Affinage

DDX10

Probable ATP-dependent RNA helicase DDX10 · UniProt Q13206

Length
875 aa
Mass
100.9 kDa
Annotated
2026-06-09
27 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX10 is a nucleolar DEAD-box RNA helicase that functions in small-subunit (SSU) ribosome biogenesis, where it (and its yeast ortholog Dbp4) is a component of U3 snoRNP/SSU processome assembly intermediates and associates with nucleolin, RRP5, and the U3-specific protein Mpp10 (PMID:19332556, PMID:25535329). DDX10 is required for SSU processome formation and cotranscriptional pre-rRNA cleavage; its depletion impairs early pre-rRNA processing and traps U14 snoRNA on pre-rRNA, and its C-terminal extension outside the catalytic core mediates U14 snoRNA release (PMID:25535329). Beyond ribosome assembly, DDX10 positively regulates type I interferon production and acts as an antiviral factor, and during PRRSV infection it is translocated to the cytoplasm and degraded through SQSTM1/p62-mediated selective autophagy driven by the viral E protein (PMID:36779599); it also promotes AIM2 inflammasome activation by binding the HIN-200 domain of AIM2 and stabilizing AIM2 protein (PMID:32519665). DDX10 supports proliferation across several cancers and physically engages partners including IMP4, RPL35, fibrillarin, and Rab27b in these contexts (PMID:33973712, PMID:35109823, PMID:41338403, PMID:40352946). The t(11;p15q22) inversion fuses NUP98 in-frame with DDX10, and the conserved YIHRAGRTAR helicase motif together with a 24-amino-acid segment that recruits NOL10 — a cooperating regulator of serine biosynthesis and ATF4 mRNA stability — is required for leukemogenic transformation (PMID:9166830, PMID:20339440, PMID:40263434). DDX10 additionally interacts with α-synuclein, which sequesters it from the nucleolus and stabilizes α-synuclein oligomers (PMID:33657088).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 Low

    Established DDX10 as a candidate DEAD-box RNA helicase, framing a hypothesis that it acts in ribosome biogenesis before any functional assay existed.

    Evidence positional cloning and sequence analysis

    PMID:8660968

    Open questions at the time
    • sequence prediction only, no functional assay
    • no localization or substrate data
    • helicase activity not demonstrated
  2. 1997 High

    Showed DDX10 is recurrently fused to NUP98 by chromosomal inversion, defining its first disease association and pointing to an oncogenic gain-of-function specifically in the NUP98-DDX10 orientation.

    Evidence RT-PCR and breakpoint cloning across four leukemia patients

    PMID:9166830

    Open questions at the time
    • mechanism of transformation not defined
    • did not test which DDX10 domains are required
    • no normal cellular function established
  3. 2009 Medium

    Placed human DDX10 in a defined 50S U3 snoRNP SSU-processome assembly intermediate, providing the first physical evidence for its predicted ribosome biogenesis role.

    Evidence sucrose gradient sedimentation, co-IP, and depletion in human cells

    PMID:19332556

    Open questions at the time
    • catalytic activity not demonstrated
    • no rRNA processing readout in human cells
    • function of nucleolin/RRP5 association unresolved
  4. 2010 Medium

    Demonstrated that the conserved helicase motif of DDX10 is required for NUP98-DDX10 transformation, linking the enzyme's ATP/RNA-binding function to leukemogenesis.

    Evidence site-directed mutagenesis and CD34+ cell transformation assays

    PMID:20339440

    Open questions at the time
    • RNA substrate of the fusion not identified
    • downstream target genes undefined
    • single lab
  5. 2014 High

    Defined the mechanistic step DDX10/Dbp4 catalyzes: SSU processome formation and cotranscriptional pre-rRNA cleavage, with the C-terminal extension required for U14 snoRNA release.

    Evidence immunoprecipitation, electron microscopy, sedimentation, and domain truncation in yeast

    PMID:24357410 PMID:25535329

    Open questions at the time
    • human enzyme not directly assayed for U14 release
    • ATP-dependent unwinding not reconstituted in vitro
    • structural basis unknown
  6. 2020 Medium

    Extended DDX10 function beyond the nucleolus into innate immunity by showing it stabilizes AIM2 and is required for inflammasome activation.

    Evidence co-IP domain mapping, CRISPR knockout in THP-1, and IL-1β/caspase-1 readouts

    PMID:32519665

    Open questions at the time
    • mechanism of AIM2 stabilization unknown
    • whether helicase activity is required not tested
    • single lab
  7. 2021 Medium

    Connected DDX10 to disease beyond cancer and to proliferation control, showing it sequesters/stabilizes α-synuclein oligomers and that IMP4 acts downstream in lung cancer growth.

