DDX3X is a DEAD-box RNA helicase that binds RNA and uses an ATP-dependent cycle to remodel short RNA duplexes. It promotes translation of selected mRNAs and supports formation of functional 80S initiation complexes through interactions with translation-initiation machinery. DDX3X also performs separable noncatalytic signaling roles: it helps recruit IRF3 to IKKΞ΅ during antiviral interferon induction and stimulates casein kinase 1 in Wnt signaling. The protein shuttles between nucleus and cytoplasm and can enter stress granules and other conditional assemblies. Its cellular effects depend on transcript, stimulus and cell type. Pathogenic DDX3X variants are associated with neurodevelopmental disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:23478265 Human DEAD box helicase 3 couples IΞΊB kinase Ξ΅ to interferon... | ACCEPT | Summary: DDX3X contributes to cytoplasmic antiviral receptor signaling through the IKKΞ΅βIRF3 module. Reason: The selected original PMID:23478265 Methods/Results show that DDX3X depletion reduces IRF3 phosphorylation after Sendai-virus stimulation in human A549 cells, while purified and cell-based experiments connect DDX3X to IKKΞ΅ activation and IRF3 recruitment. This supports participation downstream in cytoplasmic antiviral signaling, not the claim that DDX3X is itself the initiating pattern-recognition receptor. The paper discusses RIG-I-pathway context but the inspected functional experiments do not isolate one upstream receptor sufficiently to force a narrower receptor-specific replacement. Supporting Evidence: |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: The literal InterPro mapping is supported by the matched DEAD/DEAH helicase domain, but nucleic acid binding is broader than the existing RNA-binding and experimentally supported DNA-binding annotations. Reason: The literal InterPro mapping is supported by the matched DEAD/DEAH helicase domain, but nucleic acid binding is broader than the existing RNA-binding and experimentally supported DNA-binding annotations. Retain the domain evidence while preferring those existing substrate-specific assertions. Proposed refinement: Substrate-specific RNA and independently measured non-core DNA binding are already reviewed. The InterPro assertion remains valid at its original breadth. Proposed replacements: RNA binding DNA binding |
| GO:0003677 DNA binding | IDA PMID:21589879 A motif unique to the human DEAD-box protein DDX3 is importa... | KEEP AS NON CORE | Summary: Purified DDX3X binds DNA as well as RNA. Reason: The original binding assays support DNA association. This substrate interaction is retained without assigning sequence-specific transcriptional regulation or a physiological DNA-unwinding core. |
| GO:0003678 DNA helicase activity | IDA PMID:21589879 A motif unique to the human DEAD-box protein DDX3 is importa... | KEEP AS NON CORE | Summary: DNA unwinding was reported for particular substrates in vitro. Reason: Garbelli et al. tested an 18/38-mer DNA duplex and observed unwinding with a 5-prime overhang, but not with a 3-prime overhang. Sharma et al. found no appreciable unwinding of a 16-bp DNA duplex with a 25-nt 3-prime tail. These conditions do not directly retest the earlier positive substrate. Retain the experimental annotation with this unresolved scope; do not infer directional translocation or a physiological DNA-helicase role. The 2026 editorial correction replaces or clarifies figure panels and records missing underlying data, including original images for Figures 6AβB; this limits retrospective verification of the source-specific DNA result. Supporting Evidence: PMID:21589879 human DDX3 can unwind partially double stranded (ds) DNA substrates |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: Retain the curated UV-crosslinking RNA-interactome observation in human HeLa cells, corroborated by direct DDX3 RNA-binding and helicase experiments. Reason: Retain the curated UV-crosslinking RNA-interactome observation in human HeLa cells, corroborated by direct DDX3 RNA-binding and helicase experiments. The complete abstract was read; the source-specific target table was not independently inspected. Supporting Evidence: |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: Retain the curated human RNA-interactome annotation, consistent with independently established DDX3 RNA binding. Reason: Retain the curated human RNA-interactome annotation, consistent with independently established DDX3 RNA binding. The source describes photo-crosslinking and oligo(dT) capture; target-table details remain attributed to the curator. Supporting Evidence: |
| GO:0003723 RNA binding | IDA PMID:21589879 A motif unique to the human DEAD-box protein DDX3 is importa... | ACCEPT | Summary: Direct RNA binding accompanies DDX3X RNA remodeling. Reason: RNA binding was tested with purified protein by mobility shifts and viral-RNA pull-down. Deleting residues 250-259 weakened nucleic-acid association. The broad term fits the range of tested RNA substrates. Supporting Evidence: |
| GO:0003724 RNA helicase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The RNA-helicase IBD at Eukaryota node PTN002774595 lies on the actual DDX3X lineage. Reason: The RNA-helicase IBD at Eukaryota node PTN002774595 lies on the actual DDX3X lineage. Experimental descendant records include DDX3X itself, and human purified-protein RNA-unwinding assays independently establish the activity. The self-donor is valid experimental grounding, not circular evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002774595 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. No target-specific loss was established. |
| GO:0003724 RNA helicase activity | IDA PMID:21589879 A motif unique to the human DEAD-box protein DDX3 is importa... | ACCEPT | Summary: DDX3X directly unwinds RNA duplexes. Reason: Purified full-length human DDX3X separated an RNA duplex in ATP-containing reactions; ATPase-defective and domain-deletion controls support the enzymatic assignment. This is the principal catalytic activity. |
| GO:0003724 RNA helicase activity | IDA PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | ACCEPT | Summary: DDX3X RNA helicase activity is independently established by purified-protein unwinding experiments in PMID21589879. Reason: DDX3X RNA helicase activity is independently established by purified-protein unwinding experiments in PMID21589879. PMID31575075 directly measures RNA-dependent ATP hydrolysis of recombinant human DDX3X(1β580) and uses this as a functional control for nuclear-export mutants; its inspected Methods do not describe a separate duplex-unwinding assay. Retain the established activity with curator deference without recasting the ATPase control as direct unwinding evidence. Supporting Evidence: |
| GO:0003724 RNA helicase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The matched DEAD-box Q-motif region and literal InterPro/EC mappings support RNA helicase activity, which is independently established with purified human DDX3X. Reason: The matched DEAD-box Q-motif region and literal InterPro/EC mappings support RNA helicase activity, which is independently established with purified human DDX3X. Retain the electronic assertion as core chemistry. |
| GO:0003724 RNA helicase activity | TAS PMID:9381176 Functional coherence of the human Y chromosome. | ACCEPT | Summary: RNA helicase activity is independently established for DDX3X. Reason: RNA helicase activity is independently established for DDX3X. Retain this older author statement with curator deference; its complete abstract concerns sex-chromosome homologues and does not itself expose a target-specific biochemical assay. Supporting Evidence: |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: The mRNA-binding IBD at PTN002776867 is inherited by the actual DDX3X leaf. Reason: The mRNA-binding IBD at PTN002776867 is inherited by the actual DDX3X leaf. Current descendants include experimentally supported mRNA and mRNA-UTR binding, including DDX3X itself. Human target-RNA experiments agree with this ancestral placement; no claim of poly(A)-tail-specific recognition is required. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002776867 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. No target-specific loss was established. |
| GO:0003729 mRNA binding | IDA PMID:29062139 DDX3 regulates endoplasmic reticulum stress-induced ATF4 exp... | ACCEPT | Summary: In human Hep3B cells, anti-DDX3 RNA immunoprecipitation followed by qRT-PCR enriched ATF4 mRNA relative to IgG and control transcripts. Reason: In human Hep3B cells, anti-DDX3 RNA immunoprecipitation followed by qRT-PCR enriched ATF4 mRNA relative to IgG and control transcripts. This supports mRNA association by DDX3-containing complexes and is consistent with its central RNA-remodeling and translation functions; it does not establish a purified direct-binding affinity or a unique ATF4-specific interface. Supporting Evidence: |
| GO:0003924 GTPase activity | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | KEEP AS NON CORE | Summary: Purified human CAP-Rf hydrolyzed GTP in the radiolabeled nucleotide assay. Reason: Purified human CAP-Rf hydrolyzed GTP in the radiolabeled nucleotide assay. Retain this secondary in-vitro substrate activity without assigning a GTPase-switch mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | KEEP AS NON CORE | Summary: Yeast two-hybrid, purified-fragment binding and cellular co-immunoprecipitation support association with HCV core. Reason: Yeast two-hybrid, purified-fragment binding and cellular co-immunoprecipitation support association with HCV core. Different core truncations behaved differently; retain the positive viral interaction without generalizing every construct. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10329544 Hepatitis C virus core protein interacts with a human DEAD b... | KEEP AS NON CORE | Summary: The source reports binding between the human DDX3 C-terminal region and HCV core by yeast two-hybrid and in vitro assays, with infected-cell redistribution. Reason: The source reports binding between the human DDX3 C-terminal region and HCV core by yeast two-hybrid and in vitro assays, with infected-cell redistribution. Retain the processed viral-partner annotation without inferring a new host enzymatic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10336476 Hepatitis C virus core protein binds to a DEAD box RNA helic... | KEEP AS NON CORE | Summary: The complete abstract explicitly reports DBX/DDX3 interaction with HCV core by yeast two-hybrid, in vitro and mammalian-cell experiments. Reason: The complete abstract explicitly reports DBX/DDX3 interaction with HCV core by yeast two-hybrid, in vitro and mammalian-cell experiments. Retain the positive viral interaction with the imported processed-chain accession unchanged. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17855521 DDX3 DEAD-box RNA helicase is required for hepatitis C virus... | KEEP AS NON CORE | Summary: The source explicitly discusses the DDX3-HCV core interaction and tests DDX3 dependence of HCV replication in HuH7 cells. Reason: The source explicitly discusses the DDX3-HCV core interaction and tests DDX3 dependence of HCV replication in HuH7 cells. Retain the curated interaction with independent same-pair corroboration; the original pair-specific controls were not independently recovered. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | MODIFY | Summary: Human-cell co-immunoprecipitation detects DDX3 with eIF2alpha and survives RNase A. Reason: Human-cell co-immunoprecipitation detects DDX3 with eIF2alpha and survives RNase A. Refine to translation initiation factor binding without claiming an isolated subunit interface or catalytic activation of eIF2. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | KEEP AS NON CORE | Summary: RNase-resistant co-immunoprecipitation detects PABP1 association with DDX3. Reason: RNase-resistant co-immunoprecipitation detects PABP1 association with DDX3. Retain the supported interaction; it is not evidence that DDX3 binds the poly(A) tail through the same site. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | KEEP AS NON CORE | Summary: Cellular and recombinant assays support DDX3 association with TAP/NXF1. Reason: Cellular and recombinant assays support DDX3 association with TAP/NXF1. Retain this receptor-cargo interaction without assigning an mRNA-export receptor activity to DDX3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18628297 Human DDX3 functions in translation and interacts with the t... | MODIFY | Summary: Reciprocal eIF3b immunoprecipitation from RNase-treated human HeLa extracts recovers DDX3. Reason: Reciprocal eIF3b immunoprecipitation from RNase-treated human HeLa extracts recovers DDX3. The supported translation-factor class is more informative than generic binding; the assay does not isolate a direct eIF3b interface. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18628297 Human DDX3 functions in translation and interacts with the t... | MODIFY | Summary: Human DDX3 co-purifies with the eIF3 complex, including its identified subunits. Reason: Human DDX3 co-purifies with the eIF3 complex, including its identified subunits. Refine to translation initiation factor binding while preserving the distinction between complex association and direct contact with isolated eIF3C. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | KEEP AS NON CORE | Summary: Co-immunoprecipitation in infected and transfected human cells supports DDX3 association with vaccinia K7. Reason: Co-immunoprecipitation in infected and transfected human cells supports DDX3 association with vaccinia K7. Retain this positive viral interaction, with the imported strain accession preserved. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | MODIFY | Summary: Human-cell co-immunoprecipitation and N-terminal DDX3 pull-down support IKKepsilon association. Reason: Human-cell co-immunoprecipitation and N-terminal DDX3 pull-down support IKKepsilon association. Its verified serine/threonine kinase class provides a supported refinement; DDX3 does not acquire kinase activity. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | MODIFY | Summary: Fas immunoprecipitation from human Jurkat cells recovers DDX3 in the receptor-associated complex. Reason: Fas immunoprecipitation from human Jurkat cells recovers DDX3 in the receptor-associated complex. Refine to the demonstrated death-receptor class without claiming ligand activity or purified direct Fas-DDX3 binding. Proposed replacements: death receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | MODIFY | Summary: Human-cell co-immunoprecipitation supports association with GSK3alpha. Reason: Human-cell co-immunoprecipitation supports association with GSK3alpha. The kinase class justifies this refinement; it does not establish that DDX3 activates or phosphorylates the partner. