Affinage

PQBP1

Polyglutamine-binding protein 1 · UniProt O60828

Length
265 aa
Mass
30.5 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PQBP1 is a multifunctional polar-amino-acid- and WW-domain-containing protein that operates in both the nucleus and cytoplasm to couple RNA processing, translational control, and innate immune sensing to neuronal development and survival (PMID:10332029, PMID:23512658). In the nucleus it acts as an alternative-splicing and alternative-polyadenylation effector: it binds spliceosomal factors including the U2 snRNP component SF3B1, WBP11/SIPP1, and the U5-15kD protein, with the C-terminal YxxPxxVL motif docking into the U5-15kD hydrophobic groove, and its loss reshapes splicing of target transcripts and impairs dendritic and neurite outgrowth (PMID:20410308, PMID:23512658, PMID:24781215, PMID:18599155). PQBP1 binds exonic regions of pre-mRNAs directly and also engages upstream UGUA elements to block CFIm recruitment, thereby controlling poly(A)-site selection in cell-cycle and progenitor genes; through these activities it governs splicing decisions such as Numb exon 9 inclusion and BAX exon 2 skipping that set the balance between progenitor proliferation and differentiation or apoptosis (PMID:38342602, PMID:39037895, PMID:41507200). It additionally chaperones nuclear import of the splicing factor TXNL4A by a karyopherin-β2 piggyback mechanism (PMID:32041777). In the cytoplasm PQBP1 binds non-phosphorylated eEF2 to suppress eEF2K-mediated Thr56 phosphorylation, promoting translational elongation and hippocampal mGluR-dependent long-term depression, and partners with FMRP/dFMR1 in neuronal RNA granules to control translation of specific mRNAs (PMID:26002102, PMID:33662272). PQBP1 also serves as an innate immune sensor that decorates intact HIV-1 capsids—through charge-complementing contacts between its N-terminal acidic residues and the arginine ring of the CA hexamer—and recruits cGAS to drive an IRF3-dependent interferon response, and it directly binds extracellular tau to activate cGAS-STING-NFκB-driven microglial inflammation (PMID:26046437, PMID:34782623, PMID:35809572, PMID:38128824). Finally, PQBP1 binds polyglutamine tracts and represses transcription, an activity hijacked by expanded-polyglutamine ataxin-1 that redirects PQBP1 to the RNA Pol II C-terminal domain to suppress transcription and trigger apoptosis (PMID:10332029, PMID:12062018). PQBP1 mutations cause X-linked intellectual disability syndromes (Golabi-Ito-Hall and Renpenning), where loss of splicing-factor and ligand binding, mislocalization of partners, or gain-of-function gains of new binding surfaces produce microcephaly and neuronal dysfunction (PMID:20410308, PMID:24781215, PMID:32041777, PMID:41507200).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1999 High

    Established PQBP1 as a nuclear polyglutamine-binding protein that represses transcription, defining its founding activity and domain architecture.

    Evidence Yeast two-hybrid, in vitro binding, transcription reporter and viability assays

    PMID:10332029

    Open questions at the time
    • Did not define direct transcriptional mechanism
    • Physiological splicing role not yet known
  2. 2002 High

    Showed that expanded-polyglutamine ataxin-1 enhances PQBP1 binding to the Pol II CTD, reducing CTD phosphorylation and inducing apoptosis, linking PQBP1 to polyQ disease pathology.

    Evidence Co-immunoprecipitation, transcription and apoptosis assays in cell lines

    PMID:12062018

    Open questions at the time
    • Did not establish whether this mechanism operates in neurons in vivo
  3. 2003 Medium

    Demonstrated that excess PQBP1 alone causes progressive neurodegeneration in mice, showing dosage sensitivity of PQBP1 activity.

    Evidence Transgenic mouse overexpression with histopathology

    PMID:12651867

    Open questions at the time
    • Molecular basis of toxicity not resolved
    • Single lab, ubiquitous overexpression
  4. 2008 Medium

    Identified SIPP1/WBP11 as a PQBP1 partner driving dynamic nuclear inclusion formation, pointing toward a splicing-related nuclear function.

    Evidence Overexpression, immunofluorescence, site-directed mutagenesis, FRAP

    PMID:18599155

    Open questions at the time
    • Functional consequence of inclusions unknown
    • Relationship to physiological splicing unclear
  5. 2009 Medium

    Linked PQBP1 to cognition by showing knockdown impairs anxiety-related behavior and chromatin-associated gene induction, rescued by an HDAC inhibitor.

    Evidence siRNA knockdown mouse, behavioral tests, IHC, pharmacological rescue

    PMID:19661183

    Open questions at the time
    • Direct chromatin mechanism not defined
    • Connection to splicing function not made
  6. 2010 High

    Connected a WW-domain disease mutation (Y65C, Golabi-Ito-Hall) to loss of proline-rich ligand binding and reduced splicing efficiency, establishing splicing dysfunction as a disease mechanism.

    Evidence In vitro binding with mutagenesis, patient lymphoblast co-IP, RT-PCR splicing assay

    PMID:20410308

    Open questions at the time
    • Genome-wide splicing targets not yet mapped
  7. 2011 Medium

    Revealed a cytoplasmic PQBP1 pool in RNA-dependent complexes with FMRP and RNA-binding/transport proteins, including stress-granule association, expanding its role beyond the nucleus.

