{"gene":"NUP153","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1994,"finding":"Human NUP153 (hnup153) encodes a nucleoporin with 33 copies of the XFXFG repeat and four zinc finger motifs; the protein bears O-linked N-acetylglucosamine moieties characteristic of nucleoporins.","method":"cDNA sequencing and sequence analysis","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — primary sequence characterization, single study, no functional mutagenesis but establishes domain architecture","pmids":["8110839"],"is_preprint":false},{"year":1996,"finding":"Nup153 localizes to the nucleoplasmic face (basket) of the nuclear pore complex; its N-terminal domain is sufficient for NPC targeting (can redirect cytoplasmic pyruvate kinase to the nuclear face); overexpression of Nup153 causes accumulation of nuclear poly(A)+ RNA, indicating inhibition of mRNA export, dependent on the C-terminal FG-repeat domain.","method":"Overexpression of GFP/domain constructs in BHK cells, in situ hybridization for poly(A)+ RNA, subcellular targeting assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct targeting assays with domain deletions, replicated functional phenotype across multiple constructs","pmids":["8794857"],"is_preprint":false},{"year":1998,"finding":"Nup153 N-terminal domain contains two distinct targeting regions: one for NPC assembly and one for targeting to the inner face of the nuclear envelope; the zinc finger and C-terminal domains have no role in targeting.","method":"Deletion analysis with reporter fusion constructs expressed in mammalian cells","journal":"Chromosoma","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic deletion mapping, single lab, direct targeting assays","pmids":["9745047"],"is_preprint":false},{"year":1998,"finding":"Nup153 and Tpr are the major physiological binding sites for importin β at the nuclear face of the NPC; importin β binds directly to multiple sites in the Nup153 FXFG repeat region; Nup153 can accommodate a complete import complex (importin α, β, and NLS substrate); GMP-PNP disassembles Nup153–importin β complexes.","method":"Immunoprecipitation from Xenopus egg extracts and isolated nuclei, direct binding assays with recombinant proteins, competition experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — reciprocal IP, direct binding with purified components, physiological context (egg extracts + assembled pores), multiple orthogonal methods","pmids":["9531546"],"is_preprint":false},{"year":1998,"finding":"Nup153 contains separate binding sites for importin α/β (classical NLS import pathway) and transportin (M9 import pathway); dominant-negative Nup153 fragments selectively block one pathway without affecting the other.","method":"Dominant-negative fragment inhibition assays in Xenopus import assays, binding studies","journal":"Current biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — dominant-negative dissection with pathway specificity, replicated with orthogonal receptor systems","pmids":["9889100"],"is_preprint":false},{"year":1999,"finding":"Nup153 N-terminus contains an M9 NLS that binds transportin 1 (TRN1); Nup153 interacts with both import and export receptors in a RanGTP-regulated manner (RanGTP dissociates import receptor complexes, but is required for export receptor interactions); Nup153 binds RanGDP via its zinc finger domain (zinc finger Ran-binding motif); Nup153 shuttles between nuclear and cytoplasmic faces of the NPC.","method":"Phage display, co-immunoprecipitation, GST pulldown, mobility assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — phage display identification plus direct binding assays, Ran-regulation demonstrated with multiple orthogonal methods","pmids":["10202161"],"is_preprint":false},{"year":1999,"finding":"Nup153 is required for nuclear export of snRNA, mRNA, 5S rRNA, and NES-mediated protein export (HIV Rev pathway), but not for tRNA export or importin β recycling; Nup153 uniquely among tested nucleoporins associates with poly(G) and poly(U) RNA in vitro.","method":"Anti-Nup153 antibody injection into Xenopus oocytes, export assays for multiple RNA/protein classes, RNA-binding assays with homoribopolymers","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — antibody injection with multiple export substrates tested, RNA binding assays with controls, Xenopus oocyte system","pmids":["10069809"],"is_preprint":false},{"year":2000,"finding":"Nup153 is incorporated into the nuclear envelope at the same time as lamina assembly during nuclear reconstitution; lamin B3 co-immunoprecipitates with Nup153 and interacts specifically with its C-terminal domain; blocking lamina assembly prevents Nup153 NE recruitment; disrupting pre-assembled lamina displaces Nup153 but not other nucleoporins.","method":"Cell-free Xenopus egg extract nuclear assembly assays, co-immunoprecipitation, dominant-negative lamin mutant (XlaminBΔ2+)","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reconstitution system with functional perturbation, domain mapping of lamin B3–Nup153 interaction, multiple orthogonal approaches","pmids":["10921874"],"is_preprint":false},{"year":2000,"finding":"Nup153, along with RanBP2, emerin, and LBR, is recruited to reforming nuclear envelopes early in telophase (5 min after anaphase onset) prior to recovery of nuclear import function (8 min), establishing its role in early NPC reassembly.","method":"Live fluorescence imaging of GFP-tagged proteins and immunofluorescence at timed intervals in HeLa cells","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct live imaging with precise timing, single lab, localization without full functional dissection","pmids":["10671368"],"is_preprint":false},{"year":2001,"finding":"Nup153 depletion during nuclear reconstitution causes loss of several nuclear basket components, uneven NPC distribution in the NE, and NPC mobility within the NE; importin α/β-mediated import is strongly reduced (due to defective import complex translocation, not receptor recycling), while transportin-mediated import is unaffected.","method":"Nup153 immunodepletion from Xenopus egg extracts, nuclear reconstitution, immunogold electron microscopy, nuclear import assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — reconstitution with immunodepletion, EM ultrastructure, pathway-specific import assays, multiple orthogonal methods","pmids":["11598013"],"is_preprint":false},{"year":2001,"finding":"A conserved RNA binding domain mapping to amino acids 250–400 within the Nup153 N-terminal region directly binds RNA and associates with endogenous RNA targets; this domain is functionally conserved across Drosophila, Xenopus, and human Nup153.","method":"Domain deletion/mapping with recombinant fragments, RNA-binding assays in vitro, cross-species comparison","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA binding with recombinant protein, cross-species functional conservation, single lab","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; Nup153 competes with the cytoplasmic retention factor SARA and nuclear partner FAST-1 for binding to the hydrophobic corridor on the MH2 surface of Smad2; TGFβ receptor phosphorylation does not alter Smad2 affinity for Nup153.","method":"Co-immunoprecipitation, GST pulldown with purified proteins, nuclear import/export assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding with purified components, competition assays, functional shuttling assays, multiple orthogonal methods","pmids":["12191473"],"is_preprint":false},{"year":2003,"finding":"Nup153 directly binds to Tpr; cellular depletion of Nup153 by RNAi mislocalizes Tpr to the nuclear interior; the Nup153-Tpr interaction is sensitive to specific Tpr amino acid substitution mutations; Nup153 depletion also mislocalizes Nup50 but not other nucleoporins.","method":"RNAi depletion, affinity chromatography, yeast two-hybrid, sequential NPC assembly analysis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — RNAi, yeast two-hybrid, affinity chromatography, mutagenesis confirming specificity, multiple orthogonal methods","pmids":["12802065"],"is_preprint":false},{"year":2003,"finding":"Nup153 recruits the COPI coatomer complex to the nuclear membrane during mitosis, directing nuclear envelope breakdown; COPI plays a role in NE breakdown via vesiculation.","method":"Xenopus in vitro nuclear envelope breakdown assay, co-immunoprecipitation, dominant-negative experiments","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vitro reconstitution, direct interaction, functional perturbation with defined phenotype","pmids":["12967567"],"is_preprint":false},{"year":2004,"finding":"The Nup153 RNA binding domain (aa 250-400) preferentially associates with single-stranded RNA with little sequence preference, as demonstrated by testing a range of RNA substrates with different structural features.","method":"In vitro RNA binding assays with recombinant Nup153 domain and diverse RNA substrates","journal":"RNA","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assay, single lab, single method","pmids":["14681581"],"is_preprint":false},{"year":2004,"finding":"Nup153 and Nup98 exchange dynamically on and off the NPC in a transcription-dependent manner; inhibition of Pol I and Pol II transcription blocks Nup153 exchange; distinct domains within Nup153 link its mobility to different RNA polymerases.","method":"FRAP (fluorescence recovery after photobleaching) with GFP-Nup153, transcription inhibition, domain mapping","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FRAP live imaging, transcription inhibitors, domain analysis, single lab","pmids":["14718558"],"is_preprint":false},{"year":2005,"finding":"The Nup153 FXFG repeat region mediates nuclear entry of BR granule mRNPs into the nuclear basket; entry into the basket is a two-step process: mRNP first binds to basket fibril tips, then is transferred into the basket in a Nup153-dependent step.","method":"Anti-Nup153 antibody injection into Chironomus tentans salivary glands, electron microscopy tracking of Balbiani ring granules","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — antibody inhibition with EM visualization of transport intermediates, single organism model","pmids":["16195343"],"is_preprint":false},{"year":2005,"finding":"PU.1 nuclear import requires energy but not soluble carriers; PU.1 interacts directly with Nup153 and Nup62; binding of PU.1 to Nup153 (but not Nup62) increases dramatically in the presence of RanGTP, forming a PU.1-RanGTP-Nup153 complex; RanGTP propels PU.1 toward the nuclear side of the NPC by increasing its affinity for Nup153.","method":"GST pulldown, nuclear import assays in permeabilized cells, ultrastructural immunogold localization, RanGMPPNP competition","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding assays, ultrastructural confirmation, RanGTP mechanistic dissection, multiple orthogonal methods","pmids":["15632149"],"is_preprint":false},{"year":2005,"finding":"Nup358 zinc finger domain binds COPI and inhibits nuclear envelope breakdown; both Nup153 and Nup358 play non-redundant roles in COPI recruitment to the nuclear rim during NE breakdown; a single zinc finger is the minimal interface for COPI association, though tandem zinc fingers are optimal.","method":"Xenopus in vitro NE breakdown assay, dominant-negative zinc finger domain expression, antibody inhibition, COPI recruitment assays","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro reconstitution, domain mapping, antibody inhibition, single lab","pmids":["16314393"],"is_preprint":false},{"year":2007,"finding":"Nup153 RNA binding domain discriminates between RNA targets based on a loose sequence motif rather than general single-stranded RNA preference; specific subregions of a cellular mRNA account for its association with Nup153.","method":"Systematic