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | MODIFY | Summary: Co-immunoprecipitation and DDX3 truncation analysis support GSK3beta association through the DDX3 C-terminal region. Reason: Co-immunoprecipitation and DDX3 truncation analysis support GSK3beta association through the DDX3 C-terminal region. Retain the demonstrated kinase-binding class without transferring GSK3 catalytic activity. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18985028 Hepatitis C virus infection protein network. | UNDECIDED | Summary: The original establishes an HCV-human interaction screen, but the exact DDX3-processed-core experiment was not recovered in the inspected text or current literal interaction query. Reason: The original establishes an HCV-human interaction screen, but the exact DDX3-processed-core experiment was not recovered in the inspected text or current literal interaction query. Other HCV-core papers corroborate the association but do not authenticate this source-specific record; preserve the curator assertion pending its target table. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19913487 Structural basis for targeting of human RNA helicase DDX3 by... | KEEP AS NON CORE | Summary: The source reports a crystal structure of vaccinia K7 with an N-terminal DDX3 peptide and tests key tandem phenylalanines. Reason: The source reports a crystal structure of vaccinia K7 with an N-terminal DDX3 peptide and tests key tandem phenylalanines. Retain the viral binding interaction without treating the engineered peptide as a natural isoform. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20127681 DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 t... | MODIFY | Summary: The source reports DDX3 association with RIG-I-like receptors, supporting the curated RIG-I interaction. Reason: The source reports DDX3 association with RIG-I-like receptors, supporting the curated RIG-I interaction. Refine by the verified intracellular signaling-receptor class with curator deference; original pair-specific controls remain unavailable, and receptor activation is not inferred from binding alone. Proposed replacements: signaling receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20127681 DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 t... | MODIFY | Summary: The source abstract reports direct interaction of DDX3 residues 622β662 with the IPS-1/MAVS CARD-like region. Reason: The source abstract reports direct interaction of DDX3 residues 622β662 with the IPS-1/MAVS CARD-like region. MAVS assembles multiple antiviral signaling partners, supporting scaffold-protein binding without assigning a MAVS-like membrane scaffold function to DDX3. Proposed replacements: scaffold protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20657822 Hepatitis B virus polymerase blocks pattern recognition rece... | MODIFY | Summary: Controlled co-immunoprecipitation directly detects DDX3-IKKepsilon association, reduced by HBV polymerase expression. Reason: Controlled co-immunoprecipitation directly detects DDX3-IKKepsilon association, reduced by HBV polymerase expression. Refine by the partner's kinase class without requiring that the binding assay itself establish catalytic activation. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20862261 Hepatitis C virus core-derived peptides inhibit genotype 1b ... | KEEP AS NON CORE | Summary: Purified human DDX3 helicase domain and HCV core fragments bind in GST pull-downs, and HuH7 co-immunoprecipitation confirms the 16β36 core segment. Reason: Purified human DDX3 helicase domain and HCV core fragments bind in GST pull-downs, and HuH7 co-immunoprecipitation confirms the 16β36 core segment. The 16β35 control fails to bind. Retain this specific viral interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21730191 DEAD-box RNA helicase Belle/DDX3 and the RNA interference pa... | KEEP AS NON CORE | Summary: The actual human section and Figure 4C report reciprocal co-immunoprecipitation of DDX3 and hCAP-H from HeLa lysates. Reason: The actual human section and Figure 4C report reciprocal co-immunoprecipitation of DDX3 and hCAP-H from HeLa lysates. Retain the condensin-subunit association without transferring the fly experiments wholesale or claiming purified direct binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | KEEP AS NON CORE | Summary: The complete source abstract explicitly reports PABP1 as a direct DDX3 interaction partner. Reason: The complete source abstract explicitly reports PABP1 as a direct DDX3 interaction partner. Retain that positive binding claim with curator deference; the original biochemical control details were not recovered. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22323517 The DEAD-box helicase DDX3 supports the assembly of function... | MODIFY | Summary: DDX3X associates with the translation initiation factor eIF2. Reason: The eIF2 association was RNA dependent in the purified-component assay. Retain that experimentally observed association using the identified functional partner class, without claiming an RNA-independent interface or direct binding to an isolated eIF2 alpha subunit. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22323517 The DEAD-box helicase DDX3 supports the assembly of function... | MODIFY | Summary: DDX3X interacts with the translation initiation factor eIF3. Reason: The purified-component assay supports an RNA-independent eIF3 interaction. eIF3C identifies the complex in this source; the experiment does not isolate a specific eIF3C contact surface. The functional partner class is more informative than generic protein binding. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22616990 Modulation of the type I interferon pathways by culture-adap... | KEEP AS NON CORE | Summary: Source-specific physical interaction records identify the HCV core partner; the abstract reports core substitutions that reduce DDX3 binding. Reason: Source-specific physical interaction records identify the HCV core partner; the abstract reports core substitutions that reduce DDX3 binding. Retain the positive viral association and preserve the literal strain accession. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22810585 Viral immune modulators perturb the human molecular network ... | KEEP AS NON CORE | Summary: The source-specific interaction record supports DDX3-K7 association within the viral-host interaction survey. Reason: The source-specific interaction record supports DDX3-K7 association within the viral-host interaction survey. Retain the positive assay context without inferring a native human physiological pathway from viral binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | KEEP AS NON CORE | Summary: The source abstract and literal pair record support DDX3-PABP1 association in translation-initiation experiments. Reason: The source abstract and literal pair record support DDX3-PABP1 association in translation-initiation experiments. Retain this positive interaction; PABP RNA-binding activity is not transferred to DDX3 merely from association. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | MODIFY | Summary: The source and literal pair record identify EIF4G1, a translation-initiation factor. Reason: The source and literal pair record identify EIF4G1, a translation-initiation factor. Refine the binding class while preserving the distinction between association, purified direct contact and proposed initiation mechanisms. Proposed replacements: translation initiation factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23413191 RNA helicase DDX3 is a regulatory subunit of casein kinase 1... | MODIFY | Summary: The CK1Ξ΅ association supports protein serine/threonine kinase binding. Reason: The original PMID:23413191 abstract explicitly reports Wnt-dependent DDX3 binding to CK1Ξ΅ and direct stimulation of its kinase activity; its complete Methods remain unavailable. Independently inspected PMID:29222110 uses human DDX3X and CK1Ξ΅, purified full-length/fragment and peptide-binding assays, and cellular kinase-sensor controls. These corroborate the positive association with the imported P49674 partner and its serine/threonine kinase class. They do not establish every interface proposed by molecular docking or transfer activation properties to the naturally short DDX3X product. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:23816991 Exploration of binary virus-host interactions using an infec... | MODIFY | Summary: The positive source-specific complementation record identifies influenza PB2. Reason: The positive source-specific complementation record identifies influenza PB2. PB2 is a subunit of the viral RNA-polymerase complex, and the binding term explicitly includes polymerase complexes; this does not assign autonomous polymerase catalysis to PB2 or DDX3. Proposed replacements: RNA polymerase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23840900 Human DDX3 interacts with the HIV-1 Tat protein to facilitat... | MODIFY | Summary: Purified GST-DDX3 binds recombinant HIV-1 Tat, and reciprocal cellular immunoprecipitations include RNase treatment. Reason: Purified GST-DDX3 binds recombinant HIV-1 Tat, and reciprocal cellular immunoprecipitations include RNase treatment. Tat is an established transcriptional activator, supporting the partner-class refinement without assigning Tat-like activity to DDX3. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24169621 Elucidating novel hepatitis C virus-host interactions using ... | KEEP AS NON CORE | Summary: Source-specific affinity-purification records identify the processed HCV core partner. Reason: Source-specific affinity-purification records identify the processed HCV core partner. Retain the viral association with its strain and processed-chain identifiers unchanged; the assay does not establish a new catalytic role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24855944 The TRPM7 chanzyme is cleaved to release a chromatin-modifyi... | MODIFY | Summary: The source tests mouse TRPM7 C-terminal kinase fragments in human 293T cells: DDX3 associates with the long and medium fragments but not the shorter fragment, all of which contain the kinase domain. Reason: The source tests mouse TRPM7 C-terminal kinase fragments in human 293T cells: DDX3 associates with the long and medium fragments but not the shorter fragment, all of which contain the kinase domain. Refine by the serine/threonine-kinase partner class; this is not evidence of binding the membrane-channel pore or of DDX3 phosphorylation. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26030138 Identification of Novel Proteins Co-Purifying with Cockayne ... | MODIFY | Summary: The original reports reciprocal tagged CSB-DDX3 co-immunoprecipitation in human cells. Reason: The original reciprocal tagged co-immunoprecipitations in human CS1AN cells support the DDX3XβCSB association. Independently curated CSB biochemistry establishes DNA-dependent ATP hydrolysis. GO:0051117 describes binding to an ATPase and is more specific than enzyme binding. This supported partner-class refinement does not require DDX3X to activate CSB/ERCC6 and does not establish a purified direct interface or transfer the partnerβs other functions to DDX3X. Proposed replacements: ATPase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26100019 The DHX33 RNA Helicase Promotes mRNA Translation Initiation. | MODIFY | Summary: The actual source Figure 7 reports DDX3 co-immunoprecipitation with wild-type and K94R DHX33 in HCC1806 cells, persisting after RNase treatment. Reason: The original HCC1806 experiments recover DDX3X with both wild-type and K94R DHX33, including after RNase treatment. DHX33 is an established ATP-hydrolyzing RNA helicase. GO:0051117 describes binding to an ATPase and is more specific than enzyme binding. This supported partner-class refinement does not require DDX3X to activate DHX33 and does not establish a purified direct interface or transfer the partnerβs other functions to DDX3X. Proposed replacements: ATPase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27736973 The DEAD-Box RNA Helicase DDX3 Interacts with NF-ΞΊB Subunit ... | MODIFY | Summary: Human-cell co-immunoprecipitation and purified GST-DDX3/His-p65 pull-down support RELA binding. Reason: Human-cell co-immunoprecipitation and purified GST-DDX3/His-p65 pull-down support RELA binding. The verified transcription-factor class is more informative than generic binding; DDX3 is not thereby a sequence-specific DNA-binding factor. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27980081 DDX3 directly regulates TRAF3 ubiquitination and acts as a s... | KEEP AS NON CORE | Summary: The source abstract supports direct TRAF3 interaction and assembly of MAVS, IKKepsilon and IRF3-containing complexes. Reason: The source abstract supports direct TRAF3 interaction and assembly of MAVS, IKKepsilon and IRF3-containing complexes. Retain this heterogeneous signaling-association annotation with curator deference, without claiming that all listed proteins contact DDX3 directly or that the unrecovered TBKBP1-specific experiment was independently read. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28128295 RNA helicase DDX3 maintains lipid homeostasis through upregu... | MODIFY | Summary: RNase-resistant assays support HNF4/SHP association, and controlled nuclear co-immunoprecipitation detects CBP/p300. Reason: RNase-resistant assays support HNF4/SHP association, and controlled nuclear co-immunoprecipitation detects CBP/p300. Refine to the demonstrated transcription-regulator and histone-acetyltransferase partner classes without assigning acetyltransferase activity to DDX3 or purified direct binding to every partner. Proposed replacements: transcription factor binding histone acetyltransferase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28611246 Inhibition of Avian Influenza A Virus Replication in Human C... | MODIFY | Summary: The literal positive records identify wild-type and residue-627 variant influenza PB2 in a tagged co-immunoprecipitation screen. Reason: The literal positive records identify wild-type and residue-627 variant influenza PB2 in a tagged co-immunoprecipitation screen. PB2 belongs to the viral RNA-polymerase complex; refine the binding class while preserving the spoke-expansion and construct limits. Proposed replacements: RNA polymerase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28733330 The helicase, DDX3X, interacts with poly(A)-binding protein ... | KEEP AS NON CORE | Summary: The original finds RNA-dependent PABP1/caprin-1 co-isolation and an eIF4E-associated fraction recovered by cap affinity. Reason: The original finds RNA-dependent PABP1/caprin-1 co-isolation and an eIF4E-associated fraction recovered by cap affinity. It does not detect eIF4E in the reciprocal DDX3 immunoprecipitate and explicitly considers indirect association. Retain this heterogeneous positive interaction set without presenting every pair as purified direct binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28842590 DDX3 localizes to the centrosome and prevents multipolar mit... | MODIFY | Summary: Controlled HCT116 co-immunoprecipitation detects DDX3 with Ser15-phosphorylated p53, whereas total-p53 antibody does not recover the same complex. Reason: Controlled HCT116 co-immunoprecipitation detects DDX3 with Ser15-phosphorylated p53, whereas total-p53 antibody does not recover the same complex. Refine to transcription-factor binding with this state-specific assay limitation; no universal direct p53 contact is asserted. