Affinage

NXF1

Nuclear RNA export factor 1 · UniProt Q9UBU9

Length
619 aa
Mass
70.2 kDa
Annotated
2026-04-29
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NXF1 (TAP) is the principal mRNA nuclear export receptor in metazoans, coupling pre-mRNA processing to nuclear pore complex (NPC) translocation through coordinated interactions with adaptor proteins, nucleoporins, and its obligate heterodimeric partner NXT1/p15. NXF1 adopts an autoinhibited conformation in which its RNA-binding domain is masked by intramolecular contacts; TREX subunits Aly/REF and THOC5 bind non-overlapping surfaces on NXF1 to induce an open, RNA-binding-competent state, while SR proteins SRSF3 and SRSF7 function as sequence-specific adaptors that recruit NXF1 to mRNA 3′ ends and couple alternative polyadenylation to export (PMID:22893130, PMID:26944680, PMID:19165146). The NXF1–NXT1 heterodimer translocates mRNP through the NPC via at least two FG-nucleoporin-binding sites provided by its NTF2-like and UBA domains, docks preferentially at cytoplasmic filament nucleoporin RanBP2/Nup358, and releases cargo on the cytoplasmic face through Dbp5 helicase activity (PMID:12101235, PMID:14729961, PMID:31375530). NXF1 also autoregulates its own expression through a constitutive transport element within a retained intron, and its nuclear re-import requires redundant karyopherins recognizing dual NLS epitopes in the N-terminal tail (PMID:16971948, PMID:21965294).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Establishing NXF1's modular domain architecture (RRM, LRR, NTF2-like, UBA) and that each domain contributes distinct functions — RNA binding, heterodimerization with p15/NXT1, and nucleoporin interaction — provided the first structural framework for understanding how a single protein can bind cargo and traverse the NPC.

    Evidence Domain deletion analysis with RNA-binding, localization, and export reporter assays for NXF1–3 paralogs

    PMID:11073998

    Open questions at the time
    • No atomic-resolution structure at this stage
    • Relative contributions of domains to bulk vs. specific mRNA export unknown
  2. 2001 High

    Demonstrating that NXT1/p15 is an obligate cofactor that enhances NXF1 binding to nucleoporins — and that the LRR and UBA domains are both essential for mRNA export — defined the heterodimer as the functional export unit and identified nucleoporin binding as the rate-limiting step.

    Evidence In vitro nucleoporin binding assays with recombinant proteins; RNAi in Drosophila; domain mutagenesis with export reporters

    PMID:11259411 PMID:11579093 PMID:11739738

    Open questions at the time
    • Mechanism of NXT1-induced enhancement of nucleoporin affinity not structurally resolved
    • Identity of all relevant FG-nucleoporin partners incomplete
  3. 2001 Medium

    Identification of U2AF35 as a direct NXF1-binding partner that recruits NXF1 to spliced mRNP linked mRNA export to the splicing machinery, establishing the principle that adaptor proteins couple processing to export.

    Evidence Yeast two-hybrid, in vitro binding, mRNP immunoprecipitation, and export reporters

    PMID:11724776

    Open questions at the time
    • Relative contribution of U2AF vs. other adaptors to bulk mRNA export not quantified
    • No structural detail of the U2AF–NXF1 interface
  4. 2002 High

    Domain-swap experiments showing that two nucleoporin-binding modules (any combination of NTF2-like and UBA) are both necessary and sufficient for NPC translocation established a 'bivalent grip' model for FG-repeat-mediated transport, while revealing that NXT1's role is confined to nucleoporin binding rather than directionality.

    Evidence Tandem domain duplication and swap mutants with mRNA export reporters

    PMID:12101235

    Open questions at the time
    • How directionality is imposed if not by NXT1 remained open
    • Energetics of translocation through FG meshwork unresolved
  5. 2002 Medium

    Discovery that NXF1 directly binds a LINE-1 3′ UTR element (L1-NBE) using a partially distinct binding surface revealed that NXF1 exports endogenous intronless retrotransposon mRNAs, broadening its cargo repertoire beyond spliced mRNA.