    Evidence Co-IP, immunofluorescence, RNase-dependency, stress-granule induction

    PMID:21933836

    Open questions at the time
    • Direct mRNA targets of cytoplasmic complexes undefined
    • Functional consequence of SG association unclear
  8. 2013 High

    Defined PQBP1 as a genome-wide alternative-splicing effector acting through SF3B1, and showed disease mutants fail to support neurite outgrowth, unifying its biochemistry with neuronal phenotype.

    Evidence MS interactome, RIP, RNA-seq, neuronal knockdown, mutant complementation

    PMID:23512658

    Open questions at the time
    • Direct RNA-binding specificity not yet mapped at nucleotide resolution
  9. 2013 High

    Established a non-splicing cytoplasmic role: PQBP1 inhibits Dynamin 2 GTPase to promote neuronal ciliogenesis, with a WW-domain XLID mutation disrupting this function.

    Evidence Localization, in vivo cortical knockdown, co-IP, GTPase assay, epistasis, mutant analysis

    PMID:23994472

    Open questions at the time
    • Regulation of the Dynamin 2 interaction not defined
    • Relationship to splicing role not integrated
  10. 2014 High

    Crystal structure of the PQBP1–U5-15kD complex defined the YxxPxxVL recognition motif and explained why frameshift XLID mutations that delete this motif are pathogenic.

    Evidence X-ray crystallography, mutagenesis, binding assay

    PMID:24781215

    Open questions at the time
    • Did not address how WW-domain partners influence this interaction
  11. 2014 High

    Showed PQBP1 loss causes microcephaly by lengthening NSPC M phase via APC gene dysregulation, with Apc4 and in utero AAV-PQBP1 rescuing the phenotype, connecting splicing/transcription control to brain size.

    Evidence Conditional KO mouse, cell-cycle imaging, expression profiling, genetic and gene-therapy rescue

    PMID:25070536

    Open questions at the time
    • Whether APC effects are direct splicing targets not fully resolved
  12. 2014 Medium

    Demonstrated developmental specificity by showing PQBP1 controls FGFR2 alternative splicing and FGF target induction in Xenopus, with WBP11 as a partner.

    Evidence Morpholino knockdown, RT-PCR splicing, animal cap assays, in situ hybridization

    PMID:25209246

    Open questions at the time
    • Mammalian conservation of FGFR2 regulation untested
    • Single lab
  13. 2015 High

    Identified PQBP1 as an innate immune sensor that binds reverse-transcribed HIV-1 DNA and recruits cGAS for an IRF3 response, with patient cells showing attenuated immunity.

    Evidence RNAi screen in primary MDDCs, DNA binding, cGAS co-IP, IRF3 assay, patient cell validation

    PMID:26046437

    Open questions at the time
    • Initial step of viral recognition not yet defined
    • How PQBP1 reaches viral DNA unclear
  14. 2015 Medium

    Established a conserved cytoplasmic translational role: PQBP1/dPQBP1 partners with FMRP to control translation of specific mRNAs such as Chaoptin, required for photoreceptor morphogenesis.

    Evidence Co-IP, polysome fractionation, Drosophila KO and rescue

    PMID:26002102

    Open questions at the time
    • Mechanism of mRNA selection undefined
    • Drosophila ortholog model
  15. 2016 Medium

    Revealed negative allosteric coupling between PQBP1's WW domain (WBP11) and C-terminal (U5-15kD) interfaces, showing the two RNA-processing partnerships are mutually regulated.

    Evidence SPR, pulldown, NMR

    PMID:27314904

    Open questions at the time
    • In vivo relevance of the allostery untested
    • Single biophysical study
  16. 2017 High

    Showed specific frameshift mutations create a new epitope that binds and degrades non-phosphorylated FMRP, defining a gain-of-function disease mechanism affecting synaptic scaling.

    Evidence Co-IP, ubiquitination assay, synaptic scaling, Drosophila NMJ rescue

    PMID:28073926

    Open questions at the time
    • Whether all frameshift mutations act this way unclear
  17. 2018 High

    Placed PQBP1 downstream of SRRM2 stability and linked PQBP1 loss to synapse-gene mis-splicing in Alzheimer's models, with AAV-PQBP1 rescuing cognition.

    Evidence Phosphoproteomics, conditional KO, RNA-seq, co-IP, AAV rescue in AD models

    PMID:30283027

    Open questions at the time
    • Direct PQBP1 binding to affected transcripts not all mapped
  18. 2019 Medium

    Showed XLID frameshift mutants form stable dimers and lose binding to phosphorylated Pol II CTD, arguing toxicity arises from loss of transcriptional regulation rather than aggregation.

    Evidence SAXS, biophysical characterization, fluorescence anisotropy CTD binding

    PMID:30951824

    Open questions at the time
    • Cellular consequence of dimerization untested
    • Single in vitro study
  19. 2020 High

    Defined PQBP1 as a nuclear-import chaperone for TXNL4A via karyopherin-β2 piggyback, with the P244L XLID mutation disrupting this transport.

    Evidence Recombinant binding assays, immunofluorescence, disease-mutant analysis

    PMID:32041777

    Open questions at the time
    • Whether import defect drives disease phenotypes in vivo not shown
  20. 2021 High

    Established a direct translational-elongation mechanism: PQBP1 binds non-phosphorylated eEF2 to block eEF2K phosphorylation, promoting elongation and mGluR-LTD.

