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Showing DDX19B — DDX19 is a alias.

DDX19B

ATP-dependent RNA helicase DDX19B · UniProt Q9UMR2

Length
479 aa
Mass
53.9 kDa
Annotated
2026-06-09
44 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX19B (Dbp5) is a DEAD-box RNA-dependent ATPase that drives the terminal, directional step of mRNA nuclear export at the cytoplasmic face of the nuclear pore complex (PMID:10428971, PMID:15574330). It is tethered to the NPC through direct binding to the N-terminal beta-propeller of nucleoporin NUP214/Nup159, an interaction that is mutually exclusive with RNA binding and that lowers the enzyme's RNA-binding and ATPase activities, positioning the enzyme for cycles of engagement and release (PMID:15574330, PMID:19219046). Its ATPase activity is allosterically controlled: Gle1, together with inositol hexakisphosphate (InsP6) and Nup42, forms an activating complex that promotes ATP loading, slows ADP release, and accelerates the rate-limiting Pi-release step, while an autoinhibitory N-terminal alpha-helix suppresses activity in the unengaged state (PMID:16783363, PMID:16783364, PMID:19244245, PMID:28869701, PMID:35286399). Through nucleotide-dependent conformational switching—with the ADP-bound state mediating remodeling—Dbp5 displaces mRNP-bound proteins such as Nab2 to impose directionality on export (PMID:18082609, PMID:21576266). Beyond mRNA export, DDX19B has multiple distinct activities: it relocalizes to the nucleus upon ATR/Chk1 signaling to resolve R-loops during replication stress via its helicase activity, with Chk1-mediated phosphorylation disrupting its NUP214 anchor (PMID:28314779); it promotes translation termination by stabilizing pre-termination ribosomal complexes and enhancing release-factor function at stop-codon recognition (PMID:17272721, PMID:28180304); it mediates Gle1-dependent tRNA export and pre-ribosomal subunit export through mechanisms distinct from mRNA export (PMID:26872259, PMID:31453808, PMID:38189406); it spatially restricts CBC-dependent translation by tethering the initiation factor CTIF at the perinuclear region (PMID:34232997); and it negatively regulates type I interferon signaling by disrupting TBK1/IKKε–IRF3 interactions and promoting TBK1/IKKε degradation (PMID:30699353). Its export function is further tuned by SUMOylation at K26, which enhances Gle1 interaction (PMID:35080244).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 High

    Established where the enzyme acts and that its catalytic activity is essential for mRNA export, anchoring DDX19B to the NPC cytoplasmic fibrils.

    Evidence ImmunoEM, direct binding, conditional yeast depletion, and dominant-negative DEAD-box mutant in Xenopus oocytes

    PMID:10428971

    Open questions at the time
    • Molecular basis of the NUP214/Nup159 interaction not yet resolved
    • How ATPase activity couples to export directionality unknown
  2. 2004 High

    Defined the structural basis of NPC tethering, showing the Nup159 beta-propeller directly binds Dbp5 and that this anchoring is required for export.

    Evidence X-ray crystallography of the Nup159 N-terminal domain with structure-guided mutagenesis and yeast export assays

    PMID:15574330

    Open questions at the time
    • Did not resolve how anchoring relates to the catalytic cycle
    • Activator requirements not addressed
  3. 2006 High

    Identified the cofactors that switch Dbp5 from a weak intrinsic enzyme to an active one, establishing Gle1 and InsP6 as direct activators.

    Evidence In vitro kinetic ATPase and RNA-binding assays with genetic suppression in yeast (two concurrent studies)

    PMID:16783363 PMID:16783364

    Open questions at the time
    • Stoichiometry and structural basis of the activation complex unresolved
    • Role of Nup42 not yet incorporated
  4. 2007 High

    Revealed the physiological output of the ATPase cycle—mRNP remodeling—and that the ADP-bound state, not hydrolysis per se, drives displacement of bound RNA-binding proteins.