    Evidence In vitro RNA selection, gel-shift competition, domain deletion, and export assays in Xenopus oocytes and human cells

    PMID:12003494

    Open questions at the time
    • Physiological significance for L1 retrotransposition not directly tested
    • Structural basis of differential binding mode unresolved
  6. 2003 Medium

    Mapping NXF1 interactions with Rae1/Gle2 and Nup98 GLFG repeats, and showing competitive binding, suggested an ordered hand-off mechanism through sequential nucleoporin stations during NPC transit.

    Evidence Co-IP and pulldown with defined protein domains; binary and ternary complex formation

    PMID:12637516

    Open questions at the time
    • Order of nucleoporin encounters during transit not established in vivo
    • Affinity measurements for different FG-repeat types lacking
  7. 2004 High

    RanBP2/Nup358 was identified as the major cytoplasmic-face docking site for NXF1–NXT1, and its depletion caused specific mRNA export block without affecting CRM1 export, establishing the terminal NPC station for the NXF1 pathway.

    Evidence RNAi of RanBP2 in Drosophila cells; NXF1 localization by fluorescence microscopy; poly(A)+ RNA FISH

    PMID:14729961

    Open questions at the time
    • Mechanism of NXF1 release from RanBP2 into the cytoplasm unknown
    • Contribution of other cytoplasmic nucleoporins not excluded
  8. 2006 High

    Discovery that NXF1's own intron 10 contains a functional CTE whose retention produces an exported, translated short isoform revealed an autoregulatory feedback loop — the export receptor controls its own mRNA processing and export.

    Evidence RT-PCR, polyribosome fractionation, immunoblotting, and CTE export assays in Xenopus oocytes

    PMID:16971948

    Open questions at the time
    • Physiological conditions that modulate the ratio of full-length to short isoform unknown
    • Function of the small NXF1 protein product uncharacterized
  9. 2009 High

    THOC5 was shown to bind a surface on the NXF1 NTF2-like domain non-overlapping with Aly/REF, allowing simultaneous engagement, and was required specifically for HSP70 mRNA export — establishing that TREX subunits act as transcript-selective co-adaptors rather than generic loading factors.

    Evidence GST pulldown mapping; co-IP; siRNA with FISH for HSP70 mRNA

    PMID:19165146

    Open questions at the time
    • Full repertoire of THOC5-dependent transcripts unknown at this stage
    • Structural basis of simultaneous Aly/THOC5 binding not resolved
  10. 2010 High

    Arginine methylation of Aly/REF was shown to weaken its RNA affinity without disrupting the Aly–NXF1 protein interaction, thereby facilitating cargo handover from Aly to NXF1 — the first post-translational mechanism regulating adaptor-to-receptor RNA transfer.

    Evidence Mass spectrometry of methylation sites; in vitro RNA-binding with methylated/unmethylated REF; in vivo RIP; export assays

    PMID:20129943

    Open questions at the time
    • Whether other TREX adaptors are similarly regulated by PTMs unknown
    • Enzymes responsible for REF methylation not identified in this study
  11. 2011 High

    The intramolecular autoinhibition model was established: NXF1's N-terminal domains fold back to mask the RNA-binding surface, and TREX components (Aly + THOC5) relieve this inhibition to generate an open, RNA-competent conformation — explaining why NXF1 alone does not bind bulk mRNA.

    Evidence Biochemical conformation assay with recombinant proteins; siRNA double knockdown with RIP and FISH

    PMID:22893130

    Open questions at the time
    • Atomic-resolution structure of the closed autoinhibited conformation not available
    • Whether additional factors can also open NXF1 independently of TREX unknown
  12. 2011 High

    Identification of dual NLS epitopes (N-terminal basic and PY-NLS) recognized by multiple redundant karyopherins explained the robustness of NXF1 nuclear re-import and showed that mislocalization of NXF1 to the cytoplasm impairs mRNA export.

    Evidence Binding assays with recombinant karyopherins; NLS mutagenesis; localization microscopy; export assays

    PMID:21965294

    Open questions at the time
    • Relative contribution of each karyopherin under physiological conditions unknown
    • Whether NLS accessibility is regulated during the export cycle unresolved
  13. 2015 High

    The 3.4 Å crystal structure of NXF1 (RRM–LRR–NTF2-like)–NXT1 revealed a domain-swapped dimer forming a symmetric RNA-binding platform that explains recognition of the 2-fold symmetric CTE stem-loop, providing the first near-complete structural view of the export receptor.

    Evidence X-ray crystallography; biochemical RNA-binding assays; cellular export reporters

    PMID:25628361

    Open questions at the time
    • Structure of NXF1 bound to cellular mRNA (non-CTE) lacking
    • UBA domain not resolved in this crystal form
  14. 2016 High

    Transcriptome-wide iCLIP demonstrated that SR proteins SRSF3 and SRSF7 are major NXF1 adaptors that bind adjacent to NXF1 on mRNA last exons, conferring sequence specificity and coupling alternative polyadenylation to export — expanding the adaptor concept beyond TREX.

    Evidence iCLIP; siRNA knockdown with mRNA export assays; co-IP; reporter assays

    PMID:26944680

    Open questions at the time
    • Whether SR-mediated and TREX-mediated NXF1 recruitment are sequential or parallel on the same transcript unclear
    • Contribution of each SR protein to individual transcript export not fully resolved
  15. 2019 High

    NXF1 was found to coordinate transcription termination and alternative polyadenylation: its depletion causes Pol II accumulation at 3′ ends and proximal PAS usage, and it cooperates with CFI-68 to export long 3′ UTR isoforms, linking NXF1 to co-transcriptional RNA processing beyond splicing.

    Evidence siRNA; RNA-seq; 3′-seq; Pol II ChIP-seq; RIP; co-IP

    PMID:30819645

    Open questions at the time
    • Whether NXF1 directly modulates Pol II processivity or acts indirectly through RNA topology unknown
    • Mechanism of CFI-68–NXF1 cooperation at UGUA motifs not structurally defined
  16. 2019 High

    Super-resolution and live-cell imaging placed NXF1 predominantly at the cytoplasmic face of the NPC and showed it functions as a mobile NPC component: mRNP docking does not require NXF1, but cytoplasmic release does, with Dbp5 helicase providing the terminal remodeling step conserved from yeast to humans.

    Evidence Super-resolution microscopy; FLIM-FRET in single NPCs; Mex67–Nup116 fusion rescue in yeast; dominant-negative NXF1 experiments