    Evidence Co-IP, in vitro kinase assay, puromycin labeling, mGluR-LTD electrophysiology, KO

    PMID:33662272

    Open questions at the time
    • How nuclear and cytoplasmic functions are partitioned unclear
  21. 2021 High

    Extended PQBP1 immune sensing to neurodegeneration by showing it directly binds extracellular tau to drive cGAS-STING-NFκB microglial inflammation, with microglial depletion preventing cognitive impairment.

    Evidence Direct binding, cGAS-STING readouts, microglia-specific inducible KO, cognition tests

    PMID:34782623

    Open questions at the time
    • Structural basis of tau recognition undefined
  22. 2021 Medium

    Identified LATS2 as a kinase partner enhancing PQBP1-dependent cGAS-STING responses to HIV-1, independent of canonical Hippo YAP/TAZ signaling.

    Evidence Co-IP, kinase assay, interferon reporter, HIV-1 infection

    PMID:34385679

    Open questions at the time
    • PQBP1 phosphorylation site not fully validated
    • Single lab
  23. 2022 High

    Showed that PQBP1 decorates the intact HIV-1 capsid as the primary recognition event upstream of cGAS recruitment, resolving how cGAS reaches viral DNA.

    Evidence Proximity ligation, co-IP, capsid binding, imaging time-course

    PMID:35809572

    Open questions at the time
    • Atomic basis of capsid contact not yet defined
  24. 2023 High

    Provided the structural basis for capsid recognition, mapping N-terminal acidic residues of PQBP1 to the arginine ring of the CA hexamer central channel.

    Evidence Structural analysis of CA hexamer, mutagenesis, in vitro capsid binding

    PMID:38128824

    Open questions at the time
    • How capsid binding triggers cGAS conformational activation unresolved
  25. 2023 Medium

    Showed PQBP1 promotes Numb exon 9 inclusion to maintain striatal progenitor proliferation, linking a defined splicing event to neurodevelopmental outcome.

    Evidence Striatum-specific conditional KO, RNA-seq, RT-PCR, proliferation assays, histology

    PMID:36943865

    Open questions at the time
    • Whether Numb mis-splicing alone explains the phenotype untested
  26. 2024 High

    Demonstrated PQBP1 binds exonic pre-mRNA regions and drives BAX exon 2 skipping to evade apoptosis, defining a pro-tumorigenic splicing role and an ASO therapeutic strategy.

    Evidence spyCLIP-seq, RNA-seq, knockdown/overexpression, ASO rescue, xenograft

    PMID:38342602

    Open questions at the time
    • Generality across cancer types not established
  27. 2024 High

    Established a new RNA-processing axis: PQBP1 binds UGUA elements and blocks CFIm recruitment to control alternative polyadenylation in cell-cycle genes governing NPC fate.

    Evidence CLIP-seq, RNA-seq, APA-seq, CFIm co-IP, in vitro binding, knockdown/KO

    PMID:39037895

    Open questions at the time
    • How splicing and APA functions are coordinated unclear
  28. 2026 High

    Resolved that the Y65C mutation combines partial loss-of-function (misfolding, reduced levels) with gain-of-function enhanced binding to 3'-end processing machinery, distorting APA profiles and progenitor transitions.

    Evidence Y65C knock-in mice, progenitor analysis, mutant co-IP, APA profiling, stability assays