    Evidence yeast genetic screen, co-IP, microscopy, and IMP4 rescue in lung cancer cells

    PMID:33657088 PMID:33973712

    Open questions at the time
    • physiological relevance of α-synuclein interaction in neurons untested
    • how IMP4 mediates the growth effect unresolved
    • single labs
  8. 2023 High

    Defined a regulated degradation pathway for DDX10 and assigned it a positive role in type I interferon production, establishing it as an antiviral host factor targeted by virus.

    Evidence co-IP, ATG5/ATG7/SQSTM1 knockouts, translocation imaging, and IFN reporter assays during PRRSV infection

    PMID:36779599

    Open questions at the time
    • molecular step by which DDX10 promotes IFN unknown
    • whether RNA helicase activity is required for IFN role untested
    • human relevance beyond PRRSV model unclear
  9. 2022 Medium

    Identified additional cancer-context partners and downstream programs, linking DDX10 to RPL35 and to autophagy regulation in colorectal cancer.

    Evidence LC-MS/MS, co-IP, siRNA knockdown with proliferation/apoptosis readouts and ATG10 epistasis

    PMID:35109823 PMID:39110225

    Open questions at the time
    • whether DDX10 directly regulates ATG10 unknown
    • mechanism linking RPL35 binding to phenotype unclear
    • single labs
  10. 2025 High

    Resolved the cooperating dependency of the NUP98::DDX10 fusion, showing a 24-residue DDX10 segment recruits NOL10 to drive serine biosynthesis and ATF4 mRNA stability required for leukemia.

    Evidence domain mutagenesis, co-IP, Nol10-knockout mouse leukemia model, and metabolic/mRNA stability assays

    PMID:40263434

    Open questions at the time
    • how NOL10 reprograms serine metabolism mechanistically unresolved
    • whether NOL10 dependency applies to other NUP98 fusions untested
    • role of normal DDX10-NOL10 interaction unclear
  11. 2025 Medium

    Broadened DDX10's cytoplasmic and tumor-immune roles, implicating it in Rab27b-mediated exosomal PD-L1 secretion and in fibrillarin-coupled Wnt/β-catenin signaling.

    Evidence co-IP/phase separation assay, RNA immunoprecipitation, knockdown with exosome, T cell, and Wnt-pathway readouts

    PMID:40352946 PMID:41338403

    Open questions at the time
    • how a nucleolar helicase engages cytoplasmic exosome machinery unresolved
    • directness of Wnt pathway regulation unclear
    • single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether DDX10's diverse functions across ribosome biogenesis, innate immunity, autophagy, and cancer share a common biochemical activity, and whether its ATP-dependent RNA unwinding is required outside the SSU processome.
  • no in vitro reconstitution of human DDX10 helicase activity
  • RNA substrates in immune and cancer contexts unidentified
  • structural basis of partner selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0140657 ATP-dependent activity 2 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005730 nucleolus 3 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
AIM2FBLIMP4NOL10NUP98RAB27BRPL35SQSTM1
Complex memberships
SSU processomeU3 snoRNP