    PMID:31375530 PMID:31753862

    Open questions at the time
    • How Dbp5 specifically strips NXF1 from mRNP at the cytoplasmic face not structurally resolved
    • Whether NXF1 residence time at the NPC is regulated under stress conditions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the atomic structure of autoinhibited NXF1, how multiple adaptor pathways (TREX, SR proteins, U2AF) are coordinated on a single transcript, and how NXF1-dependent export is regulated during stress, viral infection, and differentiation.
  • No structure of full-length NXF1 in the autoinhibited closed conformation
  • Hierarchical rules for adaptor engagement on individual transcripts undefined
  • Regulatory mechanisms modulating NXF1 activity under physiological stress not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005635 nuclear envelope 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-9609507 Protein localization 5 R-HSA-74160 Gene expression (Transcription) 2
Partners
ALYREFNXT1RANBP2RBM15BSRSF3SRSF7THOC5U2AF1
Complex memberships
NXF1-NXT1 heterodimerTREX complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 NXF1 (TAP) has a conserved modular architecture comprising an RNP-type RNA-binding domain, leucine-rich repeats (LRR), an NTF2-like domain that heterodimerizes with p15/NXT1, and a UBA-like domain that mediates interaction with nucleoporins. NXF2, a human paralog, binds RNA, localizes to the nuclear envelope, and has RNA export activity, while NXF3 lacks these activities. Domain deletion analysis, RNA-binding assays, nuclear envelope localization by microscopy, RNA export reporter assays Molecular and cellular biology High 11073998
2001 Overexpression of TAP/p15 (NXF1/NXT1) heterodimers bypasses nuclear retention and stimulates nuclear mRNA export. The LRR domain is essential for this activity, and the UBA-like domain strongly contributes. Heterodimer formation between NXF1 and p15 is required for efficient mRNA export. mRNA export reporter assays, domain deletion mutants, tethering assays in transfected cells The Journal of biological chemistry High 11259411
2002 NXF1-mediated mRNA export requires at minimum two nucleoporin-binding sites; these can be provided by the NTF2-like scaffold plus UBA-like domain, or by two copies of either domain in tandem. The function of the NTF2-like scaffold (and therefore p15) is confined to nucleoporin binding, not to imparting directionality or regulating cargo interactions per se. Domain swap/tandem duplication mutants expressed in cells; mRNA export reporter assays Molecular and cellular biology High 12101235
2002 NXT1/p15 functions as a critical cofactor for NXF1 (Tap)-mediated mRNA export by enhancing NXF1 binding to nucleoporins. Without NXT1, NXF1 cannot effectively interact with nuclear pore complex components, and both NXF1 nucleocytoplasmic shuttling and mRNA export are severely attenuated. Tap/NXT1 heterodimer forms a ternary complex with nucleoporins in vitro and in vivo. Co-IP, in vitro nucleoporin binding assays, mRNA export reporter assays in human and Drosophila cells; RNAi knockdown of Drosophila NXT1 causing poly(A)+ RNA nuclear accumulation Molecular and cellular biology High 11739738
2002 The C-terminal FG-nucleoporin binding domain of NXF1 (Tap) adopts a distinctive four-helix structure joined to adjacent modules by a flexible Pro-rich linker. The F617A mutation suppresses FG-nucleoporin binding by this domain, establishing the structural basis for nuclear shuttling. NMR solution structure; site-directed mutagenesis (F617A) Nature structural biology High 11875519
2001 NXT1/p15 stimulates binding of a Tap–RNA complex to nucleoporins in vitro, and this interaction is necessary for nuclear export of an intron-containing viral mRNA in vivo. NXF1 contains separate domains for nucleoporin binding and NXT1 binding, both critical for export. NXT1 regulates the affinity of the Tap–RNA complex for nucleoporins, including p62. In vitro nucleoporin binding assays with recombinant proteins; site-directed mutagenesis; nuclear export reporter assays in vivo The Journal of biological chemistry High 11579093