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29261807 Characterization of host proteins interacting with the lymph... | MODIFY | Summary: LCMV L-HA pulldown and immunoblotting identify endogenous DDX3 in infected and L-transfected human cells, with untagged/empty-vector controls. Reason: LCMV L-HA pulldown and immunoblotting identify endogenous DDX3 in infected and L-transfected human cells, with untagged/empty-vector controls. L is the viral RNA polymerase, supporting the binding-class refinement without asserting a purified interface or DDX3 polymerase activity. Proposed replacements: RNA polymerase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29899501 The TRPV4 channel links calcium influx to DDX3X activity and... | MODIFY | Summary: Reciprocal tagged and endogenous human-cell co-immunoprecipitations and proximity assays support DDX3-TRPV4 association. Reason: Reciprocal tagged and endogenous human-cell co-immunoprecipitations and proximity assays support DDX3-TRPV4 association. TRPV4 is a transmembrane cation transporter; refine by this class without claiming DDX3 itself transports ions. Proposed replacements: transmembrane transporter binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30131165 Investigating nucleo-cytoplasmic shuttling of the human DEAD... | KEEP AS NON CORE | Summary: Retain the curated XPO1/exportin association with independent DDX3 nuclear-export corroboration. Reason: Retain the curated XPO1/exportin association with independent DDX3 nuclear-export corroboration. The source abstract and official transport-receptor classification support the context; unrecovered source-specific binding controls are not represented as independently read. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | MODIFY | Summary: The source abstract explicitly identifies direct DDX3-IKKalpha interaction. Reason: The source abstract explicitly identifies direct DDX3-IKKalpha interaction. Refine to its established kinase class with curator deference; the original assay details remain unavailable and this binding annotation does not itself encode kinase activation. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | KEEP AS NON CORE | Summary: Human DDX3X physically associates with XPO1/exportin-1 through its N-terminal nuclear export signal. Reason: Human DDX3X physically associates with XPO1/exportin-1 through its N-terminal nuclear export signal. The source combines cellular co-immunoprecipitation with purified DDX3X fragments, exportin-1 and Ran-GTP in sedimentation experiments; NES mutations disrupt association. Retain this positive receptorβcargo interaction under the supported generic-binding policy. This is not nuclear hormone receptor binding, and DDX3X does not thereby acquire exportin activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Three literal two-hybrid records support the DDX3-TFF2 pair. Reason: Three literal two-hybrid records support the DDX3-TFF2 pair. Retain the positive screen result while leaving physiological colocalization and processing unresolved; the secreted partner and yeast assay do not by themselves establish a native extracellular DDX3 function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Multiple literal two-hybrid records support TARDBP binding, including a 1β260 partner fragment. Reason: Multiple literal two-hybrid records support TARDBP binding, including a 1β260 partner fragment. Retain the positive interaction without transferring the partner RNA-binding function or asserting a native stress-granule mechanism from this screen alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The literal records identify human Q6P582/MZT2A, including a 38β158 fragment. Reason: The literal records identify human Q6P582/MZT2A, including a 38β158 fragment. Retain the positive two-hybrid interaction with construct limits; its centrosomal assembly role does not establish a motor or catalytic class for the tested partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Three literal two-hybrid records identify Q8TF63. Reason: Three literal two-hybrid records identify Q8TF63. Its curated functional evidence establishes promoter binding and transactivation, supporting transcription-factor binding as a partner-class refinement without asserting DDX3 regulates that promoter physiologically. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The matched ATP-binding helicase domain and direct ATP-dependent biochemical assays support ATP binding as an integral part of DDX3X catalysis. Reason: The matched ATP-binding helicase domain and direct ATP-dependent biochemical assays support ATP binding as an integral part of DDX3X catalysis. This does not require a separate cofactor-binding core. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: The curated secretory-granule exocytosis reaction includes an exact O00571 DDX3X member in its extracellular output set. Reason: The curated secretory-granule exocytosis reaction includes an exact O00571 DDX3X member in its extracellular output set. Retain this context-dependent compartment assertion while distinguishing modeled neutrophil granule cargo release from the protein's intracellular RNA and signaling functions. Extracellular enzymatic activity is not required for this location annotation. Supporting Evidence: Reactome:R-HSA-6798748 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: The curated ficolin-rich granule exocytosis reaction includes an exact O00571 DDX3X member in its extracellular output set. Reason: The curated ficolin-rich granule exocytosis reaction includes an exact O00571 DDX3X member in its extracellular output set. This supports a context-dependent extracellular location rather than a general secreted-protein role or extracellular helicase activity. Supporting Evidence: Reactome:R-HSA-6800434 |
| GO:0005634 nucleus | EXP PMID:15507209 Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE ... | MODIFY | Summary: The source describes DDX3 at nuclear pores and shuttling between nucleus and cytoplasm. Reason: The complete PMID:15507209 abstract explicitly places DDX3 at nuclear membrane pores and describes nucleocytoplasmic shuttling. Refine the broad nuclear location to nuclear pore, preserving that observed compartment rather than substituting nucleoplasm from an unrelated reaction. Localization at the pore does not imply that DDX3 is a constitutive pore subunit; the full original imaging controls were not independently recovered. Proposed replacements: nuclear pore |
| GO:0005634 nucleus | EXP PMID:16818630 DDX3, a DEAD box RNA helicase with tumor growth-suppressive ... | MODIFY | Summary: The source reports nuclear and cytoplasmic human DDX3 localization. Reason: The source reports nuclear and cytoplasmic human DDX3 localization. Preserve that observation while using the supported, more specific nucleoplasm location elsewhere; the broad term does not establish a separate core function. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | EXP PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | MODIFY | Summary: Fractionation and export-blocking experiments support nuclear DDX3. Reason: Fractionation and export-blocking experiments support nuclear DDX3. Nucleoplasm is already represented more specifically; the source observation is retained rather than contradicted. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | EXP PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | MODIFY | Summary: Fractionation and export inhibition reveal nuclear DDX3. Reason: Fractionation and export inhibition reveal nuclear DDX3. Preserve the observation through the supported more specific nucleoplasm location. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | EXP PMID:22034099 The DEAD-box RNA helicase DDX3 interacts with DDX5, co-local... | MODIFY | Summary: The source supports nucleocytoplasmic DDX3 localization and altered mRNP export after DNA damage. Reason: The source supports nucleocytoplasmic DDX3 localization and altered mRNP export after DNA damage. Preserve the positive nuclear observation while preferring the existing nucleoplasm annotation; detailed source assays were not independently recovered beyond the abstract. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MODIFY | Summary: The nuclear IBD at Eukaryota node PTN002774649 lies on the DDX3X lineage and has experimental descendant grounding, including human DDX3X. Reason: The nuclear IBD at Eukaryota node PTN002774649 lies on the DDX3X lineage and has experimental descendant grounding, including human DDX3X. The inference is biologically sound, but the existing nucleoplasm annotation is more specific for the nuclear pool. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002774649 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. The source itself is valid; the review favors an existing narrower term. Proposed replacements: nucleoplasm Supporting Evidence: GO_REF:0000033 Reactome:R-HSA-9921600 |
| GO:0005634 nucleus | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | MODIFY | Summary: Immunostaining and fractionation support nuclear CAP-Rf. Reason: Immunostaining and fractionation support nuclear CAP-Rf. Preserve this observation through the more specific supported nucleoplasm location. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IDA PMID:10329544 Hepatitis C virus core protein interacts with a human DEAD b... | MODIFY | Summary: Human-cell imaging in the HCV-core study supports nuclear DDX3, including speckles. Reason: The complete PMID:10329544 abstract reports predominantly nuclear-speckle localization of DDX3 in HeLa cells. Refine nucleus to nuclear speck, which preserves the source-specific nuclear compartment. This does not assert that all nuclear DDX3 is speckle-associated; the full original imaging controls were not independently recovered. Proposed replacements: nuclear speck |
| GO:0005634 nucleus | IDA PMID:29899501 The TRPV4 channel links calcium influx to DDX3X activity and... | MODIFY | Summary: The original demonstrates calcium- and TRPV4-dependent nuclear accumulation of DDX3 in human cells. Reason: The original demonstrates calcium- and TRPV4-dependent nuclear accumulation of DDX3 in human cells. More specific supported nucleoplasm annotations retain the compartment evidence. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IDA PMID:30131165 Investigating nucleo-cytoplasmic shuttling of the human DEAD... | MODIFY | Summary: Retain the curated nuclear-shuttling observation with source-access limits explicit. Reason: Retain the curated nuclear-shuttling observation with source-access limits explicit. More specific supported nucleoplasm annotations retain the compartment evidence. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IDA PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | MODIFY | Summary: The source directly observes nuclear accumulation of human DDX3X after exportin inhibition, nuclear-export-signal mutation and viral-RNA challenge. Reason: The source directly observes nuclear accumulation of human DDX3X after exportin inhibition, nuclear-export-signal mutation and viral-RNA challenge. Preserve this positive observation; nucleus is a broad location already represented by the more specific nucleoplasm annotation and does not need a separate core-level location assertion. Proposed refinement: The independently established nucleoplasm location refines the broader nuclear observation. The original source is not relabeled as a nucleoplasm-specific assay and nuclear-pore/shuttling observations remain valid. Proposed replacements: nucleoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MODIFY | Summary: The literal UniProt subcellular mapping preserves supported nuclear localization. Reason: The literal UniProt subcellular mapping supports nuclear localization and explicitly describes association with nuclear pores on the outer side of the nuclear membrane, citing PMID:15507209. Retain both the independently established nucleoplasm pool and the source-supported pore location as specific replacements. These describe distinct observed pools, not exclusive localization or constitutive membership of the pore complex. Proposed replacements: nucleoplasm nuclear pore Supporting Evidence: GO_REF:0000044 Reactome:R-HSA-9921600 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9921600 | ACCEPT | Summary: The dengue-capsid binding reaction explicitly contains human O00571 DDX3X, residues 2β662, in the nucleoplasm. Reason: The dengue-capsid binding reaction explicitly contains human O00571 DDX3X, residues 2β662, in the nucleoplasm. This curated location agrees with independent human-cell nuclear trafficking observations. The infection-specific interaction does not restrict all nuclear DDX3X to viral infection, and the modeled mature-chain coordinates are not an experimentally distinguished alternative isoform. Supporting Evidence: Reactome:R-HSA-9921600 |
| GO:0005737 cytoplasm | EXP PMID:15507209 Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE ... | MODIFY | Summary: The source describes nucleocytoplasmic shuttling. Reason: The source describes nucleocytoplasmic shuttling. Preserve the cytoplasmic observation while preferring the existing cytosol annotation for the soluble cytoplasmic pool. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:16818630 DDX3, a DEAD box RNA helicase with tumor growth-suppressive ... | MODIFY | Summary: The source reports cytoplasmic DDX3 as well as nuclear localization. Reason: The source reports cytoplasmic DDX3 as well as nuclear localization. Cytosol and stress-granule annotations supply greater specificity without implying that all cytoplasmic protein is granule-associated. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | MODIFY | Summary: The source demonstrates cytoplasmic DDX3 and stress-dependent granule localization. Reason: PMID:18596238 reports cytoplasmic DDX3 and transient localization to cytoplasmic stress granules under stress. Refine the broad location to cytosol and cytoplasmic stress granule, preserving the soluble pool and the condition-dependent granule observation already captured by the source-specific stress-granule annotation. This does not place all cytoplasmic DDX3 in granules. Proposed replacements: cytosol cytoplasmic stress granule |
