splicing factor, proline- & glutamine-rich; polypyrimidine tract-binding protein-associated-splicing factor; PTB-associated-splicing factor; PSF; DNA-binding p52/p100 complex, 100 kD subunit; 100 kD DNA-pairing protein; hPOMp100 (SFPQ, PSF)

Function

• DNA-binding protein & RNA binding protein
• involved in several nuclear processes
• essential pre-mRNA splicing factor required early in spliceosome formation & for splicing catalytic step 2, probably as an heteromer with NONO
• binds to pre-mRNA in spliceosome C complex
• specifically binds to intronic polypyrimidine tracts
• 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 & polyadenylation process as component of a snRNP-free complex with SNRPA/U1A
• 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 invasion of ssDNA between a duplex DNA & produces a D-loop formation
• 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 & enhances its jumping between separate DNA helices
• SFPQ-NONO heteromer may be involved in DNA nonhomologous end joining (NHEJ) required for double-strand break repair & V(D)J recombination & may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates & cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex
• SFPQ is involved in transcriptional regulation
• transcriptional repression is probably mediated by an interaction of SFPQ with SIN3A & subsequent recruitment of histone deacetylases (HDACs)
• SFPQ-NONO/SF-1 complex binds to the CYP17 promoter & regulates basal & cAMP-dependent transcriptional activity
• SFPQ isoform long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA & probably THRA, & acts as transcriptional corepressor in absence of hormone ligands
• binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) & inhibits IGF1-stimulated transcriptional activity
• phosphorylated on multiple Ser & Thr during apoptosis
• in vitro phosphorylated by PKC
• phosphorylation stimulates binding to DNA & D-loop formation, but inhibits binding to RNA
• interacts with PSPC1 (putative)
• monomer & component of the SFPQ-NONO complex, which is probably a heterotetramer of two 52 kD (NONO) & two 100 kD (SFPQ) subunits
• SFPQ is a component of spliceosome & U5.4/6 snRNP complexes
• interacts with SNRPA/U1A
• component of a snRNP-free complex with SNRPA/U1A
• part of complex consisting of SFPQ, NONO & MATR3
• interacts with polypyrimidine tract-binding protein 1/PTB
• part of a complex consisting of SFPQ, NONO & NR5A1/SF-1
• interacts with RXRA, probably THRA, & SIN3A
• interacts with TOP1
• part of a complex consisting of SFPQ, NONO & TOP1
• interacts with SNRNP70 in apoptotic cells (putative)
• interacts with RNF43

Structure

• the N-terminus is blocked
• Arg-7, Arg-9, Arg-19 & Arg-25 are dimethylated, probably to asymmetric dimethylarginine
• contains 2 RRM domains (RNA recognition motif)

Compartment

predominantly in nuclear matrix

Alternative splicing

named isoforms=2 additional isoforms seem to exist

Pathology

• chromosomal translocation t(X;1)(p11.2;p34) involving SFPQ with TFE3 may be a cause of papillary renal cell carcinoma

Notes

• originally thought to be myoblast cell surface antigen 24.1D5 & a possible membrane-bound protein ectokinase

More general terms

• nuclear protein
• RNA-binding protein
• phosphoprotein
• antigen

Component of

• spliceosome

Database

• UniProt: http://www.uniprot.org/uniprot/P23246.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6421
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6421
• OMIM: https://mirror.omim.org/entry/605199