RNA mutagenesis, in vitro binding assays with synthetic RNA oligonucleotides and recombinant Nup153 RNA-binding domain","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical assays with systematic mutagenesis, single lab","pmids":["17242408"],"is_preprint":false},{"year":2007,"finding":"In Drosophila, Nup153 FG repeats are specifically required for importin α/β-mediated nuclear import; the remainder of the protein maintains pore integrity; Nup153 depletion selectively impairs import but not CRM1-dependent export.","method":"RNAi knockdown in Drosophila S2 cells, import/export functional assays, domain rescue experiments","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic RNAi screen with functional assays, domain-level dissection, Drosophila model","pmids":["17682050"],"is_preprint":false},{"year":2009,"finding":"HIV-1 integrase (IN) binds directly to the FxFG-rich C-terminal domain of NUP153 (NUP153C); NUP153C added in excess inhibits nuclear import of IN; known NUP153C binding partners compete with IN for NUP153 binding and inhibit IN nuclear import; overexpression of NUP153C in cells reduces HIV vector infectivity by blocking nuclear translocation of viral cDNA.","method":"Semipermeabilized cell nuclear import assay, direct binding (GST pulldown/co-immunoprecipitation), competition assays, infectivity assays","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding with purified proteins, functional nuclear import assay, competition experiments, cellular infectivity readout","pmids":["19369352"],"is_preprint":false},{"year":2009,"finding":"Nup153 depletion reduces HIV-1 2-LTR circles moderately and integrated proviruses substantially, suggesting NUP153 acts at the nuclear import step of HIV-1 PIC; capsid mutations N74D and P90A render HIV-1 insensitive to NUP153 depletion; simultaneous depletion of NUP153 and TNPO3 yields synergistic inhibitory effects.","method":"siRNA knockdown, quantitative PCR for viral replication intermediates (late RT products, 2-LTR circles, integrated proviruses), chimeric MLV/HIV-1 viruses","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic knockdown with multiple viral intermediates quantified, chimeric virus epistasis, capsid mutagenesis","pmids":["21593146"],"is_preprint":false},{"year":2009,"finding":"Nup153 depletion causes a delay in late mitosis with increased unresolved midbodies; more severe depletion causes a pronounced early mitotic defect and accumulation of cells with multilobed nuclei; the FG-rich region of Nup153 is required to rescue defects in late mitosis but not the multilobed nuclei phenotype, indicating two separable Nup153 functions in mitosis.","method":"siRNA knockdown in HeLa cells, live cell imaging, rescue with FG-domain mutants","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA with threshold depletion, FG-domain rescue experiments, live imaging, single lab","pmids":["19158386"],"is_preprint":false},{"year":2010,"finding":"Nup153 and Megator (Mtor) bind to ~25% of the Drosophila genome in continuous domains (NARs); these domains are 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; chromatin binding is independent of sub-nuclear localization.","method":"ChIP-chip (chromatin immunoprecipitation with microarray), RNAi knockdown, 3D imaging","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide ChIP with functional RNAi knockdown and 3D localization, multiple orthogonal methods","pmids":["20174442"],"is_preprint":false},{"year":2010,"finding":"Nup153 interacts directly with Mad1 (spindle assembly checkpoint protein) via Nup153's N-terminal domain; Nup153 overexpression causes multinucleated cells, multipolar spindles, and spindle checkpoint inactivation via Mad1 hypophosphorylation; Nup153 depletion reduces Mad1 at nuclear pores and delays Mad1 dissociation from kinetochores, keeping the spindle checkpoint active.","method":"In vitro binding assays, overexpression/RNAi in HeLa cells, immunofluorescence, phosphorylation analysis","journal":"Nucleus","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding, loss- and gain-of-function phenotypes, single lab","pmids":["21327106"],"is_preprint":false},{"year":2010,"finding":"Nup153 depletion by RNAi alters nuclear lamina organization and Sun1 localization, and causes cytoskeletal rearrangement that impairs cell migration in human breast carcinoma cells.","method":"RNAi knockdown, immunofluorescence, cell migration assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with defined phenotypic readouts (lamina, cytoskeleton, migration), single lab","pmids":["20561986"],"is_preprint":false},{"year":2011,"finding":"NUP153 is specifically required for nuclear import of 53BP1; NUP153 knockdown prevents 53BP1 from entering nuclei in newly forming daughter cells, leading to decreased IR-induced 53BP1 foci, delayed DNA repair, and impaired survival after IR; the C-terminal part of NUP153 is required for 53BP1 import through an NUP153–importin-β interplay.","method":"siRNA screen, live-cell imaging, co-immunoprecipitation, domain mapping, IR-induced foci assays","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA screen validated functionally, live imaging, domain mapping, multiple pathway readouts, importin-β mechanistic link","pmids":["22075984"],"is_preprint":false},{"year":2011,"finding":"Nup153 exhibits multiple binding sites for both A-type and B-type lamins; both the N-terminal domain and C-terminal domain of Nup153 directly interact with the Ig-fold domain of lamin A and B; specific mutations in the lamin A Ig-fold domain selectively affect Nup153 binding.","method":"GST pulldown assays, blot overlay assays with purified proteins, lamin Ig-fold mutant analysis","journal":"Nucleus","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding with purified proteins, domain mapping, mutagenesis, single lab","pmids":["21983083"],"is_preprint":false},{"year":2011,"finding":"β-catenin directly interacts with the FG repeats of Nup153 (as well as Nup62 and Nup98) via specific Arm repeat sequences (R3-8 for import, R10-12 for export/import); knockdown of Nup153 and Nup62 impedes β-catenin nuclear import/export; Tyr-654 phosphorylation stimulates Arm R10-12 transport activity.","method":"FRAP assays in live cells, in vitro binding assays with purified components, siRNA knockdown, proteomics","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding, FRAP, siRNA, phosphorylation effect, single lab","pmids":["22110128"],"is_preprint":false},{"year":2012,"finding":"The Nup153–Nup50 interface involves a dual site: (1) Nup50 N-terminal domain binds a unique N-terminal region of Nup153 critical for Nup50 NPC localization; (2) a second site at the distal Nup153 tail depends on importin α; disruption of the Nup153–Nup50 interface decreases nuclear import efficiency.","method":"Domain deletion mapping, co-immunoprecipitation, NPC localization assays, import efficiency assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding, domain mapping, functional import assay, single lab","pmids":["23007389"],"is_preprint":false},{"year":2012,"finding":"Nup153 binds both SUMO proteases SENP1 and SENP2 via two distinct sites (N-terminal domain and C-terminal FG-rich region); Nup153 is itself a substrate for sumoylation, kept in check by SENP1 and SENP2; depletion of SENP1/SENP2 or dominant-negative mutants increase Nup153 sumoylation; SENP1 levels are influenced by Nup153 abundance, but SENP2 is not.","method":"Co-immunoprecipitation, domain mapping, RNAi, sumoylation assays, dominant-negative SENP constructs","journal":"Nucleus","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding, PTM identification, domain mapping, bidirectional regulation shown, single lab","pmids":["22688647"],"is_preprint":false},{"year":2013,"finding":"The HIV-1 capsid (CA) N-terminal domain directly interacts with the FG-repeat-enriched Nup153 C-terminal domain (NUP153C); different FG motifs mediate binding to HIV-1 versus EIAV capsids; HIV-1 CA binding maps to residues lining the α-helix 3/4 hydrophobic pocket (Asn57 critical); this pocket is shared with PF74 inhibitor and CPSF6; PF74 and CPSF6 compete with NUP153C for binding to the HIV-1 CA pocket; NUP153C-CA interaction underlies HIV-1 infection of non-dividing cells.","method":"Trim-NUP153C restriction assay, in vitro binding with purified proteins, mutagenesis, competition assays with PF74/CPSF6, infection assays in dividing/non-dividing cells","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — direct binding with purified proteins, systematic mutagenesis, competition assays, cellular functional readout, multiple orthogonal methods","pmids":["24130490"],"is_preprint":false},{"year":2015,"finding":"Nup153 depletion in mouse embryonic stem cells causes derepression of developmental genes and early differentiation without defects in nuclear import of pluripotency factors; Nup153 binds around transcriptional start sites of developmental genes and mediates recruitment of polycomb-repressive complex 1 (PRC1) to a subset of its target loci.","method":"RNAi depletion, ChIP-seq, RNA-seq, nuclear import assays for pluripotency factors","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide ChIP-seq, transcriptomics, functional rescue, PRC1 recruitment assays, multiple orthogonal methods","pmids":["26080816"],"is_preprint":false},{"year":2015,"finding":"Nup153 is required for interphase NPC assembly but not for post-mitotic NPC reassembly; Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix during interphase, facilitating recruitment of the Nup107-160 complex to NPC assembly sites; transportin and Ran regulate Nup153–membrane interaction.","method":"RNAi depletion, in vitro membrane binding assays, domain mapping, fluorescence microscopy, Ran/transportin perturbation","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct membrane binding, domain mapping, epistasis with Ran/transportin, functional NPC assembly assay, multiple orthogonal methods","pmids":["26051542"],"is_preprint":false},{"year":2016,"finding":"Prelamin A accumulation causes mislocalization of NUP153, disrupts the Ran gradient, and thereby impairs nuclear import of 53BP1, resulting in DNA damage response defects in vascular smooth muscle cells; NUP153 is important for nuclear localization of Ran.","method":"siRNA knockdown, immunofluorescence, nuclear fractionation, 53BP1 import assays in cells expressing prelamin A","journal":"Aging cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mechanistic link from prelamin A to NUP153 mislocalization to Ran gradient disruption to 53BP1 import defect, single lab","pmids":["27464478"],"is_preprint":false},{"year":2017,"finding":"Nup153 interacts with Sox2 in adult neural progenitor cells; depletion of Nup153 disrupts Sox2 genomic localization and open chromatin configurations at Nup153 target genes; Nup153 binding to gene promoters correlates with increased expression, while binding to transcriptional end sites correlates with decreased expression; Nup153 depletion promotes gliogenic fate switch in vivo.","method":"Co-immunoprecipitation, ChIP-seq, ATAC-seq, shRNA knockdown, in vivo neural progenitor differentiation assays","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct interaction, genome-wide chromatin profiling, loss-of-function with in vivo fate readout, multiple orthogonal methods","pmids":["28919367"],"is_preprint":false},{"year":2017,"finding":"Nup153 and Nup50 promote 53BP1 recruitment to DNA damage foci by antagonizing BRCA1-dependent events; the requirement for Nup153 in 53BP1 foci formation is abrogated in BRCA1/BARD1-deficient cells but not BRCA2-deficient cells, placing Nup153 in a pathway that counteracts BRCA1 activity.","method":"siRNA knockdown, 53BP1 foci assays with etoposide/olaparib, genetic epistasis with