    PMID:41507200

    Open questions at the time
    • Relative contribution of loss vs gain to human disease severity unquantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PQBP1's distinct nuclear (splicing/APA/transcription), cytoplasmic (translation), and immune-sensing activities are partitioned and coordinated within a single neuron, and which are decisive for each XLID phenotype, remains unresolved.
  • No unified model partitioning the functions by compartment or stimulus
  • Which activity dominates in each disease context is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2 GO:0140299 molecular sensor activity 2 GO:0003677 DNA binding 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005829 cytosol 3 GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
CGASDNM2EEF2FMRPLATS2SF3B1TXNL4AWBP11
Complex memberships
spliceosome (SF3B1/U5-15kD-associated)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PQBP1 (PQBP-1) was identified as a nuclear protein that directly binds polyglutamine tracts (including those of Brn-2, huntingtin, and ataxin-1) with higher affinity for expanded repeats, and inhibits transcriptional activation by Brn-2. Overexpression suppresses cell growth and enhances susceptibility to stress. The protein contains a WW domain, polar amino acid repeat sequences essential for polyglutamine binding, a putative nuclear localization signal, and a C2 domain. Yeast two-hybrid screen (binding), in vitro binding assays, nuclear localization by immunofluorescence, transcription reporter assays, cell viability assays Human molecular genetics High 10332029
2002 Mutant ataxin-1 (expanded polyglutamine) enhances PQBP-1 binding to the C-terminal domain of RNA polymerase II large subunit, reducing phosphorylated Pol II levels and transcription, and inducing apoptotic cell death. This interaction is positively influenced by expanded polyglutamine sequences. In vitro and in vivo binding assays, co-immunoprecipitation, transcription assays, apoptosis assays in cell lines Neuron High 12062018
2003 Transgenic overexpression of human PQBP-1 in mice causes a late-onset, progressive motor neuron disease-like phenotype with loss of Purkinje cells, granular cells in cerebellum, and spinal motor neurons, demonstrating that excessive PQBP-1 activity causes neuronal dysfunction. Transgenic mouse model (ubiquitous human PQBP-1 expression), behavioral analysis, histopathology Human molecular genetics Medium 12651867
2010 The Y65C missense mutation in the WW domain of PQBP1 (Golabi-Ito-Hall syndrome) diminishes binding of the WW domain and full-length protein to proline-rich ligands. In patient-derived lymphoblasts, the PQBP1-Y65C/WBP11 splicing factor complex was compromised and pre-mRNA splicing efficiency was substantially decreased. In vitro binding assays with recombinant proteins, co-immunoprecipitation from patient lymphoblasts, RT-PCR splicing efficiency assay The Journal of biological chemistry High 20410308
2011 PQBP1 localizes not only in nuclear speckles but also in a cytoplasmic pool in neurons, where it associates with RNA-binding proteins KSRP, SFPQ/PSF, DDX1, Caprin-1, and dynactin subunits p150(Glued) and p27 in RNA-dependent complexes. PQBP1 co-localizes with FMRP in neuronal RNA granules and relocalizes to stress granules upon arsenite-induced oxidative stress. The cellular distribution of PQBP1 influences stress granule assembly. Co-immunoprecipitation, immunofluorescence microscopy, RNA-dependency assay (RNase treatment), stress granule induction assay Human molecular genetics Medium 21933836
2013 PQBP1 functions as an alternative mRNA splicing effector by associating with splicing factors including the U2 snRNP component SF3B1. Loss of PQBP1 reduces SF3B1 substrate mRNA association and causes significant changes in alternative splicing patterns. In primary neurons, PQBP1 depletion reduces dendritic outgrowth. Disease-linked PQBP1 mutants are deficient in splicing factor associations and cannot complement neurite outgrowth defects. Mass spectrometry (interactome), RIP (RNA immunoprecipitation), RNA-seq (splicing analysis), PQBP1 knockdown in primary neurons, neurite outgrowth assay, complementation with disease mutants Genes & development High 23512658
2013 PQBP1 is localized at the base of the neuronal primary cilium and its knockdown profoundly impairs ciliary morphogenesis in neurons and in the mouse cerebral cortex in vivo. PQBP1 interacts with Dynamin 2 and inhibits its GTPase activity; Dynamin 2 knockdown suppresses the PQBP1-knockdown ciliary phenotype. A XLID-causing WW domain mutation of PQBP1 disrupts both Dynamin 2 binding/inhibition and ciliogenesis. Immunofluorescence localization, in vivo cortical knockdown, co-immunoprecipitation (PQBP1-Dynamin 2), GTPase activity assay, epistasis (double knockdown), disease mutant analysis Cell reports High 23994472
2014 Crystal structure of the C-terminal fragment of PQBP1 in complex with the spliceosomal protein U5-15kD reveals that the U5-15kD hydrophobic groove recognizes a YxxPxxVL motif in PQBP1. Mutations within this motif abolish interaction in vitro and cause loss-of-function. All known PQBP1 frameshift mutations causing mental retardation eliminate the YxxPxxVL motif, providing a molecular mechanism for intellectual disability. X-ray crystallography, in vitro mutagenesis, binding assay Nature communications High 24781215
