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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
Note:
- originally thought to be myoblast cell surface antigen 24.1D5 & a possible membrane-bound protein ectokinase [3]
General
antigen
nuclear protein
phosphoprotein
RNA-binding protein
Properties
SIZE: entity length = 707 aa
MW = 76 kD
COMPARTMENT: cell nucleus
MOTIF: 3 X 3 AA repeats of R-G-G {9-27}
MOTIF: consensus repeat {9-11}
proline-rich region
SITE: 10-266
MOTIF: proline residue (SEVERAL)
glycine-rich region {10-15}
consensus repeat {19-21}
glycine-rich region {20-27}
consensus repeat {25-27}
Ser phosphorylation site {S33}
proline-rich region
SITE: 56-65
MOTIF: proline residue (SEVERAL)
glutamine-rich region {67-71}
MOTIF: glutamine residue (SEVERAL)
glutamine-rich region {95-98}
MOTIF: glutamine residue (SEVERAL)
proline-rich region
SITE: 99-103
MOTIF: proline residue (SEVERAL)
proline-rich region
SITE: 184-188
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S273}
Ser phosphorylation site {S283}
RNP motif
NAME: RNP motif
SITE: 297-369
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
RNP motif
NAME: RNP motif
SITE: 371-452
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
arginine-rich region {571-574}
MOTIF: arginine residue (SEVERAL)
glycine-rich region {613-616}
glycine-rich region {635-641}
breakpoint {662-663}
Thr phosphorylation site {T687}
Database Correlations
OMIM 605199
UniProt P23246
PFAM correlations
Entrez Gene 6421
Kegg hsa:6421
References
- UniProt :accession P23246
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/PSFID167.html
- 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: 2480877