    Evidence In vitro RNP displacement assays with nucleotide-state biochemistry plus nab2/dbp5 genetic analysis

    PMID:18082609

    Open questions at the time
    • Whether other mRNP proteins besides Nab2 are remodeled in vivo not fully mapped
    • Mechanism converting remodeling into directionality not yet defined
  5. 2007 High

    Extended Dbp5 function beyond export into translation termination, linking it physically and genetically to release factors and stop-codon recognition.

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

    PMID:17272721

    Open questions at the time
    • Molecular step at which Dbp5 acts in termination not yet defined
    • Whether this requires NPC localization unclear
  6. 2009 High

    Provided the structural logic for mutually exclusive RNA versus NUP214 binding and for N-terminal autoinhibition, explaining how the enzyme alternates states during the cycle.

    Evidence Multiple X-ray structures (RNA/AMPPNP, NUP214-bound, free and ADP-bound states) with ATPase/RNA-binding biochemistry and mutagenesis

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

    Open questions at the time
    • How conformational switching is timed at the pore in vivo not resolved
    • Functional test of the Nup214/RNA competition model partly interpretive
  7. 2009 Medium

    Identified RBM15 as an mRNA-export factor that bridges DBP5 to mRNA, adding a substrate-loading partner to the export pathway.

    Evidence Co-IP, co-localization, RNA-IP and RNAi with mRNA export readout in human cells

    PMID:19786495

    Open questions at the time
    • Direct versus indirect nature of DBP5-RBM15 contact not fully resolved
    • Single-lab data without reciprocal structural validation
  8. 2011 High

    Resolved the multi-step nucleotide cycle at the NPC, assigning ADP release and ATP re-loading roles to Nup159 and Gle1-IP6 respectively.

    Evidence In vitro nucleotide exchange reconstitution plus in vivo bypass/suppressor genetics and FRAP in yeast and human cells

    PMID:21576265 PMID:21576266

    Open questions at the time
    • Precise ordering of cofactor engagement during export contested by later kinetics
    • How the rapid (<1 s) NPC residence maps onto remodeling unclear
  9. 2013 Medium

    Connected DBP5 to histone-mRNA translation machinery via a defined SLIP1-binding motif.

    Evidence Co-crystal structure of SLIP1 with the DBP5 SBM and pull-down assays

    PMID:23804756

    Open questions at the time
    • Functional consequence of the DBP5-SLIP1 interaction not tested
    • In vivo relevance not established
  10. 2015 High

    Defined the rate-limiting kinetics of the intrinsic cycle, showing Pi release limits turnover and ADP binds more tightly than ATP.

    Evidence Stopped-flow and fluorescence-based Pi-release and equilibrium ATPase analysis

    PMID:26730886

    Open questions at the time
    • How cofactors override the rate-limiting step addressed only later
    • Behavior on physiological mRNP substrates not measured
  11. 2015 High

    Uncovered an export-independent role in nuclear import of the SRF coactivator MKL1, demonstrating functional separation of RNA-binding from helicase and NPC-binding activities.

    Evidence RNAi, separation-of-function mutants, Co-IP, and nuclear import assays in mammalian cells

    PMID:25585691

    Open questions at the time
    • Mechanism by which RNA binding alters MKL1 conformation not defined
    • Generality to other Importin-β cargoes unknown
  12. 2016 Medium

    Showed Dbp5 also exports pre-ribosomal subunits via an ATPase-independent, Gle1-independent mechanism distinct from mRNA export.

    Evidence Temperature-sensitive and ATPase-deficient dbp5 mutants, genetic interaction, and Co-IP with Nmd3 in yeast

    PMID:26872259

    Open questions at the time
    • Molecular basis of the ATPase-independent activity unknown
    • Whether the human ortholog shares this role untested
  13. 2017 High

    Established a DNA-damage role: ATR/Chk1-triggered nuclear relocalization lets Dbp5 resolve R-loops, with phosphorylation disrupting its NUP214 anchor.

