total_usd":0.42512,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"Human NUP153 (hnup153) encodes a nucleoporin with 33 copies of the XFXFG pentapeptide repeat, O-linked N-acetylglucosamine modifications, and four zinc finger motifs related to those in mdm-2 and Drosophila small optic lobes, defining its primary structure and domain architecture.\",\n      \"method\": \"cDNA sequence analysis\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 structural/sequence characterization; single study, foundational domain mapping\",\n      \"pmids\": [\"8110839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Nup153 localizes to the nucleoplasmic face of the nuclear pore complex (NPC) basket via its N-terminal domain, while its C-terminal XFXFG-repeat domain is required for mRNA export; overexpression of Nup153 causes dramatic nuclear accumulation of poly(A)+ RNA without affecting protein import.\",\n      \"method\": \"Overexpression of deletion constructs in BHK cells, fluorescence microscopy of poly(A)+ RNA distribution\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — domain dissection with specific phenotypic readout, replicated in multiple constructs\",\n      \"pmids\": [\"8794857\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The N-terminal domain of Nup153 contains two distinct targeting regions: one mediates assembly into the NPC and the other targets proteins to the inner face of the nuclear envelope, while the zinc finger and C-terminal domains have no targeting role.\",\n      \"method\": \"Deletion mutagenesis with reporter (pyruvate kinase) fusion constructs expressed in cells\",\n      \"journal\": \"Chromosoma\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — systematic deletion analysis with orthogonal reporter, multiple constructs\",\n      \"pmids\": [\"9745047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Nup153 is a major physiological binding site for importin β at the nuclear face of the NPC; importin β binds directly to multiple sites within the Nup153 FXFG repeat region, and Nup153 can bind a complete import complex containing importin α, importin β, and an NLS substrate, consistent with a role in the terminal step of nuclear import.\",\n      \"method\": \"Immunoprecipitation from Xenopus egg extracts and isolated nuclei; in vitro binding with purified recombinant proteins\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding demonstrated with purified proteins and confirmed in physiological extract context\",\n      \"pmids\": [\"9531546\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Nup153 contains separate binding sites for importin α/β (classical NLS pathway) and transportin (M9 pathway); dominant-negative Nup153 fragments containing each site selectively block the corresponding import pathway without affecting the other.\",\n      \"method\": \"In vitro nuclear import assays in Xenopus oocyte extracts with dominant-negative Nup153 fragments\",\n      \"journal\": \"Current biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstituted import assays with pathway-specific dominant-negative fragments, strong functional dissection\",\n      \"pmids\": [\"9889100\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Nup153 contains an M9 nuclear localization sequence in its N-terminus that binds transportin 1 (TRN1); Nup153 also contains a zinc finger Ran-binding domain that binds RanGDP; Nup153 interacts with both import and export receptors in a RanGTP-regulated fashion (RanGTP dissociates import receptor complexes but is required for export receptor interactions); Nup153 shuttles between nuclear and cytoplasmic faces of the NPC.\",\n      \"method\": \"Phage display screen for TRN1 interactors; co-immunoprecipitation; RanGTP-regulated binding assays; in vitro transport assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods identifying novel Ran-binding domain and M9 NLS, highly cited\",\n      \"pmids\": [\"10202161\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Nup153 is required for nuclear export of snRNA, mRNA, 5S rRNA, and NES-protein (HIV Rev) export pathways but not for tRNA export or importin β recycling; Nup153 can directly associate with poly(G) and poly(U) RNA in vitro, suggesting an RNA-binding capacity unique among tested nucleoporins.\",\n      \"method\": \"Anti-Nup153 antibody microinjection into Xenopus oocytes; RNA export assays; homoribopolymer binding assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — antibody perturbation in oocytes combined with in vitro RNA binding; multiple RNA export classes tested\",\n      \"pmids\": [\"10069809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Nup153 incorporation into the nuclear envelope requires prior lamina assembly; lamin B3 specifically co-immunoprecipitates with Nup153 via the C-terminal domain of Nup153; preventing lamina assembly blocks Nup153 recruitment while other nucleoporins assemble normally.\",\n      \"method\": \"Co-immunoprecipitation of in vitro translated proteins; Xenopus cell-free nuclear assembly with dominant-negative lamin mutant; immunofluorescence\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — cell-free reconstitution plus direct binding, multiple orthogonal approaches\",\n      \"pmids\": [\"10921874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Nup153 localizes to the nuclear ring of the NPC (basket base); NPCs assembled without Nup153 lack nuclear basket components, are unevenly distributed and mobile within the nuclear envelope (not anchored), and show strongly reduced importin α/β-mediated import while transportin-mediated import is unaffected.\",\n      \"method\": \"Immunogold electron microscopy; Xenopus egg extract nuclear reconstitution with Nup153 immunodepletion; nuclear transport assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro NPC assembly with depletion; multiple structural and functional readouts\",\n      \"pmids\": [\"11598013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"During telophase in living HeLa cells, Nup153 is recruited to reforming nuclear envelopes very early (along with emerin, LBR, and RanBP2), prior to recovery of nuclear import function, establishing the temporal order of NPC reassembly.