2014 Conditional knockout of Pqbp1 in neural stem progenitor cells (NSPCs) causes microcephaly by elongating the M phase of the cell cycle, reducing the NSPC pool. Gene expression changes in NSPCs affect anaphase-promoting complex genes via aberrant transcription and RNA splicing. Exogenous Apc4 rescues the cell cycle and proliferation phenotypes. In utero AAV-PQBP1 gene therapy at E10 rescues microcephaly and behavioral abnormalities. Conditional knockout mouse, cell cycle analysis (live imaging/flow), gene expression profiling, rescue by AAV and by Apc4 overexpression Molecular psychiatry High 25070536
2014 PQBP1 knockdown in Xenopus embryos inhibits FGF target gene induction (but not BMP, Nodal, or Wnt) and changes alternative splicing of FGFR2 transcripts, altering incorporation of cassette exons that generate receptor variants with different ligand specificities. The splicing factor WBP11 acts as a PQBP1 binding partner with similar developmental functions. Morpholino knockdown in Xenopus, RT-PCR splicing analysis, animal cap explant assay, in situ hybridization Development (Cambridge, England) Medium 25209246
2015 PQBP1 directly binds reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate immune response in dendritic cells. MDDCs from Renpenning syndrome patients with PQBP1 mutations show severely attenuated innate immune responses to HIV-1. Targeted RNAi screen in primary MDDCs, direct DNA binding assay, co-immunoprecipitation (PQBP1-cGAS), IRF3 activation assay, patient-derived MDDC functional assay Cell High 26046437
2015 In Drosophila photoreceptor cells, cytoplasmic dPQBP1 regulates translation of specific mRNAs (including Chaoptin) by interacting with dFMR1, which binds target mRNAs and facilitates their assembly into translating ribosomes. This function is conserved for human PQBP1 and FMRP. Loss of dPQBP1 causes defective rhabdomere morphogenesis due to impaired Chaoptin translation. Co-immunoprecipitation (dPQBP1-dFMR1), polysome fractionation, immunostaining, genetic KO in Drosophila, rescue experiments Human molecular genetics Medium 26002102
2016 Binding of PQBP1 to its partner WBP11 (via the WW domain) allosterically reduces the binding affinity of PQBP1 to U5-15kD (via its C-terminal YxxPxxVL motif), demonstrating negative allosteric modulation between the two PQBP1 interaction surfaces. In vitro binding assays (surface plasmon resonance, pulldown), NMR FEBS letters Medium 27314904
2017 PQBP1 mutations c.459_462delAGAG and c.463_464dupAG encode a new C-terminal epitope that preferentially binds non-phosphorylated FMRP and promotes its ubiquitin-mediated degradation. This impairs FMRP function, up-regulates targets such as MAP1B, and disrupts FMRP-dependent synaptic scaling. In Drosophila NMJ, the c.463_464dupAG transgene causes synaptic overgrowth rescued by dFMRP expression, supporting a gain-of-function pathogenic mechanism. Co-immunoprecipitation, ubiquitination assay, synaptic scaling assay in primary neurons, Drosophila NMJ transgenic rescue Human molecular genetics High 28073926
2018 SRRM2 phosphorylation at Ser1068 (by ERK1/2) inhibits its nuclear translocation and interaction with T-complex protein subunit α. SRRM2 deficiency destabilizes PQBP1 in neurons and impairs splicing of synapse-related genes. Conditional knockout of PQBP1 in neurons recapitulates synapse and splicing phenotypes. AAV-PQBP1 rescues RNA splicing, synapse phenotype, and cognitive decline in two AD mouse models. Phospho-proteomics, PQBP1-conditional KO mouse, RNA-seq (splicing), AAV gene therapy rescue, co-immunoprecipitation Molecular psychiatry High 30283027
2020 PQBP1 facilitates the nuclear import of the splicing factor TXNL4A via a piggyback mechanism through the nuclear import receptor karyopherin β2. The PQBP1-TXNL4A interaction requires the C-terminal YxxPxxVL motif; the XLID missense mutation P244L in PQBP1 disrupts this interaction and consequently mislocalizes TXNL4A. Recombinant protein expression, in vitro binding assays, immunofluorescence microscopy in HeLa cells, disease mutant analysis The Journal of biological chemistry High 32041777
2021 PQBP1 senses extrinsic tau (3R/4R) proteins by direct interaction and triggers an innate immune response through the cGAS-STING pathway, leading to NFκB nuclear translocation, NFκB-dependent inflammatory gene transcription, and microglial brain inflammation. Microglia-specific, tamoxifen-inducible depletion of PQBP1 in vitro and in vivo abolishes tau-induced inflammation and prevents cognitive impairment in mice. Direct protein-protein interaction assay (tau-PQBP1), cGAS-STING pathway activation assay, microglia-specific conditional KO (tamoxifen-inducible), in vivo mouse cognition tests, NFκB reporter assay Nature communications High 34782623
2021 PQBP1 specifically binds to non-phosphorylated eEF2 and suppresses eEF2K-mediated phosphorylation at Thr56, thereby promoting translational elongation. Loss of PQBP1 reduces global protein synthesis. PQBP1 regulates hippocampal mGluR-dependent long-term depression and associated behaviors through this eEF2K/eEF2 pathway. Co-immunoprecipitation, in vitro kinase assay, puromycin incorporation assay (global translation), mGluR-LTD electrophysiology, PQBP1 knockout/knockdown Molecular cell High 33662272
2021 LATS2 (Hippo pathway kinase) interacts with PQBP1 and enhances cGAS-STING-mediated innate immune response to HIV-1 reverse-transcribed DNA, upregulating type-I interferon and cytokines. This function is independent of canonical YAP/TAZ downstream signaling and involves LATS2 kinase activity with a potential phosphorylation site on PQBP1. Co-immunoprecipitation (LATS2-PQBP1), kinase activity assay, interferon reporter assay, HIV-1 infection assay, phosphorylation site identification Cell death and differentiation Medium 34385679