BRCA1/BARD1/BRCA2 depletion","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with multiple DSB repair factors, pathway placement, single lab","pmids":["28751496"],"is_preprint":false},{"year":2017,"finding":"Nup153 depletion results in reduced SUMO1 modification of 53BP1 and displacement of SENP1 from NPCs; artificial NPC tethering of SENP1 restores NHEJ and 53BP1 sumoylation in Nup153-depleted cells; Nup153 is specifically required for NHEJ (not HR through SENP1), while Tpr contributes to both NHEJ and HR, and Nup50 only to NHEJ.","method":"siRNA knockdown, SUMO modification assays, NHEJ/HR reporter assays, forced NPC targeting of SENP1","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic rescue experiment (artificial SENP1 tethering), multiple repair pathway assays, single lab","pmids":["28576968"],"is_preprint":false},{"year":2018,"finding":"Crystal structures of hexameric HIV-1 capsid in complex with NUP153-derived FG peptides reveal that capsid N57 residue is critical for NUP153 interaction; HIV-1 viruses with N57 substitutions infect dividing but not non-dividing cells, blocking nuclear translocation while allowing reverse transcription; N57 mutant capsids lose interaction with both Nup153 and CPSF6; small molecules PF74 and BI-2 prevent FG-nucleoporin interactions with HIV-1 core.","method":"X-ray crystallography, capsid mutagenesis, infection assays in dividing/non-dividing cells, viral replication intermediate quantification, integration site analysis","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional mutagenesis validation, mechanistic dissection of nuclear import vs. integration, multiple orthogonal methods","pmids":["29997211"],"is_preprint":false},{"year":2018,"finding":"Seh1 (SEH1L) is required for association of both the GATOR2 complex and Nup153 with mitotic chromosomes, but not for the Nup107 complex association with mitotic chromosomes.","method":"Chemical genetics (auxin-inducible degron), quantitative chromosome proteomics","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chemical genetics with quantitative proteomics, functional specificity demonstrated, single lab","pmids":["29618633"],"is_preprint":false},{"year":2020,"finding":"Vpx of SIVsmPBj1.9 physically interacts with NUP153; MAPK/ERK2-mediated phosphorylation of Vpx is required for its interaction with NUP153; MAPK/ERK2-packaging defective SIV fails to efficiently import its viral genome into nuclei; Vpx-NUP153 interaction is evolutionarily conserved in SIV isolates and HIV-2.","method":"Co-immunoprecipitation, superresolution structured illumination microscopy, viral infection assays with MAPK/ERK2-deficient virions","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct interaction, phosphorylation-dependent binding, functional nuclear import readout, single lab","pmids":["31913756"],"is_preprint":false},{"year":2020,"finding":"Mad1 depletion delays recruitment of Nup153 to anaphase chromatin; the Nup153-Mad1 interaction requires a nuclear envelope to be present; both Nup153 and Mad1 depletion alter NE architecture (membrane curvature at NPCs, expanded inner-outer membrane spacing); Nup153 depletion causes interphase NPC assembly defects with cytoplasmic nucleoporin displacement, but Mad1 depletion does not.","method":"RNAi depletion, time-lapse microscopy, electron microscopy, 3D-SIM, proximity ligation assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple imaging modalities, functional dissection of separable roles, single lab","pmids":["33023979"],"is_preprint":false},{"year":2022,"finding":"Nup153 disruption during telophase interferes with ongoing addition of B-type lamins, lamin B receptor, and SUN1 to the expanding NE, but minimally affects lamin A and SUN2 targeting, revealing two functionally separable phases of NE formation and a role for Nup153 in recruiting a specific subset of NE proteins.","method":"Nup153 functional disruption, live-cell imaging, immunofluorescence during telophase","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional perturbation with specific NE protein tracking, temporal dissection, single lab","pmids":["36044344"],"is_preprint":false},{"year":2022,"finding":"NUP153 promotes HCC cell proliferation via the c-Myc/P15 axis: NUP153 knockdown upregulates P15INK4b and downregulates c-Myc; c-Myc overexpression partially reverses P15 upregulation and G1/S arrest caused by NUP153 silencing.","method":"siRNA knockdown, rescue with c-Myc overexpression, qRT-PCR, Western blot, cell cycle analysis","journal":"Digestive and liver disease","confidence":"Low","confidence_rationale":"Tier 3 / Weak — knockdown/rescue assay, pathway placement by epistasis, single lab, no direct molecular mechanism","pmids":["35288064"],"is_preprint":false},{"year":2023,"finding":"NUP153 engages the assembled HIV-1 CA lattice through a bipartite motif: a canonical FG motif targeting the CA hexamer, and a novel triple-arginine (RRR) motif targeting the CA tri-hexamer interface; both motifs contribute to HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies in vitro.","method":"Cryo-EM/X-ray crystallography of CA lattice-NUP153 complexes, mutagenesis, HIV-1 infection assays, in vitro CA assembly stabilization assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — structural characterization of bipartite binding plus mutagenesis of both motifs with functional infection readout, multiple orthogonal methods","pmids":["36943880"],"is_preprint":false},{"year":2023,"finding":"RTEL1 interacts with NUP153 via a distinct C-terminal domain, and this interaction can promote nuclear internalization of peptides that diffuse through the nuclear pore; RTEL1 depletion leads to nuclear envelope destabilization in S-phase cells.","method":"Co-immunoprecipitation, domain mapping, peptide nuclear import assays, RTEL1 knockout/knockdown, high-resolution microscopy","journal":"Cells","confidence":"Low","confidence_rationale":"Tier 3 / Weak — direct interaction shown but NUP153-specific mechanistic details limited; functional consequence (NE stability) linked to RTEL1 rather than NUP153 per se","pmids":["38132118"],"is_preprint":false},{"year":2024,"finding":"Nup153 is the anchor for kinesin Kif1a at the nuclear envelope in radial glial progenitors, mediating G1-specific basal nuclear migration (interkinetic nuclear migration); identified by co-immunoprecipitation and functional rescue experiments.","method":"Co-immunoprecipitation, RNAi knockdown, live imaging of nuclear migration in brain slices","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct interaction, functional knockdown with specific nuclear migration readout, in vivo context, single lab","pmids":["39666457"],"is_preprint":false},{"year":2025,"finding":"SPOP (Cul3 substrate adaptor) directly binds Nup153 in a complex, multivalent interaction, and targets it for ubiquitylation and proteasomal degradation; SPOP substrate-binding mutant (F102C) fails to degrade Nup153; RNAi depletion of SPOP stabilizes Nup153; loss of SPOP activity strengthens Mad1 localization at the nuclear envelope (which is tethered there by Nup153).","method":"Co-immunoprecipitation, ubiquitylation assays, RNAi depletion, SPOP mutant (F102C) expression, Mad1 localization assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct interaction, ubiquitylation demonstrated with loss-of-function mutant controls, RNAi stabilization, downstream functional consequence, replicated in peer-reviewed and preprint","pmids":["39785820"],"is_preprint":false},{"year":2025,"finding":"NUP153 promotes HBV replication by enhancing HBV core promoter activity through upregulation of HNF4α via ERK signaling; NUP153 knockdown inhibits HBV replication without affecting cccDNA levels; NUP153 overexpression increases cccDNA transcription and virion production.","method":"RNAi knockdown, CRISPR/Cas9 knockout, luciferase reporter assays, cytoplasmic/nuclear fractionation, mouse hydrodynamic injection model","journal":"Journal of medical virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mechanistic pathway (ERK-HNF4α-HBV promoter) with multiple loss/gain-of-function approaches and in vivo confirmation, single lab","pmids":["40014546"],"is_preprint":false},{"year":2025,"finding":"NUP153 is recruited to the orthoflavivirus amplification site on the ER; NUP153 interacts with viral proteins NS3 and NS5 and a conserved G-rich motif on viral RNA; these interactions specifically promote structural viral protein production, leading to efficient virion assembly and release.","method":"Fluorescence microscopy, knockdown, crosslinking immunoprecipitation sequencing (CLIP-seq), mass spectrometry, in vitro and biophysical binding assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct protein-protein and protein-RNA interactions confirmed biochemically, functional knockdown, multiple orthogonal methods (CLIP-seq, MS, biophysics, imaging)","pmids":["41951628"],"is_preprint":false},{"year":2024,"finding":"Nup153 and TPR are required for TREX-2-dependent export of hsp70 mRNA in Drosophila; Nup153 knockdown causes TPR relocation to the nucleoplasm; Nup153 depletion causes TREX-2 subunits to relocate from nuclear pores to the nucleoplasm; both nucleoporins are required for TREX-2 subunit association with nuclear pores.","method":"RNAi knockdown, mRNA export assays, immunofluorescence localization of TREX-2 subunits","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with direct mRNA export readout and TREX-2 localization, Drosophila model, single lab","pmids":["40943515"],"is_preprint":false},{"year":2024,"finding":"Nup153 docks splicing machinery to the nuclear pore; BioID proximity labeling reveals enrichment of spliceosome complex components (E, A, B, B*, P) near Nup153; splicing components' presence at NPC is reduced upon splicing inhibition and depends partly on Nup153; Nup153-bound genes (~500) show Nup153-dependent splicing defects, suggesting co-transcriptional splicing at the NPC.","method":"BioID proximity labeling, in situ proximity ligation assay, STED microscopy, DamID, RNAi knockdown with splicing assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple interaction confirmation methods and functional splicing assay; preprint, not yet peer-reviewed","pmids":["bio_10.1101_2024.09.30.615666"],"is_preprint":true}],"current_model":"NUP153 is a multifunctional nucleoporin residing at the nuclear basket of the NPC that (1) mediates nuclear import of specific cargos (importin α/β and transportin pathways, 53BP1, PU.1, Smad2, β-catenin) by providing direct binding sites for import receptors in its FG-repeat C-terminal domain and serving as a Ran-regulated docking platform; (2) promotes nuclear export of multiple RNA classes (mRNA, snRNA, 5S rRNA) and NES-proteins through its basket position; (3) anchors structural partners (Tpr, Nup50) at the NPC and maintains nuclear basket architecture; (4) facilitates interphase NPC assembly by binding the inner nuclear membrane via an N-terminal amphipathic helix to recruit the Nup107-160 complex; (5) connects lamins A/B to the NPC; (6) participates in mitotic NE breakdown by recruiting the COPI complex, and in post-mitotic NE reassembly by directing B-type lamin and SUN1 targeting; (7) regulates gene expression and chromatin organization by binding developmental gene promoters and recruiting PRC1 in stem cells, and by interacting with Sox2; (8) serves as a direct docking site for HIV-1 (and other lentiviral) capsid FG and RRR motifs, enabling nuclear import of viral cores into non-dividing cells; and (9) is subject to ubiquitin-mediated degradation by the SPOP–Cul3 E3 ligase and to sumoylation controlled by SENP1/SENP2."