\",\n      \"method\": \"Live fluorescence imaging of GFP-tagged nuclear envelope proteins in HeLa cells; immunofluorescence at precise mitotic time points\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct live-cell imaging with precise temporal resolution, single study\",\n      \"pmids\": [\"10671368\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Nup153 contains a novel RNA binding domain mapping to amino acids 250–400 that directly binds RNA; this domain is functionally conserved across Drosophila, Xenopus, and human Nup153, and recombinant Nup153 fragments interact with endogenous RNA targets.\",\n      \"method\": \"In vitro RNA binding assays with recombinant Nup153 fragments; cross-species domain analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with direct binding assays; cross-species conservation confirmed\",\n      \"pmids\": [\"11567018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Smad2 directly interacts with nucleoporins CAN/Nup214 and Nup153; these interactions mediate constitutive nucleocytoplasmic shuttling of Smad2 and compete with binding to the cytoplasmic retention factor SARA and nuclear partner FAST-1 via a hydrophobic corridor on Smad2 MH2 domain; TGFβ receptor phosphorylation does not affect Smad2 affinity for Nup153 but alters its interactions with SARA and Smad4.\",\n      \"method\": \"Direct protein interaction assays; competition binding experiments; nuclear accumulation assays in TGFβ-stimulated cells\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding with competition assays and functional transport readout; highly cited\",\n      \"pmids\": [\"12191473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Nup153 directly binds Tpr (a nuclear filament protein) and is required for Tpr localization to the NPC periphery; in the absence of Nup153 (via RNAi), Tpr mislocalizes to the nuclear interior; depletion of Nup153 also causes mislocalization of Nup50; the specificity of the Nup153–Tpr interaction is confirmed by Tpr mutations that abolish NPC binding and eliminate direct Nup153 binding.\",\n      \"method\": \"RNAi depletion; affinity chromatography; yeast two-hybrid interaction studies; immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (RNAi, affinity chromatography, yeast two-hybrid, mutagenesis) identifying direct interaction and dependency\",\n      \"pmids\": [\"12802065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Nup153 recruits the COPI coatomer complex to the nuclear membrane at mitosis via its zinc finger domain, thereby directing nuclear envelope breakdown; this involves vesiculation as an important step and COPI recruitment provides feedback to other aspects of nuclear disassembly.\",\n      \"method\": \"Xenopus egg extract nuclear envelope breakdown assay; immunodepletion; functional rescue experiments\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstituted Xenopus extract system with immunodepletion and rescue; specific domain mapped\",\n      \"pmids\": [\"12967567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nup153 is a dynamic (mobile) nucleoporin that exchanges on and off the NPC in a transcription-dependent manner; its exchange is inhibited when RNA Pol I and Pol II transcription is blocked; distinct domains control NPC localization versus transcription-coupled mobility.\",\n      \"method\": \"Fluorescence recovery after photobleaching (FRAP) of GFP-Nup153 in live cells; transcription inhibitors; deletion analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct live-cell FRAP with domain mapping and pharmacological perturbation\",\n      \"pmids\": [\"14718558\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The Nup153 RNA binding domain (amino acids 250–400) associates preferentially with single-stranded RNA with little sequence preference.\",\n      \"method\": \"In vitro RNA binding assays testing diverse RNA substrates with purified recombinant Nup153 RBD fragment\",\n      \"journal\": \"RNA\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution, single study\",\n      \"pmids\": [\"14681581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"PU.1 undergoes carrier-independent nuclear import requiring energy and direct interaction with Nup153; RanGTP dramatically increases PU.1 binding to Nup153 (forming a PU.1·RanGTP·Nup153 complex), suggesting RanGTP propels PU.1 toward the nuclear basket; gold-labeled PU.1 accumulates at the nuclear side of the pore in permeabilized cells.\",\n      \"method\": \"GFP-PU.1 transport assays; direct binding assays with purified Nup153 and Nup62; immunoelectron microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro binding plus ultrastructural localization, RanGTP stimulation provides mechanistic detail\",\n      \"pmids\": [\"15632149\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nup153 zinc finger domain binds the COPI complex and is required for nuclear envelope breakdown; both Nup153 and Nup358/RanBP2 zinc finger domains independently recruit COPI to the NPC and play non-redundant roles (cytoplasmic and nuclear faces) in coordinating nuclear envelope disassembly.\",\n      \"method\": \"Xenopus extract nuclear envelope breakdown assay; dominant-negative zinc finger domain expression; COPI binding assays; antibody inhibition\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstituted in vitro system with domain-specific dominant negatives and antibody inhibition\",\n      \"pmids\": [\"16314393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The Nup153 RNA binding domain discriminates between RNA targets via recognition of a loose sequence motif, preferentially binding specific subregions of mRNA over structured RNAs (tRNA, snRNA, dsRNA), indicating sequence-dependent rather than purely general single-stranded RNA recognition.