2003 NXF1 (TAP) forms a stable binary and ternary complex with the nucleoporins Rae1/Gle2 and Nup98. Gle2 requires two sites on TAP for stable interaction. TAP has highest affinity for a specific region within the GLFG domain of Nup98, not all FG repeats equally. Gle2 and Nup98 may compete for TAP binding, suggesting Gle2 delivers TAP to Nup98. Co-IP, pulldown with defined protein domains; binary and ternary complex formation assays The Journal of biological chemistry Medium 12637516
2004 RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the cytoplasmic filaments of the nuclear pore complex. Depletion of RanBP2 from Drosophila cells inhibits mRNA export and strongly reduces NXF1 localization at the NPC, releasing NXF1 into the cytoplasm; CRM1-dependent export and other nuclear/cytoplasmic proteins are unaffected. RNAi depletion of RanBP2 in Drosophila cells; fluorescence microscopy of NXF1 localization; poly(A)+ RNA FISH Molecular and cellular biology High 14729961
2006 NXF1 (Tap) contains an alternatively spliced intron 10 that harbors a functional constitutive transport element (CTE). The resulting intron-retaining Tap mRNA is exported to the cytoplasm and translated into a small Tap protein detectable in human and monkey cells, demonstrating autoregulation through CTE-mediated export of its own intron-containing mRNA. RT-PCR, polyribosome fractionation, immunoblotting for small Tap protein, reporter export assays in Xenopus oocytes Nature High 16971948
2006 Y14 (splicing factor) and NXF1 form mRNA export complexes that preferentially localize within and around nuclear speckles (SC35 domains) in living cells. BiFC and FRAP/FLIP reveal that roughly half the Y14–NXF1 complexes are immobile in vivo and depleted by ATP in permeabilized cells, suggesting ATP-dependent retention of a subset of mRNPs at speckles despite association with export proteins. Bimolecular fluorescence complementation (BiFC) in live MCF7 cells; FRAP; FLIP; co-immunoprecipitation The Journal of cell biology Medium 16431928
2001 U2AF35 (small subunit of splicing factor U2AF) directly binds a distinct region of NXF1 (TAP) that also targets TAP to spliced mRNP. U2AF65 overexpression recruits U2AF35 and TAP to spliced mRNP and stimulates nuclear export, suggesting U2AF participates in mRNA export by facilitating TAP recruitment. Yeast two-hybrid, in vitro binding assays, immunoprecipitation of mRNP, export reporter assays The Journal of biological chemistry Medium 11724776
2009 THOC5 (a TREX complex subunit) binds a distinct surface on the NTF2-like domain of NXF1 (Tap-p15), at a site non-overlapping with the Aly/REF binding site, allowing simultaneous binding. THOC5 is required for nuclear export of HSP70 mRNA but not bulk mRNA, identifying it as a specific export co-adaptor. GST pulldown mapping of binding surfaces; co-immunoprecipitation; siRNA knockdown with mRNA export assays (FISH for HSP70 mRNA) The EMBO journal High 19165146
2010 Arginine methylation of REF/ALY reduces its RNA-binding activity in vitro and in vivo. This reduced affinity is essential for efficient displacement of RNA from REF by NXF1 (TAP), promoting handover of mRNA cargo to NXF1. Arginine methylation does not affect the REF–TAP protein–protein interaction. Mass spectrometry mapping of methylation sites; in vitro RNA-binding assays with methylated/unmethylated REF; in vivo RNA immunoprecipitation; mRNA export assays Nucleic acids research High 20129943
2011 NXF1 uses an intramolecular interaction to inhibit its own RNA-binding activity. When TREX subunits Aly and THOC5 contact NXF1, NXF1 adopts an open conformation that exposes its RNA-binding domain, enabling RNA binding. Combined knockdown of Aly and THOC5 reduces NXF1 bound to mRNA in vivo and causes severe mRNA export block. Biochemical conformation assay; RNA-binding assays with recombinant proteins; siRNA double knockdown with RNA immunoprecipitation and FISH Nature communications High 22893130
