PQBP1
Domain
The WW domain may play a role as a transcriptional activator directly or via association with the transcription machinery. The WW domain mediates interaction with WBP11, ATN1, SF3B1 and the C-terminal domain of the RNA polymerase II large subunit.
Except for the WW domain, the protein is intrinsically disordered.
Function
Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (PubMed:21933836). Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:26046437). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (PubMed:26046437).
Involvement in disease
Renpenning syndrome 1
RENS1
An X-linked syndrome characterized by intellectual disability, microcephaly, short stature, and small testes. The craniofacies tends to be narrow and tall with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Widely expressed with high level in heart, skeletal muscle, pancreas, spleen, thymus, prostate, ovary, small intestine and peripheral blood leukocytes.
Cellular localization
- Nucleus
- Nucleus speckle
- Cytoplasmic granule
- Colocalizes with SRSF2 in nuclear speckles (By similarity). Colocalized with POU3F2 (PubMed:10332029). Colocalized with ATXN1 in nuclear inclusion bodies (PubMed:12062018). Localizes to cytoplasmic stress granules (PubMed:21933836).
Alternative names
NPW38, JM26, PQBP1, Polyglutamine-binding protein 1, PQBP-1, 38 kDa nuclear protein containing a WW domain, Polyglutamine tract-binding protein 1, Npw38