\",\n      \"method\": \"Systematic in vitro binding assays with synthetic RNA oligonucleotides; mapping binding determinants within cellular mRNA fragments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro binding with systematic mutagenesis of RNA, single study\",\n      \"pmids\": [\"17242408\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In Drosophila, the FG repeats of Nup153 are necessary for its function in importin α/β-mediated nuclear import, while the non-FG portion of Nup153 maintains pore integrity; Nup153 is selectively required for import but not CRM1-dependent export.\",\n      \"method\": \"RNAi knockdown of nucleoporins in Drosophila S2 cells; quantitative import and export assays; domain rescue experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — systematic RNAi screen with domain rescue, clear functional dissection\",\n      \"pmids\": [\"17682050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"HIV-1 integrase (IN) directly binds the FxFG-rich C-terminal domain of NUP153 (NUP153C); this interaction mediates nuclear import of IN independently of classical Ran-dependent pathways; excess NUP153C inhibits IN nuclear import and reduces HIV-1 vector infectivity by interfering with viral cDNA nuclear translocation.\",\n      \"method\": \"Semi-permeabilized cell nuclear import assay; direct binding assay between purified IN and NUP153C; overexpression competition experiment\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding with purified proteins combined with functional nuclear import assay and viral infectivity readout\",\n      \"pmids\": [\"19369352\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nup153 depletion by RNAi delays the late stages of mitosis and increases unresolved midbodies; more severe depletion causes multilobed nuclei accumulation early in mitosis; the FG-rich domain of Nup153 is specifically required to rescue late mitotic defects, while rescue of multilobed nuclei is FG-domain-independent, revealing two separable mitotic roles.\",\n      \"method\": \"siRNA knockdown in HeLa cells; live cell imaging; domain rescue with Nup153 deletion constructs\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — RNAi with domain-specific rescue and quantitative phenotypic analysis\",\n      \"pmids\": [\"19158386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In Drosophila, Nup153 and Megator bind continuously to 25% of the genome in large domains (10 kb–500 kb, called NARs) enriched for active transcription marks (high RNA Pol II, H4K16ac); RNAi knockdown of Nup153 alters expression of ~5,700 genes with pronounced downregulation within NARs; Nup153 depletion abolishes dosage compensation complex function on the male X chromosome, and this regulation occurs independent of nuclear periphery localization.\",\n      \"method\": \"ChIP-chip (chromatin immunoprecipitation + microarray); RNAi knockdown; expression profiling; 3D imaging\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genome-wide ChIP combined with RNAi and expression analysis; multiple orthogonal approaches\",\n      \"pmids\": [\"20174442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup153 directly binds Mad1 (spindle assembly checkpoint protein) via its N-terminal domain; overexpression of Nup153 induces multinucleated cells, multipolar spindles, and spindle checkpoint inactivation through Mad1 hypophosphorylation; depletion of Nup153 causes Mad1 loss from nuclear pores during interphase and delayed Mad1 dissociation from kinetochores in metaphase, keeping the checkpoint active.\",\n      \"method\": \"In vitro binding assay (direct Mad1-Nup153 binding); RNAi knockdown; overexpression in HeLa cells; immunofluorescence\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct in vitro binding combined with RNAi and overexpression phenotypes\",\n      \"pmids\": [\"21327106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup153 depletion by RNAi disrupts nuclear lamina organization, mislocalizes Sun1, and causes dramatic cytoskeletal rearrangement that impairs cell migration in human breast carcinoma cells.\",\n      \"method\": \"RNAi knockdown; immunofluorescence for lamins and Sun1; cell migration assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — RNAi with defined cellular phenotype but limited molecular mechanism detail\",\n      \"pmids\": [\"20561986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HIV-1 capsid (CA) protein determines the requirement for NUP153 during infection; CA mutants N74D and P90A are largely insensitive to NUP153 depletion; cyclophilin A depletion or cyclosporine A treatment also relieves NUP153 dependency; NUP153 knockdown causes a reduction in 2-LTR circles and large reduction in integrated proviruses, suggesting NUP153 function is at the nuclear import step of the viral preintegration complex.\",\n      \"method\": \"siRNA knockdown; HIV-1/MLV chimera viruses; CA missense mutants; quantitative PCR for viral integration intermediates\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic dissection with capsid mutants and chimeric viruses plus quantitative molecular readouts\",\n      \"pmids\": [\"21593146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Nup153 interacts with A-type (lamin A/C) and B-type lamins through multiple binding sites: both its N-terminal domain and C-terminal domain associate with the Ig-fold domain of lamins; mutations in the lamin A Ig-fold selectively abolish Nup153 binding.\",\n      \"method\": \"GST pull-down assays; blot overlay assays with purified proteins; lamin mutant binding analysis\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct binding with purified proteins, multiple domain interactions mapped\",\n      \"pmids\": [\"21983083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NUP153 knockdown specifically prevents 53BP1 nuclear import in newly forming daughter cells without blocking nuclear import of other DNA damage response factors; the C-terminal part of NUP153 is required for 53BP1 nuclear import; 53BP1 import involves an NUP153–importin-β interplay.