SFPQ

Description

The SFPQ (splicing factor proline and glutamine rich) is a protein-coding gene located on chromosome 1.

Splicing factor, proline- and glutamine-rich is a protein that in humans is encoded by the SFPQ gene.

SFPQ is a DNA- and RNA binding protein involved in various nuclear processes. It is a crucial pre-mRNA splicing factor essential for early spliceosome formation and splicing catalytic step II, likely as a heteromer with NONO. SFPQ binds to pre-mRNA within the spliceosome C complex and specifically binds to intronic polypyrimidine tracts. It plays a role in regulating signal-induced alternative splicing. In resting T-cells, a phosphorylated form of SFPQ is sequestered by THRAP3 from pre-mRNA. Upon T-cell activation and subsequent dephosphorylation, SFPQ is released from THRAP3, allowing it to bind to pre-mRNA splicing regulatory elements and repress exon inclusion. SFPQ interacts with U5 snRNA, potentially through binding to a purine-rich sequence on the 3' side of U5 snRNA stem 1b. It may be involved in a pre-mRNA coupled splicing and polyadenylation process as part of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer, associated with MATR3, may contribute to nuclear retention of defective RNAs. SFPQ might participate in homologous DNA pairing. In vitro, it promotes ssDNA invasion between duplex DNA, resulting in D-loop formation. The SFPQ-NONO heteromer could be involved in DNA unwinding by modulating topoisomerase I/TOP1 function. In vitro, it stimulates TOP1 dissociation from DNA after cleavage and enhances TOP1 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), essential for double-strand break repair and V(D)J recombination. It potentially stabilizes paired DNA ends. In vitro, the complex significantly enhances DNA end joining, directly binds to DNA substrates, and collaborates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to form a functional preligation complex. SFPQ participates in transcriptional regulation. It functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is achieved through SFPQ interaction 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, such as RXRA and likely THRA, acting as a transcriptional corepressor in the absence of hormone ligands. It binds the DNA sequence 5'-CTGAGTC-3' within the insulin-like growth factor response element (IGFRE) and inhibits IGF-I-stimulated transcriptional activity. SFPQ regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. It is necessary for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). SFPQ is required for the assembly of nuclear speckles (PubMed:25765647). It plays a role in regulating DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that acts as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). SFPQ forms a heterodimer with NONO (PubMed:25765647). {ECO:0000250|UniProtKB:Q8VIJ6, ECO:0000269|PubMed:10847580, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:10931916, ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:25765647, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:8045264, ECO:0000269|PubMed:8449401}

SFPQ is also known as POMP100, PPP1R140, PSF.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing