SFPQ
GeneName
SFPQ
Summary
SFPQ, also known as PSF or PTB associated splicing factor, is a 76 kDa nuclear protein that plays a crucial role in RNA processing and transcription regulation. It is predominantly localised in the nucleus, particularly within structures such as nuclear speckles and paraspeckles, and is involved in various cellular processes including chromatin remodelling, mRNA splicing, and the regulation of gene expression. SFPQ binds to chromatin and RNA, facilitating the assembly of ribonucleoprotein complexes and participating in the organisation of chromosomes. Additionally, it is implicated in the activation of the innate immune response and the repair of double-strand breaks via homologous recombination.
Importance
SFPQ is relevant to: - The regulation of gene expression and mRNA processing, which are fundamental for cellular function and response to stimuli - The modulation of innate immune responses, influencing how cells react to infections - The maintenance of genome integrity through its role in double-strand break repair - The regulation of circadian rhythms, highlighting its potential impact on metabolic and physiological processes - The study of neurobiology, particularly in the context of dendritic transport and RNA metabolism in neurons
Top Products
For researchers investigating SFPQ, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-SFPQ antibody (ab38148), which has garnered 33 citations and is highly effective in Western blotting (WB), immunocytochemistry (ICC), and immunohistochemistry (IHC). This product is a trusted choice for those looking to study SFPQ in various applications. Additionally, we offer the recombinant antibody, Anti-SFPQ antibody [EPR11847] (ab177149). This monoclonal antibody has been validated for use in WB, ICC, IHC, and flow cytometry (FC), making it a versatile option for researchers who require consistent performance across multiple techniques. With 25 citations, it is also gaining recognition in the scientific community. Together, these antibodies provide robust tools for studying SFPQ effectively.
Abcam Product Citation Summary
The data indicates that the SFPQ antibody (ab38148) has been extensively used in various applications, including western blotting, immunoprecipitation, and immunocytochemistry, across different species such as mouse, domestic pig, and human. The studies primarily focus on the interactions and mislocalization of TDP-43, particularly in the context of ALS and related neurological conditions.
Abcam Product Citation Table
Domain
The coiled coil domain mediates interaction with NONO, and can also mediate formation of long, linear homooligomers (in vitro). The coiled coil domain is required for optimal DNA binding, and optimal transcription activation.
Function
DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as a transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF1-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728).
Involvement in disease
A chromosomal aberration involving SFPQ may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;1)(p11.2;p34) with TFE3.
Post-translational modifications
The N-terminus is blocked.
Phosphorylated on multiple serine and threonine residues during apoptosis. In vitro phosphorylated by PKC. Phosphorylation stimulates binding to DNA and D-loop formation, but inhibits binding to RNA. Phosphorylation of C-terminal tyrosines promotes its cytoplasmic localization, impaired its binding to polypyrimidine RNA and led to cell cycle arrest. In resting T-cells is phosphorylated at Thr-687 by GSK3B which is proposed to promote association with THRAP and to prevent binding to PTPRC/CD45 pre-mRNA; T-cell activation leads to reduced phosphorylation at Thr-687.
Cellular localization
- Nucleus speckle
- Nucleus matrix
- Cytoplasm
- Predominantly in nuclear matrix.
Alternative names
PSF, SFPQ, 100 kDa DNA-pairing protein, Polypyrimidine tract-binding protein-associated-splicing factor, hPOMp100, PTB-associated-splicing factor