2011 The mammalian nuclear pore protein Tpr restricts nuclear export of mRNAs with retained introns that traffic through the NXF1/NXT1 pathway. Knockdown of Tpr significantly increases export and translation of CTE-containing mRNA (NXF1 pathway), but has no effect on Rev/RRE-dependent (CRM1 pathway) or completely spliced mRNA export. RNAi knockdown of Tpr; mRNA export reporter assays comparing CTE vs. RRE pathways RNA (New York, N.Y.) Medium 21613532
2011 Multiple karyopherins (importin β, karyopherin β2/transportin, importin 4, importin 11, importin α) can import NXF1 into the nucleus by recognizing two NLS epitopes in the N-terminal tail: an N-terminal basic segment and a C-terminal PY-NLS (R-X2-5-P-Y motif). Mutation of both epitopes mislocalizes NXF1 to the cytoplasm and significantly impairs mRNA export. Biochemical binding assays with recombinant karyopherins; mutagenesis of NLS epitopes; fluorescence microscopy of NXF1 localization; mRNA export assays Molecular biology of the cell High 21965294
2015 Crystal structure of human NXF1 (first three domains: RRM, LRR, NTF2-like) together with NXT1 at 3.4 Å resolution reveals a domain-swapped dimer forming a 2-fold symmetric RNA-binding platform. The linker between LRR and NTF2-like domains interacts with NXT1. This symmetric platform facilitates recognition and export of CTE-RNA (a 2-fold symmetric stem-loop), as confirmed by biochemical and cellular assays. X-ray crystallography; biochemical RNA-binding assays; mRNA export reporter assays in cells Nucleic acids research High 25628361
2016 SR proteins (SRSF1–7) function as NXF1 export adaptors, coupling pre-mRNA processing to mRNA export. iCLIP analysis shows NXF1 and SR proteins bind mRNA at adjacent sites. SRSF3 is the most potent NXF1 adaptor, conferring sequence specificity to NXF1 RNA binding in last exons. SRSF3 and SRSF7 bind different sites in last exons, regulate 3' UTR length in opposing ways, and both promote NXF1 recruitment to mRNA, coupling alternative splicing/polyadenylation to NXF1-mediated export. iCLIP transcriptome-wide mapping; siRNA knockdown with mRNA export assays; co-IP; reporter assays Genes & development High 26944680
2019 NXF1 coordinates transcriptional dynamics, alternative polyadenylation (APA), and mRNA export. NXF1 knockdown results in RNA polymerase II accumulation at the 3' end of genes and promotes usage of proximal PASs (shorter 3' UTRs). NXF1 cooperates with CFI-68 to facilitate nuclear export of long 3' UTR isoforms bearing UGUA motifs. siRNA knockdown; RNA-seq; 3'-seq for APA analysis; ChIP-seq for Pol II; RNA immunoprecipitation; co-IP Molecular cell High 30819645
2019 In living yeast, Mex67 (NXF1 ortholog) localizes to the NPC independently of mRNA, occupying FG-repeat binding sites. Its essential function is spatially restricted to the NPC: a fusion of Mex67 to nucleoporin Nup116 rescues MEX67 deletion. Mex67 functions as a mobile NPC component that receives mRNA export substrates at the central channel. Quantitative live-cell fluorescence microscopy (FRAP, single-molecule); genetic complementation with Mex67-Nup116 fusion The Journal of cell biology High 31753862
2019 NXF1 localizes consistently to the cytoplasmic side of nuclear pore complexes as shown by super-resolution microscopy. Initial mRNP binding to the NPC does not require NXF1, but release into the cytoplasm does. FLIM-FRET inside single NPCs shows that Dbp5 helicase-mediated mRNA release is conserved from yeast to humans. Super-resolution microscopy; FLIM-FRET in single NPCs; dominant-negative NXF1 and mRNA export block experiments The Journal of cell biology High 31375530