2022 Upon HIV-1 infection, PQBP1 decorates the intact viral capsid as a primary recognition step, and this capsid binding is required for subsequent cGAS recruitment to the capsid in a PQBP1-dependent manner. This positions cGAS at the site of viral DNA generation during reverse transcription and capsid disassembly. Proximity ligation assay, co-immunoprecipitation, capsid binding assay, fluorescence microscopy, HIV-1 infection time-course experiments Molecular cell High 35809572
2023 PQBP1 binds to HIV-1 capsids through charge-complementing contacts between acidic residues in its N-terminal region and an arginine ring in the central channel of the HIV-1 CA hexamer, revealing the molecular basis of capsid recognition. Structural analysis (cryo-EM/crystallography of CA hexamer), mutagenesis, in vitro capsid binding assays Journal of molecular biology High 38128824
2023 PQBP1 promotes exon 9 inclusion of Numb via alternative splicing in striatal progenitors, maintaining a variant that mediates progenitor proliferation. PQBP1 deletion in striatal progenitors causes reduced proliferation, increased differentiation, and depleted progenitor pool leading to defective striatal development. Conditional KO mouse (striatum-specific), RNA-seq splicing analysis, RT-PCR validation, BrdU/EdU proliferation assay, in vivo histology Cell reports Medium 36943865
2024 PQBP1 preferentially binds to exon regions of pre-mRNAs and promotes BAX exon 2 skipping in ovarian cancer cells, generating a truncated BAX isoform subject to nonsense-mediated mRNA decay, thereby reducing apoptosis and promoting tumor progression. PQBP1 depletion or splice-switching antisense oligonucleotides restore BAX exon 2 inclusion and BAX expression, inhibiting tumor growth. spyCLIP-seq (direct RNA binding), RNA-seq (alternative splicing), PQBP1 knockdown/overexpression, antisense oligonucleotide rescue, in vivo xenograft tumor model Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 38342602
2024 PQBP1 directly interacts with upstream UGUA elements in pre-mRNAs and impedes recruitment of the CFIm complex, thereby influencing polyadenylation site selection within cell-cycle-related genes in neural progenitor cells. Loss of PQBP1 shifts alternative polyadenylation profiles and disrupts the balance between NPC proliferation and differentiation. Multi-omics (CLIP-seq, RNA-seq, APA-seq), PQBP1 knockdown/KO, CFIm complex co-immunoprecipitation, in vitro binding assay Cell reports High 39037895
2026 The PQBP1 Y65C missense mutation causes PQBP1 misfolding and reduced protein levels (partial loss-of-function), impairing apical progenitor proliferation and microcephaly in knock-in mice. Additionally, Y65C causes a gain-of-function by enhancing interactions with core components of the mRNA 3' end processing machinery, preserving proliferative alternative polyadenylation profiles that interfere with the apical-to-basal progenitor transition. Pqbp1-Y65C knock-in mice, brain progenitor cell analysis (IHC, EdU labeling), co-immunoprecipitation (Y65C mutant with 3' end processing machinery), APA profiling, protein stability assays Nature communications High 41507200
2008 PQBP1 overexpression induces nuclear inclusions whose formation is dramatically enhanced by co-expression of the pre-mRNA splicing factor SIPP1. Site-directed mutagenesis shows that multiple independent interaction sites between SIPP1 and PQBP1 are required for inclusion facilitation. The inclusions are highly dynamic, do not colocalize with known nuclear structures, and their formation does not require energy. Transfection/overexpression, immunofluorescence, site-directed mutagenesis, FRAP (fluorescence recovery after photobleaching) European journal of cell biology Medium 18599155
2009 PQBP1 knockdown in mice impairs anxiety-related cognition and reduces c-fos upregulation and histone H3 acetylation in amygdala, prefrontal cortex, and hippocampus after behavioral tests. The HDAC inhibitor 4-phenylbutyric acid rescues gene expression and behavioral phenotypes, linking PQBP1 to chromatin-dependent gene expression in cognitive circuits. Transgenic siRNA knockdown mouse, behavioral tests (open field, EPM, novel object recognition), immunohistochemistry (c-fos, H3 acetylation), pharmacological rescue (HDAC inhibitor) Human molecular genetics Medium 19661183
2019 Frameshift PQBP-1 mutants K192Sfs*7 and R153Sfs*41 form stable dimers (unlike monomeric wild-type), have more folded content and higher thermal stability, and show significantly weakened binding to phosphorylated RNA Pol II CTD heptapeptide (YpSPTpSPS), suggesting their toxicity arises from loss of transcriptional regulatory function rather than aggregation. Small-angle X-ray scattering (SAXS), biophysical characterization, fluorescence anisotropy binding assay with labeled Pol II CTD peptide Journal of structural biology Medium 30951824
2025 High-fat diet (HFD) suppresses PPARγ-mediated transcriptional expression of PQBP1, leading to alternative splicing changes in synapse-related genes (CASK, Cacnb1, Cyfip2, Syt1) that impair presynaptic vesicle release and cognitive function. AAV-PQBP1 or AAVs expressing individual target genes rescue synapse and cognitive dysfunctions in HFD mice. RNA-seq (alternative splicing), chromatin assays, primary neuron electrophysiology/vesicle release assay, AAV rescue in vivo, immunohistochemistry bioRxiv (preprint)preprint Medium 40502014