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DDX10 encodes a putative DEAD-box RNA helicase with predicted involvement in ribosome biogenesis, based on high sequence similarity to DEAD-box RNA helicases involved in ribosome biogenesis. Positional cloning, sequence analysis Genomics Low 8660968
1997 Inversion 11(p15q22) fuses NUP98 (nucleoporin) in-frame with DDX10 (putative RNA helicase) to produce the NUP98-DDX10 chimeric transcript; only the NUP98-DDX10 direction (not DDX10-NUP98) appears implicated in tumorigenesis. Positional cloning, RT-PCR, molecular characterization of translocation breakpoints in four patients Blood High 9166830
2009 Human DDX10 (ortholog of yeast Dbp4) is a component of a novel 50S U3 snoRNP assembly intermediate of the SSU processome; this complex accumulated when pre-rRNA transcription was blocked or tUTP proteins were depleted, and DDX10 was associated with the RNA-binding proteins nucleolin and RRP5 in this intermediate. Sucrose gradient sedimentation, co-immunoprecipitation, depletion experiments Molecular and cellular biology Medium 19332556
2010 The conserved helicase motif YIHRAGRTAR in DDX10 (required for ATP binding, RNA binding, and helicase function) is required for the in vitro transforming ability of NUP98-DDX10; mutation of this motif diminishes leukemogenic transformation of CD34+ cells. Site-directed mutagenesis of helicase motif, transformation assay of primary human CD34+ cells, nuclear localization assay Leukemia Medium 20339440
2013 Yeast Dbp4 (DDX10 ortholog) interacts with nucleolar proteins Bfr2 and Enp2 in two distinct complexes: a 50S complex (not containing U3 snoRNA but containing U14 snoRNA associated with Dbp4) and an 80S SSU processome (containing U3 snoRNA); Bfr2 and Enp2 are required for early 18S rRNA processing steps. Sucrose gradient sedimentation, co-immunoprecipitation, northern blotting, genetic depletion Nucleic acids research Medium 24357410
2014 Yeast Dbp4 (DDX10 ortholog) is required for SSU processome formation and cotranscriptional pre-rRNA cleavage: depletion of Dbp4 impairs early pre-rRNA cleavage, causes U14 snoRNA to remain associated with pre-rRNA, compromises SSU processome formation visible by electron microscopy, and its C-terminal extension (outside the catalytic core) is required for U14 snoRNA release from pre-rRNA. Dbp4 associates with U3 snoRNA and the U3-specific protein Mpp10 in whole-cell extracts but does not associate with U14 snoRNA. Immunoprecipitation, electron microscopy, sucrose density gradient analysis, genetic depletion, domain truncation analysis Molecular and cellular biology High 25535329
2021 DDX10 (and yeast ortholog Dbp4) physically interacts with α-synuclein; α-synuclein sequesters DDX10 outside the nucleolus in both yeast and human cells, and this interaction stabilizes a fraction of α-synuclein oligomeric species. Downregulation of DBP4/DDX10 rescues cells from α-synuclein toxicity, while overexpression produces a synthetic lethal phenotype. Yeast genetic screen, co-immunoprecipitation, fluorescence microscopy (localization), genetic overexpression/knockdown with growth/toxicity readouts PLoS genetics Medium 33657088
2021 DDX10 knockdown in lung cancer cells inhibits proliferation in vitro and in vivo; DDX10 positively correlates with the U3 snoRNP component IMP4, and IMP4 overexpression rescues the anti-proliferative effect of DDX10 knockdown, placing IMP4 downstream of DDX10. shRNA knockdown, in vitro proliferation assay, xenograft (in vivo), rescue experiment with IMP4 overexpression Thoracic cancer Medium 33973712
2020 DDX10 promotes AIM2 inflammasome activation by interacting with the HIN-200 domain of AIM2 and stabilizing AIM2 protein expression; DDX10 knockout in THP-1 macrophages inhibits AIM2 inflammasome activation (reduced caspase-1 cleavage and IL-1β release), and DDX10 co-localizes with AIM2 in HEK293T cells. Co-immunoprecipitation, ELISA (IL-1β), Western blot (caspase-1 cleavage), CRISPR knockout, immunofluorescence/confocal microscopy Xi bao yu fen zi mian yi xue za zhi Medium 32519665
2022 DDX10 interacts with RPL35 (identified by LC-MS/MS and confirmed by co-immunoprecipitation) and is linked to RNA splicing and E2F targets in colorectal cancer cells; DDX10 knockdown reduces CRC cell proliferation, migration, and invasion. LC-MS/MS proteomics, co-immunoprecipitation, shRNA knockdown, cell proliferation/migration/invasion assays, in vivo xenograft Cancer cell international Medium 35109823
2023 PRRSV infection promotes DDX10 translocation from the nucleus to the cytoplasm for autophagic degradation. The viral envelope (E) protein interacts with DDX10, induces autophagy, and reduces DDX10 protein levels in wild-type cells but not in ATG5 or ATG7 KO cells. SQSTM1/p62 cargo receptor interacts with both DDX10 and E protein and mediates selective autophagic degradation of DDX10. DDX10 positively regulates type I interferon production, contributing to its antiviral effect against PRRSV. Co-immunoprecipitation, CRISPR knockout (ATG5, ATG7, SQSTM1), fluorescence microscopy (nuclear-cytoplasmic translocation), ectopic expression, siRNA knockdown, interferon reporter assays Autophagy High 36779599
2024 DDX10 deletion in colorectal cancer cells increases ATG10 expression and activates autophagy; inhibition of ATG10 or treatment with the autophagy inhibitor 3-MA partially rescues the anti-proliferative and pro-apoptotic effects of DDX10 silencing, placing ATG10-dependent autophagy downstream of DDX10 in CRC cell regulation. siRNA knockdown, autophagy inhibitor (3-MA), Western blot, EDU staining (proliferation), TUNEL (apoptosis), sphere formation assay Journal of cancer research and clinical oncology Medium 39110225
2025 Twenty-four amino acids within the DDX10 moiety of NUP98::DDX10 are required for cell immortalization and leukemogenesis; NOL10 (nucleolar protein 10) interacts with these 24 amino acids and is a critical dependency of NUP98::DDX10 leukemia. NOL10 acts cooperatively with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA; loss of Nol10 in a mouse model impairs NUP98::DDX10 leukemia progression. Domain mapping/mutagenesis, co-immunoprecipitation, mouse leukemia model with Nol10 knockout, mRNA stability assay, metabolic pathway analysis Leukemia High 40263434
2025 DDX10 physically interacts with Rab27b via phase separation and promotes Rab27b-mediated exosome secretion and PD-L1 loading into exosomes in oral squamous cell carcinoma; DDX10 knockdown inhibits exosomal PD-L1 secretion and restores T cell function and infiltration. Co-immunoprecipitation (phase separation assay), siRNA knockdown, exosome isolation, flow cytometry/immunofluorescence, T cell functional assays Research (Washington, D.C.) Medium 40352946
2025 DDX10 binds to fibrillarin (FBL) in DLBCL cells (confirmed by RNA immunoprecipitation); DDX10 and FBL positively regulate each other, and silencing either suppresses DLBCL cell viability, proliferation, invasion, and downregulates β-catenin, cyclin D1, and c-Myc (Wnt/β-catenin pathway components). RNA immunoprecipitation, siRNA knockdown, cell viability/invasion assays, Western blot (Wnt pathway proteins) Molecular and cellular probes Medium 41338403