},"narrative":{"mechanistic_narrative":"NUP153 is a nuclear-basket nucleoporin that organizes the nucleoplasmic face of the nuclear pore complex (NPC) and serves as a hub coupling nucleocytoplasmic transport to nuclear envelope architecture, mitotic NPC dynamics, and chromatin regulation [PMID:8794857, PMID:9531546]. It is targeted to the NPC by its N-terminal domain and exposes an FG/FXFG-repeat C-terminal domain that provides the principal docking sites for transport receptors: it is a major physiological binding site for importin β, accommodates complete importin α/β–NLS import complexes, and carries separable binding sites for the classical and transportin (M9) import pathways, while a zinc-finger Ran-binding motif and RanGTP regulation gate receptor association and direct cargo toward the nuclear interior [PMID:9531546, PMID:9889100, PMID:10202161, PMID:15632149]. Through these activities NUP153 mediates import of specific cargos including 53BP1, PU.1, Smad2, and β-catenin and is required for export of mRNA, snRNA, 5S rRNA, and NES-bearing proteins; a conserved N-terminal RNA-binding domain (aa 250–400) binds single-stranded RNA with loose sequence selectivity [PMID:10069809, PMID:11567018, PMID:12191473, PMID:15632149, PMID:22075984, PMID:22110128]. NUP153 anchors the basket components Tpr and Nup50 and connects the NPC to the nuclear lamina by binding A- and B-type lamins [PMID:10921874, PMID:12802065, PMID:21983083, PMID:23007389]. It drives interphase NPC assembly by binding the inner nuclear membrane via an N-terminal amphipathic helix to recruit the Nup107-160 complex, and participates in mitotic envelope breakdown by recruiting COPI and in post-mitotic envelope reassembly by directing B-type lamin and SUN1 targeting [PMID:26051542, PMID:12967567, PMID:36044344]. Beyond transport, NUP153 acts in gene regulation: it binds developmental gene promoters and recruits PRC1 in embryonic stem cells and interacts with Sox2 to shape chromatin accessibility and cell-fate decisions [PMID:26080816, PMID:28919367]. NUP153 is a direct docking site for the HIV-1 capsid, engaging the assembled CA lattice through an FG motif and a triple-arginine (RRR) motif at residues lining the capsid hydrophobic pocket (capsid N57), enabling nuclear import of viral cores into non-dividing cells [PMID:19369352, PMID:21593146, PMID:24130490, PMID:36943880]. Its abundance is controlled by SPOP–Cul3-mediated ubiquitylation and proteasomal degradation and by sumoylation balanced by SENP1/SENP2 [PMID:39785820, PMID:22688647].","teleology":[{"year":1994,"claim":"Establishing the primary architecture defined NUP153 as an FG-repeat, zinc-finger nucleoporin, framing the structural basis for its later transport and Ran-binding functions.","evidence":"cDNA sequencing and sequence analysis of human NUP153","pmids":["8110839"],"confidence":"Medium","gaps":["No functional assignment to the repeat or zinc-finger domains","No localization data"]},{"year":1996,"claim":"Localization to the nuclear basket and domain dissection answered where NUP153 resides and which domain does what, linking N-terminal targeting to NPC anchoring and the C-terminal FG region to mRNA export.","evidence":"GFP/domain overexpression, poly(A)+ in situ hybridization, and subcellular targeting assays in BHK cells","pmids":["8794857"],"confidence":"High","gaps":["Mechanism of FG-dependent export not resolved","No receptor partners yet identified"]},{"year":1999,"claim":"Identifying importin β, transportin, and Ran interactions established NUP153 as a Ran-regulated docking platform with pathway-specific receptor binding sites, the core of its import function.","evidence":"IP from Xenopus extracts, recombinant binding, dominant-negative fragment inhibition, phage display, GST pulldowns","pmids":["9531546","9889100","10202161"],"confidence":"High","gaps":["In vivo cargo specificity not yet defined","Stoichiometry of receptor docking at native pores not resolved"]},{"year":1999,"claim":"Antibody injection and RNA-binding assays defined NUP153 as required for export of multiple RNA classes and NES-proteins and as an intrinsic RNA-binding nucleoporin, distinguishing it functionally from other Nups.","evidence":"Anti-Nup153 antibody injection in Xenopus oocytes, multi-substrate export assays, homoribopolymer binding","pmids":["10069809","11567018","14681581","17242408"],"confidence":"High","gaps":["Physiological RNA targets in cells not comprehensively mapped","Sequence determinants only loosely defined"]},{"year":2003,"claim":"Depletion and interaction mapping showed NUP153 anchors Tpr and Nup50 and is required for basket integrity and even NPC distribution, defining its structural-scaffold role.","evidence":"RNAi, immunodepletion/reconstitution in Xenopus, yeast two-hybrid, immunogold EM, domain mapping","pmids":["11598013","12802065","23007389"],"confidence":"High","gaps":["How scaffolding feeds back on transport efficiency only partly resolved"]},{"year":2003,"claim":"Reconstitution assays placed NUP153 in mitotic and assembly events: it recruits COPI to drive NE breakdown, and binds lamins to couple the NPC to the lamina.","evidence":"Xenopus NE-breakdown assays, dominant-negative perturbation, co-IP, lamin Ig-fold mutant analysis","pmids":["12967567","10921874","16314393","28] placeholder"],"confidence":"High","gaps":["Redundancy with Nup358 in COPI recruitment not fully delineated","Lamin-NPC connection mechanism in vivo not fully resolved"]},{"year":2011,"claim":"Identification of specific cargos (53BP1, PU.1, Smad2, β-catenin) connected NUP153 transport activity to DNA-damage response and signaling pathways, giving its receptor-docking role physiological output.","evidence":"siRNA screens, co-IP, GST pulldowns, import/export and IR-foci assays","pmids":["22075984","15632149","12191473","22110128"],"confidence":"High","gaps":["Generality of cargo selectivity unclear","Direct vs. indirect contributions to 53BP1 function debated across studies"]},{"year":2015,"claim":"ChIP-seq and stem-cell assays revealed a transport-independent gene-regulatory role: NUP153 binds promoters, recruits PRC1, and binds Sox2 to control developmental gene expression and cell fate.","evidence":"RNAi/shRNA, ChIP-seq, RNA-seq, ATAC-seq, co-IP, in vivo differentiation assays","pmids":["26080816","28919367","20174442"],"confidence":"High","gaps":["Mechanism coupling NPC residence to chromatin binding not resolved","Direct vs. indirect promoter binding not fully separated"]},{"year":2015,"claim":"Membrane-binding and domain mapping resolved how NUP153 initiates interphase NPC assembly, via an N-terminal amphipathic helix recruiting the Nup107-160 complex.","evidence":"RNAi, in vitro membrane binding, domain mapping, Ran/transportin perturbation","pmids":["26051542"],"confidence":"High","gaps":["Structural basis of helix-membrane insertion not solved","Coupling to lipid composition unclear"]},{"year":2018,"claim":"Crystallographic and lattice-binding studies defined NUP153 as a direct HIV-1 capsid docking factor, with FG and RRR motifs engaging the CA hexamer/tri-hexamer to enable nuclear import into non-dividing cells.","evidence":"X-ray crystallography, cryo-EM, capsid mutagenesis, competition with PF74/CPSF6, infection assays","pmids":["19369352","21593146","24130490","29997211","36943880"],"confidence":"High","gaps":["How capsid uncoating couples to NUP153 release not resolved","In vivo contribution relative to other Nups not fully quantified"]},{"year":2025,"claim":"Identifying SPOP-Cul3 ubiquitylation and SENP1/SENP2-balanced sumoylation established post-translational control of NUP153 abundance, with downstream effects on Mad1 tethering at the NE.","evidence":"Co-IP, ubiquitylation assays, SPOP F102C mutant, RNAi, sumoylation assays, dominant-negative SENPs","pmids":["39785820","22688647"],"confidence":"High","gaps":["Physiological signals triggering NUP153 turnover unknown","Functional consequences of sumoylation cycling not fully defined"]},{"year":2025,"claim":"Recent work extended NUP153 roles to additional viruses (HBV, orthoflavivirus, SIV/HIV-2 Vpx) and to nuclear migration and mRNA-export machinery, broadening its functional reach.","evidence":"RNAi/CRISPR knockdown, CLIP-seq, mass spectrometry, co-IP, reporter and infection assays, in vivo models","pmids":["40014546","41951628","31913756","39666457","40943515"],"confidence":"Medium","gaps":["Mechanistic links to ERK/HNF4α and viral RNA binding are early","Tissue-specific significance not established"]},{"year":null,"claim":"How NUP153's separable activities—transport docking, basket scaffolding, membrane binding, and chromatin/promoter regulation—are spatially and temporally coordinated within a single protein remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated structural model linking domains to all functions","Switching between NPC-resident and chromatin-bound pools not understood"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4,5,27,30]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[6,10,14,19]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[12,34]},{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[21,32,45]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[33,36]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[7,8,34,43]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[5,15]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[24,33,40]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,4,5,6,27]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[13,23,34,43]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[24,33,36]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[6,51]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[21,22,32,45,49,50]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[27,37,38]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[33,36]}],"complexes":["nuclear pore complex (nuclear basket)"],"partners":["TPR","NUP50","IMPORTIN-Β","TRANSPORTIN-1","LMNA/LMNB","SENP1","SPOP","MAD1"],"other_free_text":[]}},"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":62,"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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pathology","url":"https://pubmed.ncbi.nlm.nih.gov/40120667","citation_count":3,"is_preprint":false},{"pmid":"40607419","id":"PMC_40607419","title":"The functional and clinical significance of nucleoporin NUP153 across human cancers: a systematic study based on multi-omics analysis and bench work validation.","date":"2025","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40607419","citation_count":2,"is_preprint":false},{"pmid":"40014546","id":"PMC_40014546","title":"Novel Function of NUP153 in HNF4α Transcriptional Upregulation Contributes to Promoting HBV Replication.","date":"2025","source":"Journal of medical virology","url":"https://pubmed.ncbi.nlm.nih.gov/40014546","citation_count":2,"is_preprint":false},{"pmid":"39843146","id":"PMC_39843146","title":"The role of ABI2 in modulating nuclear proteins: Therapeutic implications for NUP54 and NUP153 in TNBC.","date":"2025","source":"Advances in protein chemistry and structural 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EZHIP","date":"2025-05-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.26.656136","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.09.30.615666","title":"Nucleoporin Nup153 docks the splicing machinery to the nuclear pore for efficient mRNA processing","date":"2024-10-01","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.30.615666","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.29.620935","title":"<i>Drosophila melanogaster</i>  employs nuclear architecture for recruitment of dosage compensation","date":"2024-11-02","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.29.620935","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.09.617312","title":"Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single particle 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33 copies of the XFXFG repeat and four zinc finger motifs; the protein bears O-linked N-acetylglucosamine moieties characteristic of nucleoporins.