| GO:0005737 cytoplasm | EXP PMID:20127681 DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 t... | MODIFY | Summary: The source places DDX3 in the cytoplasm, including a fraction near mitochondrial MAVS. Reason: The source places DDX3 in the cytoplasm, including a fraction near mitochondrial MAVS. Retain the evidence through more specific supported cytosol locations without treating peripheral MAVS association as mitochondrial matrix residence. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:21170385 Hepatitis C virus core protein abrogates the DDX3 function t... | MODIFY | Summary: Human hepatoma-cell experiments place DDX3 in the cytoplasm and near mitochondria with the IPS-1/MAVS signaling context. Reason: Human hepatoma-cell experiments place DDX3 in the cytoplasm and near mitochondria with the IPS-1/MAVS signaling context. Cytoplasm is broader than the existing cytosol annotation; proximity to mitochondria does not establish matrix import. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:21730191 DEAD-box RNA helicase Belle/DDX3 and the RNA interference pa... | MODIFY | Summary: The human HeLa experiments show a cytoplasmic DDX3 pool and mitotic redistribution. Reason: The human HeLa experiments show a cytoplasmic DDX3 pool and mitotic redistribution. More specific supported cytosol annotations retain the compartment evidence. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | MODIFY | Summary: Cytoplasmic DDX3 redistribution into stress granules is explicitly reported. Reason: The complete PMID:21883093 abstract explicitly reports stress-induced DDX3 redistribution into stress granules, but not processing bodies. Refine the broad cytoplasmic location to cytosol and cytoplasmic stress granule, preserving the independently established diffuse pool and the source-specific stress response. The full original was not recovered, and no processing-body localization or constitutive granule residence is inferred. Proposed replacements: cytosol cytoplasmic stress granule |
| GO:0005737 cytoplasm | EXP PMID:22034099 The DEAD-box RNA helicase DDX3 interacts with DDX5, co-local... | MODIFY | Summary: The source reports cytoplasmic DDX3/DDX5 association during cell-cycle progression and redistribution after damage. Reason: The source reports cytoplasmic DDX3/DDX5 association during cell-cycle progression and redistribution after damage. Retain the observation, with the existing cytosol annotation providing a more specific compartment. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:23413191 RNA helicase DDX3 is a regulatory subunit of casein kinase 1... | MODIFY | Summary: Cytoplasmic residence is retained but is broader than the supported cytosolic location. Reason: A cytoplasmic location is consistent with the CK1 regulatory role and the independently supported human cytosolic DDX3X pool. The original PMID:23413191 full localization assay was not recovered, so its detailed imaging conditions are not reconstructed from the abstract. Retain the positive location assertion while using the already supported cytosol annotation for the more informative compartment; this is a specificity judgment, not a negative localization claim. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:27105836 Venezuelan equine encephalitis virus non-structural protein ... | MODIFY | Summary: The source detects cytoplasmic DDX3 in human U87MG cells in the viral nsP3 interaction experiments. Reason: The source detects cytoplasmic DDX3 in human U87MG cells in the viral nsP3 interaction experiments. Retain this positive observation while preferring the existing cytosol annotation. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:29062139 DDX3 regulates endoplasmic reticulum stress-induced ATF4 exp... | MODIFY | Summary: The source directly detects diffuse cytoplasmic DDX3 in human Hep3B cells and partial stress-granule colocalization after sorafenib. Reason: PMID:29062139 Results and Figure 1C directly show diffuse cytoplasmic DDX3 in untreated human Hep3B cells and partial colocalization with FMRP-positive stress granules after sorafenib, with a substantial diffuse pool remaining. Refine cytoplasm to cytosol and cytoplasmic stress granule so both observed populations are retained. Localization in these granules does not imply that DDX3 is required for their assembly in this treatment context. Proposed replacements: cytosol cytoplasmic stress granule |
| GO:0005737 cytoplasm | EXP PMID:29222110 A CK1 FRET biosensor reveals that DDX3X is an essential acti... | MODIFY | Summary: The cytoplasmic CK1-regulatory context is compatible with the more specific cytosolic annotation. Reason: The actual PMID:29222110 original describes human DDX3X/CK1 co-expression, DDX3X-dependent responses of a cytoplasm-targeted kinase sensor, and comparable wild-type/mutant DDX3X colocalization with CK1Ξ΅. The sensor fluorescence reports kinase activity rather than directly measuring DDX3X distribution, and the supplement pixels were not independently inspected. The broad cytoplasm annotation is retained as compatible but is less informative than the independently supported cytosol location. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | EXP PMID:33674311 RNF39 mediates K48-linked ubiquitination of DDX3X and inhibi... | MODIFY | Summary: The paper combines human-cell interaction experiments with localization in mouse fibroblasts and macrophages. Reason: The paper combines human-cell interaction experiments with localization in mouse fibroblasts and macrophages. Preserve those organism-specific observations without relabeling the mouse imaging as human; the broad cytoplasmic assertion is consistent with, and less specific than, existing human cytosol evidence. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | MODIFY | Summary: The current HPA data record reports cytosol as the main location and plasma membrane as an additional location, with approved immunofluorescence reliability. Reason: The current HPA data record reports cytosol as the main location and plasma membrane as an additional location, with approved immunofluorescence reliability. Cytoplasm is broader than the existing cytosol annotation. This assessment uses the data record, not a new inspection of microscopy images. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:10329544 Hepatitis C virus core protein interacts with a human DEAD b... | MODIFY | Summary: The original reports DDX3 redistribution to perinuclear cytoplasm with HCV-core expression. Reason: The complete PMID:10329544 abstract reports low-level DDX3 throughout the cytoplasm in HeLa cells and redistribution with HCV-core expression into distinct spots in the perinuclear region. Retain cytosol for the independently supported diffuse pool and perinuclear region of cytoplasm for the source-specific redistribution. The perinuclear observation does not identify an organelle or establish exclusive perinuclear residence; the full original controls were not recovered. Proposed replacements: cytosol perinuclear region of cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | MODIFY | Summary: Human-cell fractionation and microscopy support predominantly cytoplasmic DDX3 before export inhibition. Reason: Human-cell fractionation and microscopy support predominantly cytoplasmic DDX3 before export inhibition. Cytosol supplies the more specific supported location. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | MODIFY | Summary: The source observes cytoplasmic DDX3 and its redistribution into stress-granule-like structures in the viral Npro/arsenate experiments. Reason: PMID:24965446 Results and Figure 3B show cytoplasmic DDX3-Myc in human HeLa cells and redistribution into stress-granule-like structures after sodium arsenate in the viral Npro experiments. Refine the broad location to cytosol and cytoplasmic stress granule, preserving the conditional localization. These observations do not establish that DDX3 transports or retains other proteins in granules, and the separate DCP1a observations do not identify DDX3 as a processing-body component. Proposed replacements: cytosol cytoplasmic stress granule |
| GO:0005737 cytoplasm | IDA PMID:27736973 The DEAD-Box RNA Helicase DDX3 Interacts with NF-ΞΊB Subunit ... | MODIFY | Summary: Human-cell imaging and fractionation support cytoplasmic DDX3-p65 association. Reason: Human-cell imaging and fractionation support cytoplasmic DDX3-p65 association. The positive evidence is retained through the more specific cytosol annotation. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:28733330 The helicase, DDX3X, interacts with poly(A)-binding protein ... | MODIFY | Summary: The original detects a cytoplasmic population in spreading human MRC5 fibroblasts. Reason: PMID:28733330 separates a soluble cytosolic DDX3X pool and directly images endogenous DDX3X at the leading edge of spreading human MRC5 fibroblasts in Figure 4. Retain cytosol and cell leading edge as complementary source-supported locations, the latter already represented by the same-source annotation. The current ontology does not provide an is_a or part_of path from cell leading edge to cytoplasm; this is a biological location refinement, not a claimed typed descendant relationship or exclusive peripheral localization. Proposed replacements: cytosol cell leading edge |
| GO:0005737 cytoplasm | IDA PMID:30131165 Investigating nucleo-cytoplasmic shuttling of the human DEAD... | MODIFY | Summary: Retain the curated cytoplasmic location accompanying nuclear export. Reason: Retain the curated cytoplasmic location accompanying nuclear export. More specific supported cytosol annotations retain the compartment evidence. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | MODIFY | Summary: Retain the curated cytoplasmic signaling location through the more specific supported cytosol assertion, without claiming that the unrecovered original localization images were inspected. Reason: Retain the curated cytoplasmic signaling location through the more specific supported cytosol assertion, without claiming that the unrecovered original localization images were inspected. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | MODIFY | Summary: The source directly measures cytosolic full-length DDX3X and its redistribution during exportin inhibition, NES mutation and viral challenge. Reason: The source directly measures cytosolic full-length DDX3X and its redistribution during exportin inhibition, NES mutation and viral challenge. The positive localization is retained through more specific cytosolic and nuclear-compartment annotations; broad cytoplasm adds no separate location specificity. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: The literal UniProt subcellular mapping supports cytoplasmic localization, which is broader than the existing cytosol annotation and specific cytoplasmic assemblies. Reason: The literal UniProt mapping supports cytoplasmic localization and explicitly identifies a stress-granule pool with publication-level provenance, including PMID:18596238 and PMID:29062139. Refine the broad location to cytosol and cytoplasmic stress granule, preserving diffuse and condition-dependent granular pools. The separately represented centrosome and lamellipodium observations remain valid; this replacement is not an exhaustive or exclusive location list. Proposed replacements: cytosol cytoplasmic stress granule |
| GO:0005737 cytoplasm | IMP PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | MODIFY | Summary: The source detects cytoplasmic CAP-Rf and redistribution with HCV core. Reason: The source detects cytoplasmic CAP-Rf and redistribution with HCV core. Cytosol is the more specific supported location; this does not deny conditional nuclear trafficking. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IMP PMID:26100019 The DHX33 RNA Helicase Promotes mRNA Translation Initiation. | MODIFY | Summary: Retain the curated cytoplasmic location in the translation-complex study. Reason: Retain the curated cytoplasmic location in the translation-complex study. More specific supported cytosol annotations retain the compartment evidence. Proposed refinement: The independently established cytosol location refines the broad cytoplasmic assertion. This does not place all cytoplasmic protein in stress granules or exclude membrane-associated pools. Proposed replacements: cytosol |
| GO:0005739 mitochondrion | IDA PMID:28869602 Targeting mitochondrial translation by inhibiting DDX3: a no... | KEEP AS NON CORE | Summary: Mitochondrial fractionation and colocalization in breast-cancer cells support a mitochondrial-associated DDX3 pool. Reason: Mitochondrial fractionation and colocalization in breast-cancer cells support a mitochondrial-associated DDX3 pool. Retain this contextual localization without assigning a matrix, inner-membrane, import mechanism or constitutive mitochondrial residence. Supporting Evidence: |
| GO:0005813 centrosome | IDA PMID:28842590 DDX3 localizes to the centrosome and prevents multipolar mit... | KEEP AS NON CORE | Summary: Human HCT116 and U2OS imaging places DDX3 at centrosomes through the cell cycle; p53 depletion and rescue affect that localization. Reason: Human HCT116 and U2OS imaging places DDX3 at centrosomes through the cell cycle; p53 depletion and rescue affect that localization. Retain this contextual compartment without making centrosomal structural activity a core function. Supporting Evidence: |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The literal centrosome mapping agrees with independent human-cell centrosomal localization. Reason: The literal centrosome mapping agrees with independent human-cell centrosomal localization. Retain this context-specific pool without assigning DDX3 a centrosome-specific catalytic function. |
| GO:0005829 cytosol | IDA PMID:28869602 Targeting mitochondrial translation by inhibiting DDX3: a no... | ACCEPT | Summary: The source detects DDX3 in the cytosolic fraction as well as in mitochondrial extracts, with relative distribution varying between cell lines. Reason: The source detects DDX3 in the cytosolic fraction as well as in mitochondrial extracts, with relative distribution varying between cell lines. Cytosol is consistent with the principal RNA-remodeling and signaling activities; mitochondrial association does not negate it. Supporting Evidence: |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:18628297 Human DDX3 functions in translation and interacts with the t... | KEEP AS NON CORE | Summary: RNase-resistant reciprocal immunoprecipitation robustly places human DDX3 with eIF3. Reason: RNase-resistant reciprocal immunoprecipitation robustly places human DDX3 with eIF3. Retain this associated translation-initiation complex context without describing DDX3 as one of the canonical constitutive eIF3 subunits. Supporting Evidence: |