2003 The Nxf1 natural allele Mvb1 from Mus musculus castaneus suppresses the effects of retrovirus insertional mutations by controlling levels of correctly processed mRNA, revealing an unexpected link between the mRNA export receptor NXF1 and pre-mRNA processing. Positional complementation cloning; congenic mouse strains; mRNA processing assays Nature genetics Medium 14517553
2009 RBM15B/OTT3 directly interacts with NXF1 via its C-terminal region (mapped by mutagenesis) and also binds Aly/REF, functioning as a cofactor of NXF1 to regulate mRNA export. OTT3 (and the paralog RBM15) associates with the nuclear envelope and splicing factor compartment. Co-immunoprecipitation; mutational analysis; subcellular localization by microscopy The Journal of biological chemistry Medium 19586903
2009 EBV protein EB2 contains an N-terminal nuclear export signal (NES, aa 61–146) with arginine-rich domains that directly interact with NXF1/TAP, and this interaction mediates CRM1-independent nuclear export of viral and reporter mRNAs. Co-IP; domain deletion mapping; RNA export reporter assays; tethering assays with MS2-coat protein Journal of virology Medium 19793817
2011 U2AF65 interacts directly and specifically with expanded CAG repeat RNA via its RRM3 domain. U2AF65, expanded CAG RNA, and NXF1 form an RNA/protein complex in which U2AF65 acts as an adaptor to link the expanded CAG RNA to NXF1 for nuclear export. Reduction of U2AF50/65 function exacerbates nuclear accumulation of expanded CAG RNA and toxicity in Drosophila and mouse models. RNA immunoprecipitation; co-immunoprecipitation; RNAi and mutant analysis in Drosophila; polyQ transgenic mice Human molecular genetics Medium 21725067
2002 An element in the 3' UTR of human LINE-1 retrotransposons (L1-NBE) binds NXF1 (TAP) in vitro as strongly as the viral CTE, but uses a different and only partially overlapping binding domain on NXF1. L1-NBE can mediate nuclear export of unspliced RNAs in Xenopus oocytes and human cells, suggesting NXF1 mediates export of endogenous intronless retrotransposon mRNAs. In vitro RNA selection (SELEX-like); gel mobility shift competition assays; domain deletion of NXF1; export reporter assays in Xenopus oocytes and human cells RNA (New York, N.Y.) Medium 12003494
2024 ISGylation of hnRNPA2B1 (mediated by PCAT6 lncRNA scaffolding ISG15) protects hnRNPA2B1 from ubiquitin-mediated degradation. As an m6A reader, hnRNPA2B1 selectively mediates nuclear export of m6A-tagged mRNAs via the ALYREF/NXF1 complex, promoting stemness gene expression in breast cancer. Co-immunoprecipitation; RNA immunoprecipitation; siRNA knockdown; m6A-seq; nuclear/cytoplasmic fractionation Advanced science Medium 38626369
2021 SRSF1 and SRSF7 bind clustered motifs within the cytoplasmic accumulation region (CAR-N) of intronless lncRNA NKILA, facilitating TREX complex recruitment and subsequent NXF1-dependent (TREX-TAP pathway) nuclear export of NKILA. NKILA lacking CAR-N is retained in the nucleus and cannot inhibit breast cancer cell migration. RNP pulldown with mass spectrometry; siRNA screening; RNA FISH; co-IP; nuclear/cytoplasmic fractionation; knock-in cell models Nucleic acids research Medium 34096602
2010 NXF1/TAP is required for nuclear export of specific influenza A virus mRNAs. siRNA depletion of NXF1 inhibits nuclear export of intronless HA mRNA and spliced M2/unspliced M1 transcripts (late genes), while early gene mRNAs show less dependency. This indicates influenza co-opts the NXF1 mRNA export pathway for a subset of its mRNAs. siRNA knockdown of NXF1, Aly, and UAP56; RNA FISH/fractionation for viral mRNA localization; comparison to DRB treatment The Journal of general virology Medium 20071484
2014 NXF1 is required for nuclear export of both spliced and unspliced murine leukemia virus (MLV) RNA transcripts. A cis-acting element in the MLV pol gene (CAE) interacts with NXF1, and NXF1 disruption abolishes CAE function and causes nuclear retention or degradation of viral RNAs. siRNA knockdown of NXF1; RNA FISH and nuclear/cytoplasmic fractionation; CAE-NXF1 interaction by pulldown Journal of virology Medium 24478440

