InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Sfpq

Summary

InnateDB Protein

IDBP-189418.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Sfpq

Protein Name

splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated)

Synonyms

1110004P21Rik; 2810416M14Rik; 5730453G22Rik; 9030402K04Rik; AU021830; D4Ertd314e; Gm12940; OTTMUSG00000009329; PSF; REP1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000030623

InnateDB Gene

IDBG-189416 (Sfpq)

Protein Structure

UniProt Annotation

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 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. 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 avtivity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and 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) and inhibits IGF-I-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. {ECO:0000269PubMed:21680841, ECO:0000269PubMed:22966205}.

Subcellular Localization

Nucleus matrix {ECO:0000269PubMed:21680841}. Cytoplasm {ECO:0000250}. Note=Predominantly in nuclear matrix.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 119 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	20 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	119 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0000976	transcription regulatory region sequence-specific DNA binding
GO:0003676	nucleic acid binding
GO:0003723	RNA binding
GO:0005515	protein binding
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000380	alternative mRNA splicing, via spliceosome
GO:0006281	DNA repair
GO:0006351	transcription, DNA-templated
GO:0042754	negative regulation of circadian rhythm
GO:0045892	negative regulation of transcription, DNA-templated
GO:0070932	histone H3 deacetylation