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). American heart journal 308 16442908
2015 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1. Cell 177 26046437
2021 Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation. Nature communications 163 34782623
2002 Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron 160 12062018
1999 PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. Human molecular genetics 160 10332029
2009 Secondhand smoke (SHS) exposure is associated with circulating markers of inflammation and endothelial function in adult men and women. Atherosclerosis 74 19700161
2013 PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth. Genes & development 63 23512658
1988 Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2). American journal of medical genetics 56 3177467
2010 Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing. The Journal of biological chemistry 52 20410308
2006 Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene. Journal of medical genetics 50 16740914
2011 The X-chromosome-linked intellectual disability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules. Human molecular genetics 48 21933836
2018 The intellectual disability gene PQBP1 rescues Alzheimer's disease pathology. Molecular psychiatry 47 30283027
2010 The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males. Clinical genetics 44 20950397
2022 Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA. Molecular cell 41 35809572
2014 In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells. Molecular psychiatry 39 25070536
2004 Genotype-phenotype studies in three families with mutations in the polyglutamine-binding protein 1 gene (PQBP1). Clinical genetics 38 15355434
2003 PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype. Human molecular genetics 34 12651867
2014 Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15 kD. Nature communications 32 24781215
2005 PQBP-1 is expressed predominantly in the central nervous system during development. The European journal of neuroscience 31 16190883
2021 PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation. Molecular cell 30 33662272
2012 Molecular insights into the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1. FEBS letters 29 22710169
2006 A two base pair deletion in the PQBP1 gene is associated with microphthalmia, microcephaly, and mental retardation. European journal of human genetics : EJHG 29 17033686
2014 Antenatal exposure of maternal secondhand smoke (SHS) increases fetal lung expression of RAGE and induces RAGE-mediated pulmonary inflammation. Respiratory research 27 25338658
1994 Non-specific X-linked mental retardation: linkage analysis in MRX2 and MRX4 families revisited. American journal of medical genetics 26 7943041
2009 Knock-down of PQBP1 impairs anxiety-related cognition in mouse. Human molecular genetics 25 19661183
2001 PQBP-1 (Np/PQ): a polyglutamine tract-binding and nuclear inclusion-forming protein. Brain research bulletin 25 11719261
2018 Purity Determination by Capillary Electrophoresis Sodium Hexadecyl Sulfate (CE-SHS): A Novel Application For Therapeutic Protein Characterization. Analytical chemistry 24 29357216
2014 The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling. Development (Cambridge, England) 24 25209246
2010 Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 20962230
1994 The kinetic studies on the intramolecular SH, S-S exchange reaction of bovine mercaptalbumin. Biochimica et biophysica acta 24 8155715
2009 Nematode homologue of PQBP1, a mental retardation causative gene, is involved in lipid metabolism. PloS one 23 19119319
2017 Analysis of Listeria using exogenous volatile organic compound metabolites and their detection by static headspace-multi-capillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS). Analytical and bioanalytical chemistry 22 28484808
2015 X chromosome-linked intellectual disability protein PQBP1 associates with and regulates the translation of specific mRNAs. Human molecular genetics 22 26002102
2006 Exonic microdeletions in the X-linked PQBP1 gene in mentally retarded patients: a pathogenic mutation and in-frame deletions of uncertain effect. European journal of human genetics : EJHG 22 16493439
2006 Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration. Journal of neurochemistry 22 16987236
2017 Mutations of PQBP1 in Renpenning syndrome promote ubiquitin-mediated degradation of FMRP and cause synaptic dysfunction. Human molecular genetics 19 28073926
2011 Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1. European journal of human genetics : EJHG 19 21267006
2000 Genomic organization and alternative transcripts of the human PQBP-1 gene. Gene 19 11163963
1996 hDIP--a potential transcriptional regulator related to murine TSC-22 and Drosophila shortsighted (shs)--is expressed in a large number of human tissues. Biochimica et biophysica acta 19 8982256
2019 High Expression of PQBP1 and Low Expression of PCK2 are Associated with Metastasis and Recurrence of Osteosarcoma and Unfavorable Survival Outcomes of the Patients. Journal of Cancer 18 31205570
2013 The XLID protein PQBP1 and the GTPase Dynamin 2 define a signaling link that orchestrates ciliary morphogenesis in postmitotic neurons. Cell reports 18 23994472
2011 A novel frame shift mutation in the PQBP1 gene identified in a Tunisian family with X-linked mental retardation. European journal of medical genetics 18 21315190
2021 Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice. Environmental health perspectives 17 34009016
2006 Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship. FEBS letters 17 16597440
1998 Cytotoxin produced by Escherichia coli isolated from chickens with swollen head syndrome (SHS). Veterinary microbiology 17 9695284
2017 PQBP1, an intrinsically disordered/denatured protein at the crossroad of intellectual disability and neurodegenerative diseases. Neurochemistry international 16 28627366
2010 Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and enhance exclusion of the mutant exon. Human mutation 16 19847789
2021 The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway. Cell death and differentiation 15 34385679
2010 Whole gene duplication of the PQBP1 gene in syndrome resembling Renpenning. American journal of medical genetics. Part A 15 21204222
1998 A gene for non-specific X-linked mental retardation (MRX55) is located in Xp11. Annales de genetique 13 9599645
2022 PQBP1: The Key to Intellectual Disability, Neurodegenerative Diseases, and Innate Immunity. International journal of molecular sciences 12 35682906
2018 Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA. Molecular immunology 12 29807326
2014 Segmental isotope-labeling of the intrinsically disordered protein PQBP1. FEBS letters 12 25447530
2013 Sox2 transcriptionally regulates PQBP1, an intellectual disability-microcephaly causative gene, in neural stem progenitor cells. PloS one 12 23874697
2024 Splicing Factor PQBP1 Curtails BAX Expression to Promote Ovarian Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 38342602
2024 Dynamic regulation of alternative polyadenylation by PQBP1 during neurogenesis. Cell reports 11 39037895
