Affinage

DDX19B

ATP-dependent RNA helicase DDX19B · UniProt Q9UMR2

Length
479 aa
Mass
53.9 kDa
Annotated
2026-04-28
44 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX19B is a DEAD-box RNA-dependent ATPase that functions as the principal mRNP remodeling enzyme at the cytoplasmic face of the nuclear pore complex, imposing directionality on mRNA export by displacing RNA-binding proteins such as Nab2 and Mex67/NXF1 from exiting transcripts in its ADP-bound state (PMID:18082609, PMID:33002012). Its ATPase cycle is spatially regulated at the NPC through anchoring to NUP214, activation by a Gle1–InsP6–Nup42 complex that couples ATP binding and accelerates rate-limiting Pi release, and an N-terminal autoregulatory helix that modulates interdomain conformation (PMID:10428971, PMID:16783363, PMID:28869701, PMID:19244245, PMID:35286399). Beyond mRNA export, DDX19B participates in translation termination by stabilizing pre-termination complexes and delivering eRF1, in tRNA export through a Gle1-dependent ATPase cycle, in ATR/Chk1-directed nuclear relocalization to resolve R-loops at replication–transcription conflicts, and in spatial control of CBC-dependent translation by tethering CTIF at the perinuclear region (PMID:17272721, PMID:28180304, PMID:38189406, PMID:28314779, PMID:34232997). DDX19B also negatively regulates type I interferon signaling by recruiting Lamtor2 to disrupt TBK1/IKKε–IRF3 interactions and promote kinase degradation (PMID:30699353).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 High

    Establishing DDX19B as an NPC-associated ATPase required for mRNA export resolved how directional transport is powered at the nuclear pore: hDbp5 localizes to cytoplasmic NPC fibrils via NUP214, and a DEAD-box mutation dominantly blocks mRNA export.

    Evidence Co-IP, immunoelectron microscopy, and dominant-negative microinjection in Xenopus oocytes

    PMID:10428971

    Open questions at the time
    • Mechanism of mRNP remodeling unknown
    • Regulatory cofactors unidentified
    • Structural basis for NUP214 interaction unresolved
  2. 2004 High

    Determining the crystal structure of the Nup159 β-propeller bound to Dbp5 established the structural basis for NPC tethering and showed it is essential for mRNA export in vivo.

    Evidence X-ray crystallography (2.5 Å) with structure-guided mutagenesis and in vivo export assays in yeast

    PMID:15574330

    Open questions at the time
    • Nucleotide-state dependence of docking unclear
    • How tethering translates to remodeling activity unknown
  3. 2006 High

    Identification of Gle1–InsP6 as a direct activating complex for DDX19B's ATPase activity revealed the spatial regulatory logic: cofactors concentrated at the NPC stimulate the enzyme precisely where mRNP remodeling must occur.

    Evidence In vitro ATPase kinetics, genetic suppression, and in vivo mRNA export assays in two independent studies

    PMID:16783363 PMID:16783364

    Open questions at the time
    • Kinetic mechanism of activation (which step accelerated) unresolved
    • InsP6 binding site on complex unknown
  4. 2007 High

    Demonstrating that DDX19B displaces the RNA-binding protein Nab2 specifically in its ADP-bound state established the remodeling mechanism: ADP binding, not ATP hydrolysis per se, drives the conformational change that strips export factors from mRNA.

    Evidence In vitro RNP remodeling assays with nucleotide-state mutants plus in vivo genetics

    PMID:18082609

    Open questions at the time
    • Full spectrum of displaced RNA-binding proteins unknown
    • Whether remodeling is processive or single-turnover unclear
  5. 2007 High

    Discovery that Dbp5 physically interacts with eRF1 and is required for stop-codon recognition expanded its functional repertoire beyond mRNA export to translation termination.