| GO:0005886 plasma membrane | EXP PMID:23413191 RNA helicase DDX3 is a regulatory subunit of casein kinase 1... | KEEP AS NON CORE | Summary: Contextual plasma-membrane association is independently supported; the original Wnt-study localization assay remains unverified. Reason: The plasma-membrane compartment is independently supported by human HeLa experiments in PMID:29899501: after removal of excess cytosolic signal, tagged DDX3X colocalizes with membrane TRPV4, and channel activation reduces this association. Retain this contextual location with curator deference. The detailed membrane assay in the original PMID:23413191 study remains unrecovered; its abstract establishes CK1/Wnt regulation, not the localization protocol. Independent corroboration supports the same compartment without claiming that the earlier experiment was recovered or that DDX3X is an integral membrane protein. |
| GO:0005886 plasma membrane | IDA PMID:29899501 The TRPV4 channel links calcium influx to DDX3X activity and... | KEEP AS NON CORE | Summary: After removal of excess cytosolic signal, the original resolves a DDX3 population with TRPV4 at the plasma membrane; channel activation reduces association. Reason: After removal of excess cytosolic signal, the original resolves a DDX3 population with TRPV4 at the plasma membrane; channel activation reduces association. Retain this peripheral membrane location without implying a transmembrane DDX3 product. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The literal cell-membrane mapping is corroborated by human-cell DDX3/TRPV4 association and membrane-associated fluorescence. Reason: The literal cell-membrane mapping is corroborated by human-cell DDX3/TRPV4 association and membrane-associated fluorescence. Retain the contextual peripheral association without implying that DDX3 is an integral membrane protein. |
| GO:0006413 translational initiation | IMP PMID:26100019 The DHX33 RNA Helicase Promotes mRNA Translation Initiation. | ACCEPT | Summary: Translation initiation is independently demonstrated for DDX3. Reason: Translation initiation is independently demonstrated for DDX3. The source directly places it in an RNase-resistant DHX33-containing initiation complex; retain the curated functional annotation with deference for the target-specific perturbation details not independently recovered. Supporting Evidence: |
| GO:0007059 chromosome segregation | IMP PMID:21730191 DEAD-box RNA helicase Belle/DDX3 and the RNA interference pa... | KEEP AS NON CORE | Summary: The actual human HeLa experiments show chromosome-segregation defects and reduced chromosomal hCAP-H localization after DDX3 knockdown, with hCAP-H expression retained. Reason: The actual human HeLa experiments show chromosome-segregation defects and reduced chromosomal hCAP-H localization after DDX3 knockdown, with hCAP-H expression retained. Keep this demonstrated mitotic context outside the compact core synthesis. Supporting Evidence: |
| GO:0007276 gamete generation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The gamete-generation IBD at Eumetazoa node PTN002774652 lies on the DDX3X lineage. Reason: The gamete-generation IBD at Eumetazoa node PTN002774652 lies on the DDX3X lineage. Descendant experimental records cover germ-cell development, oogenesis and spermatogenesis. No target-specific loss was established, so retain the conserved developmental inference as non-core rather than reject it because the direct experiments are in other descendants. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002774652 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. No target-specific loss was established. Supporting Evidence: GO_REF:0000033 |
| GO:0008134 transcription factor binding | IDA PMID:16818630 DDX3, a DEAD box RNA helicase with tumor growth-suppressive ... | KEEP AS NON CORE | Summary: The complete abstract explicitly reports DDX3 interaction with Sp1 and Sp1-site-dependent p21-promoter activation. Reason: The complete abstract explicitly reports DDX3 interaction with Sp1 and Sp1-site-dependent p21-promoter activation. Retain transcription-factor binding in that context with curator deference; full original assay details remain unavailable. Supporting Evidence: |
| GO:0008143 poly(A) binding | IDA PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | UNDECIDED | Summary: The inspected experiment selects UV-crosslinked polyadenylated mRNPs and supports DDX3 binding to mRNA. Reason: The inspected experiment selects UV-crosslinked polyadenylated mRNPs and supports DDX3 binding to mRNA. GO:0008143 specifically requires contact with an adenylyl sequence; selection through the poly(A) tail does not identify the protein's contact site. Tail-specific controls in the complete original and supplements could not be fully verified, so preserve the source assertion as unresolved rather than claim that poly(A) binding is absent. Supporting Evidence: |
| GO:0008190 eukaryotic initiation factor 4E binding | IDA PMID:17667941 Candidate tumor suppressor DDX3 RNA helicase specifically re... | KEEP AS NON CORE | Summary: The complete abstract reports DDX3 binding to the dorsal surface of eIF4E, motif dependence and interference with eIF4G recruitment. Reason: The complete abstract reports DDX3 binding to the dorsal surface of eIF4E, motif dependence and interference with eIF4G recruitment. Retain this specific inhibitory interaction in its experimental context; direct original access remains limited. Supporting Evidence: |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: DDX3 contributes to suppression of death-receptor-induced caspase activation in the tested human cells. Reason: DDX3 contributes to suppression of death-receptor-induced caspase activation in the tested human cells. Retain this extrinsic-apoptosis context without interpreting DDX3 cleavage as a protease activity or assuming universal pro-death behavior. Supporting Evidence: |
| GO:0009615 response to virus | IDA PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | KEEP AS NON CORE | Summary: Sendai-virus challenge induces endogenous DDX3-IKKepsilon association and DDX3-dependent IRF responses. Reason: Sendai-virus challenge induces endogenous DDX3-IKKepsilon association and DDX3-dependent IRF responses. Retain this infection context rather than a uniform response to every virus. Supporting Evidence: |
| GO:0010494 cytoplasmic stress granule | IDA PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | KEEP AS NON CORE | Summary: Human HeLa-cell imaging after arsenite treatment directly detects DDX3 in cytoplasmic stress granules. Reason: Human HeLa-cell imaging after arsenite treatment directly detects DDX3 in cytoplasmic stress granules. Retain this conditional location, not a claim that all cellular DDX3 resides there. Supporting Evidence: |
| GO:0010494 cytoplasmic stress granule | IDA PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | KEEP AS NON CORE | Summary: The source abstract and recovered supplementary caption place human DDX3 in PABP1-positive stress granules. Reason: The source abstract and recovered supplementary caption place human DDX3 in PABP1-positive stress granules. This is a supported stress-dependent compartment rather than a constitutive location. Supporting Evidence: |
| GO:0010494 cytoplasmic stress granule | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The literal stress-granule mapping agrees with multiple direct observations of DDX3 recruitment under stress. Reason: The literal stress-granule mapping agrees with multiple direct observations of DDX3 recruitment under stress. Retain this inducible compartment without equating every cytoplasmic DDX3 molecule with a stress-granule constituent. Supporting Evidence: GO_REF:0000044 |
| GO:0010628 positive regulation of gene expression | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | KEEP AS NON CORE | Summary: CAP-Rf increases reporter expression in human hepatoma cells, enhanced by HCV core. Reason: The original human HuH-7 reporter experiment shows increased reporter output with CAP-Rf/DDX3X, further enhanced by HCV core. This positive gene-expression endpoint is retained as contextual. It does not distinguish transcription, RNA handling or translation as the causal stage, so a specific translation replacement is not inferred for this source. The separate NAS cyclin-E1 summary at row126 invokes an already established translation-regulatory role and can be refined on that basis; the two source-level judgments preserve different evidential resolution. Supporting Evidence: |
| GO:0010628 positive regulation of gene expression | NAS PMID:22492871 Endometrial miR-181a and miR-98 expression is altered during... | MODIFY | Summary: The cited discussion invokes DDX3-dependent cyclin-E1 expression, consistent with more specific translational-control evidence already represented in the annotations. Reason: The cited discussion invokes DDX3-dependent cyclin-E1 expression, consistent with more specific translational-control evidence already represented in the annotations. Positive regulation of gene expression is an unnecessarily broad summary of those established effects. Proposed refinement: The NAS cyclin-E1 expression summary invokes an already supported translational-control role. This is distinct from the unresolved causal stage of the positive CAP-Rf reporter assay retained at row125. Proposed replacements: positive regulation of translation |
| GO:0010629 negative regulation of gene expression | IBA GO_REF:0000033 | MODIFY | Summary: The negative-expression IBD at Eumetazoa node PTN002774722 lies on the target lineage and includes target experimental grounding for negative regulation of translation. Reason: The negative-expression IBD at Eumetazoa node PTN002774722 lies on the target lineage and includes target experimental grounding for negative regulation of translation. Retain the ancestral inference as sound, while the existing negative-translation and transcription-regulation assertions express the supported effects more specifically. This is not rejection of a self-donor. Proposed refinement: The on-lineage IBD is biologically sound and experimentally grounded; the already reviewed negative regulation of translation supplies the specific inherited functional description. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002774722 SUPPORTS TRANSFER The literal IBD dated 20251221 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. The source itself is valid; the review favors an existing narrower term. Proposed replacements: negative regulation of translation |
| GO:0016055 Wnt signaling pathway | IMP PMID:26235985 Mutations in DDX3X Are a Common Cause of Unexplained Intelle... | ACCEPT | Summary: Human DDX3X constructs tested in zebrafish and human-cell Wnt reporters support participation in Wnt signaling. Reason: Human DDX3X constructs tested in zebrafish and human-cell Wnt reporters support participation in Wnt signaling. Variant effects depend on assay context and are not uniformly gain-of-function. Retain the pathway role, consistent with the independently established CK1-activator mechanism, without treating fish phenotypes as direct human developmental measurements. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | EXP PMID:15507209 Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE ... | ACCEPT | Summary: ATP hydrolysis is an established DDX3X activity. Reason: ATP hydrolysis is an established DDX3X activity. Retain the source experimental assertion with curator deference because the complete original was not independently recovered; later purified-human-protein experiments directly corroborate the chemistry. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:17357160 Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substr... | ACCEPT | Summary: ATP hydrolysis is an experimentally established component of DDX3X activity. Reason: The accessible original abstract explicitly reports ATPase measurements. Full Methods were not recovered for this paper; independent full-text biochemical studies corroborate ATP hydrolysis. Relaxed nucleotide hydrolysis specificity does not imply that every nucleotide supports RNA unwinding. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:31300642 The mechanism of RNA duplex recognition and unwinding by DEA... | ACCEPT | Summary: The DDX3X catalytic core hydrolyzes ATP in RNA-containing reactions. Reason: The human residues 132-607 construct was tested for RNA-dependent ATPase activity and duplex unwinding. This engineered core is not a natural alternative product. ATP hydrolysis is integrated into the RNA-helicase function rather than listed as a separate physiological core. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | EXP PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | ACCEPT | Summary: Purified recombinant human DDX3X(1β580) hydrolyzes ATP in the presence of poly(I:C). Reason: Purified recombinant human DDX3X(1β580) hydrolyzes ATP in the presence of poly(I:C). Wild-type and nuclear-export-signal mutants retain this activity, whereas K230E is deficient. This directly supports the ATPase chemistry integral to RNA remodeling, without treating the engineered truncation as a natural short isoform or claiming an unwinding assay was performed here. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | ACCEPT | Summary: Purified His-CAP-Rf directly hydrolyzes ATP in the radiolabeled nucleotide assay. Reason: Purified His-CAP-Rf directly hydrolyzes ATP in the radiolabeled nucleotide assay. This supports the ATPase chemistry central to DDX3 RNA remodeling. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | IDA PMID:21589879 A motif unique to the human DEAD-box protein DDX3 is importa... | ACCEPT | Summary: Full-length DDX3X exhibits nucleic-acid-stimulated ATP hydrolysis. Reason: Direct radiolabeled-ATP assays and catalytically impaired controls support this activity. The relative stimulation by RNA and DNA varies between biochemical studies, without undermining the ATP-hydrolysis assignment. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: The literal RHEA:13065 mapping is ATP hydrolysis and agrees with direct DDX3X biochemical assays. Reason: The literal RHEA:13065 mapping is ATP hydrolysis and agrees with direct DDX3X biochemical assays. Retain the catalytic assertion without inferring a distinct metabolic pathway from ATP consumption. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | MODIFY | Summary: The nucleotide-hydrolysis assay is positive, but the specific ATPase and secondary GTPase/CTPase assertions already describe its demonstrated substrates. Reason: The nucleotide-hydrolysis assay is positive, but the specific ATPase and secondary GTPase/CTPase assertions already describe its demonstrated substrates. Preserve the chemistry without a duplicate broad hydrolase assertion. Proposed refinement: The same original substrate assays already support ATP hydrolysis and secondary GTPase/CTPase activities; retain these measured specific chemistries rather than add a broad hydrolase outcome. Supporting Evidence: |