\",\n      \"method\": \"siRNA screen; live-cell imaging; cell and molecular biology approaches including fractionation; domain mapping\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — functional siRNA screen with live-cell imaging, domain mapping, and specific cargo dependency\",\n      \"pmids\": [\"22075984\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"β-catenin Arm repeats R3-8 and R10-12 directly interact in vitro with FG repeats of Nup153 (as well as Nup62 and Nup98), enabling Ran/transport receptor-independent NPC traversal; knockdown of Nup153 (and Nup62/Nup358) impedes β-catenin nuclear import/export rate.\",\n      \"method\": \"FRAP in living cells; in vitro binding with purified components; proteomics screen (RanBP2/Nup358 identification); siRNA knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro binding with purified proteins combined with FRAP and siRNA functional assays\",\n      \"pmids\": [\"22110128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nup153 scaffolds Nup50 at the NPC via a dual interface: (1) the unique N-terminal domain of Nup153 is critical for Nup50 pore localization; (2) a second site in the Nup153 C-terminal FG region is importin α-dependent; disruption of the Nup153–Nup50 interface decreases nuclear import efficiency.\",\n      \"method\": \"Deletion mutagenesis; co-immunoprecipitation; nuclear import assays; rescue experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — domain mapping with functional import readout and rescue experiments\",\n      \"pmids\": [\"23007389\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nup153 interacts with SUMO proteases SENP1 and SENP2 at two distinct sites (N-terminal domain and C-terminal FG region); Nup153 itself is a substrate for sumoylation and this modification is kept in check by SENP1/SENP2; SENP1 levels are regulated by Nup153 abundance, while SENP2 is not sensitive to Nup153 levels.\",\n      \"method\": \"Co-immunoprecipitation; RNAi depletion; dominant-negative SENP expression; sumoylation assays for endogenous Nup153\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple binding site mapping plus post-translational modification of Nup153 established\",\n      \"pmids\": [\"22688647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The FG-repeat-enriched C-terminal domain of NUP153 directly binds the N-terminal domain of HIV-1 capsid (CA) protein; this interaction maps to the CA α-helix 3/4 hydrophobic pocket also targeted by CPSF6 and PF74; different FG motifs mediate HIV-1 versus EIAV capsid binding; PF74 and CPSF6 compete with NUP153(C) for the same CA pocket; the NUP153(C)–CA interaction underlies HIV-1 infection of non-dividing cells.\",\n      \"method\": \"Trim-NUP153(C) restriction assay (intracellular binding readout); direct binding assays with purified proteins; mutagenesis of NUP153(C) and CA; competition assays; cell-cycle dependency experiments\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding with purified proteins, mutagenesis, competition assays, and functional viral infectivity readout; highly cited\",\n      \"pmids\": [\"24130490\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup153 depletion in mouse embryonic stem cells causes derepression of developmental genes and induction of differentiation; Nup153 binds around the transcriptional start site of developmental genes and mediates recruitment of Polycomb Repressive Complex 1 (PRC1) to a subset of its target loci; this epigenetic silencing function is not mediated through nuclear import of pluripotency factors.\",\n      \"method\": \"RNAi knockdown; ChIP-seq; gene expression analysis; PRC1 recruitment assays\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genome-wide ChIP-seq with functional RNAi and mechanistic exclusion of alternative (transport) mechanisms\",\n      \"pmids\": [\"26080816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup153 is required for NPC assembly during interphase but not during mitotic exit; it functions in interphasic NPC formation by binding directly to the inner nuclear membrane via an N-terminal amphipathic helix; this membrane binding facilitates recruitment of the Nup107-160 complex to assembly sites; transportin and Ran regulate the Nup153–membrane interaction to direct NPC assembly during interphase.\",\n      \"method\": \"siRNA knockdown; in vitro membrane binding assay; domain mutagenesis; co-immunoprecipitation; live-cell imaging\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro membrane binding with domain mutagenesis plus cell-based functional assays\",\n      \"pmids\": [\"26051542\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Prelamin A accumulation mislocalizes NUP153, disrupts the Ran gradient (NUP153 is required for nuclear Ran localization), and thereby impairs nuclear import of 53BP1, causing defective DNA damage response in vascular smooth muscle cells.\",\n      \"method\": \"Immunofluorescence; nuclear fractionation; siRNA and overexpression in cells expressing prelamin A; small molecule rescue (Remodelin)\",\n      \"journal\": \"Aging cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — mechanistic chain established but single lab, partially based on localization studies\",\n      \"pmids\": [\"27464478\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 interacts directly with Sox2 in adult neural progenitor cells; genome-wide binding shows Nup153 and Sox2 co-regulate hundreds of genes; Nup153 binding at gene promoters correlates with increased expression while binding at transcriptional end sites correlates with decreased expression; Nup153 depletion disrupts Sox2 genomic localization and promotes differentiation in vitro and a gliogenic fate switch in vivo.