    Evidence Live-cell imaging, in vitro R-loop helicase assays, siRNA, phosphomimetic mutants, and DNA fiber assays

    PMID:28314779

    Open questions at the time
    • Identity of the Chk1 phospho-site and full signaling cascade not exhaustively mapped
    • Genomic sites of R-loop resolution not defined
  14. 2017 High

    Mechanistically dissected the human DDX19 role in translation termination, placing its action at stop-codon recognition and ribosome complex stabilization.

    Evidence Reconstituted mammalian translation system with eRF1(AGQ), non-hydrolyzable GTP, and co-sedimentation

    PMID:28180304

    Open questions at the time
    • In vivo contribution to termination in human cells not quantified
    • Relationship to its export role unclear
  15. 2017 High

    Integrated Nup42 into the activation module, defining a trimeric Nup42-Gle1-Dbp5 complex required for efficient export.

    Evidence In vitro ATPase reconstitution, trimeric pull-down, and mRNA export assays in yeast and human cells

    PMID:28869701

    Open questions at the time
    • Spatial organization of the trimeric complex on the fibril not resolved
    • Dynamics of assembly during the cycle unknown
  16. 2018 Medium

    Revised the Nup159/Gle1 nucleotide-cycle model, arguing Gle1 slows ADP release and Nup159 promotes Gle1 release rather than acting as a nucleotide exchange factor.

    Evidence Solution-based in vitro kinetic and equilibrium binding assays

    PMID:29782832

    Open questions at the time
    • Contradicts the prior 2011 ADP-release model and not independently replicated
    • In vivo validation of the revised mechanism lacking
  17. 2019 Medium

    Identified an unexpected innate-immune role, with DDX19 dampening type I interferon by disrupting TBK1/IKKε–IRF3 signaling and driving kinase degradation.

    Evidence Co-IP, ectopic expression/knockdown, TALEN Ddx19 knockout mice, and viral infection assays

    PMID:30699353

    Open questions at the time
    • Whether this requires catalytic activity or is independent of RNA processing unclear
    • Single-lab finding; mechanism of Lamtor2 recruitment incompletely defined
  18. 2019 Medium

    Revealed an Xpo1-dependent NES enabling Dbp5 shuttling that is dispensable for mRNA export but required for tRNA export.

    Evidence Alanine-scanning mutagenesis, GFP-Dbp5 reporter, and tRNA/mRNA export assays in yeast

    PMID:31453808

    Open questions at the time
    • Mechanistic role of shuttling in tRNA handling not defined
    • Conservation in human cells untested
  19. 2021 Medium

    Defined a perinuclear translation-control function in which DDX19B sequesters CTIF and hands it to CBP80 to spatially restrict CBC-dependent translation.

    Evidence Co-IP, proximity ligation, translation and NMD reporter assays, and dominant-negative mutants in human cells

    PMID:34232997

    Open questions at the time
    • How DDX19B coordinates CTIF handover with export timing unresolved
    • Single-lab study without structural detail
  20. 2022 High

    Quantitatively explained Gle1 activation through thermodynamic coupling to ATP binding and acceleration of the rate-limiting Pi-release step.

    Evidence In vitro kinetic and equilibrium ATPase cycle analysis with stopped-flow kinetics

    PMID:35286399

    Open questions at the time
    • Integration with Nup159/Nup42 effects in a full cycle not reconstituted
    • Cooperativity with InsP6 quantified only partially
  21. 2022 Medium

    Showed SUMOylation at K26 is a regulatory layer that enhances Gle1 interaction and supports mRNA export.

    Evidence In vivo SUMOylation assays, K26R mutagenesis, Co-IP, and mRNA export rescue in human cells

    PMID:35080244

    Open questions at the time
    • SUMO ligase and stimulus controlling K26 modification unknown
    • Structural effect on the Gle1 interface undefined
  22. 2024 High

    Established a Los1-parallel tRNA export pathway in which tRNA synergizes with Gle1 to activate Dbp5, requiring a functional ATPase cycle and Gle1 binding.