| GO:0017148 negative regulation of translation | IMP PMID:17667941 Candidate tumor suppressor DDX3 RNA helicase specifically re... | KEEP AS NON CORE | Summary: The source abstract reports cap-dependent translation repression and eIF4E interaction, alongside increased IRES-driven translation. Reason: The source abstract reports cap-dependent translation repression and eIF4E interaction, alongside increased IRES-driven translation. Retain this conditional inhibitory function without replacing the independently established positive translation roles. Supporting Evidence: |
| GO:0022627 cytosolic small ribosomal subunit | IDA PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | KEEP AS NON CORE | Summary: Human DDX3 co-sediments with initiation factors in 40S-enriched fractions and is absent from polysomes in this experiment. Reason: Human DDX3 co-sediments with initiation factors in 40S-enriched fractions and is absent from polysomes in this experiment. Retain peripheral small-subunit association without calling it a constitutive ribosomal protein. Supporting Evidence: |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The literal lamellipodium mapping is consistent with DDX3 accumulation at the leading edge in migration experiments. Reason: The literal lamellipodium mapping is consistent with DDX3 accumulation at the leading edge in migration experiments. Retain this contextual localization without converting it into actin-binding or actin-polymerase activity. |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The differentiation IBD at Eumetazoa node PTN002774652 lies on the DDX3X lineage and is grounded in descendant germ-cell-development and oogenesis experiments. Reason: The differentiation IBD at Eumetazoa node PTN002774652 lies on the DDX3X lineage and is grounded in descendant germ-cell-development and oogenesis experiments. Retain this developmental inference as non-core; it does not specify every somatic differentiation program or demonstrate a human lineage-specific mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002774652 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. No target-specific loss was established. Supporting Evidence: GO_REF:0000033 |
| GO:0030307 positive regulation of cell growth | IMP PMID:18628297 Human DDX3 functions in translation and interacts with the t... | KEEP AS NON CORE | Summary: Two DDX3 RNAi treatments inhibit growth of human HeLa cells alongside reduced reporter protein expression. Reason: Two DDX3 RNAi treatments inhibit growth of human HeLa cells alongside reduced reporter protein expression. Retain the cellular growth phenotype as a context of translation function, not an additional molecular activity. Supporting Evidence: |
| GO:0030307 positive regulation of cell growth | IMP PMID:20837705 DDX3 regulates cell growth through translational control of ... | KEEP AS NON CORE | Summary: DDX3 depletion and rescue affect growth of the tested human cells in conjunction with cyclin-E1 translational control. Reason: DDX3 depletion and rescue affect growth of the tested human cells in conjunction with cyclin-E1 translational control. Retain the context-dependent growth effect without making growth promotion universal across tissues or replacing the direct molecular activities with a generic phenotype. Supporting Evidence: |
| GO:0030308 negative regulation of cell growth | IDA PMID:16818630 DDX3, a DEAD box RNA helicase with tumor growth-suppressive ... | KEEP AS NON CORE | Summary: The source abstract reports colony-growth suppression and increased p21-promoter activity. Reason: The source abstract reports colony-growth suppression and increased p21-promoter activity. Retain this tumor-cell context without claiming a universal antiproliferative role; complete original experimental details remain unavailable. Supporting Evidence: |
| GO:0031252 cell leading edge | IDA PMID:28733330 The helicase, DDX3X, interacts with poly(A)-binding protein ... | KEEP AS NON CORE | Summary: The original directly images endogenous DDX3 with PABP1 and caprin-1 at the leading edge of spreading human MRC5 fibroblasts. Reason: The original directly images endogenous DDX3 with PABP1 and caprin-1 at the leading edge of spreading human MRC5 fibroblasts. Retain this contextual localization without asserting focal-adhesion membership. Supporting Evidence: |
| GO:0031333 negative regulation of protein-containing complex assembly | IDA PMID:17667941 Candidate tumor suppressor DDX3 RNA helicase specifically re... | KEEP AS NON CORE | Summary: The abstract specifically reports DDX3 interference with eIF4E-eIF4G association and eIF4F assembly. Reason: The abstract specifically reports DDX3 interference with eIF4E-eIF4G association and eIF4F assembly. Retain that defined inhibitory complex-assembly context rather than a general inhibition of protein complexes. Supporting Evidence: |
| GO:0031369 translation initiation factor binding | IDA PMID:22323517 The DEAD-box helicase DDX3 supports the assembly of function... | ACCEPT | Summary: DDX3X interacts with translation initiation factors. Reason: The study demonstrates eIF3 association with purified components; eIF2 association is RNA dependent. These contacts support an auxiliary role in initiation, while the proposed bridging mechanism remains a model. Supporting Evidence: |
| GO:0031369 translation initiation factor binding | IDA PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | ACCEPT | Summary: The source reports DDX3 binding to initiation factors and cooperation in early 43S engagement on structured mRNAs. Reason: The source reports DDX3 binding to initiation factors and cooperation in early 43S engagement on structured mRNAs. This is consistent with the independently established auxiliary translation-initiation function. Supporting Evidence: |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:23478265 Human DEAD box helicase 3 couples IΞΊB kinase Ξ΅ to interferon... | ACCEPT | Summary: DDX3X enhances IRF3 activation and type I interferon promoter output. Reason: The actual PMID:23478265 original combines DDX3X knockdown/overexpression in human cells, Sendai-virus stimulation, IRF3 phosphorylation and ifnb-promoter reporter assays with purified-protein experiments. The S102A substitution preserves IKKΞ΅ binding/activation but disrupts IRF3 recruitment and downstream phosphorylation/reporter enhancement; S102D restores the functional interaction. These mechanistically linked effects support positive regulation of type I interferon production without making every interferon family member a separately tested output. Supporting Evidence: |
| GO:0032727 positive regulation of interferon-alpha production | IDA PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | ACCEPT | Summary: The source links DDX3 to NIK/IKKalpha-dependent IRF7 activation and type-I interferon production. Reason: The source links DDX3 to NIK/IKKalpha-dependent IRF7 activation and type-I interferon production. Retain the curated IFN-alpha response as part of the supported immune-signaling function, with subtype-specific original details attributed to the curator. Supporting Evidence: |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:27980081 DDX3 directly regulates TRAF3 ubiquitination and acts as a s... | ACCEPT | Summary: The source places DDX3-dependent TRAF3/MAVS complex formation in the pathway leading to IFN-beta induction. Reason: The source places DDX3-dependent TRAF3/MAVS complex formation in the pathway leading to IFN-beta induction. This corroborates the independently established signaling-adaptor function; full original assay details remain unavailable. Supporting Evidence: |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | ACCEPT | Summary: In hPIV-3-infected human A549 cells, DDX3X expression and nuclear trafficking alter IFNB1 transcription and secreted IFN-beta. Reason: In hPIV-3-infected human A549 cells, DDX3X expression and nuclear trafficking alter IFNB1 transcription and secreted IFN-beta. The nuclear-export-defective construct can increase IFN-beta despite permitting greater viral replication, so the source supports IFN-beta regulation without equating IFN-beta abundance with the entire antiviral effect. Supporting Evidence: |
| GO:0032728 positive regulation of interferon-beta production | TAS PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | ACCEPT | Summary: Human DDX3 constructs enhance TBK1-dependent IFN-beta reporters, while mouse-cell knockdown reduces endogenous IFN-beta induction. Reason: Human DDX3 constructs enhance TBK1-dependent IFN-beta reporters, while mouse-cell knockdown reduces endogenous IFN-beta induction. Retain the conserved signaling function with those species and assay distinctions explicit. Supporting Evidence: |
| GO:0032728 positive regulation of interferon-beta production | TAS PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | ACCEPT | Summary: Human-cell DDX3 expression and RNAi alter Sendai-virus- and kinase-induced IFN-beta promoter responses, supporting the central antiviral signaling role. Reason: Human-cell DDX3 expression and RNAi alter Sendai-virus- and kinase-induced IFN-beta promoter responses, supporting the central antiviral signaling role. Supporting Evidence: |
| GO:0033592 RNA strand annealing activity | IDA PMID:27546789 RNA Remodeling Activity of DEAD Box Proteins Tuned by Protei... | UNDECIDED | Summary: The inspected original directly demonstrates DDX3X-mediated RNA compaction, whereas its accessible annealing experiments explicitly describe LAF-1. Reason: The inspected original directly demonstrates DDX3X-mediated RNA compaction, whereas its accessible annealing experiments explicitly describe LAF-1. DDX3X-specific annealing controls in the unavailable supplementary material could not be verified. Preserve the curated assertion as unresolved; compaction alone is not an annealing measurement, and this does not show that DDX3X lacks the activity. Supporting Evidence: |
| GO:0034063 cytoplasmic stress granule assembly | IDA PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | KEEP AS NON CORE | Summary: Knockdown and rescue described in the source abstract support DDX3-dependent stress-granule assembly. Reason: Knockdown and rescue described in the source abstract support DDX3-dependent stress-granule assembly. The reported ATPase/helicase-independent effect is a stress context and should not be reduced to RNA unwinding alone. Supporting Evidence: |
| GO:0034157 positive regulation of toll-like receptor 7 signaling pathway | IDA PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | KEEP AS NON CORE | Summary: Retain the curated TLR7-specific extension of DDX3-dependent IKKalpha/IRF7 signaling. Reason: Retain the curated TLR7-specific extension of DDX3-dependent IKKalpha/IRF7 signaling. The complete abstract supports this pathway context; unrecovered original stimulus and cell controls are not presented as independently inspected. Supporting Evidence: |
| GO:0034161 positive regulation of toll-like receptor 8 signaling pathway | IDA PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | KEEP AS NON CORE | Summary: The reviewed UniProt functional account explicitly attributes TLR8-dependent CHUK activation to this paper. Reason: The reviewed UniProt functional account explicitly attributes TLR8-dependent CHUK activation to this paper. Retain that source-specific curated extension with deference and an explicit original-access limitation; the abstract's emphasis on TLR7/9 does not establish a TLR8 error. Supporting Evidence: |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: The Reactome secretory-granule input set contains an exact O00571 DDX3X member with the secretory-granule-lumen compartment. Reason: The Reactome secretory-granule input set contains an exact O00571 DDX3X member with the secretory-granule-lumen compartment. Retain the curated proteomic context as a non-core location; neither constitutive secretion nor an extracellular catalytic function follows from set membership. Supporting Evidence: Reactome:R-HSA-6798748 |
| GO:0035556 intracellular signal transduction | IDA PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | MODIFY | Summary: The demonstrated intracellular signaling is represented more specifically by the existing pattern-recognition and interferon-regulation annotations. Reason: The demonstrated intracellular signaling is represented more specifically by the existing pattern-recognition and interferon-regulation annotations. Preserve the positive experiments without a separate broad signaling assertion. Proposed refinement: The established cytoplasmic pattern-recognition pathway is a verified descendant of intracellular signal transduction and is supported by the reviewed TBK1/IKK/IRF3 context. No new pathway participation is asserted. Proposed replacements: cytoplasmic pattern recognition receptor signaling pathway |
| GO:0035591 signaling adaptor activity | IDA PMID:23478265 Human DEAD box helicase 3 couples IΞΊB kinase Ξ΅ to interferon... | ACCEPT | Summary: DDX3X recruits IKKΞ΅ and IRF3 to coordinate antiviral signaling. Reason: The selected PMID:23478265 original shows direct binding of recombinant DDX3X to IRF3 and IKKΞ΅, distinct but neighboring interaction regions, and stimulus-dependent association of endogenous signaling proteins with expressed DDX3X in human cells. S102A preserves the IKKΞ΅ interaction and kinase activation while losing IRF3 recruitment and phosphorylation, separating recruitment from generic binding or necessity. This supports the noncatalytic signaling-adaptor role described by GO:0035591; it does not deny DDX3X ATPase activity in a separate RNA-remodeling role or assign kinase activity to DDX3X. Proposed higher-order IKKΞ΅ organization remains a model, not a measured architecture. Supporting Evidence: |
| GO:0035613 RNA stem-loop binding | IDA PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | ACCEPT | Summary: The source explicitly reports direct DDX3 binding to structural features at the 5β² end of target mRNAs. Reason: The source explicitly reports direct DDX3 binding to structural features at the 5β² end of target mRNAs. Retain this RNA-substrate recognition assertion, with full assay details attributed to the curator. Supporting Evidence: |