    Evidence Co-IP, genetic epistasis with eRF1/eRF3/Pab1, helicase-mutant analysis, and in vivo termination assays in yeast

    PMID:17272721

    Open questions at the time
    • Whether mRNA export and termination functions are mechanistically coupled unknown
    • Mammalian reconstitution lacking at this stage
  6. 2009 High

    A series of crystal structures of human DDX19B in multiple nucleotide/ligand states revealed mutually exclusive RNA and NUP214 binding, the N-terminal autoregulatory helix, and the Gle1-binding interface, providing an integrated structural framework for its catalytic cycle.

    Evidence X-ray crystallography of DDX19B–RNA–AMPPNP, DDX19B–NUP214, DDX19B open/closed states, and DDX19B C-terminal domain, all with biochemical and mutagenesis validation

    PMID:19208808 PMID:19219046 PMID:19244245 PMID:19805289

    Open questions at the time
    • Full reconstituted NPC-like complex structure lacking
    • How N-terminal helix regulation integrates with Gle1 activation kinetically unclear
  7. 2011 High

    Reconstitution of the nucleotide cycle showed that Nup159 promotes ADP release (later refined to Gle1 dissociation) while Gle1–IP6 primes ATP binding, defining the ordered cofactor logic at the NPC; FRAP revealed sub-second dynamic NPC association of DDX19B.

    Evidence In vitro nucleotide-binding/release assays, Dbp5-Nup159 bypass mutants, FRAP in yeast and human cells

    PMID:21576265 PMID:21576266

    Open questions at the time
    • Exact role of Nup159 (nucleotide exchange vs. Gle1 release) debated
    • Single-molecule kinetics at NPCs lacking
  8. 2015 High

    Detailed pre-steady-state kinetics quantified the DDX19B ATPase cycle — weak ATP binding (~4 mM Kd), 10-fold tighter ADP binding, and rate-limiting Pi release accelerated ~20-fold by RNA — establishing the biophysical basis for cofactor regulation.

    Evidence Stopped-flow kinetics and equilibrium binding assays

    PMID:26730886

    Open questions at the time
    • Gle1's kinetic mechanism not yet quantified at this stage
    • Physiological nucleotide concentrations not modeled
  9. 2015 Medium

    Identification of DDX19B's role in MKL1 nuclear import — requiring RNA binding but not helicase or NPC-binding activities — established the first export-independent nuclear import function for this helicase.

    Evidence siRNA knockdown, domain-mutant rescue, Co-IP, and nuclear import assays in mammalian cells

    PMID:25585691

    Open questions at the time
    • Mechanism by which RNA binding alters MKL1 conformation unresolved
    • Not independently replicated
    • Whether this function is conserved in yeast unknown
  10. 2016 Medium

    Showing that DDX19B is required for pre-ribosomal subunit export but in an ATPase-independent manner distinguished this function mechanistically from mRNA export, suggesting a scaffolding or capture role at the NPC.

    Evidence Yeast temperature-sensitive mutants, ATPase-deficient alleles, Co-IP with Nmd3, fluorescence microscopy

    PMID:26872259

    Open questions at the time
    • Whether DDX19B directly contacts pre-ribosomal particles or acts indirectly unknown
    • Human validation lacking
  11. 2017 High

    Reconstitution with mammalian DDX19 confirmed its role in translation termination — increasing termination complex formation and peptide release — extending the yeast findings and showing nucleotide-dependent association with pre-termination complexes.

    Evidence Reconstituted mammalian in vitro translation system with sucrose gradient sedimentation

    PMID:28180304

    Open questions at the time
    • Structural basis for DDX19–ribosome interaction unknown
    • Whether mRNA export and termination pools of DDX19B are distinct in vivo unclear
  12. 2017 High

    Discovery that DDX19B relocalizes from NPCs to the nucleus under replication stress via ATR/Chk1 phosphorylation to resolve R-loops established a DNA damage response function: Chk1-phosphorylation disrupts NUP214 binding, and nuclear DDX19B's helicase activity unwinds DNA:RNA hybrids.

    Evidence Live-cell imaging, R-loop immunofluorescence, in vitro helicase assay, phosphorylation mutants, DNA fiber assays

    PMID:28314779

    Open questions at the time
    • Specific Chk1 phosphorylation site(s) not fully mapped
    • Whether R-loop resolution is a direct helicase activity on DNA:RNA hybrids in vivo confirmed only indirectly
  13. 2017 High

    Establishing that Nup42 is required for Gle1-mediated DDX19B activation — forming a Nup42–Gle1–Dbp5 trimeric complex with InsP6 — completed the NPC-resident activating module architecture.