\",\n      \"method\": \"cDNA sequencing and sequence analysis\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — primary sequence characterization, single study, no functional mutagenesis but establishes domain architecture\",\n      \"pmids\": [\"8110839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Nup153 localizes to the nucleoplasmic face (basket) of the nuclear pore complex; its N-terminal domain is sufficient for NPC targeting (can redirect cytoplasmic pyruvate kinase to the nuclear face); overexpression of Nup153 causes accumulation of nuclear poly(A)+ RNA, indicating inhibition of mRNA export, dependent on the C-terminal FG-repeat domain.\",\n      \"method\": \"Overexpression of GFP/domain constructs in BHK cells, in situ hybridization for poly(A)+ RNA, subcellular targeting assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct targeting assays with domain deletions, replicated functional phenotype across multiple constructs\",\n      \"pmids\": [\"8794857\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Nup153 N-terminal domain contains two distinct targeting regions: one for NPC assembly and one for targeting to the inner face of the nuclear envelope; the zinc finger and C-terminal domains have no role in targeting.\",\n      \"method\": \"Deletion analysis with reporter fusion constructs expressed in mammalian cells\",\n      \"journal\": \"Chromosoma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic deletion mapping, single lab, direct targeting assays\",\n      \"pmids\": [\"9745047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Nup153 and Tpr are the major physiological binding sites for importin β at the nuclear face of the NPC; importin β binds directly to multiple sites in the Nup153 FXFG repeat region; Nup153 can accommodate a complete import complex (importin α, β, and NLS substrate); GMP-PNP disassembles Nup153–importin β complexes.\",\n      \"method\": \"Immunoprecipitation from Xenopus egg extracts and isolated nuclei, direct binding assays with recombinant proteins, competition experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — reciprocal IP, direct binding with purified components, physiological context (egg extracts + assembled pores), multiple orthogonal methods\",\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 import pathway) and transportin (M9 import pathway); dominant-negative Nup153 fragments selectively block one pathway without affecting the other.\",\n      \"method\": \"Dominant-negative fragment inhibition assays in Xenopus import assays, binding studies\",\n      \"journal\": \"Current biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — dominant-negative dissection with pathway specificity, replicated with orthogonal receptor systems\",\n      \"pmids\": [\"9889100\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Nup153 N-terminus contains an M9 NLS that binds transportin 1 (TRN1); Nup153 interacts with both import and export receptors in a RanGTP-regulated manner (RanGTP dissociates import receptor complexes, but is required for export receptor interactions); Nup153 binds RanGDP via its zinc finger domain (zinc finger Ran-binding motif); Nup153 shuttles between nuclear and cytoplasmic faces of the NPC.\",\n      \"method\": \"Phage display, co-immunoprecipitation, GST pulldown, mobility assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phage display identification plus direct binding assays, Ran-regulation demonstrated with multiple orthogonal methods\",\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-mediated protein export (HIV Rev pathway), but not for tRNA export or importin β recycling; Nup153 uniquely among tested nucleoporins associates with poly(G) and poly(U) RNA in vitro.\",\n      \"method\": \"Anti-Nup153 antibody injection into Xenopus oocytes, export assays for multiple RNA/protein classes, RNA-binding assays with homoribopolymers\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — antibody injection with multiple export substrates tested, RNA binding assays with controls, Xenopus oocyte system\",\n      \"pmids\": [\"10069809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Nup153 is incorporated into the nuclear envelope at the same time as lamina assembly during nuclear reconstitution; lamin B3 co-immunoprecipitates with Nup153 and interacts specifically with its C-terminal domain; blocking lamina assembly prevents Nup153 NE recruitment; disrupting pre-assembled lamina displaces Nup153 but not other nucleoporins.\",\n      \"method\": \"Cell-free Xenopus egg extract nuclear assembly assays, co-immunoprecipitation, dominant-negative lamin mutant (XlaminBΔ2+)\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reconstitution system with functional perturbation, domain mapping of lamin B3–Nup153 interaction, multiple orthogonal approaches\",\n      \"pmids\": [\"10921874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Nup153, along with RanBP2, emerin, and LBR, is recruited to reforming nuclear envelopes early in telophase (5 min after anaphase onset) prior to recovery of nuclear import function (8 min), establishing its role in early NPC reassembly.\",\n      \"method\": \"Live fluorescence imaging of GFP-tagged proteins and immunofluorescence at timed intervals in HeLa cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live imaging with precise timing, single lab, localization without full functional dissection\",\n      \"pmids\": [\"10671368\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Nup153 depletion during nuclear reconstitution causes loss of several nuclear basket components, uneven NPC distribution in the NE, and NPC mobility within the NE; importin α/β-mediated import is strongly reduced (due to defective import complex translocation, not receptor recycling), while transportin-mediated import is unaffected.\",\n      \"method\": \"Nup153 immunodepletion from Xenopus egg extracts, nuclear reconstitution, immunogold electron microscopy, nuclear import assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — reconstitution with immunodepletion, EM ultrastructure, pathway-specific import assays, multiple orthogonal methods\",\n      \"pmids\": [\"11598013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"A conserved RNA binding domain mapping to amino acids 250–400 within the Nup153 N-terminal region directly binds RNA and associates with endogenous RNA targets; this domain is functionally conserved across Drosophila, Xenopus, and human Nup153.\",\n      \"method\": \"Domain deletion/mapping with recombinant fragments, RNA-binding assays in vitro, cross-species comparison\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA binding with recombinant protein, cross-species functional conservation, single lab\",\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; Nup153 competes with the cytoplasmic retention factor SARA and nuclear partner FAST-1 for binding to the hydrophobic corridor on the MH2 surface of Smad2; TGFβ receptor phosphorylation does not alter Smad2 affinity for Nup153.\",\n      \"method\": \"Co-immunoprecipitation, GST pulldown with purified proteins, nuclear import/export assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding with purified components, competition assays, functional shuttling assays, multiple orthogonal methods\",\n      \"pmids\": [\"12191473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Nup153 directly binds to Tpr; cellular depletion of Nup153 by RNAi mislocalizes Tpr to the nuclear interior; the Nup153-Tpr interaction is sensitive to specific Tpr amino acid substitution mutations; Nup153 depletion also mislocalizes Nup50 but not other nucleoporins.\",\n      \"method\": \"RNAi depletion, affinity chromatography, yeast two-hybrid, sequential NPC assembly analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RNAi, yeast two-hybrid, affinity chromatography, mutagenesis confirming specificity, multiple orthogonal methods\",\n      \"pmids\": [\"12802065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Nup153 recruits the COPI coatomer complex to the nuclear membrane during mitosis, directing nuclear envelope breakdown; COPI plays a role in NE breakdown via vesiculation.\",\n      \"method\": \"Xenopus in vitro nuclear envelope breakdown assay, co-immunoprecipitation, dominant-negative experiments\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vitro reconstitution, direct interaction, functional perturbation with defined phenotype\",\n      \"pmids\": [\"12967567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The Nup153 RNA binding domain (aa 250-400) preferentially associates with single-stranded RNA with little sequence preference, as demonstrated by testing a range of RNA substrates with different structural features.\",\n      \"method\": \"In vitro RNA binding assays with recombinant Nup153 domain and diverse RNA substrates\",\n      \"journal\": \"RNA\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assay, single lab, single method\",\n      \"pmids\": [\"14681581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nup153 and Nup98 exchange dynamically on and off the NPC in a transcription-dependent manner; inhibition of Pol I and Pol II transcription blocks Nup153 exchange; distinct domains within Nup153 link its mobility to different RNA polymerases.\",\n      \"method\": \"FRAP (fluorescence recovery after photobleaching) with GFP-Nup153, transcription inhibition, domain mapping\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRAP live imaging, transcription inhibitors, domain analysis, single lab\",\n      \"pmids\": [\"14718558\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The Nup153 FXFG repeat region mediates nuclear entry of BR granule mRNPs into the nuclear basket; entry into the basket is a two-step process: mRNP first binds to basket fibril tips, then is transferred into the basket in a Nup153-dependent step.\",\n      \"method\": \"Anti-Nup153 antibody injection into Chironomus tentans salivary glands, electron microscopy tracking of Balbiani ring granules\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — antibody inhibition with EM visualization of transport intermediates, single organism model\",\n      \"pmids\": [\"16195343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"PU.1 nuclear import requires energy but not soluble carriers; PU.1 interacts directly with Nup153 and Nup62; binding of PU.1 to Nup153 (but not Nup62) increases dramatically in the presence of RanGTP, forming a PU.1-RanGTP-Nup153 complex; RanGTP propels PU.1 toward the nuclear side of the NPC by increasing its affinity for Nup153.\",\n      \"method\": \"GST pulldown, nuclear import assays in permeabilized cells, ultrastructural immunogold localization, RanGMPPNP competition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding assays, ultrastructural confirmation, RanGTP mechanistic dissection, multiple orthogonal methods\",\n      \"pmids\": [\"15632149\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nup358 zinc finger domain binds COPI and inhibits nuclear envelope breakdown; both Nup153 and Nup358 play non-redundant roles in COPI recruitment to the nuclear rim during NE breakdown; a single zinc finger is the minimal interface for COPI association, though tandem zinc fingers are optimal.\",\n      \"method\": \"Xenopus in vitro NE breakdown assay, dominant-negative zinc finger domain expression, antibody inhibition, COPI recruitment assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro reconstitution, domain mapping, antibody inhibition, single lab\",\n      \"pmids\": [\"16314393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Nup153 RNA binding domain discriminates between RNA targets based on a loose sequence motif rather than general single-stranded RNA preference; specific subregions of a cellular mRNA account for its association with Nup153.