2017 Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice. Cell and tissue research 11 28948356
2016 Two RNAs or DNAs May Artificially Fuse Together at a Short Homologous Sequence (SHS) during Reverse Transcription or Polymerase Chain Reactions, and Thus Reporting an SHS-Containing Chimeric RNA Requires Extra Caution. PloS one 11 27148738
2006 In vitro bioactivity and osteoblast response of porous NiTi synthesized by SHS using nanocrystalline Ni-Ti reaction agent. Journal of biomedical materials research. Part A 11 16637041
2002 PQBP-1 increases vulnerability to low potassium stress and represses transcription in primary cerebellar neurons. Biochemical and biophysical research communications 11 12051705
2023 SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression. Nucleic acids research 10 36546765
2023 PQBP1 regulates striatum development through balancing striatal progenitor proliferation and differentiation. Cell reports 10 36943865
2020 The Renpenning syndrome-associated protein PQBP1 facilitates the nuclear import of splicing factor TXNL4A through the karyopherin β2 receptor. The Journal of biological chemistry 10 32041777
2020 Enhancement of covalent aggregate quantification of protein therapeutics by non-reducing capillary gel electrophoresis using sodium hexadecyl sulfate (CE-SHS). Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 10 32585496
2003 Characterization of a plasmid-encoded adhesin of an avian pathogenic Escherichia coli (APEC) strain isolated from a case of swollen head syndrome (SHS). Veterinary microbiology 10 12860081
2023 Molecular Determinants of PQBP1 Binding to the HIV-1 Capsid Lattice. Journal of molecular biology 9 38128824
2018 First Korean Case of Renpenning Syndrome with Novel Mutation in PQBP1 Diagnosed by Targeted Exome Sequencing, and Literature Review. Annals of clinical and laboratory science 9 30143497
2018 Phenotypic and molecular insights into PQBP1-related intellectual disability. American journal of medical genetics. Part A 9 30244542
2016 Allosteric modulation of the binding affinity between PQBP1 and the spliceosomal protein U5-15kD. FEBS letters 9 27314904
2020 PQBP1, an intellectual disability causative gene, affects bone development and growth. Biochemical and biophysical research communications 8 31959475
2019 Frameshift PQBP-1 mutants K192Sfs*7 and R153Sfs*41 implicated in X-linked intellectual disability form stable dimers. Journal of structural biology 7 30951824
2008 Nature of the nuclear inclusions formed by PQBP1, a protein linked to neurodegenerative polyglutamine diseases. European journal of cell biology 7 18599155
2023 Behavioral and Cognitive Performance Following Exposure to Second-Hand Smoke (SHS) from Tobacco Products Associated with Oxidative-Stress-Induced DNA Damage and Repair and Disruption of the Gut Microbiome. Genes 6 37761842
2023 Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome. Molecular psychiatry 6 38030819
2021 A mild clinical and neuropsychological phenotype of Renpenning syndrome: A new case report with a maternally inherited PQBP1 missense mutation. Applied neuropsychology. Child 6 34470565
2019 RAGE and AXL expression following secondhand smoke (SHS) exposure in mice. Experimental lung research 6 31762322
2024 Availability of Receptors for Advanced Glycation End-Products (RAGE) Influences Differential Transcriptome Expression in Lungs from Mice Exposed to Chronic Secondhand Smoke (SHS). International journal of molecular sciences 5 38732159
2023 Identification of a DNA methylation signature for Renpenning syndrome (RENS1), a spliceopathy. European journal of human genetics : EJHG 5 36797465
2023 The role of PQBP1 in neural development and function. Biochemical Society transactions 5 36815699
2023 Inflammatory Cytokine Elaboration Following Secondhand Smoke (SHS) Exposure Is Mediated in Part by RAGE Signaling. International journal of molecular sciences 5 37958629
2012 Comparative aspects of polyglutamine binding domain in PQBP-1 among Vertebrata. Gene 5 23022625
2019 Microphthalmos-anophthalmos-coloboma (MAC) spectrum in two brothers with Renpenning syndrome due to a truncating mutation in the polyglutamine tract binding protein 1 (PQBP1) gene. Ophthalmic genetics 4 31718390
2012 A restricted level of PQBP1 is needed for the best longevity of Drosophila. Neurobiology of aging 4 22901698
2025 Renpenning syndrome related to a missense variant in polyglutamine-binding protein 1 (PQBP1): Two pediatric cases from a Chinese family and literature review. Applied neuropsychology. Child 3 39932334
2025 World no-tobacco: effects of second-hand smoke (SHS) and vapors on the developing and adult brain. Frontiers in pharmacology 3 40115268
2023 PQBP1 regulates the cellular inflammation induced by avian reovirus and interacts with the viral p17 protein. Virus research 3 37201645
2021 Generation of an urine-derived induced pluripotent stem cell line WMUi017-A from a X-linked Renpenning syndrome (X-RSY) patient with the hemizygous PQBP1 gene mutation p.P609A (c.1825C>G). Stem cell research 3 33477035
2017 Role of second-hand smoke (SHS)-induced proteostasis/autophagy impairment in pediatric lung diseases. Molecular and cellular pediatrics 3 28150141
2011 Comparative genetics of the poly-Q tract of ataxin-1 and its binding protein PQBP-1. Biochemical genetics 3 21964520
2024 Role of PQBP1 in Pathogen Recognition-Impact on Innate Immunity. Viruses 2 39205314
2026 The missense mutation Y65C in PQBP1 causes microcephaly and cognitive deficits through a combination of partial loss-of-function and gain-of-function effects. Nature communications 1 41507200
2025 [Clinical analysis of a child with heterotopic ventricular gray matter Renpenning syndrome caused by PQBP1 gene mutation and a literature review]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 40372223
2021 Fatal Attraction: The Case of Toxic Soluble Dimers of Truncated PQBP-1 Mutants in X-Linked Intellectual Disability. International journal of molecular sciences 1 33668121
2019 Induced pluripotent stem cells (iPSCs) derived from a renpenning syndrome patient with c.459_462delAGAG mutation in PQBP1 (PEIi001-A). Stem cell research 1 31698189
2015 The effects of Secondhand Smoke (SHS) exposure on microvascular endothelial function among healthy women. Tobacco induced diseases 1 26346914
2026 Disrupting PQBP1-eEF2 protein-protein interaction: From synaptic translation to immunity and cancer. Neurochemistry international 0 41960772
2026 Renpenning syndrome caused by the c.459_462delAGAG mutation in PQBP1: a case report and literature review. Frontiers in genetics 0 41978772
2025 PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment. bioRxiv : the preprint server for biology 0 40502014
2025 Inflammatory Molecule Elaboration in Secondhand Smoke (SHS)-Induced or Conditional RAGE Transgenic Modeling of Chronic Rhinosinusitis (CRS). Current issues in molecular biology 0 41020862
2025 Childhood exposure to second-hand smoke (SHS) and risk of breast cancer in postmenopausal never smokers: the Multiethnic Cohort (MEC) study. Breast cancer research : BCR 0 41449415

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