    Evidence In vitro ATPase reconstitution with yeast and human proteins, Co-IP, mRNA export assays

    PMID:28869701

    Open questions at the time
    • Structural model of complete trimeric activating complex lacking
    • Stoichiometry at NPCs unknown
  14. 2018 High

    Revised kinetic analysis showed Nup159 does not accelerate ADP release but instead weakens the Gle1–ADP–Dbp5 ternary complex ~18-fold, redefining Nup159's role as facilitating Gle1 recycling rather than acting as a nucleotide exchange factor.

    Evidence Stopped-flow kinetics and fluorescence equilibrium binding assays

    PMID:29782832

    Open questions at the time
    • Whether Nup159 also modulates other steps in the full NPC context unknown
    • Reconciliation with the 2011 model not fully settled
  15. 2019 High

    Discovery that DDX19B negatively regulates type I interferon production — by recruiting Lamtor2 to disrupt TBK1/IKKε–IRF3 interactions and promote kinase degradation — revealed an innate immune signaling function validated by knockout mice with augmented IFN production.

    Evidence Reciprocal Co-IP, TALEN-generated knockout mice, virus infection assays

    PMID:30699353

    Open questions at the time
    • Whether this immune function requires ATPase or RNA-binding activities unknown
    • Mechanism of Lamtor2 recruitment unclear
  16. 2019 Medium

    Identification of an N-terminal Xpo1-dependent NES in Dbp5 and separation-of-function alleles showing that nuclear shuttling is dispensable for mRNA export but specifically required for tRNA export established tRNA export as a distinct DDX19B function.

    Evidence Systematic alanine scanning mutagenesis (456 viable mutants), tRNA export assays in yeast

    PMID:31453808

    Open questions at the time
    • Mechanism of DDX19B action on tRNA substrates unknown at this point
    • Human tRNA export role not tested
  17. 2021 Medium

    Demonstrating that DDX19B tethers CTIF at the perinuclear region in a translationally incompetent state and hands it to CBP80 upon mRNA export established DDX19B as a spatial organizer of CBC-dependent translation and nonsense-mediated decay.

    Evidence Co-IP, fluorescence microscopy, siRNA knockdown, dominant-negative mutants, NMD reporter assays

    PMID:34232997

    Open questions at the time
    • Structural basis for DDX19B–CTIF interaction unknown
    • Whether this mechanism operates on all or a subset of mRNAs unclear
  18. 2022 High

    Quantitative kinetic dissection showed Gle1 activates DDX19B by two mechanisms — thermodynamic coupling that stabilizes the ATP-bound state (>100-fold preferential binding) and acceleration of rate-limiting Pi release (~20-fold) — providing the definitive kinetic model for the activating complex.

    Evidence Kinetic and equilibrium fluorescence assays, in vitro ATPase reconstitution

    PMID:35286399

    Open questions at the time
    • How InsP6 and Nup42 quantitatively modulate these two mechanisms not fully integrated
    • In vivo validation of kinetic parameters lacking
  19. 2022 Medium

    Identification of SUMOylation at K26 as a modification that enhances DDX19B–Gle1 interaction and is required for full mRNA export rescue added a post-translational regulatory layer to the ATPase cycle.

    Evidence In vivo SUMOylation assay, Co-IP, siRNA rescue with K26R mutant

    PMID:35080244

    Open questions at the time
    • SUMOylation dynamics and triggering signals unknown
    • Whether K26 SUMOylation affects other DDX19B functions (termination, R-loop resolution) untested
  20. 2024 Medium

    Direct demonstration that Dbp5 binds tRNA and functions in tRNA export parallel to Los1 — with tRNA synergizing with Gle1 to fully activate Dbp5 ATPase — defined the molecular mechanism for the tRNA export role first genetically identified in 2019.