\",\n      \"method\": \"Systematic RNA mutagenesis, in vitro binding assays with synthetic RNA oligonucleotides and recombinant Nup153 RNA-binding domain\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical assays with systematic mutagenesis, single lab\",\n      \"pmids\": [\"17242408\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In Drosophila, Nup153 FG repeats are specifically required for importin α/β-mediated nuclear import; the remainder of the protein maintains pore integrity; Nup153 depletion selectively impairs import but not CRM1-dependent export.\",\n      \"method\": \"RNAi knockdown in Drosophila S2 cells, import/export functional assays, domain rescue experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic RNAi screen with functional assays, domain-level dissection, Drosophila model\",\n      \"pmids\": [\"17682050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"HIV-1 integrase (IN) binds directly to the FxFG-rich C-terminal domain of NUP153 (NUP153C); NUP153C added in excess inhibits nuclear import of IN; known NUP153C binding partners compete with IN for NUP153 binding and inhibit IN nuclear import; overexpression of NUP153C in cells reduces HIV vector infectivity by blocking nuclear translocation of viral cDNA.\",\n      \"method\": \"Semipermeabilized cell nuclear import assay, direct binding (GST pulldown/co-immunoprecipitation), competition assays, infectivity assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding with purified proteins, functional nuclear import assay, competition experiments, cellular infectivity readout\",\n      \"pmids\": [\"19369352\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nup153 depletion reduces HIV-1 2-LTR circles moderately and integrated proviruses substantially, suggesting NUP153 acts at the nuclear import step of HIV-1 PIC; capsid mutations N74D and P90A render HIV-1 insensitive to NUP153 depletion; simultaneous depletion of NUP153 and TNPO3 yields synergistic inhibitory effects.\",\n      \"method\": \"siRNA knockdown, quantitative PCR for viral replication intermediates (late RT products, 2-LTR circles, integrated proviruses), chimeric MLV/HIV-1 viruses\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic knockdown with multiple viral intermediates quantified, chimeric virus epistasis, capsid mutagenesis\",\n      \"pmids\": [\"21593146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nup153 depletion causes a delay in late mitosis with increased unresolved midbodies; more severe depletion causes a pronounced early mitotic defect and accumulation of cells with multilobed nuclei; the FG-rich region of Nup153 is required to rescue defects in late mitosis but not the multilobed nuclei phenotype, indicating two separable Nup153 functions in mitosis.\",\n      \"method\": \"siRNA knockdown in HeLa cells, live cell imaging, rescue with FG-domain mutants\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA with threshold depletion, FG-domain rescue experiments, live imaging, single lab\",\n      \"pmids\": [\"19158386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup153 and Megator (Mtor) bind to ~25% of the Drosophila genome in continuous domains (NARs); these domains are 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; chromatin binding is independent of sub-nuclear localization.\",\n      \"method\": \"ChIP-chip (chromatin immunoprecipitation with microarray), RNAi knockdown, 3D imaging\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide ChIP with functional RNAi knockdown and 3D localization, multiple orthogonal methods\",\n      \"pmids\": [\"20174442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup153 interacts directly with Mad1 (spindle assembly checkpoint protein) via Nup153's N-terminal domain; Nup153 overexpression causes multinucleated cells, multipolar spindles, and spindle checkpoint inactivation via Mad1 hypophosphorylation; Nup153 depletion reduces Mad1 at nuclear pores and delays Mad1 dissociation from kinetochores, keeping the spindle checkpoint active.\",\n      \"method\": \"In vitro binding assays, overexpression/RNAi in HeLa cells, immunofluorescence, phosphorylation analysis\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding, loss- and gain-of-function phenotypes, single lab\",\n      \"pmids\": [\"21327106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup153 depletion by RNAi alters nuclear lamina organization and Sun1 localization, and causes cytoskeletal rearrangement that impairs cell migration in human breast carcinoma cells.\",\n      \"method\": \"RNAi knockdown, immunofluorescence, cell migration assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with defined phenotypic readouts (lamina, cytoskeleton, migration), single lab\",\n      \"pmids\": [\"20561986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NUP153 is specifically required for nuclear import of 53BP1; NUP153 knockdown prevents 53BP1 from entering nuclei in newly forming daughter cells, leading to decreased IR-induced 53BP1 foci, delayed DNA repair, and impaired survival after IR; the C-terminal part of NUP153 is required for 53BP1 import through an NUP153–importin-β interplay.\",\n      \"method\": \"siRNA screen, live-cell imaging, co-immunoprecipitation, domain mapping, IR-induced foci assays\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA screen validated functionally, live imaging, domain mapping, multiple pathway readouts, importin-β mechanistic link\",\n      \"pmids\": [\"22075984\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Nup153 exhibits multiple binding sites for both A-type and B-type lamins; both the N-terminal domain and C-terminal domain of Nup153 directly interact with the Ig-fold domain of lamin A and B; specific mutations in the lamin A Ig-fold domain selectively affect Nup153 binding.\",\n      \"method\": \"GST pulldown assays, blot overlay assays with purified proteins, lamin Ig-fold mutant analysis\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding with purified proteins, domain mapping, mutagenesis, single lab\",\n      \"pmids\": [\"21983083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"β-catenin directly interacts with the FG repeats of Nup153 (as well as Nup62 and Nup98) via specific Arm repeat sequences (R3-8 for import, R10-12 for export/import); knockdown of Nup153 and Nup62 impedes β-catenin nuclear import/export; Tyr-654 phosphorylation stimulates Arm R10-12 transport activity.\",\n      \"method\": \"FRAP assays in live cells, in vitro binding assays with purified components, siRNA knockdown, proteomics\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding, FRAP, siRNA, phosphorylation effect, single lab\",\n      \"pmids\": [\"22110128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The Nup153–Nup50 interface involves a dual site: (1) Nup50 N-terminal domain binds a unique N-terminal region of Nup153 critical for Nup50 NPC localization; (2) a second site at the distal Nup153 tail depends on importin α; disruption of the Nup153–Nup50 interface decreases nuclear import efficiency.\",\n      \"method\": \"Domain deletion mapping, co-immunoprecipitation, NPC localization assays, import efficiency assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding, domain mapping, functional import assay, single lab\",\n      \"pmids\": [\"23007389\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nup153 binds both SUMO proteases SENP1 and SENP2 via two distinct sites (N-terminal domain and C-terminal FG-rich region); Nup153 is itself a substrate for sumoylation, kept in check by SENP1 and SENP2; depletion of SENP1/SENP2 or dominant-negative mutants increase Nup153 sumoylation; SENP1 levels are influenced by Nup153 abundance, but SENP2 is not.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, RNAi, sumoylation assays, dominant-negative SENP constructs\",\n      \"journal\": \"Nucleus\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding, PTM identification, domain mapping, bidirectional regulation shown, single lab\",\n      \"pmids\": [\"22688647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The HIV-1 capsid (CA) N-terminal domain directly interacts with the FG-repeat-enriched Nup153 C-terminal domain (NUP153C); different FG motifs mediate binding to HIV-1 versus EIAV capsids; HIV-1 CA binding maps to residues lining the α-helix 3/4 hydrophobic pocket (Asn57 critical); this pocket is shared with PF74 inhibitor and CPSF6; PF74 and CPSF6 compete with NUP153C for binding to the HIV-1 CA pocket; NUP153C-CA interaction underlies HIV-1 infection of non-dividing cells.\",\n      \"method\": \"Trim-NUP153C restriction assay, in vitro binding with purified proteins, mutagenesis, competition assays with PF74/CPSF6, infection assays in dividing/non-dividing cells\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — direct binding with purified proteins, systematic mutagenesis, competition assays, cellular functional readout, multiple orthogonal methods\",\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 early differentiation without defects in nuclear import of pluripotency factors; Nup153 binds around transcriptional start sites of developmental genes and mediates recruitment of polycomb-repressive complex 1 (PRC1) to a subset of its target loci.\",\n      \"method\": \"RNAi depletion, ChIP-seq, RNA-seq, nuclear import assays for pluripotency factors\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide ChIP-seq, transcriptomics, functional rescue, PRC1 recruitment assays, multiple orthogonal methods\",\n      \"pmids\": [\"26080816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup153 is required for interphase NPC assembly but not for post-mitotic NPC reassembly; Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix during interphase, facilitating recruitment of the Nup107-160 complex to NPC assembly sites; transportin and Ran regulate Nup153–membrane interaction.\",\n      \"method\": \"RNAi depletion, in vitro membrane binding assays, domain mapping, fluorescence microscopy, Ran/transportin perturbation\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct membrane binding, domain mapping, epistasis with Ran/transportin, functional NPC assembly assay, multiple orthogonal methods\",\n      \"pmids\": [\"26051542\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Prelamin A accumulation causes mislocalization of NUP153, disrupts the Ran gradient, and thereby impairs nuclear import of 53BP1, resulting in DNA damage response defects in vascular smooth muscle cells; NUP153 is important for nuclear localization of Ran.\",\n      \"method\": \"siRNA knockdown, immunofluorescence, nuclear fractionation, 53BP1 import assays in cells expressing prelamin A\",\n      \"journal\": \"Aging cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mechanistic link from prelamin A to NUP153 mislocalization to Ran gradient disruption to 53BP1 import defect, single lab\",\n      \"pmids\": [\"27464478\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 interacts with Sox2 in adult neural progenitor cells; depletion of Nup153 disrupts Sox2 genomic localization and open chromatin configurations at Nup153 target genes; Nup153 binding to gene promoters correlates with increased expression, while binding to transcriptional end sites correlates with decreased expression; Nup153 depletion promotes gliogenic fate switch in vivo.