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The tandem affinity purification (TAP) method: a general procedure of protein complex purification. Methods (San Diego, Calif.) 1369 11403571
1994 Homozygous human TAP peptide transporter mutation in HLA class I deficiency. Science (New York, N.Y.) 244 7517574
2016 SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export. Genes & development 237 26944680
1998 TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Current biology : CB 228 9427624
1994 Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cells. FEBS letters 180 8082812
2000 TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Molecular and cellular biology 173 11073998
2012 TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nature communications 165 22893130
2004 The ABCs of immunology: structure and function of TAP, the transporter associated with antigen processing. Physiology (Bethesda, Md.) 152 15304636
2018 Veterinary pharmaceutical residues from natural water to tap water: Sales, occurrence and fate. Journal of hazardous materials 148 30179788
2007 Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2. Molecular cell 129 17434126
2009 Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. The EMBO journal 117 19165146
2006 Ubiquitin-associated domain of Mex67 synchronizes recruitment of the mRNA export machinery with transcription. Proceedings of the National Academy of Sciences of the United States of America 115 17056718
2001 Overexpression of TAP/p15 heterodimers bypasses nuclear retention and stimulates nuclear mRNA export. The Journal of biological chemistry 114 11259411
2003 Complex formation among the RNA export proteins Nup98, Rae1/Gle2, and TAP. The Journal of biological chemistry 113 12637516
2016 Relationship between antibiotic- and disinfectant-resistance profiles in bacteria harvested from tap water. Chemosphere 103 26966812
2006 An intron with a constitutive transport element is retained in a Tap messenger RNA. Nature 101 16971948
2002 Formation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Molecular and cellular biology 98 11739738
1999 Function of the transport complex TAP in cellular immune recognition. Biochimica et biophysica acta 95 10581370
2004 RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the nuclear pore complex and functions in nuclear mRNA export. Molecular and cellular biology 88 14729961
2002 Nuclear export of mRNA by TAP/NXF1 requires two nucleoporin-binding sites but not p15. Molecular and cellular biology 86 12101235
2010 Individual influenza A virus mRNAs show differential dependence on cellular NXF1/TAP for their nuclear export. The Journal of general virology 84 20071484
2019 Anthropogenic gadolinium in tap water and in tap water-based beverages from fast-food franchises in six major cities in Germany. The Science of the total environment 81 31412473
1994 Altered natural killer cell repertoire in Tap-1 mutant mice. Proceedings of the National Academy of Sciences of the United States of America 81 8022815
2015 Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution. PLoS pathogens 78 25880312
1998 Chimeric chemoreceptors in Escherichia coli: signaling properties of Tar-Tap and Tap-Tar hybrids. Journal of bacteriology 76 9473047
1999 Specificity of the proteasome and the TAP transporter. Current opinion in immunology 72 10322157
2001 The transporter associated with antigen processing (TAP): structural integrity, expression, function, and its clinical relevance. Molecular medicine (Cambridge, Mass.) 69 11471551
1997 Interferon-gamma rapidly increases peptide transporter (TAP) subunit expression and peptide transport capacity in endothelial cells. The Journal of biological chemistry 69 9195970
2011 The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA (New York, N.Y.) 68 21613532
2008 Features of TAP-independent MHC class I ligands revealed by quantitative mass spectrometry. European journal of immunology 67 18446792
2018 Identification of non-mutated neoantigens presented by TAP-deficient tumors. The Journal of experimental medicine 63 30115740
2002 Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1. Nature structural biology 63 11875519
1997 Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity 60 9175835
2012 Role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. PLoS genetics 59 22956913
2006 In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains. The Journal of cell biology 59 16431928
2001 U2AF participates in the binding of TAP (NXF1) to mRNA. The Journal of biological chemistry 58 11724776
1988 T cell receptor/CD3 negative variants are unresponsive to stimulation through the Ly-6 encoded molecule, TAP. Journal of immunology (Baltimore, Md. : 1950) 58 2842394
2012 Functional and genetic characterization of the tap efflux pump in Mycobacterium bovis BCG. Antimicrobial agents and chemotherapy 57 22232275
2021 Spotlight on TAP and its vital role in antigen presentation and cross-presentation. Molecular immunology 55 34973498
2010 Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1. Nucleic acids research 54 20129943
2001 Enhanced expression of human ABC-transporter tap is associated with cellular resistance to mitoxantrone. FEBS letters 54 11513878
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2019 The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export. Molecular cell 45 30819645
2023 Tumor Area Positivity (TAP) score of programmed death-ligand 1 (PD-L1): a novel visual estimation method for combined tumor cell and immune cell scoring. Diagnostic pathology 44 37076889
2009 Genetic variants in TAP are associated with high-grade cervical neoplasia. Clinical cancer research : an official journal of the American Association for Cancer Research 44 19188174
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2021 TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming. Nature immunology 41 33790474
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2011 EBV protein BNLF2a exploits host tail-anchored protein integration machinery to inhibit TAP. Journal of immunology (Baltimore, Md. : 1950) 39 21296983
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2000 Synergistic induction of the Tap-1 gene by IFN-gamma and lipopolysaccharide in macrophages is regulated by STAT1. Journal of immunology (Baltimore, Md. : 1950) 37 10975834
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2010 Export of adenoviral late mRNA from the nucleus requires the Nxf1/Tap export receptor. Journal of virology 29 21123381
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