    Evidence Co-IP, in vitro ATPase assays with tRNA, dominant-negative overexpression, genetic epistasis in yeast

    PMID:38189406

    Open questions at the time
    • Whether DDX19B remodels tRNP complexes analogously to mRNP remodeling unknown
    • Human tRNA export function not yet demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for the complete NPC-resident DDX19B activation complex in situ, how the multiple functions (mRNA export, tRNA export, translation termination, R-loop resolution, immune signaling) are partitioned among cellular pools, and whether substrate-specific cofactor interactions determine functional selectivity.
  • No cryo-EM or cryo-ET structure of DDX19B at the intact NPC
  • Partitioning of DDX19B pools among its many functions not quantified
  • Regulation by SUMOylation and Chk1 phosphorylation not integrated into a unified model

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0003723 RNA binding 4 GO:0098772 molecular function regulator activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005635 nuclear envelope 5 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-9609507 Protein localization 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
CTIFERF1GLE1LAMTOR2NUP214NUP42RBM15SLIP1
Complex memberships
Gle1–Nup42–InsP6 activation complexNUP214–DDX19B NPC docking complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human DBP5 (hDbp5/DDX19B) localizes to the cytoplasmic fibrils of the nuclear pore complex (NPC) via a direct interaction with the nucleoporin CAN/NUP214 (N-terminal region); a DEAD-box mutation (Glu→Gln) acts as a dominant-negative inhibitor of mRNA export in Xenopus oocytes, establishing that RNA-dependent ATPase activity is required for mRNA export. Co-immunoprecipitation, immunoelectron microscopy, direct binding assays, dominant-negative microinjection in Xenopus oocytes The EMBO journal High 10428971
2004 The N-terminal beta-propeller domain of yeast Nup159 (human NUP214 ortholog) directly binds Dbp5/DDX19; structure-based mutations in a conserved loop abolish Dbp5 binding in vitro, mislocalize Dbp5 from the NPC in vivo, and block mRNA export, demonstrating that NPC tethering of Dbp5 via Nup159 is essential for mRNA export. X-ray crystallography (2.5 Å), in vitro binding assays, structure-guided mutagenesis, in vivo mRNA export assays Molecular cell High 15574330
2006 Inositol hexakisphosphate (InsP6) and the NPC-associated protein Gle1 together stimulate the RNA-dependent ATPase activity of Dbp5/DDX19B; InsP6 requires both Dbp5 and Gle1 for maximal binding and lowers the RNA concentration needed for half-maximal ATPase activity; overexpression of DBP5 suppresses mRNA export defects caused by InsP6/Gle1 loss. In vitro ATPase kinetic assays, genetic suppression, in vivo mRNA export assays Nature cell biology High 16783363
2006 Gle1 is a direct cellular activator of Dbp5/DDX19B: Gle1 alone stimulates Dbp5 RNA binding and ATP hydrolysis, and InsP6 potentiates Gle1-mediated activation; a Gle1 point mutant deficient for Dbp5 stimulation in vitro shows mRNA export defects in vivo; dominant suppressor mutations in DBP5 and GLE1 mimic InsP6 effects in vitro. In vitro ATPase and RNA-binding assays, dominant suppressor mutagenesis, in vivo mRNA export assays Nature cell biology High 16783364
2007 Dbp5/DDX19B acts as an RNP remodeling protein at the NPC by displacing the RNA-binding protein Nab2 from mRNA; this remodeling requires the ADP-bound (not ATP-bound) form of Dbp5, indicating that ADP binding rather than ATP hydrolysis drives the conformational change for protein displacement. In vitro RNP remodeling assays, nucleotide-state-specific mutants, in vivo genetic analysis of nab2 and dbp5 mutants Molecular cell High 18082609