\",\n      \"method\": \"Co-immunoprecipitation, ChIP-seq, ATAC-seq, shRNA knockdown, in vivo neural progenitor differentiation assays\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct interaction, genome-wide chromatin profiling, loss-of-function with in vivo fate readout, multiple orthogonal methods\",\n      \"pmids\": [\"28919367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 and Nup50 promote 53BP1 recruitment to DNA damage foci by antagonizing BRCA1-dependent events; the requirement for Nup153 in 53BP1 foci formation is abrogated in BRCA1/BARD1-deficient cells but not BRCA2-deficient cells, placing Nup153 in a pathway that counteracts BRCA1 activity.\",\n      \"method\": \"siRNA knockdown, 53BP1 foci assays with etoposide/olaparib, genetic epistasis with BRCA1/BARD1/BRCA2 depletion\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with multiple DSB repair factors, pathway placement, single lab\",\n      \"pmids\": [\"28751496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup153 depletion results in reduced SUMO1 modification of 53BP1 and displacement of SENP1 from NPCs; artificial NPC tethering of SENP1 restores NHEJ and 53BP1 sumoylation in Nup153-depleted cells; Nup153 is specifically required for NHEJ (not HR through SENP1), while Tpr contributes to both NHEJ and HR, and Nup50 only to NHEJ.\",\n      \"method\": \"siRNA knockdown, SUMO modification assays, NHEJ/HR reporter assays, forced NPC targeting of SENP1\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic rescue experiment (artificial SENP1 tethering), multiple repair pathway assays, single lab\",\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 peptides reveal that capsid N57 residue is critical for NUP153 interaction; HIV-1 viruses with N57 substitutions infect dividing but not non-dividing cells, blocking nuclear translocation while allowing reverse transcription; N57 mutant capsids lose interaction with both Nup153 and CPSF6; small molecules PF74 and BI-2 prevent FG-nucleoporin interactions with HIV-1 core.\",\n      \"method\": \"X-ray crystallography, capsid mutagenesis, infection assays in dividing/non-dividing cells, viral replication intermediate quantification, integration site analysis\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional mutagenesis validation, mechanistic dissection of nuclear import vs. integration, multiple orthogonal methods\",\n      \"pmids\": [\"29997211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Seh1 (SEH1L) is required for association of both the GATOR2 complex and Nup153 with mitotic chromosomes, but not for the Nup107 complex association with mitotic chromosomes.\",\n      \"method\": \"Chemical genetics (auxin-inducible degron), quantitative chromosome proteomics\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chemical genetics with quantitative proteomics, functional specificity demonstrated, single lab\",\n      \"pmids\": [\"29618633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Vpx of SIVsmPBj1.9 physically interacts with NUP153; MAPK/ERK2-mediated phosphorylation of Vpx is required for its interaction with NUP153; MAPK/ERK2-packaging defective SIV fails to efficiently import its viral genome into nuclei; Vpx-NUP153 interaction is evolutionarily conserved in SIV isolates and HIV-2.\",\n      \"method\": \"Co-immunoprecipitation, superresolution structured illumination microscopy, viral infection assays with MAPK/ERK2-deficient virions\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction, phosphorylation-dependent binding, functional nuclear import readout, single lab\",\n      \"pmids\": [\"31913756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mad1 depletion delays recruitment of Nup153 to anaphase chromatin; the Nup153-Mad1 interaction requires a nuclear envelope to be present; both Nup153 and Mad1 depletion alter NE architecture (membrane curvature at NPCs, expanded inner-outer membrane spacing); Nup153 depletion causes interphase NPC assembly defects with cytoplasmic nucleoporin displacement, but Mad1 depletion does not.\",\n      \"method\": \"RNAi depletion, time-lapse microscopy, electron microscopy, 3D-SIM, proximity ligation assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple imaging modalities, functional dissection of separable roles, single lab\",\n      \"pmids\": [\"33023979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Nup153 disruption during telophase interferes with ongoing addition of B-type lamins, lamin B receptor, and SUN1 to the expanding NE, but minimally affects lamin A and SUN2 targeting, revealing two functionally separable phases of NE formation and a role for Nup153 in recruiting a specific subset of NE proteins.\",\n      \"method\": \"Nup153 functional disruption, live-cell imaging, immunofluorescence during telophase\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional perturbation with specific NE protein tracking, temporal dissection, single lab\",\n      \"pmids\": [\"36044344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NUP153 promotes HCC cell proliferation via the c-Myc/P15 axis: NUP153 knockdown upregulates P15INK4b and downregulates c-Myc; c-Myc overexpression partially reverses P15 upregulation and G1/S arrest caused by NUP153 silencing.\",\n      \"method\": \"siRNA knockdown, rescue with c-Myc overexpression, qRT-PCR, Western blot, cell cycle analysis\",\n      \"journal\": \"Digestive and liver disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — knockdown/rescue assay, pathway placement by epistasis, single lab, no direct molecular mechanism\",\n      \"pmids\": [\"35288064\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NUP153 engages the assembled HIV-1 CA lattice through a bipartite motif: a canonical FG motif targeting the CA hexamer, and a novel triple-arginine (RRR) motif targeting the CA tri-hexamer interface; both motifs contribute to HIV-1 nuclear import; NUP153 stabilizes tubular CA assemblies in vitro.\",\n      \"method\": \"Cryo-EM/X-ray crystallography of CA lattice-NUP153 complexes, mutagenesis, HIV-1 infection assays, in vitro CA assembly stabilization assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — structural characterization of bipartite binding plus mutagenesis of both motifs with functional infection readout, multiple orthogonal methods\",\n      \"pmids\": [\"36943880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RTEL1 interacts with NUP153 via a distinct C-terminal domain, and this interaction can promote nuclear internalization of peptides that diffuse through the nuclear pore; RTEL1 depletion leads to nuclear envelope destabilization in S-phase cells.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, peptide nuclear import assays, RTEL1 knockout/knockdown, high-resolution microscopy\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — direct interaction shown but NUP153-specific mechanistic details limited; functional consequence (NE stability) linked to RTEL1 rather than NUP153 per se\",\n      \"pmids\": [\"38132118\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Nup153 is the anchor for kinesin Kif1a at the nuclear envelope in radial glial progenitors, mediating G1-specific basal nuclear migration (interkinetic nuclear migration); identified by co-immunoprecipitation and functional rescue experiments.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown, live imaging of nuclear migration in brain slices\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction, functional knockdown with specific nuclear migration readout, in vivo context, single lab\",\n      \"pmids\": [\"39666457\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SPOP (Cul3 substrate adaptor) directly binds Nup153 in a complex, multivalent interaction, and targets it for ubiquitylation and proteasomal degradation; SPOP substrate-binding mutant (F102C) fails to degrade Nup153; RNAi depletion of SPOP stabilizes Nup153; loss of SPOP activity strengthens Mad1 localization at the nuclear envelope (which is tethered there by Nup153).\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assays, RNAi depletion, SPOP mutant (F102C) expression, Mad1 localization assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct interaction, ubiquitylation demonstrated with loss-of-function mutant controls, RNAi stabilization, downstream functional consequence, replicated in peer-reviewed and preprint\",\n      \"pmids\": [\"39785820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NUP153 promotes HBV replication by enhancing HBV core promoter activity through upregulation of HNF4α via ERK signaling; NUP153 knockdown inhibits HBV replication without affecting cccDNA levels; NUP153 overexpression increases cccDNA transcription and virion production.\",\n      \"method\": \"RNAi knockdown, CRISPR/Cas9 knockout, luciferase reporter assays, cytoplasmic/nuclear fractionation, mouse hydrodynamic injection model\",\n      \"journal\": \"Journal of medical virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mechanistic pathway (ERK-HNF4α-HBV promoter) with multiple loss/gain-of-function approaches and in vivo confirmation, single lab\",\n      \"pmids\": [\"40014546\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NUP153 is recruited to the orthoflavivirus amplification site on the ER; NUP153 interacts with viral proteins NS3 and NS5 and a conserved G-rich motif on viral RNA; these interactions specifically promote structural viral protein production, leading to efficient virion assembly and release.\",\n      \"method\": \"Fluorescence microscopy, knockdown, crosslinking immunoprecipitation sequencing (CLIP-seq), mass spectrometry, in vitro and biophysical binding assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct protein-protein and protein-RNA interactions confirmed biochemically, functional knockdown, multiple orthogonal methods (CLIP-seq, MS, biophysics, imaging)\",\n      \"pmids\": [\"41951628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Nup153 and TPR are required for TREX-2-dependent export of hsp70 mRNA in Drosophila; Nup153 knockdown causes TPR relocation to the nucleoplasm; Nup153 depletion causes TREX-2 subunits to relocate from nuclear pores to the nucleoplasm; both nucleoporins are required for TREX-2 subunit association with nuclear pores.\",\n      \"method\": \"RNAi knockdown, mRNA export assays, immunofluorescence localization of TREX-2 subunits\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with direct mRNA export readout and TREX-2 localization, Drosophila model, single lab\",\n      \"pmids\": [\"40943515\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Nup153 docks splicing machinery to the nuclear pore; BioID proximity labeling reveals enrichment of spliceosome complex components (E, A, B, B*, P) near Nup153; splicing components' presence at NPC is reduced upon splicing inhibition and depends partly on Nup153; Nup153-bound genes (~500) show Nup153-dependent splicing defects, suggesting co-transcriptional splicing at the NPC.