    Evidence Genetic epistasis with los1/msn5, in vivo co-IP with tRNA, and in vitro ATPase assays ± Gle1 in yeast

    PMID:38189406

    Open questions at the time
    • How Dbp5 selects tRNA substrates without canonical export factors unclear
    • Whether the human ortholog performs the same role untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single enzyme integrates and switches among mRNA export, R-loop resolution, translation termination, tRNA/ribosomal export, perinuclear translation control, and innate-immune regulation remains unresolved.
  • Signals that route DDX19B between NPC and nuclear/cytosolic pools not unified
  • Reconciliation of the competing Nup159/Gle1 nucleotide-cycle models pending
  • Relative in vivo contribution of each function in human cells unquantified

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 3 GO:0016787 hydrolase activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005635 nuclear envelope 2 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
CTIFERF1GLE1NAB2NUP214NUP42RBM15TBK1
Complex memberships
Nup42-Gle1-Dbp5 activation complexTBK1-IKKε-Lamtor2-DDX19-IRF3 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human DBP5 (hDbp5/DDX19B) localizes to cytoplasmic fibrils of the nuclear pore complex via direct interaction with the N-terminal region of nucleoporin CAN/NUP214 (yeast Nup159p); in a conditional yeast strain where Nup159p is degraded, Dbp5 dissociates from the NPC and redistributes to the cytoplasm. A dominant-negative DEAD-box (Glu→Gln) mutant of hDbp5 injected into Xenopus oocytes inhibits mRNA nuclear export. Immunoelectron microscopy, direct protein interaction assays, conditional yeast depletion strain, Xenopus oocyte microinjection with dominant-negative mutant The EMBO journal High 10428971
2004 The N-terminal domain of Nup159 (yeast) forms a seven-bladed beta-propeller that directly tethers Dbp5 to the cytoplasmic face of the NPC; structure-guided mutations in a conserved loop abolish in vitro Dbp5 binding, cause Dbp5 mislocalization in vivo, and block mRNA export. X-ray crystallography (2.5 Å), structure-based mutagenesis, in vitro binding assay, in vivo localization and mRNA export assays in yeast Molecular cell High 15574330
2006 Gle1 and inositol hexakisphosphate (InsP6) together stimulate the RNA-dependent ATPase activity of Dbp5 at the nuclear pore; InsP6 increases Dbp5 ATPase activity in a Gle1-dependent manner, lowers the effective RNA concentration for half-maximal ATPase activity, and maximal InsP6 binding requires both Dbp5 and Gle1. Overexpression of DBP5 suppresses mRNA export defects of an ipk1 nup42 mutant defective in InsP6 production. In vitro kinetic ATPase assays, genetic epistasis/suppression in yeast, in vitro binding assays Nature cell biology High 16783363
2006 Gle1 is a direct cellular activator of Dbp5; Dbp5 alone cannot stably bind RNA or effectively hydrolyze ATP under physiological conditions, but Gle1 dramatically stimulates both activities. InsP6 binds directly to Gle1 and potentiates Gle1-mediated stimulation of Dbp5. A gle1 point mutant deficient for Dbp5 stimulation in vitro displays mRNA export defects in vivo; dominant mutations in DBP5 and GLE1 that rescue InsP6-deficient phenotypes mimic InsP6 effects in vitro. In vitro ATPase and RNA-binding assays, direct binding assays, in vivo mRNA export assays in yeast, structure-guided mutagenesis Nature cell biology High 16783364
2007 Dbp5 functions as an mRNP remodeling protein by displacing the RNA-binding protein Nab2 from RNA; the ADP-bound form of Dbp5 (not ATP hydrolysis per se) is required for this RNP remodeling activity. In vivo, nab2 and dbp5 mutant analyses confirm that Nab2-bound mRNP is a physiological Dbp5 target at the NPC. In vitro RNP remodeling/displacement assay, nucleotide-state biochemistry, in vivo genetic analysis of nab2/dbp5 double mutants in yeast Molecular cell High 18082609