2007 Dbp5/DDX19B functions in translation termination in S. cerevisiae: it physically interacts with release factor eRF1, genetically interacts with eRF1, eRF3, and Pab1, and its helicase activity is required for efficient stop-codon recognition and for recruitment of eRF3 into termination complexes. Co-immunoprecipitation, genetic interaction analysis, helicase-activity mutants, in vivo translation termination assays Science High 17272721
2009 Crystal structures of human DDX19B bound to RNA+AMPPNP and bound to NUP214 reveal that RNA binding and NUP214 binding to DDX19B are mutually exclusive; NUP214 decreases both RNA binding and ATPase activities of DDX19B; interactions are mediated by conserved residues. X-ray crystallography, in vitro ATPase and RNA-binding assays, mutagenesis Nature structural & molecular biology High 19219046
2009 Crystal structures of human DDX19B in RNA-bound/prehydrolysis (closed cleft) and free/posthydrolysis (open cleft) states reveal an N-terminal alpha-helix that inserts between the two conserved RecA-like domains in the open conformation to negatively autoregulate ATPase activity; biochemical data confirm this N-terminal autoregulatory function. X-ray crystallography, biochemical ATPase assays, truncation analysis The Journal of biological chemistry High 19244245
2009 Crystal structure of the Nup214 N-terminal domain in complex with DDX19B (ADP-bound state) at 2.5 Å; the interaction surfaces show opposing surface potentials (helicase positive, Nup214 negative); binding interfaces are evolutionarily conserved, providing a structural basis for NPC docking of DDX19B. X-ray crystallography (2.5 Å), structural and biochemical analysis Proceedings of the National Academy of Sciences of the United States of America High 19208808
2009 Crystal structure of the C-terminal domain of Dbp5/DDX19B (1.8 Å) reveals a RecA-like fold with a unique C-terminal alpha-helix and loop; structure-guided mutagenesis of conserved charged surface residues identifies the Gle1-binding interface; mutations that weaken Gle1 binding and ATPase stimulation in vitro are lethal in vivo. X-ray crystallography, structure-guided mutagenesis, in vitro ATPase assays, yeast viability assays Proceedings of the National Academy of Sciences of the United States of America High 19805289
2009 RBM15 directly binds human DBP5 and facilitates DBP5's contact with mRNA in vivo; RBM15 co-localizes with DBP5 and NXF1 at the nuclear envelope; silencing RBM15 leads to cytoplasmic depletion and nuclear accumulation of mRNA, indicating RBM15 promotes recognition of NXF1-mRNP by DBP5 at the NPC. Co-immunoprecipitation, RNA immunoprecipitation, siRNA knockdown, fluorescence microscopy Nucleic acids research Medium 19786495
2011 Nup159 functions as an ADP release factor for Dbp5/DDX19B: in vitro reconstitution assays show Nup159 is specifically required for ADP release from Dbp5, while Gle1-IP6 stimulates ATP binding to prime Dbp5 for RNA loading; a dbp5 mutant with reduced ADP binding bypasses the need for Nup159 interaction in vivo. In vitro nucleotide-binding and release assays, reconstitution, in vivo mutant analysis Genes & development High 21576266
2011 ATP binding and hydrolysis are required for efficient Dbp5 association with NPCs; RNA-binding-deficient Dbp5 mutants are dominant-negative for mRNA export by competing with wild-type Dbp5 for Gle1 at NPCs; FRAP shows Dbp5 associates with NPCs very dynamically (~<1 sec); Dbp5-Gle1 interaction can be independent of Nup159. Mutant analysis, dominant-negative assays, FRAP (yeast and human cells), in vivo mRNA export assays Genes & development High 21576265