\",\n      \"method\": \"Co-immunoprecipitation; ChIP-seq; ATAC-seq (open chromatin); shRNA knockdown; in vitro and in vivo differentiation assays\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding combined with genome-wide analyses and in vivo functional readout\",\n      \"pmids\": [\"28919367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 (with Nup50) promotes 53BP1 recruitment to DNA double-strand break foci independently of its role in 53BP1 nuclear import; this recruitment function requires antagonism of BRCA1/BARD1-mediated events and places Nup153 and Nup50 in the molecular pathway regulating NHEJ vs. HR pathway choice.\",\n      \"method\": \"siRNA knockdown; DSB focus formation assays (etoposide, olaparib); epistasis with BRCA1/BARD1/BRCA2 knockdown\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with defined pathway placement; single study\",\n      \"pmids\": [\"28751496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 localizes SENP1 to nuclear pores; loss of Nup153 displaces SENP1, reduces 53BP1 sumoylation (a prerequisite for efficient 53BP1 accumulation at DSBs), and impairs NHEJ; artificial tethering of SENP1 to NPCs in the absence of Nup153 restores NHEJ and 53BP1 sumoylation.\",\n      \"method\": \"siRNA knockdown; artificial SENP1 tethering; NHEJ reporter assay; SUMO modification assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mechanistic rescue experiment linking Nup153 to SENP1 localization, 53BP1 sumoylation, and NHEJ\",\n      \"pmids\": [\"28576968\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Crystal structures of hexameric HIV-1 capsid in complex with NUP153-derived FG-repeat peptides guided mutagenesis; HIV-1 capsid N57 residue is critical for interaction with both NUP153 and CPSF6; N57 mutant HIV-1 infects dividing but not non-dividing cells, undergoes reverse transcription but not nuclear translocation, and shows diminished integration into transcriptionally active genes resembling CPSF6 knockout patterns.\",\n      \"method\": \"X-ray crystallography; structure-based mutagenesis; infectivity assays in dividing vs. non-dividing cells; integration site analysis\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with mutagenesis and functional viral assays\",\n      \"pmids\": [\"29997211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Seh1 is required for the association of Nup153 (and GATOR2) with mitotic chromosomes but is not needed for Nup107 complex chromosome association, revealing a Seh1-dependent pathway for Nup153 mitotic chromosome targeting.\",\n      \"method\": \"Chemical genetics (auxin-inducible degron); quantitative chromosome proteomics; immunofluorescence\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — chemical genetics with quantitative proteomics; single study\",\n      \"pmids\": [\"29618633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mad1 depletion delays recruitment of Nup153 to anaphase chromatin and prolongs anaphase; the Nup153–Mad1 association requires a nuclear envelope to be present; both Nup153 and Mad1 depletion alter NPC architecture (membrane curvature and inner/outer nuclear membrane spacing); Nup153 depletion also causes interphase NPC assembly defects independent of Mad1.\",\n      \"method\": \"siRNA depletion; in situ proximity ligation assay; time-lapse microscopy; electron microscopy; 3D-SIM\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal approaches including ultrastructural analysis and live imaging\",\n      \"pmids\": [\"33023979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Disrupting Nup153 function during telophase impairs ongoing addition of B-type lamins, lamin B receptor, and SUN1 to the expanding nuclear envelope after initial chromatin enclosure, while lamin A and SUN2 recruitment is minimally affected; this reveals two functionally separable phases of nuclear envelope formation in mammalian cells with Nup153 acting in the expansion phase.\",\n      \"method\": \"siRNA knockdown; dominant-negative Nup153 constructs; live-cell imaging; immunofluorescence during telophase\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mechanistic temporal dissection of NE assembly with specific protein-level readouts\",\n      \"pmids\": [\"36044344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NUP153 engages assembled HIV-1 CA lattice through a bipartite motif: a canonical FG motif that binds the CA hexamer, and a newly identified triple-arginine (RRR) motif that targets the CA tri-hexamer interface; both motifs are required for HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies in vitro.\",\n      \"method\": \"Cryo-EM structure of CA assemblies with NUP153 peptides; mutagenesis; HIV-1 infection assays; in vitro CA assembly stabilization assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure with mutagenesis and functional infection assays\",\n      \"pmids\": [\"36943880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RTEL1 interacts with NUP153 through a distinct C-terminal domain; this interaction contributes to nuclear internalization of peptides; RTEL1 overexpression protects against nuclear envelope anomalies caused by protein import inhibition in an S-phase-specific manner.\",\n      \"method\": \"Co-immunoprecipitation; domain deletion mapping; nuclear transport assays with peptides; live-cell high-resolution microscopy\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — direct interaction mapping and functional rescue, single study\",\n      \"pmids\": [\"38132118\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Nup153 is the nucleoporin anchor for the kinesin Kif1a at the nuclear envelope, required for G1-specific basal nuclear migration (interkinetic nuclear migration) in radial glial progenitor cells; this interaction is specific to G1 phase basal migration.\",\n      \"method\": \"Co-immunoprecipitation; siRNA/shRNA knockdown; live-cell imaging of nuclear migration in brain progenitors\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding identified with functional cell biological readout in vivo-relevant progenitor system\",\n      \"pmids\": [\"39666457\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SPOP (a Cul3 E3 ligase substrate adaptor) directly binds Nup153 in a multivalent manner and targets it for ubiquitylation and proteasomal degradation; SPOP depletion stabilizes Nup153; loss of SPOP activity increases Mad1 localization at the nuclear envelope (which depends on Nup153 tethering); SPOP-F102C (substrate-binding-deficient mutant) cannot degrade Nup153.