2007 Dbp5 participates in translation termination in yeast: it physically interacts with release factor eRF1, genetically interacts with both eRF1 and eRF3 and poly(A)-binding protein Pab1, its helicase activity is required for efficient stop-codon recognition, and intact Dbp5 is essential for recruitment of eRF3 into termination complexes. Co-immunoprecipitation (physical interaction with eRF1), genetic interaction analysis, in vivo translation termination assays, dbp5 helicase mutant analysis in yeast Science (New York, N.Y.) High 17272721
2009 Crystal structures of human DBP5 bound to RNA+AMPPNP and bound to the cytoplasmic nucleoporin NUP214 reveal that RNA binding and NUP214 binding are mutually exclusive. NUP214 decreases both RNA-binding and ATPase activities of DBP5 in vitro; the interaction is mediated by conserved residues. X-ray crystallography (two structures), in vitro ATPase assays, in vitro RNA-binding assays, mutagenesis Nature structural & molecular biology High 19219046
2009 X-ray crystallography of human DDX19 in RNA-bound (closed cleft) and free (open cleft, posthydrolysis) states reveals an N-terminal alpha-helix that inserts between the conserved RecA-like domains of the free protein to negatively autoregulate ATPase activity; biochemical assays confirm the autoregulatory function of the N-terminal region. X-ray crystallography (two conformational states), in vitro ATPase biochemical assays The Journal of biological chemistry High 19244245
2009 Crystal structure of the Nup214 N-terminal domain in complex with DDX19 in its ADP-bound state reveals that the helicase interaction surface carries a positive charge and the Nup214 surface a negative charge; this structural framework suggests a basis for competitive displacement of Nup214 by RNA during mRNP remodeling. X-ray crystallography (2.5 Å co-crystal structure) Proceedings of the National Academy of Sciences of the United States of America Medium 19208808
2009 Crystal structure of the C-terminal domain of Dbp5 at 1.8 Å reveals a RecA-like fold with a unique C-terminal alpha-helix and a distinctive loop; structure-guided mutagenesis of charged surface residues identifies specific residues required for Gle1 binding and Gle1-stimulated ATPase activity, and the same mutations block yeast growth, establishing a threshold level of Dbp5 ATPase activity required for mRNA export. X-ray crystallography (1.8 Å), structure-based mutagenesis, in vitro ATPase assays, in vivo yeast growth and mRNA export assays Proceedings of the National Academy of Sciences of the United States of America High 19805289
2009 The nuclear export factor RBM15 binds specifically to human DBP5 and facilitates direct DBP5 contact with mRNA in vivo; RBM15 co-localizes with DBP5 and NXF1 at the nuclear envelope. Gene silencing of RBM15 causes cytoplasmic depletion and nuclear accumulation of mRNA, indicating RBM15 is required for efficient mRNA export. Co-immunoprecipitation, co-localization by microscopy, RNA immunoprecipitation, RNAi knockdown with mRNA export readout Nucleic acids research Medium 19786495
2011 Nup159 is specifically required for ADP release from Dbp5; Gle1-IP6 stimulates ATP binding to Dbp5 (priming it for RNA loading); in vivo, a dbp5 mutant with reduced ADP binding (R256D/R259D) bypasses the need for Nup159 interaction. This establishes Nup159 as an ADP release factor and Gle1-IP6 as a driver of ATP re-loading, defining a multi-step nucleotide cycle for Dbp5 at the NPC. In vitro nucleotide exchange/release assays (reconstitution), in vivo suppressor/bypass genetics in yeast, mRNA export assays Genes & development High 21576266
2011 ATP binding and hydrolysis are required for efficient Dbp5 association with NPCs. RNA-binding-deficient Dbp5 mutants act as dominant negatives for mRNA export in both yeast and human cells by competing with wild-type Dbp5 for Gle1 at NPCs; the Dbp5-Gle1 interaction is rate-limiting for export and can occur independently of Nup159. FRAP shows Dbp5 associates with NPCs very dynamically (<1 s). Mutagenesis (ATP binding, hydrolysis, RNA-binding mutations), dominant-negative analysis in yeast and human cells, FRAP at NPCs, in vivo mRNA export assays Genes & development High 21576265