2013 DBP5/DDX19B contains a SLIP1-binding motif (SBM) and directly interacts with SLIP1 (a MIF4G-domain protein involved in translation initiation); crystal structure of SLIP1 bound to the DBP5 SBM was determined at 3.25 Å, identifying a physical link between the mRNA export factor and translational machinery. X-ray crystallography (3.25 Å), pull-down assays Nucleic acids research Medium 23804756
2015 Kinetic analysis of the Dbp5/DDX19B ATPase cycle shows that ATP binds weakly (KT ~4 mM) while ADP binds ~10-fold more tightly; RNA increases kcat and rate-limiting Pi release ~20-fold but Pi release remains rate-limiting even with RNA; identifying RNA binding and Pi release as critical biochemical transitions in the Dbp5 cycle. Stopped-flow kinetics, equilibrium binding assays, in vitro ATPase assays Journal of molecular biology High 26730886
2015 Ddx19/Dbp5 is required for nuclear import of the transcriptional coactivator MKL1; this function is distinct from its mRNA export role; RNA-binding activity of Ddx19 (but not helicase or NPC-binding activities) is required; Ddx19 modulates the conformation of MKL1 to facilitate its interaction with Importin-β. siRNA knockdown, domain-mutant rescue assays, co-immunoprecipitation, nuclear import assays Nature communications Medium 25585691
2016 Dbp5/DDX19B is required for nuclear export of both pre-ribosomal subunits in yeast; genetic and physical interactions occur with the ribosomal transport factor Nmd3; however, unlike mRNA export, ATPase-deficient dbp5 mutants and gle1 mutants do not block ribosomal export, indicating DDX19B supports ribosomal transport through NPC localization/capture rather than ATPase-dependent remodeling. Yeast temperature-sensitive mutants, co-immunoprecipitation, fluorescence microscopy, ATPase-deficient mutants PloS one Medium 26872259
2017 DDX19 (mammalian Dbp5 ortholog) participates in translation termination: it associates with translating ribosome fractions, interacts with pre-termination complexes in a nucleotide-dependent manner, increases termination complex formation and peptide release by eukaryotic release factors, and stabilizes ribosome complexes with elongation factors eEF1 and eEF2. Reconstituted mammalian in vitro translation system, sucrose gradient sedimentation, eRF1(AGQ) and non-hydrolysable GTP inhibitor assays Nucleic acids research High 28180304
2017 Ddx19 (human DDX19B ortholog) relocalizes from the nucleopore to the nucleus upon DNA damage or replication stress in an ATR/Chk1-dependent manner; nuclear Ddx19 resolves R-loops (DNA:RNA hybrids) via its helicase activity in vitro; mutation of a Chk1-phosphorylated residue disrupts Ddx19 interaction with Nup214 and allows nuclear relocalization; Ddx19 depletion causes R-loop accumulation, DNA damage, and replication fork progression defects. Live-cell imaging, R-loop immunofluorescence, in vitro helicase assay, ATR/Chk1 inhibitors, phosphorylation mutants, siRNA knockdown, DNA fiber assay The EMBO journal High 28314779
2017 Nup42 is required for efficient Dbp5/DDX19B activation: the Nup42 C-terminal domain binds Gle1/hGle1B at a site distinct from the Gle1-Dbp5 interface; a nup42-CTD/gle1-CTD/Dbp5 trimeric complex forms in the presence of IP6; deletion of NUP42 abrogates Gle1-Dbp5 interaction; Nup42 and IP6 stimulate Gle1/hGle1B activation of both yeast Dbp5 and human DDX19B in vitro in a non-additive manner. In vitro ATPase assays with recombinant proteins, co-immunoprecipitation, yeast and human cell mRNA export assays, structure-function mutagenesis Traffic (Copenhagen, Denmark) High 28869701