\",\n      \"method\": \"Co-immunoprecipitation; colocalization; ubiquitylation assay; RNAi stabilization; domain mutagenesis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding with substrate-binding mutant control, ubiquitylation assay, and RNAi stabilization\",\n      \"pmids\": [\"39785820\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP153 is a multifunctional nucleoporin residing at the nuclear basket of the NPC that: (1) mediates nuclear import of diverse cargos (including classical NLS substrates via importin α/β, M9-containing proteins via transportin, PU.1, 53BP1, and β-catenin) by providing direct docking sites for import receptors and cargo; (2) facilitates nuclear export of mRNA, snRNA, rRNA, and NES-proteins via its FG-repeat C-terminal domain; (3) directly engages HIV-1 and other lentiviral capsid FG-binding pockets (via FG motifs and an RRR motif) to enable nuclear import of the viral preintegration complex in non-dividing cells; (4) is required for interphasic NPC assembly through its N-terminal amphipathic helix that anchors it to the inner nuclear membrane and recruits the Nup107-160 complex; (5) scaffolds Tpr, Nup50, SENP1, SENP2, and Mad1 at the nuclear basket, regulating DNA damage repair (via 53BP1 sumoylation and NHEJ) and the spindle checkpoint; (6) undergoes constitutive RanGTP-regulated mobility and transcription-coupled exchange on and off the NPC; (7) interacts with A- and B-type lamins via both its N- and C-terminal domains, linking NPC anchoring to nuclear architecture; (8) binds chromatin and recruits PRC1 to silence developmental genes in stem cells, and interacts with Sox2 to bimodally regulate neural progenitor gene expression; and (9) is targeted for proteasomal degradation by the Cul3-SPOP E3 ligase complex.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP153 is a dynamic FG-repeat nucleoporin of the nuclear basket that serves as a central scaffold for nucleocytoplasmic transport, NPC assembly, chromatin regulation, and mitotic checkpoint control. Its C-terminal XFXFG-repeat domain provides direct docking sites for importin α/β and transportin to mediate classical NLS and M9-dependent nuclear import, and is required for mRNA, snRNA, and rRNA export; the same FG repeats and an adjacent RRR motif engage HIV-1 capsid lattices at hexamer and tri-hexamer interfaces to enable viral preintegration complex nuclear entry in non-dividing cells [PMID:9531546, PMID:9889100, PMID:10069809, PMID:24130490, PMID:36943880]. The N-terminal domain anchors NUP153 at the inner nuclear membrane via an amphipathic helix required for interphasic NPC assembly and recruitment of the Nup107-160 complex, scaffolds Tpr, Nup50, SENP1/SENP2, and Mad1 at the basket, and interacts with A- and B-type lamins to couple NPC positioning to nuclear architecture [PMID:26051542, PMID:12802065, PMID:22688647, PMID:21327106, PMID:21983083]. Beyond transport, NUP153 binds chromatin at developmental gene promoters to recruit PRC1 for epigenetic silencing in embryonic stem cells, cooperates with Sox2 to regulate neural progenitor gene expression, localizes SENP1 to NPCs to control 53BP1 sumoylation and NHEJ pathway choice, and is itself targeted for proteasomal degradation by the Cul3–SPOP E3 ligase [PMID:26080816, PMID:28919367, PMID:28576968, PMID:39785820].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Cloning of human NUP153 defined the domain architecture—33 XFXFG repeats, four zinc fingers, and O-GlcNAc modification—establishing the molecular framework for all subsequent functional dissection.\",\n      \"evidence\": \"cDNA sequencing and domain prediction\",\n      \"pmids\": [\"8110839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional data for individual domains\", \"Zinc finger ligands unknown\", \"Post-translational modification roles untested\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Systematic domain mapping revealed that the N-terminal domain targets NUP153 to the NPC and nuclear envelope, while the C-terminal FG domain serves as a direct binding platform for importin β and transportin, with separate sites mediating the classical NLS and M9 import pathways.\",\n      \"evidence\": \"Deletion-reporter fusions in cells; in vitro binding with purified importin β and dominant-negative fragment import assays in Xenopus\",\n      \"pmids\": [\"9745047\", \"9531546\", \"9889100\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How NUP153 coordinates simultaneous binding of multiple import receptors in vivo\", \"Structural basis of pathway-specific binding sites unresolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Discovery that NUP153 contains a zinc-finger Ran-binding domain and an M9 NLS for transportin, and that RanGTP differentially regulates import vs. export receptor interactions, established NUP153 as a Ran-regulated, bidirectional transport platform; simultaneously, antibody-blocking experiments showed NUP153 is required for export of mRNA, snRNA, rRNA, and NES proteins.\",\n      \"evidence\": \"Phage display; co-IP; RanGTP-regulated binding assays; antibody microinjection in Xenopus oocytes; RNA export assays\",\n      \"pmids\": [\"10202161\", \"10069809\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"RNA binding domain not yet mapped\", \"Mechanism of NUP153 shuttling between NPC faces unclear\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Reconstitution experiments demonstrated that NUP153 is essential for nuclear basket assembly and NPC anchoring; NPCs assembled without NUP153 lack basket components, are mobile in the envelope, and are selectively deficient in importin α/β-mediated import; NUP153 incorporation itself requires prior lamin assembly, linking it to the lamina.