PQBP1

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Protein-coding gene in the species Homo sapiens

title: "PQBP1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/PQBP1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Polyglutamine-binding protein 1 (PQBP1) is a protein that in humans is encoded by the PQBP1 gene.

Polyglutamine binding protein-1, which was identified as a binding protein to the polyglutamine tract sequence, is an evolutionally conserved protein expressed in various tissues including developmental and adult brains or mesodermal tissues. In cells, PQBP1 is dominantly located in the nucleus but also in the cytoplasm dependently on the cell type and stress conditions. PQBP1 has recently been found to play a role in the innate immune response of dendritic cells.

It should be of note that PQBP1 has no relationship with QBP1, an artificial synthetic peptide.

Function

PQBP1 is a nuclear polyglutamine-binding protein that contains a WW domain.

The molecular roles of PQBP1 are mainly in mRNA splicing and transcription. PQBP1 interacts with splicing proteins and RNA-binding proteins. PQBP1 deficiency critically affects mRNA splicing of cell cycle and synapse related genes. Recent results indicated implication of PQBP1 in cytoplasmic RNA metabolism and elongation of protein translation from mRNA. Research also seems to suggest that PQBP1 also plays a role in the innate immune system as a necessary adaptor for the cGAS-mediated innate response to lentiviruses such as HIV1. This PQBP-1 dependent response initiates a sensor that detects lentiviral DNA.

Clinical significance

Mutations in the PQBP1 gene, which encodes for this protein, have been known to cause X-linked intellectual disabilities (XLID), commonly referred to as Renpenning's syndrome. Recent studies indicate that PQBP-1 interaction with TXNL4A is missing in patients with frameshift mutations causing Renpenning's syndrome. PQBP-1 seems to facilitate the nuclear import of TXNL4A, however the biological function of that interaction requires further investigation. People who suffer from these disabilities share a common set of symptoms including: microcephaly, shortened stature and impaired intellectual development. There are 11 types of mutations that have been identified, but the most common being frameshift mutations. Other syndromic XLIDs such as Golabi-Ito-Hall syndrome and non-syndromic ID patients were also associated with PQBP1 gene mutations.

Mutant Ataxin-1 and Huntingtin, disease proteins of spinocerebellar ataxia type-1 and Huntington's disease respectively, interact with PQBP1 and disturbed the functions of PQBP1. Moreover, recent investigations revealed pathological roles of PQBP1 in neurons and microglia under neurodegeneration of Alzheimer's disease and tauopathy. SRRM2 phosphorylation detected in neurons at the early stage of Alzheimer's disease pathology leads to reduction of SRRM2, a scaffold protein for RNA metabolism related molecules in the nucleus, which causes reduction of PQBP1 in the nucleus and acquired intellectual disability. PQBP1 was shown as an intracellular receptor for HIV1 in dendritic cells for innate immune system. Recent studies indicate that PQBP1 recognizes intact capsids of HIV-1 particles. It interacts with these capsids through its amino-terminus, and when capsid disassembles it triggers the PQBP-1 dependent recruitment of cGAS. This is crucial to activating the sensor that detects HIV-1 DNA as soon as synthesis is initiated. Similarly, PQBP1 functions as an intracellular receptor for tau proteins and trigger brain inflammation.

Animal models

Mouse models of knockdown and conditional knockout were generated, and they showed cognitive impairment and microcephaly. The KD mice possess a transgene expressing 498 bp double-strand RNA that is endogenously cleaved to siRNA suppressing PQBP1 efficiently, and did not show obvious developmental abnormality. Another knockdown model of the gene in mouse embryo primary neurons revealed a decrease in splicing efficiency and resulted in abnormal gastrulation and neuralation patterning.

Drosophila models of underexpression and overexpression were also generated. The hypomorph Drosophila model revealed molecular function of PQBP1 in learning acquisition mediated by decreased mRNA and protein expressions of NMDA receptor subunit NR1. Research indicates that in order to appropriately function, the protein must be expressed within a critical range.

References

References

  1. (December 1998). "Polar amino acid-rich sequences bind to polyglutamine tracts". Biochemical and Biophysical Research Communications.
  2. (April 2004). "Novel truncating mutations in the polyglutamine tract binding protein 1 gene (PQBP1) cause Renpenning syndrome and X-linked mental retardation in another family with microcephaly". American Journal of Human Genetics.
  3. (June 1999). "PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival". Human Molecular Genetics.
  4. (November 2001). "PQBP-1 (Np/PQ): a polyglutamine tract-binding and nuclear inclusion-forming protein". Brain Research Bulletin.
  5. (September 2005). "PQBP-1 is expressed predominantly in the central nervous system during development". The European Journal of Neuroscience.
  6. (October 2014). "The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling". Development.
  7. (December 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.
  8. (June 2015). "PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1". Cell.
  9. "OMIM: PQBP1 polyglutamine binding protein 1".
  10. (October 2018). "PQBP1, an intrinsically disordered/denatured protein at the crossroad of intellectual disability and neurodegenerative diseases". Neurochemistry International.
  11. (May 2002). "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death". Neuron.
  12. (April 2014). "Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15 kD". Nature Communications.
  13. (October 2000). "Evidence that dim1 associates with proteins involved in pre-mRNA splicing, and delineation of residues essential for dim1 interactions with hnRNP F and Npw38/PQBP-1". Gene.
  14. (July 2000). "PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15kD/dim1p via the carboxyl-terminal domain". Biochemical and Biophysical Research Communications.
  15. (April 2014). "Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15 kD". Nature Communications.
  16. (March 2013). "PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth". Genes & Development.
  17. (December 1999). "Association of two nuclear proteins, Npw38 and NpwBP, via the interaction between the WW domain and a novel proline-rich motif containing glycine and arginine". The Journal of Biological Chemistry.
  18. (February 2004). "SIPP1, a novel pre-mRNA splicing factor and interactor of protein phosphatase-1". The Biochemical Journal.
  19. (January 2010). "Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and enhance exclusion of the mutant exon". Human Mutation.
  20. (April 2021). "PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation". Molecular Cell.
  21. (August 2022). "Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA". Molecular Cell.
  22. (May 2005). "Renpenning syndrome comes into focus". American Journal of Medical Genetics. Part A.
  23. (March 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.
  24. (December 2003). "Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation". Nature Genetics.
  25. (March 2011). "The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males". Clinical Genetics.
  26. (June 2006). "Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene". Journal of Medical Genetics.
  27. (June 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.
  28. (August 2012). "Molecular insights into the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1". FEBS Letters.
  29. (October 2003). "Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington's disease". The Journal of Biological Chemistry.
  30. (October 2018). "The intellectual disability gene PQBP1 rescues Alzheimer's disease pathology". Molecular Psychiatry.
  31. (November 2021). "Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation". Nature Communications.
  32. (January 2015). "Comprehensive phosphoproteome analysis unravels the core signaling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease brain". Human Molecular Genetics.
  33. (June 2015). "PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1". Cell.
  34. (November 2009). "Knock-down of PQBP1 impairs anxiety-related cognition in mouse". Human Molecular Genetics.
  35. (April 2015). "In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells". Molecular Psychiatry.
  36. (October 2010). "Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning". The Journal of Neuroscience.
  37. (April 2006). "Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship". FEBS Letters.
  38. (January 2013). "A restricted level of PQBP1 is needed for the best longevity of Drosophila". Neurobiology of Aging.

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