2018 Nup159 does not accelerate ADP release from Dbp5/DDX19B; instead Gle1 slows ADP release; Mg2+ slows both ADP and ATP release and increases their affinities; Nup159 reduces Gle1-ADP-Dbp5 interaction ~18-fold, suggesting Nup159 aids Gle1 dissociation from ADP-bound Dbp5 rather than acting as a nucleotide exchange factor. Stopped-flow kinetics, fluorescence equilibrium binding assays, in vitro biochemical reconstitution Journal of molecular biology High 29782832
2019 DDX19B is a negative regulator of type I interferon production: it inhibits TBK1- and IKKε-mediated phosphorylation of IRF3 by disrupting TBK1/IKKε-IRF3 interactions; DDX19B recruits Lamtor2 to form a TBK1-IKKε-Lamtor2-DDX19-IRF3 complex that promotes TBK1 and IKKε degradation; Ddx19 knockout mice show augmented type I IFN production. Ectopic overexpression, siRNA knockdown, co-immunoprecipitation, TALEN-generated knockout mice, virus infection assays Cell reports High 30699353
2019 Dbp5/DDX19B contains an N-terminal Xpo1-dependent nuclear export signal; disruptions in Dbp5 nucleocytoplasmic transport result in tRNA export defects rather than mRNA export defects, indicating nuclear shuttling of Dbp5 is not essential for mRNP export but is specifically required for tRNA export. Alanine scanning mutagenesis (456 viable mutants), GFP reporter, genetic analysis, tRNA export assays in yeast eLife Medium 31453808
2020 Dbp5 associates in close proximity with both Mex67 (mRNA export receptor) and Nab2 in a cellular complex; fusion of Dbp5 to Nup159 anchors it at the cytoplasmic face of the NPC and is sufficient for cell viability, demonstrating that NPC localization of Dbp5 is the essential feature for mRNP remodeling, separable from other subcellular functions. Proximity ligation assay, co-immunoprecipitation, Dbp5-Nup159 fusion genetics, in vivo mRNA export assays PLoS genetics Medium 33002012
2021 DDX19B tethers the CBC-dependent translation initiation factor CTIF to the perinuclear region in a translationally incompetent manner; DDX19B hands CTIF over to CBP80 upon mRNA export, enabling CBC-dependent translation locally at the perinuclear region; disrupting the CTIF-DDX19B interaction causes uncontrolled translation throughout the cytosol and dysregulates nonsense-mediated mRNA decay. Co-immunoprecipitation, fluorescence microscopy, siRNA knockdown, dominant-negative mutants, NMD reporter assays Nucleic acids research Medium 34232997
2022 DDX19 (DDX19A and DDX19B) is SUMOylated at lysine 26; this modification enhances DDX19's interaction with Gle1; a SUMOylation-defective K26R mutant of human DDX19B fails to fully rescue mRNA export defects caused by DDX19 depletion. In vivo SUMOylation assay, co-immunoprecipitation, siRNA knockdown, rescue experiments with K26R mutant Journal of cell science Medium 35080244
2022 Gle1 activates Dbp5/DDX19B by two mechanisms: (1) thermodynamic coupling between Gle1 and ATP binding causes Gle1 to bind Dbp5-ATP >100-fold more tightly than other nucleotide states, slowing ATP dissociation; (2) Gle1 accelerates rate-limiting Pi release ~20-fold, maintaining Pi release as the rate-limiting step during activated cycling. Kinetic and equilibrium fluorescence assays, in vitro ATPase reconstitution Nucleic acids research High 35286399
2024 Dbp5/DDX19B directly binds tRNA and functions in tRNA export parallel to the canonical Los1 pathway; tRNA direct binding does not activate Dbp5 ATPase activity, but tRNA acts synergistically with Gle1 to fully activate Dbp5; Dbp5 is recruited to tRNA independently of Los1, Msn5, or Mex67; functional ATPase cycle and Gle1 binding are required for tRNA export. Co-immunoprecipitation, dominant-negative overexpression, genetic epistasis, in vitro ATPase assays with tRNA eLife Medium 38189406