\",\n      \"evidence\": \"Immunodepletion from Xenopus egg extracts; immunogold EM; co-IP showing lamin B3 binding; nuclear transport assays\",\n      \"pmids\": [\"11598013\", \"10921874\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which lamin interaction domain is critical for NPC anchoring\", \"Whether lamin dependency applies in somatic cells\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identification of a conserved RNA-binding domain (aa 250–400) revealed that NUP153 directly engages RNA substrates, with subsequent studies showing loose sequence selectivity favoring single-stranded mRNA over structured RNAs.\",\n      \"evidence\": \"In vitro RNA binding with recombinant fragments; cross-species comparison; systematic RNA substrate panel\",\n      \"pmids\": [\"11567018\", \"14681581\", \"17242408\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo RNA targets not identified\", \"Functional consequence of RNA binding on specific transcript export unclear\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"NUP153 was shown to scaffold Tpr and Nup50 at the nuclear basket (their localization depends on NUP153), and to recruit the COPI coatomer complex via its zinc finger domain to direct nuclear envelope breakdown at mitosis.\",\n      \"evidence\": \"RNAi; affinity chromatography; yeast two-hybrid; Xenopus NE breakdown assay with immunodepletion and rescue\",\n      \"pmids\": [\"12802065\", \"12967567\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Tpr contributes reciprocally to NUP153 stability\", \"COPI-mediated vesiculation mechanism not fully resolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"FRAP studies established that NUP153 is a constitutively mobile nucleoporin whose exchange on/off the NPC depends on active RNA Pol I/II transcription, distinguishing it from stable scaffold nucleoporins and linking it to ongoing gene expression.\",\n      \"evidence\": \"FRAP of GFP-NUP153 in live HeLa cells with transcription inhibitors; domain deletion analysis\",\n      \"pmids\": [\"14718558\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular signal coupling transcription to NUP153 mobility unknown\", \"Whether RNA binding domain mediates transcription-coupled exchange\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The FG-repeat C-terminal domain was identified as a direct binding partner for HIV-1 integrase and capsid, establishing NUP153 as a host factor for HIV-1 nuclear entry; capsid mutant analysis showed that this dependency is CA-determined and linked to the nuclear import step of the preintegration complex.\",\n      \"evidence\": \"Semi-permeabilized cell import assays; direct binding with purified proteins; CA mutant panel; qPCR for viral intermediates\",\n      \"pmids\": [\"19369352\", \"21593146\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of NUP153–CA interaction not yet resolved\", \"Whether NUP153 guides integration site selection\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Genome-wide ChIP in Drosophila revealed NUP153 binds large chromatin domains enriched for active transcription marks and regulates thousands of genes including dosage compensation targets, establishing a transport-independent gene-regulatory role; separately, direct binding to Mad1 linked NUP153 to spindle assembly checkpoint regulation.\",\n      \"evidence\": \"ChIP-chip; RNAi expression profiling in S2 cells; direct in vitro Mad1–NUP153 binding; RNAi and overexpression phenotypes\",\n      \"pmids\": [\"20174442\", \"21327106\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How NUP153 chromatin binding is distinguished from NPC-tethered vs. intranuclear pools\", \"Whether Mad1 regulation is conserved across species\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"NUP153 was shown to interact with both A- and B-type lamins through N- and C-terminal domains, to mediate cargo-specific nuclear import of 53BP1 via importin β, and to facilitate β-catenin NPC traversal through direct FG-repeat engagement, broadening its known transport substrates.\",\n      \"evidence\": \"GST pull-downs with purified lamins; siRNA screen for 53BP1 import; FRAP and in vitro binding for β-catenin\",\n      \"pmids\": [\"21983083\", \"22075984\", \"22110128\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural details of lamin Ig-fold–NUP153 interface lacking\", \"Whether 53BP1 import function is separable from 53BP1 DSB recruitment\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Mapping of NUP153–Nup50 and NUP153–SENP1/SENP2 interactions revealed a dual-interface scaffolding system at the basket that controls import efficiency and SUMO protease localization; NUP153 itself is sumoylated and kept in check by basket-localized SENPs.\",\n      \"evidence\": \"Domain deletion; co-IP; import assays; sumoylation assays; RNAi\",\n      \"pmids\": [\"23007389\", \"22688647\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of NUP153 sumoylation on its individual activities unknown\", \"Whether SENP2 has transport-independent roles at the basket\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Structural and biochemical dissection showed NUP153 FG motifs bind directly into the CA hexamer α-helix 3/4 hydrophobic pocket (shared with CPSF6 and PF74), with different FG motifs discriminating HIV-1 from EIAV capsids, explaining lentiviral specificity.\",\n      \"evidence\": \"Trim-NUP153(C) restriction assay; direct binding; CA and NUP153 mutagenesis; competition assays\",\n      \"pmids\": [\"24130490\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of full NUP153(C)–CA complex\", \"Whether NUP153 engagement alters CA lattice stability in vivo\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"NUP153 was shown to recruit PRC1 to developmental gene promoters in ESCs for epigenetic silencing, and its N-terminal amphipathic helix was found to bind inner nuclear membrane directly to drive interphasic NPC assembly via Nup107-160 complex recruitment, separating its chromatin and structural functions.