| GO:0036493 positive regulation of translation in response to endoplasmic reticulum stress | IMP PMID:29062139 DDX3 regulates endoplasmic reticulum stress-induced ATF4 exp... | KEEP AS NON CORE | Summary: Two DDX3 siRNAs reduce stress-induced ATF4 protein and an ATF4 5-prime-UTR translation reporter in human cells; polysome analysis further supports translation regulation without a corresponding loss of ATF4 mRNA. Reason: Two DDX3 siRNAs reduce stress-induced ATF4 protein and an ATF4 5-prime-UTR translation reporter in human cells; polysome analysis further supports translation regulation without a corresponding loss of ATF4 mRNA. Retain this specific ER-stress response as a context of the broader translation function. The proposed recruitment mechanism is not directly demonstrated, and sorafenib-induced stress-granule formation remains intact after DDX3 depletion in this study. Supporting Evidence: |
| GO:0042256 cytosolic ribosome assembly | IMP PMID:22323517 The DEAD-box helicase DDX3 supports the assembly of function... | ACCEPT | Summary: DDX3X promotes joining of mature subunits into functional 80S initiation complexes. Reason: Reconstitution with affinity-purified human DDX3X enhanced 80S complex formation. The current term explicitly includes assembly of large and small subunits into a functional cytosolic ribosome. This evidence concerns translation initiation, not pre-rRNA processing or production of new ribosomal subunits. Supporting Evidence: PMID:22323517 DDX3 assists the 60S subunit joining process to assemble functional 80S ribosomes. |
| GO:0043015 gamma-tubulin binding | IDA PMID:28842590 DDX3 localizes to the centrosome and prevents multipolar mit... | KEEP AS NON CORE | Summary: The original shows gamma-tubulin co-immunoprecipitating with DDX3 in human HCT116 cells, alongside centrosomal colocalization. Reason: The original shows gamma-tubulin co-immunoprecipitating with DDX3 in human HCT116 cells, alongside centrosomal colocalization. Retain association without claiming a purified direct interface or a separate microtubule-organizing catalytic function. Supporting Evidence: |
| GO:0043024 ribosomal small subunit binding | IDA PMID:22323517 The DEAD-box helicase DDX3 supports the assembly of function... | ACCEPT | Summary: DDX3X associates with the small ribosomal subunit. Reason: Fractionation and association assays support contact with 40S-containing initiation machinery. Purified 40S also bound control beads, so that individual assay is not treated as proof of an isolated high-affinity interface; the combined experimental evidence supports the curated binding annotation. Supporting Evidence: |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:16301996 DDX3, a DEAD box RNA helicase, is deregulated in hepatitis v... | KEEP AS NON CORE | Summary: The abstract reports resistance to serum-depletion-induced apoptosis after DDX3 suppression in mouse NIH-3T3 cells, alongside human hepatocellular-carcinoma expression observations. Reason: The abstract reports resistance to serum-depletion-induced apoptosis after DDX3 suppression in mouse NIH-3T3 cells, alongside human hepatocellular-carcinoma expression observations. Retain this contextual pro-apoptotic effect with curator deference; it neither establishes a universal direction of apoptosis regulation nor identifies an intrinsic-pathway step. Supporting Evidence: |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:18846110 Identification of an antiapoptotic protein complex at death ... | MODIFY | Summary: The positive antiapoptotic experiments concern death-receptor signaling. Reason: The positive antiapoptotic experiments concern death-receptor signaling. Preserve that evidence in the existing, more specific negative regulation of extrinsic apoptotic signaling annotation. Proposed refinement: The same source measures death-receptor antiapoptotic activity already captured by the specific extrinsic-pathway term. Proposed replacements: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Supporting Evidence: |
| GO:0043186 P granule | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The P-granule IBD at Bilateria node PTN002774723 lies on the actual DDX3X lineage and is grounded in direct localization of the worm LAF-1 and VBH-1 descendants. Reason: The P-granule IBD at Bilateria node PTN002774723 lies on the actual DDX3X lineage and is grounded in direct localization of the worm LAF-1 and VBH-1 descendants. The GO definition encompasses germ-cell RNA/protein granules and is not restricted to nematodes. Retain the ancestral compartment inference as non-core, without presenting it as direct imaging of human DDX3X or conflating it with somatic stress granules. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002774723 SUPPORTS TRANSFER The literal IBD dated 20260828 is on the exact DDX3X lineage; experimental descendants and typed descendant-term joins were inspected. Imported historical donors remain unchanged. No target-specific loss was established. Supporting Evidence: GO_REF:0000033 |
| GO:0043273 CTPase activity | IDA PMID:10074132 Hepatitis C virus core protein interacts with cellular putat... | KEEP AS NON CORE | Summary: Radiolabeled CTP is hydrolyzed by purified His-CAP-Rf. Reason: Radiolabeled CTP is hydrolyzed by purified His-CAP-Rf. Retain this secondary biochemical substrate activity without proposing a distinct physiological CTPase core. Supporting Evidence: |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:23413191 RNA helicase DDX3 is a regulatory subunit of casein kinase 1... | ACCEPT | Summary: DDX3X directly stimulates CK1 serine/threonine kinase activity. Reason: The PMID:23413191 abstract explicitly reports direct CK1Ξ΅ stimulation. The independently inspected PMID:29222110 original demonstrates human DDX3X-dependent CK1 activity in live-cell FRET assays and purified kinase-substrate assays, with DDX3X residues 414β582 sufficient for stimulation. Binding peptides, kinase-dead controls and RNA competition distinguish the regulatory interaction from intrinsic DDX3X protein-kinase activity. RNA binding reduces CK1 association/activation, and CK1-mediated phosphorylation suppresses DDX3X ATPase activity under the tested conditions; this does not establish a universal mutually exclusive state in all tissues. |
| GO:0045070 positive regulation of viral genome replication | IMP PMID:20862261 Hepatitis C virus core-derived peptides inhibit genotype 1b ... | KEEP AS NON CORE | Summary: A DDX3-binding HCV-core peptide suppresses genotype 1b replicon RNA, and DDX3 overexpression restores it. Reason: A DDX3-binding HCV-core peptide suppresses genotype 1b replicon RNA, and DDX3 overexpression restores it. The same peptide does not suppress JFH1 infection under the tested protocols; retain the positive viral-replication context without universalizing across genotypes. Supporting Evidence: |
| GO:0045087 innate immune response | IMP PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | KEEP AS NON CORE | Summary: DDX3X supports the measured TBK1/IRF3-dependent innate immune response in the tested context. Reason: The original TBK1/IRF3 perturbation experiments support a contextual innate immune-response role. Current typed ontology paths place GO:0002753 under GO:0002221 and GO:0002758. GO:0002758 has is_a parents GO:0002218 and GO:0002757; its complete is_a/part_of closure contains regulation terms including GO:0045089, but not GO:0045087. Therefore the narrower signaling assertions do not logically entail this response term through the proposed path. Retain the measured immune-response context without treating regulation of the response as participation in the response by ontology alone. Supporting Evidence: |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | UNDECIDED | Summary: The source maps the E-cadherin neighborhood by proximity-dependent biotinylation in human MKN28 cells. Reason: The source maps the E-cadherin neighborhood by proximity-dependent biotinylation in human MKN28 cells. That assay can recover vicinal proteins without establishing cadherin contact. The DDX3X-specific supplementary-table evidence and any independent pair validation could not be recovered, so cadherin binding remains unresolved rather than being declared false from the broad screen alone. Supporting Evidence: |
| GO:0045727 positive regulation of translation | IDA PMID:18596238 The DEAD-box RNA helicase DDX3 associates with export messen... | ACCEPT | Summary: DDX3 depletion selectively impairs translation reporters with structured or long 5-prime untranslated regions. Reason: DDX3 depletion selectively impairs translation reporters with structured or long 5-prime untranslated regions. This supports its central translation role without asserting a requirement for all mRNAs. Supporting Evidence: |
| GO:0045727 positive regulation of translation | IDA PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | ACCEPT | Summary: The source supports enhanced translation of selected structured mRNAs through DDX3 RNA binding and initiation-factor cooperation. Reason: The source supports enhanced translation of selected structured mRNAs through DDX3 RNA binding and initiation-factor cooperation. Retain this central translation role without claiming uniform stimulation of all transcripts. Supporting Evidence: |
| GO:0045727 positive regulation of translation | IMP PMID:28842590 DDX3 localizes to the centrosome and prevents multipolar mit... | ACCEPT | Summary: Human-cell knockdown, resistant-DDX3 rescue and RNA reporter assays support positive regulation of p53 translation. Reason: Human-cell knockdown, resistant-DDX3 rescue and RNA reporter assays support positive regulation of p53 translation. The effect is not explained by p53 stabilization, supporting the translation function while retaining target and cell-context limits. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16818630 DDX3, a DEAD box RNA helicase with tumor growth-suppressive ... | KEEP AS NON CORE | Summary: The source abstract supports Sp1-site-dependent activation of the human p21 promoter. Reason: The source abstract supports Sp1-site-dependent activation of the human p21 promoter. Retain this transcriptional context with curator deference, distinguishing promoter regulation from intrinsic RNA polymerase activity. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | KEEP AS NON CORE | Summary: DDX3 increases IFN-beta promoter-reporter output through IRF signaling. Reason: DDX3 increases IFN-beta promoter-reporter output through IRF signaling. Retain this transcriptional consequence in context, without treating it as intrinsic polymerase or general transcription-factor activity. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:28128295 RNA helicase DDX3 maintains lipid homeostasis through upregu... | KEEP AS NON CORE | Summary: DDX3 increases HNF4-dependent MTP promoter activity in human hepatoma cells. Reason: DDX3 increases HNF4-dependent MTP promoter activity in human hepatoma cells. Retain this specific transcriptional context; the experiments do not imply general activation of RNA polymerase II. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | KEEP AS NON CORE | Summary: Human DDX3 stimulates TBK1-dependent IFN-beta reporters; promoter recruitment was separately assayed in mouse RAW264.7 cells. Reason: Human DDX3 stimulates TBK1-dependent IFN-beta reporters; promoter recruitment was separately assayed in mouse RAW264.7 cells. Retain this source's transcriptional context without relabeling the mouse ChIP experiment as direct human promoter occupancy. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:28842590 DDX3 localizes to the centrosome and prevents multipolar mit... | KEEP AS NON CORE | Summary: In HCT116 cells, DDX3 depletion lowers p53 mRNA without lowering its stability and increases promoter methylation/DNMT occupancy. Reason: In HCT116 cells, DDX3 depletion lowers p53 mRNA without lowering its stability and increases promoter methylation/DNMT occupancy. Retain the demonstrated transcriptional regulatory context, without assigning DNA methyltransferase activity or a universal transcriptional-activator function. Supporting Evidence: |
| GO:0045948 positive regulation of translational initiation | IMP PMID:20837705 DDX3 regulates cell growth through translational control of ... | ACCEPT | Summary: Human-cell depletion/rescue, cyclin-E1 5β²-UTR reporters and translation assays support positive control of translational initiation by DDX3. Reason: Human-cell depletion/rescue, cyclin-E1 5β²-UTR reporters and translation assays support positive control of translational initiation by DDX3. Retain this direct translation-related role without generalizing stimulation to all transcripts or conditions. Supporting Evidence: |
| GO:0048027 mRNA 5'-UTR binding | IDA PMID:22872150 DEAD-box protein DDX3 associates with eIF4F to promote trans... | ACCEPT | Summary: The source explicitly identifies DDX3 binding at target mRNA 5β² untranslated regions and links this to early initiation on structured transcripts. Reason: The source explicitly identifies DDX3 binding at target mRNA 5β² untranslated regions and links this to early initiation on structured transcripts. Retain this core RNA-recognition aspect with curator deference for unrecovered detailed binding conditions. Supporting Evidence: |
| GO:0055088 lipid homeostasis | IMP PMID:28128295 RNA helicase DDX3 maintains lipid homeostasis through upregu... | KEEP AS NON CORE | Summary: Human hepatoma-cell DDX3 knockdown changes triglyceride accumulation, ApoB secretion and MTP expression. Reason: Human hepatoma-cell DDX3 knockdown changes triglyceride accumulation, ApoB secretion and MTP expression. Retain this demonstrated cellular lipid-homeostasis context without proposing lipid-metabolic catalysis by DDX3. Supporting Evidence: |
| GO:0061702 canonical inflammasome complex | IEA GO_REF:0000044 | MODIFY | Summary: The literal inflammasome mapping is supported by the conserved DDX3X/NLRP3 association, but the existing NLRP3-inflammasome-complex assertion identifies the relevant complex more specifically. Reason: The literal inflammasome mapping is supported by the conserved DDX3X/NLRP3 association, but the existing NLRP3-inflammasome-complex assertion identifies the relevant complex more specifically. Proposed refinement: The existing NLRP3 inflammasome-complex annotation identifies the relevant canonical complex; ortholog evidence remains an ortholog inference. Proposed replacements: NLRP3 inflammasome complex |