2013 A SLIP1-binding motif (SBM) in DBP5 mediates direct interaction with SLIP1 (a MIF4G-like translation factor); crystal structure (3.25 Å) of SLIP1 bound to the DBP5 SBM was determined and interaction confirmed by pull-down assays, linking DBP5 to the histone mRNA translation machinery. X-ray crystallography (3.25 Å co-crystal), pull-down assays Nucleic acids research Medium 23804756
2015 Dbp5 kinetics: Pi release is the rate-limiting step of the intrinsic Dbp5 ATPase cycle; RNA increases kcat and Pi release rate ~20-fold, though Pi release continues to limit steady-state cycling even with RNA. ADP binds an order of magnitude more tightly than ATP (KD ~0.4 mM vs KT ~4 mM). In vitro kinetic and equilibrium ATPase analysis (stopped-flow, fluorescence-based Pi release assays) Journal of molecular biology High 26730886
2015 Ddx19 is required for nuclear import of the SRF coactivator MKL1; this function is separate from its mRNA export role. RNA-binding activity of Ddx19 is required for MKL1 nuclear import, whereas helicase activity and NPC-binding are dispensable. Ddx19 modulates the conformation of MKL1 to affect its interaction with Importin-β. RNAi knockdown, dominant-negative and mutant analysis (helicase-dead, RNA-binding, NPC-binding mutants), co-immunoprecipitation, nuclear import assays in mammalian cells Nature communications High 25585691
2016 Dbp5 is required for nuclear export of both pre-ribosomal subunits in yeast; however, unlike mRNA export, ATPase-deficient dbp5 mutants do not block ribosomal export, and gle1 mutants show no major ribosomal export defects. Dbp5 physically and genetically interacts with Nmd3 (a ribosomal transport factor). This establishes that Dbp5 uses a distinct, ATPase-independent mechanism for ribosomal subunit export. Temperature-sensitive dbp5 mutants in yeast (nuclear accumulation of pre-ribosomal subunits), genetic interaction analysis, co-immunoprecipitation with Nmd3, ATPase-deficient mutant analysis PloS one Medium 26872259
2017 Ddx19 transiently relocalizes from the nuclear pore to the nucleus upon DNA damage/replication stress in an ATR/Chk1-dependent manner; nuclear Ddx19 resolves R-loops in vitro via its helicase activity; Ddx19 depletion induces R-loop accumulation and DNA damage specifically in proliferating cells. A phosphorylation-mimetic mutation of a Chk1 target residue disrupts Ddx19 interaction with Nup214 and promotes nuclear relocalization. Live-cell imaging, immunofluorescence, in vitro helicase/R-loop resolution assay, siRNA knockdown, phosphomutant analysis, DNA fiber assays The EMBO journal High 28314779
2017 Human DDX19 participates in translation termination in vitro: it associates with translating ribosome fractions, binds pre-termination complexes in a nucleotide-dependent manner, increases efficiency of termination complex formation and peptide release by eukaryotic release factors, and stabilizes elongating ribosome complexes with eEF1 and eEF2. DDX19 activation of termination occurs at the stop codon recognition step. Reconstituted mammalian in vitro translation system, ribosome fractionation, eRF1(AGQ) mutant and non-hydrolyzable GTP analog to dissect termination steps, co-sedimentation assays Nucleic acids research High 28180304
2017 The Nup42–Gle1 interaction is integral to Dbp5/DDX19B activation and efficient mRNA export; a trimeric Nup42-CTD/Gle1-CTD/Dbp5 complex forms in the presence of IP6. Deletion of NUP42 abrogates Gle1-Dbp5 interaction. Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5 and DDX19B in non-additive manners in vitro. Disruption of Nup42 or IP6 binding interfaces on Gle1/hGle1B causes defective mRNA export in both yeast and human cells. In vitro ATPase reconstitution assays, Co-IP/pull-down (trimeric complex), in vivo mRNA export assays in yeast and human cells, structure-function mutagenesis Traffic (Copenhagen, Denmark) High 28869701
2018 Nup159 does not accelerate ADP release from Dbp5 (contradicting a previous model); instead, Gle1 slows ADP release from Dbp5, independent of Mg2+. In the presence of Nup159, the Gle1-ADP-Dbp5 interaction is weakened ~18-fold, suggesting Nup159 promotes Gle1 release from Dbp5 rather than acting as a nucleotide exchange factor. Solution-based in vitro kinetic and equilibrium binding assays (fluorescence, stopped-flow), ADP/ATP release measurements Journal of molecular biology Medium 29782832
