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)
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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[3]
More general terms
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P23246.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/PSFID167.html
- ↑ 3.0 3.1 Gower HJ et al Cloning and characterization of a myoblast cell surface antigen defined by 24.1D5 monoclonal antibody. Development. 1989 Apr;105(4):723-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2480877