\",\n      \"evidence\": \"ChIP-seq; RNAi with PRC1 recruitment assays in mESCs; in vitro membrane binding; domain mutagenesis; live-cell imaging\",\n      \"pmids\": [\"26080816\", \"26051542\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How PRC1 recruitment is coordinated with NUP153 mobility\", \"Whether amphipathic helix–membrane interaction is regulated by phosphorylation\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"NUP153 was placed in the DNA damage repair pathway: it localizes SENP1 to NPCs, which controls 53BP1 sumoylation required for NHEJ; additionally, NUP153/Nup50 promote 53BP1 focus formation at DSBs independently of its import role, antagonizing BRCA1/BARD1 to favor NHEJ over HR; NUP153 also cooperates with Sox2 at chromatin to regulate neural progenitor gene expression.\",\n      \"evidence\": \"SENP1 artificial tethering rescue; NHEJ reporter assays; epistasis analysis with BRCA1/BARD1; co-IP with Sox2; ChIP-seq and ATAC-seq in neural progenitors\",\n      \"pmids\": [\"28576968\", \"28751496\", \"28919367\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct sumoylation sites on 53BP1 regulated by NUP153–SENP1 axis not mapped\", \"Whether NUP153–Sox2 function is NPC-tethered or nucleoplasmic\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Crystal structures of HIV-1 CA hexamers with NUP153-derived FG peptides identified CA-N57 as critical for NUP153 and CPSF6 binding; N57 mutant virus infects dividing but not non-dividing cells and shows altered integration site patterns, directly linking the NUP153–CA structural interface to nuclear entry and integration targeting.\",\n      \"evidence\": \"X-ray crystallography; structure-guided mutagenesis; infectivity assays in dividing vs. non-dividing cells; integration site analysis\",\n      \"pmids\": [\"29997211\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NUP153 guides integration site selection independently of CPSF6\", \"No intact capsid lattice–NUP153 structure\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Cryo-EM resolved NUP153 engagement with assembled CA lattices via a bipartite motif: an FG motif at the hexamer pocket and an RRR motif at the tri-hexamer interface, both required for HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies, suggesting it maintains capsid integrity during nuclear entry.\",\n      \"evidence\": \"Cryo-EM of CA assemblies with NUP153 peptides; mutagenesis of FG and RRR motifs; HIV-1 infection assays; in vitro CA stabilization\",\n      \"pmids\": [\"36943880\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How bipartite binding cooperates with CPSF6 in the intact NPC context\", \"Whether NUP153 stabilization of CA tubes occurs inside the NPC channel\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"NUP153 was identified as the nuclear envelope anchor for kinesin Kif1a, required for G1-phase basal interkinetic nuclear migration in radial glial progenitors, revealing a cell-cycle-specific cytoskeletal coupling function.\",\n      \"evidence\": \"Co-immunoprecipitation; siRNA/shRNA knockdown; live-cell imaging of nuclear migration in brain progenitors\",\n      \"pmids\": [\"39666457\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether this function extends to other progenitor types\", \"Structural basis of NUP153–Kif1a interaction unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The Cul3–SPOP E3 ubiquitin ligase was identified as a direct regulator of NUP153 turnover, with SPOP binding NUP153 in a multivalent manner to target it for proteasomal degradation; SPOP loss stabilizes NUP153 and increases Mad1 at the nuclear envelope, linking NUP153 protein levels to checkpoint control.\",\n      \"evidence\": \"Co-IP; ubiquitylation assays; SPOP substrate-binding mutant control; RNAi stabilization\",\n      \"pmids\": [\"39785820\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"SPOP binding sites on NUP153 not mapped\", \"Whether SPOP-mediated degradation is cell-cycle regulated\", \"Functional consequence for spindle checkpoint fidelity not quantified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include: how NUP153's transport, chromatin-regulatory, and scaffolding functions are coordinated in space and time; the structural basis of full-length NUP153 interactions with its numerous partners; and whether NUP153 sumoylation, SPOP-mediated turnover, and transcription-coupled mobility are mechanistically linked.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No full-length NUP153 structure\", \"Functional interplay between sumoylation and ubiquitylation of NUP153 uncharacterized\", \"In vivo RNA targets of the NUP153 RNA-binding domain not identified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [10, 15, 18]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4, 29, 37]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [8, 12, 33]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [23, 32, 45]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [1, 2, 8, 33]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 22, 32, 35]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [22, 39]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 4, 8, 19, 27, 28, 29]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 6, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [21, 23, 40, 45]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [36, 37]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [22, 32]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [20, 25, 31, 38, 42]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [22, 32, 35]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [32, 35]}\n    ],\n    \"complexes\": [\n      \"Nuclear pore complex (nuclear basket)\",\n      \"Nup107-160 complex (recruiter, not subunit)\"\n    ],\n    \"partners\": [\n      \"TPR\",\n      \"NUP50\",\n      \"SENP1\",\n      \"SENP2\",\n      \"MAD1L1\",\n      \"KPNB1\",\n      \"TNPO1\",\n      \"SOX2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}