2019 DDX19 negatively regulates type I interferon production: DDX19 inhibits TBK1- and IKKε-mediated phosphorylation of IRF3 by disrupting the TBK1/IKKε–IRF3 interaction, recruits Lamtor2 to form a TBK1-IKKε-Lamtor2-DDX19-IRF3 complex, and promotes proteasomal degradation of TBK1 and IKKε. Ddx19 knockout mice show augmented type I IFN production and suppressed encephalomyocarditis virus replication. Ectopic expression/knockdown in cell lines, co-immunoprecipitation, TALEN-generated Ddx19 knockout mice, viral infection assays Cell reports Medium 30699353
2019 Dbp5 contains an N-terminal Xpo1-dependent nuclear export signal identified by alanine-scanning mutagenesis; disruption of this NES impairs nucleocytoplasmic shuttling. Dbp5 nuclear shuttling is not essential for mRNP export, but is required for tRNA export—dbp5 mutants with impaired shuttling exhibit tRNA export defects and altered tRNA dynamics during nutrient stress recovery. Alanine-scanning mutagenesis (456 viable mutants), GFP-Dbp5 reporter, in vivo tRNA and mRNA export assays, Xpo1 interaction assays in yeast eLife Medium 31453808
2021 DDX19B tethers the CBC-dependent translation initiation factor CTIF to the perinuclear region in a translationally incompetent state; upon mRNA export, DDX19B hands CTIF over to CBP80, enabling CBC-dependent translation initiation specifically in the perinuclear region. Impairing the DDX19B-CTIF interaction causes uncontrolled translation throughout the cytosol and dysregulates nonsense-mediated mRNA decay. Co-immunoprecipitation, proximity ligation assay, translation reporter assays, NMD reporter assays, dominant-negative and deletion mutant analysis in human cells Nucleic acids research Medium 34232997
2022 Gle1 activates Dbp5 ATPase by two mechanisms: (1) thermodynamic coupling between Gle1 and ATP binding to Dbp5 (Gle1 binds Dbp5-ATP >100-fold more tightly than ADP-Dbp5, and Gle1 increases ATP equilibrium binding >150-fold by slowing ATP dissociation); (2) Gle1 accelerates the rate-limiting Pi release step ~20-fold. Pi release remains rate-limiting even in the presence of Gle1. In vitro kinetic and equilibrium ATPase cycle analysis (fluorescence-based assays, stopped-flow kinetics) Nucleic acids research High 35286399
2022 DDX19 is SUMOylated at lysine 26; this SUMO modification enhances DDX19 interaction with Gle1. A SUMOylation-defective K26R mutant of human DDX19B fails to fully rescue mRNA export defects caused by DDX19 depletion, demonstrating that SUMOylation modulates DDX19B function in mRNA export. In vivo SUMOylation assays, site-directed mutagenesis (K26R), co-immunoprecipitation, mRNA export rescue assays in human cells Journal of cell science Medium 35080244
2024 Dbp5 functions in tRNA export in yeast parallel to canonical export factor Los1; Dbp5 is recruited directly to tRNA independent of Los1, Msn5, or Mex67. Unlike with mRNA, tRNA (or dsRNA) alone does not activate Dbp5 ATPase activity, but tRNA acts synergistically with Gle1 to fully activate Dbp5. A functional ATPase cycle and Gle1 binding are both required for Dbp5-mediated tRNA export. Genetic epistasis (double mutants with los1, msn5), in vivo co-immunoprecipitation with tRNA, in vitro ATPase assays with tRNA ± Gle1, dominant-negative overexpression, tRNA export assays in yeast eLife High 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 233 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 122 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.) 87 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 57 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) 40 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 26 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
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.) 15 28696814
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
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

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