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. Blood 137 9166830
2009 A novel small-subunit processome assembly intermediate that contains the U3 snoRNP, nucleolin, RRP5, and DBP4. Molecular and cellular biology 59 19332556
2023 Porcine reproductive and respiratory syndrome virus degrades DDX10 via SQSTM1/p62-dependent selective autophagy to antagonize its antiviral activity. Autophagy 53 36779599
2010 Effects of the NUP98-DDX10 oncogene on primary human CD34+ cells: role of a conserved helicase motif. Leukemia 50 20339440
1996 A human gene (DDX10) encoding a putative DEAD-box RNA helicase at 11q22-q23. Genomics 47 8660968
2014 The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities. BMC genomics 29 24450762
2015 Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer. Biochemical and biophysical research communications 26 26713367
1999 The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts. International journal of hematology 26 10222653
2005 Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia. Cancer genetics and cytogenetics 25 15721630
2022 DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35. Cancer cell international 24 35109823
2013 Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two different complexes. Nucleic acids research 23 24357410
2021 DEAD-box RNA helicase Dbp4/DDX10 is an enhancer of α-synuclein toxicity and oligomerization. PLoS genetics 22 33657088
2014 DEAD-box RNA helicase Dbp4 is required for small-subunit processome formation and function. Molecular and cellular biology 19 25535329
2021 Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells. Aging 18 33742605
2000 Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase gene, DDX10, by inversion 11 (p15q22) chromosome translocation in a patient with etoposide-related myelodysplastic syndrome. Internal medicine (Tokyo, Japan) 18 10830185
2021 DDX10 promotes human lung carcinoma proliferation by U3 small nucleolar ribonucleoprotein IMP4. Thoracic cancer 17 33973712
2022 UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury. Journal of diabetes research 14 35734237
2018 Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer. BMC cancer 14 30348128
2006 Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia. Cancer genetics and cytogenetics 13 17116492
2021 DDX10 and BYSL as the potential targets of chondrosarcoma and glioma. Medicine 9 34797290
2024 ATG10-dependent autophagy is required for DDX10 to regulate cell proliferation, apoptosis and stemness in colorectal cancer. Journal of cancer research and clinical oncology 4 39110225
2025 Loss of NOL10 leads to impaired disease progression of NUP98::DDX10 leukemia. Leukemia 3 40263434
2025 DDX10 Exacerbates Exosomal PD-L1-Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma. Research (Washington, D.C.) 2 40352946
2025 Reveal the regulatory role of DDX10 in diffuse large B-cell lymphoma: binding with FBL to promote cell proliferation and invasion. Molecular and cellular probes 1 41338403
2026 DDX10 RNA Helicase: Structure, Function, and Oncogenic Roles Across Solid and Hematologic Tumors. Genes 0 41751522
2022 [Acute myeloid leukemia harboring NUP98::DDX10]. [Rinsho ketsueki] The Japanese journal of clinical hematology 0 36351646
2020 [DDX10 promotes AIM2-inflammasome activation by maintaining AIM2 protein stability]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 32519665

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