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nature cell biology 239 16783363
1999 Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p. The EMBO journal 231 10428971
2006 Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nature cell biology 226 16783364
2007 The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events. Molecular cell 187 18082609
2009 The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner. Nature structural & molecular biology 150 19219046
2017 An ATR-dependent function for the Ddx19 RNA helicase in nuclear R-loop metabolism. The EMBO journal 120 28314779
2009 The DEXD/H-box RNA helicase DDX19 is regulated by an {alpha}-helical switch. The Journal of biological chemistry 120 19244245
2004 The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. Molecular cell 119 15574330
2007 The DEAD-box RNA helicase Dbp5 functions in translation termination. Science (New York, N.Y.) 115 17272721
2002 The mRNA export factor Dbp5 is associated with Balbiani ring mRNP from gene to cytoplasm. The EMBO journal 95 11867546
2011 The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes & development 93 21576266
2011 The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1. Genes & development 91 21576265
2011 Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. Nucleus (Austin, Tex.) 86 22064466
2009 Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19. Proceedings of the National Academy of Sciences of the United States of America 82 19208808
2019 DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKε-IRF3 Interactions and Promoting TBK1 and IKKε Degradation. Cell reports 56 30699353
2009 Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA. Nucleic acids research 55 19786495
2017 RNA helicase DDX19 stabilizes ribosomal elongation and termination complexes. Nucleic acids research 43 28180304
2017 Nup42 and IP6 coordinate Gle1 stimulation of Dbp5/DDX19B for mRNA export in yeast and human cells. Traffic (Copenhagen, Denmark) 39 28869701
2012 Dbp5 - from nuclear export to translation. Biochimica et biophysica acta 37 23128325
2016 Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs. Scientific reports 36 27653209
2013 Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins. Nucleic acids research 32 23804756
2007 Tap and Dbp5, but not Gag, are involved in DR-mediated nuclear export of unspliced Rous sarcoma virus RNA. Virology 32 17328934
2009 Structure of the C-terminus of the mRNA export factor Dbp5 reveals the interaction surface for the ATPase activator Gle1. Proceedings of the National Academy of Sciences of the United States of America 30 19805289
2011 Regulation of the Dbp5 ATPase cycle in mRNP remodeling at the nuclear pore: a lively new paradigm for DEAD-box proteins. Genes & development 25 21632821
2008 Synthetic genetic array analysis in Saccharomyces cerevisiae provides evidence for an interaction between RAT8/DBP5 and genes encoding P-body components. Genetics 25 18689878
2016 Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA-Helicase as for mRNA Export. PloS one 23 26872259
2015 P(I) Release Limits the Intrinsic and RNA-Stimulated ATPase Cycles of DEAD-Box Protein 5 (Dbp5). Journal of molecular biology 20 26730886
2019 A nuclear role for the DEAD-box protein Dbp5 in tRNA export. eLife 19 31453808
2018 Depletion of mRNA export regulator DBP5/DDX19, GLE1 or IPPK that is a key enzyme for the production of IP6, resulting in differentially altered cytoplasmic mRNA expression and specific cell defect. PloS one 19 29746542
2021 Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF-DDX19B interaction. Nucleic acids research 15 34232997
2015 RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1. Nature communications 15 25585691
2020 Dbp5/DDX19 between Translational Readthrough and Nonsense Mediated Decay. International journal of molecular sciences 14 32041247
2017 Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells. Nucleus (Austin, Tex.) 14 28696814
2022 The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release. Nucleic acids research 11 35286399
2018 Nup159 Weakens Gle1 Binding to Dbp5 But Does Not Accelerate ADP Release. Journal of molecular biology 10 29782832
2020 Dbp5 associates with RNA-bound Mex67 and Nab2 and its localization at the nuclear pore complex is sufficient for mRNP export and cell viability. PLoS genetics 9 33002012
2010 A novel dual Dbp5/DDX19 homologue from Plasmodium falciparum requires Q motif for activity. Molecular and biochemical parasitology 9 21168450
2013 A single molecule view on Dbp5 and mRNA at the nuclear pore. Nucleus (Austin, Tex.) 6 23324459
2022 SUMOylation modulates the function of DDX19 in mRNA export. Journal of cell science 5 35080244
2011 Inhibition of unwinding and ATPase activities of Plasmodium falciparum Dbp5/DDX19 homolog. Communicative & integrative biology 5 21980563
2019 Correction: Depletion of mRNA export regulator DBP5/DDX19, GLE1 or IPPK that is a key enzyme for the production of IP6, resulting in differentially altered cytoplasmic mRNA expression and specific cell defect. PloS one 3 31344122
2010 Mechanistic insights into mRNA export through structures of Dbp5. RNA biology 3 20023400
2024 Gle1 is required for tRNA to stimulate Dbp5 ATPase activity in vitro and promote Dbp5-mediated tRNA export in vivo in Saccharomyces cerevisiae. eLife 2 38189406
2023 Gle1 is required for tRNA to stimulate Dbp5 ATPase activity in vitro and to promote Dbp5 mediated tRNA export in vivo. bioRxiv : the preprint server for biology 1 37425677