| GO:0061702 canonical inflammasome complex | ISS GO_REF:0000024 | MODIFY | Summary: Mouse Ddx3x experiments support a canonical NLRP3 inflammasome association and provide credible ortholog grounding. Reason: Mouse Ddx3x experiments support a canonical NLRP3 inflammasome association and provide credible ortholog grounding. Prefer the existing specific NLRP3-complex assertion; the mouse assays are not relabeled as direct human experiments. Proposed refinement: The existing NLRP3 inflammasome-complex annotation identifies the relevant canonical complex; ortholog evidence remains an ortholog inference. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q62167 Β· Ddx3x SUPPORTS TRANSFER Mouse ortholog identity and literal experimental records are verified; selected original macrophage and tagged-cell assays support NLRP3 association/assembly. Human annotation remains an ortholog inference, not a reassigned mouse experiment. Proposed replacements: NLRP3 inflammasome complex |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Retain the curated detection in the human urinary-exosome proteome as a contextual compartment observation. Reason: Retain the curated detection in the human urinary-exosome proteome as a contextual compartment observation. The complete target-table assignment was not independently reconstructed, and this does not establish an extracellular catalytic role, secretion mechanism or universal exosome residence. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Retain the curated detection in the human parotid-saliva-exosome proteome as a contextual compartment observation. Reason: Retain the curated detection in the human parotid-saliva-exosome proteome as a contextual compartment observation. The target-table assignment was not independently reconstructed; detection does not require evidence that DDX3X performs an extracellular reaction. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Retain the curated B-cell-exosome proteomic detection as contextual localization, with curator deference for the uninspected target table. Reason: Retain the curated B-cell-exosome proteomic detection as contextual localization, with curator deference for the uninspected target table. It does not imply selective exosomal loading, constitutive secretion or extracellular helicase activity. Supporting Evidence: |
| GO:0070131 positive regulation of mitochondrial translation | IMP PMID:28869602 Targeting mitochondrial translation by inhibiting DDX3: a no... | KEEP AS NON CORE | Summary: RK-33 treatment reduced mitochondrial protein synthesis measured with cytosolic translation blocked, and DDX3 depletion altered OXPHOS-related expression. Reason: RK-33 treatment reduced mitochondrial protein synthesis measured with cytosolic translation blocked, and DDX3 depletion altered OXPHOS-related expression. These experiments support positive regulation in the tested cancer cells, while the authors explicitly leave a direct mitochondrial-translation mechanism unresolved. Retain the contextual process without adding a mitochondrial-translation core. Supporting Evidence: |
| GO:0071243 cellular response to arsenic-containing substance | IDA PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | KEEP AS NON CORE | Summary: Preserve the curator's arsenic-stress response assertion, corroborated by independent human-cell arsenite-induced DDX3 granule localization in PMID18596238. Reason: Preserve the curator's arsenic-stress response assertion, corroborated by independent human-cell arsenite-induced DDX3 granule localization in PMID18596238. The cited source reports stress-dependent assembly and rescue, but its complete arsenite-specific experiments were not independently recovered. Supporting Evidence: |
| GO:0071470 cellular response to osmotic stress | IDA PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | KEEP AS NON CORE | Summary: The recovered source Supplementary Figure S1 caption explicitly tests human HeLa/U2OS cells in high-osmolarity sorbitol medium and detects DDX3 with PABP1. Reason: The recovered source Supplementary Figure S1 caption explicitly tests human HeLa/U2OS cells in high-osmolarity sorbitol medium and detects DDX3 with PABP1. Retain this stress-response context without equating recruitment alone with a separate catalytic activity. Supporting Evidence: |
| GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production | TAS PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | KEEP AS NON CORE | Summary: DDX3 knockdown reduces Listeria-induced RANTES in mouse RAW264.7 cells. Reason: DDX3 knockdown reduces Listeria-induced RANTES in mouse RAW264.7 cells. Retain the curated conserved chemokine-response assertion with explicit ortholog context, without claiming a direct human RANTES assay was performed. Supporting Evidence: |
| GO:0072559 NLRP3 inflammasome complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Ddx3x copurifies with NLRP3 and colocalizes with NLRP3/ASC in specks; the actual source also examines tagged complexes in HEK293T cells. Reason: Mouse Ddx3x copurifies with NLRP3 and colocalizes with NLRP3/ASC in specks; the actual source also examines tagged complexes in HEK293T cells. These observations support the ortholog-based NLRP3-complex assertion. Retain it as a conditional immune assembly, without assuming native human occupancy or an isolated direct interface from co-immunoprecipitation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q62167 Β· Ddx3x SUPPORTS TRANSFER Mouse ortholog identity and literal experimental records are verified; selected original macrophage and tagged-cell assays support NLRP3 association/assembly. Human annotation remains an ortholog inference, not a reassigned mouse experiment. Supporting Evidence: GO_REF:0000024 PMID:31511697 protein DDX3X interacts with NLRP3 to drive inflammasome activation. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IMP PMID:23413191 RNA helicase DDX3 is a regulatory subunit of casein kinase 1... | ACCEPT | Summary: DDX3X promotes canonical Wnt signaling through its CK1-regulatory role. Reason: The original PMID:23413191 abstract directly identifies Wnt-dependent CK1Ξ΅ binding/activation, increased Dishevelled phosphorylation and a requirement in mammalian-cell and Xenopus/Caenorhabditis developmental Wnt signaling. Full first-paper Methods remain inaccessible, so individual constructs and species-specific assay details are not invented. The later original PMID:29222110 directly corroborates the human CK1-regulatory activity and discusses its Wnt connection. Retain this established, mechanistically linked process with curator deference; the kinase partner performs phosphorylation, whereas DDX3X contributes the activating function. |
| GO:0097193 intrinsic apoptotic signaling pathway | IMP PMID:16301996 DDX3, a DEAD box RNA helicase, is deregulated in hepatitis v... | UNDECIDED | Summary: The accessible abstract supports altered serum-depletion-induced apoptosis in mouse NIH-3T3 cells, but the complete original and pathway-discriminating assays were not recovered. Reason: The accessible abstract supports altered serum-depletion-induced apoptosis in mouse NIH-3T3 cells, but the complete original and pathway-discriminating assays were not recovered. The intrinsic-pathway definition requires the corresponding intracellular signaling route, including mitochondrial outer-membrane permeabilization. The available phenotype does not resolve that specificity; it is not evidence that an extracellular stress cannot trigger intrinsic apoptosis. Supporting Evidence: |
| GO:0098586 cellular response to virus | IDA PMID:31575075 Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX... | KEEP AS NON CORE | Summary: Human DDX3X redistributes after poly(I:C) or hPIV-3 challenge, and full-length versus nuclear-export-defective DDX3X differentially affects viral production and immune-gene expression. Reason: Human DDX3X redistributes after poly(I:C) or hPIV-3 challenge, and full-length versus nuclear-export-defective DDX3X differentially affects viral production and immune-gene expression. Retain the demonstrated cellular response while keeping its virus, cell and trafficking conditions explicit; these experiments do not establish a uniform antiviral outcome across viruses. Supporting Evidence: |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IMP PMID:20837705 DDX3 regulates cell growth through translational control of ... | KEEP AS NON CORE | Summary: DDX3 depletion/rescue and cyclin-E1 translation experiments support G1/S progression in the tested human cells. Reason: DDX3 depletion/rescue and cyclin-E1 translation experiments support G1/S progression in the tested human cells. Retain this downstream context-specific process, rather than making a cell-cycle transition the defining molecular activity or claiming the same direction in every cell type. Supporting Evidence: |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse source combines Ddx3x loss, rescue, NLRP3 association and reduced ASC-speck assembly, supporting positive regulation of NLRP3 inflammasome assembly. Reason: The mouse source combines Ddx3x loss, rescue, NLRP3 association and reduced ASC-speck assembly, supporting positive regulation of NLRP3 inflammasome assembly. Retain the credible ortholog inference as a conditional immune process. It does not establish an ATPase requirement, direct catalytic activation of caspase-1 or the architecture of a purified assembly. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q62167 Β· Ddx3x SUPPORTS TRANSFER Mouse ortholog identity and literal experimental records are verified; selected original macrophage and tagged-cell assays support NLRP3 association/assembly. Human annotation remains an ortholog inference, not a reassigned mouse experiment. |
| GO:1901223 negative regulation of non-canonical NF-kappaB signal transduction | IMP PMID:27736973 The DEAD-Box RNA Helicase DDX3 Interacts with NF-ΞΊB Subunit ... | KEEP AS NON CORE | Summary: Human-cell DDX3 suppresses NIK-driven NF-kappaB reporters and cytokine expression. Reason: Human-cell DDX3 suppresses NIK-driven NF-kappaB reporters and cytokine expression. Retain the curated NIK-pathway regulation in its tested context; the mechanistic readout emphasizes p65 and does not establish every step of a p100/RelB cascade. This is distinct from positive IKKalpha regulation reported under other conditions. Supporting Evidence: |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IMP PMID:30341167 DDX3 directly facilitates IKKΞ± activation and regulates down... | KEEP AS NON CORE | Summary: The source abstract explicitly reports reduced alternative NF-kappaB activation after DDX3 knockdown. Reason: The source abstract explicitly reports reduced alternative NF-kappaB activation after DDX3 knockdown. Retain this NIK/IKKalpha-dependent context without merging it with the contrasting p65-inhibition experiments from another source. Supporting Evidence: |
| GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: DDX3 depletion enhances death-receptor-induced caspase activation in the tested cells. Reason: DDX3 depletion enhances death-receptor-induced caspase activation in the tested cells. Retain the negative extrinsic-apoptosis regulation, while distinguishing antiapoptotic function from DDX3 being cleaved during pathway activation. Supporting Evidence: |
| GO:1902523 positive regulation of protein K63-linked ubiquitination | IDA PMID:27980081 DDX3 directly regulates TRAF3 ubiquitination and acts as a s... | KEEP AS NON CORE | Summary: The source abstract reports loss of both waves of K63-linked TRAF3 ubiquitination after DDX3 depletion and dependence on a DDX3 interaction motif. Reason: The source abstract reports loss of both waves of K63-linked TRAF3 ubiquitination after DDX3 depletion and dependence on a DDX3 interaction motif. Retain regulation of that signaling event without assigning ubiquitin-ligase catalysis to DDX3. Supporting Evidence: |
| GO:1903608 obsolete protein localization to cytoplasmic stress granule | IMP PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | MARK AS OVER ANNOTATED | Summary: The source observes DDX3 redistribution into stress granules in the viral Npro/arsenate context, rather than establishing that DDX3 performs protein transport or retention there. Reason: The source observes DDX3 redistribution into stress granules in the viral Npro/arsenate context, rather than establishing that DDX3 performs protein transport or retention there. The current GO record explicitly obsoletes this term because such colocalization was inconsistently used as localization-process evidence. Preserve the imported source term and positive compartment observation, but do not retain the stronger process attribution. Supporting Evidence: |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: The ficolin-rich granule input set has an exact O00571 DDX3X member assigned to ficolin-1-rich granule lumen. Reason: The ficolin-rich granule input set has an exact O00571 DDX3X member assigned to ficolin-1-rich granule lumen. Retain this curated neutrophil compartment context without elevating it to a defining location for all DDX3X functions or inferring secretory pathway participation from cargo membership. Supporting Evidence: Reactome:R-HSA-6800434 |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | IMP PMID:21883093 Critical roles of RNA helicase DDX3 and its interactions wit... | UNDECIDED | Summary: The source abstract supports stress survival and DDX3-dependent granule assembly, but does not identify the intrinsic apoptotic pathway. Reason: The source abstract supports stress survival and DDX3-dependent granule assembly, but does not identify the intrinsic apoptotic pathway. The relevant complete original pathway-specific controls were not recovered; preserve the positive survival observations without converting them into verified intrinsic-pathway regulation or a contradiction. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which RNA substrates and assay conditions explain the reported DNA unwinding and RNA annealing activities, and can the DNA result be independently reproduced given the 2026 correction and incomplete original data?
Q: Does DDX3X directly contact poly(A) tails in the export mRNP experiments, or do the observations reflect contact with other portions of polyadenylated transcripts?
Q: Which activities and cellular distributions distinguish the naturally occurring 646-residue product from the 662-residue product?
Q: Which molecular steps connect DDX3X to intrinsic apoptosis, mitochondrial translation and cadherin-associated neighborhoods in the source-specific contexts where those assignments remain uncertain?
Experiment: Compare sequence-verified 662- and 646-residue products in matched RNA binding/unwinding, initiation-complex reconstitution and signaling assays, with expression and folding controls.
Experiment: Retest DNA unwinding with matched 5β²- and 3β²-tailed duplexes, tag-cleaved preparations and orthogonal product detection; separately test target-specific RNA annealing and poly(A)-tail contact.
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