\",\n      \"method\": \"BioID proximity labeling, in situ proximity ligation assay, STED microscopy, DamID, RNAi knockdown with splicing assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple interaction confirmation methods and functional splicing assay; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2024.09.30.615666\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NUP153 is a multifunctional nucleoporin residing at the nuclear basket of the NPC that (1) mediates nuclear import of specific cargos (importin α/β and transportin pathways, 53BP1, PU.1, Smad2, β-catenin) by providing direct binding sites for import receptors in its FG-repeat C-terminal domain and serving as a Ran-regulated docking platform; (2) promotes nuclear export of multiple RNA classes (mRNA, snRNA, 5S rRNA) and NES-proteins through its basket position; (3) anchors structural partners (Tpr, Nup50) at the NPC and maintains nuclear basket architecture; (4) facilitates interphase NPC assembly by binding the inner nuclear membrane via an N-terminal amphipathic helix to recruit the Nup107-160 complex; (5) connects lamins A/B to the NPC; (6) participates in mitotic NE breakdown by recruiting the COPI complex, and in post-mitotic NE reassembly by directing B-type lamin and SUN1 targeting; (7) regulates gene expression and chromatin organization by binding developmental gene promoters and recruiting PRC1 in stem cells, and by interacting with Sox2; (8) serves as a direct docking site for HIV-1 (and other lentiviral) capsid FG and RRR motifs, enabling nuclear import of viral cores into non-dividing cells; and (9) is subject to ubiquitin-mediated degradation by the SPOP–Cul3 E3 ligase and to sumoylation controlled by SENP1/SENP2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP153 is a nuclear-basket nucleoporin that organizes the nucleoplasmic face of the nuclear pore complex (NPC) and serves as a hub coupling nucleocytoplasmic transport to nuclear envelope architecture, mitotic NPC dynamics, and chromatin regulation [#1, #3]. It is targeted to the NPC by its N-terminal domain and exposes an FG/FXFG-repeat C-terminal domain that provides the principal docking sites for transport receptors: it is a major physiological binding site for importin \\u03b2, accommodates complete importin \\u03b1/\\u03b2\\u2013NLS import complexes, and carries separable binding sites for the classical and transportin (M9) import pathways, while a zinc-finger Ran-binding motif and RanGTP regulation gate receptor association and direct cargo toward the nuclear interior [#3, #4, #5, #17]. Through these activities NUP153 mediates import of specific cargos including 53BP1, PU.1, Smad2, and \\u03b2-catenin and is required for export of mRNA, snRNA, 5S rRNA, and NES-bearing proteins; a conserved N-terminal RNA-binding domain (aa 250\\u2013400) binds single-stranded RNA with loose sequence selectivity [#6, #10, #11, #17, #27, #29]. NUP153 anchors the basket components Tpr and Nup50 and connects the NPC to the nuclear lamina by binding A- and B-type lamins [#7, #12, #28, #30]. It drives interphase NPC assembly by binding the inner nuclear membrane via an N-terminal amphipathic helix to recruit the Nup107-160 complex, and participates in mitotic envelope breakdown by recruiting COPI and in post-mitotic envelope reassembly by directing B-type lamin and SUN1 targeting [#34, #13, #43]. Beyond transport, NUP153 acts in gene regulation: it binds developmental gene promoters and recruits PRC1 in embryonic stem cells and interacts with Sox2 to shape chromatin accessibility and cell-fate decisions [#33, #36]. NUP153 is a direct docking site for the HIV-1 capsid, engaging the assembled CA lattice through an FG motif and a triple-arginine (RRR) motif at residues lining the capsid hydrophobic pocket (capsid N57), enabling nuclear import of viral cores into non-dividing cells [#21, #22, #32, #45]. Its abundance is controlled by SPOP\\u2013Cul3-mediated ubiquitylation and proteasomal degradation and by sumoylation balanced by SENP1/SENP2 [#48, #31].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing the primary architecture defined NUP153 as an FG-repeat, zinc-finger nucleoporin, framing the structural basis for its later transport and Ran-binding functions.\",\n      \"evidence\": \"cDNA sequencing and sequence analysis of human NUP153\",\n      \"pmids\": [\"8110839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional assignment to the repeat or zinc-finger domains\", \"No localization data\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Localization to the nuclear basket and domain dissection answered where NUP153 resides and which domain does what, linking N-terminal targeting to NPC anchoring and the C-terminal FG region to mRNA export.\",\n      \"evidence\": \"GFP/domain overexpression, poly(A)+ in situ hybridization, and subcellular targeting assays in BHK cells\",\n      \"pmids\": [\"8794857\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of FG-dependent export not resolved\", \"No receptor partners yet identified\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identifying importin \\u03b2, transportin, and Ran interactions established NUP153 as a Ran-regulated docking platform with pathway-specific receptor binding sites, the core of its import function.\",\n      \"evidence\": \"IP from Xenopus extracts, recombinant binding, dominant-negative fragment inhibition, phage display, GST pulldowns\",\n      \"pmids\": [\"9531546\", \"9889100\", \"10202161\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo cargo specificity not yet defined\", \"Stoichiometry of receptor docking at native pores not resolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Antibody injection and RNA-binding assays defined NUP153 as required for export of multiple RNA classes and NES-proteins and as an intrinsic RNA-binding nucleoporin, distinguishing it functionally from other Nups.\",\n      \"evidence\": \"Anti-Nup153 antibody injection in Xenopus oocytes, multi-substrate export assays, homoribopolymer binding\",\n      \"pmids\": [\"10069809\", \"11567018\", \"14681581\", \"17242408\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological RNA targets in cells not comprehensively mapped\", \"Sequence determinants only loosely defined\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Depletion and interaction mapping showed NUP153 anchors Tpr and Nup50 and is required for basket integrity and even NPC distribution, defining its structural-scaffold role.\",\n      \"evidence\": \"RNAi, immunodepletion/reconstitution in Xenopus, yeast two-hybrid, immunogold EM, domain mapping\",\n      \"pmids\": [\"11598013\", \"12802065\", \"23007389\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How scaffolding feeds back on transport efficiency only partly resolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Reconstitution assays placed NUP153 in mitotic and assembly events: it recruits COPI to drive NE breakdown, and binds lamins to couple the NPC to the lamina.\",\n      \"evidence\": \"Xenopus NE-breakdown assays, dominant-negative perturbation, co-IP, lamin Ig-fold mutant analysis\",\n      \"pmids\": [\"12967567\", \"10921874\", \"16314393\", \"28] placeholder\"],\n      \"pmids_note\": \"\",\n      \"confidence\": \"High\",\n      \"gaps\": [\"Redundancy with Nup358 in COPI recruitment not fully delineated\", \"Lamin-NPC connection mechanism in vivo not fully resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identification of specific cargos (53BP1, PU.1, Smad2, \\u03b2-catenin) connected NUP153 transport activity to DNA-damage response and signaling pathways, giving its receptor-docking role physiological output.\",\n      \"evidence\": \"siRNA screens, co-IP, GST pulldowns, import/export and IR-foci assays\",\n      \"pmids\": [\"22075984\", \"15632149\", \"12191473\", \"22110128\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of cargo selectivity unclear\", \"Direct vs. indirect contributions to 53BP1 function debated across studies\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"ChIP-seq and stem-cell assays revealed a transport-independent gene-regulatory role: NUP153 binds promoters, recruits PRC1, and binds Sox2 to control developmental gene expression and cell fate.\",\n      \"evidence\": \"RNAi/shRNA, ChIP-seq, RNA-seq, ATAC-seq, co-IP, in vivo differentiation assays\",\n      \"pmids\": [\"26080816\", \"28919367\", \"20174442\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism coupling NPC residence to chromatin binding not resolved\", \"Direct vs. indirect promoter binding not fully separated\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Membrane-binding and domain mapping resolved how NUP153 initiates interphase NPC assembly, via an N-terminal amphipathic helix recruiting the Nup107-160 complex.\",\n      \"evidence\": \"RNAi, in vitro membrane binding, domain mapping, Ran/transportin perturbation\",\n      \"pmids\": [\"26051542\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of helix-membrane insertion not solved\", \"Coupling to lipid composition unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Crystallographic and lattice-binding studies defined NUP153 as a direct HIV-1 capsid docking factor, with FG and RRR motifs engaging the CA hexamer/tri-hexamer to enable nuclear import into non-dividing cells.\",\n      \"evidence\": \"X-ray crystallography, cryo-EM, capsid mutagenesis, competition with PF74/CPSF6, infection assays\",\n      \"pmids\": [\"19369352\", \"21593146\", \"24130490\", \"29997211\", \"36943880\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How capsid uncoating couples to NUP153 release not resolved\", \"In vivo contribution relative to other Nups not fully quantified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying SPOP-Cul3 ubiquitylation and SENP1/SENP2-balanced sumoylation established post-translational control of NUP153 abundance, with downstream effects on Mad1 tethering at the NE.\",\n      \"evidence\": \"Co-IP, ubiquitylation assays, SPOP F102C mutant, RNAi, sumoylation assays, dominant-negative SENPs\",\n      \"pmids\": [\"39785820\", \"22688647\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological signals triggering NUP153 turnover unknown\", \"Functional consequences of sumoylation cycling not fully defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Recent work extended NUP153 roles to additional viruses (HBV, orthoflavivirus, SIV/HIV-2 Vpx) and to nuclear migration and mRNA-export machinery, broadening its functional reach.\",\n      \"evidence\": \"RNAi/CRISPR knockdown, CLIP-seq, mass spectrometry, co-IP, reporter and infection assays, in vivo models\",\n      \"pmids\": [\"40014546\", \"41951628\", \"31913756\", \"39666457\", \"40943515\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic links to ERK/HNF4\\u03b1 and viral RNA binding are early\", \"Tissue-specific significance not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUP153's separable activities\\u2014transport docking, basket scaffolding, membrane binding, and chromatin/promoter regulation\\u2014are spatially and temporally coordinated within a single protein remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No integrated structural model linking domains to all functions\", \"Switching between NPC-resident and chromatin-bound pools not understood\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017056\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4, 5, 27, 30]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [6, 10, 14, 19]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [12, 34]},\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [21, 32, 45]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [33, 36]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [7, 8, 34, 43]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [5, 15]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [24, 33, 40]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 4, 5, 6, 27]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [13, 23, 34, 43]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [24, 33, 36]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [6, 51]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [21, 22, 32, 45, 49, 50]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [27, 37, 38]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [33, 36]}\n    ],\n    \"complexes\": [\n      \"nuclear pore complex (nuclear basket)\"\n    ],\n    \"partners\": [\n      \"TPR\",\n      \"NUP50\",\n      \"importin-\\u03b2\",\n      \"transportin-1\",\n      \"LMNA/LMNB\",\n      \"SENP1\",\n      \"SPOP\",\n      \"MAD1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}