Tbio SFPQ Splicing factor, proline- and glutamine-rich

Protein Summary

Description

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 binds DNA (PubMed:25765647). 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. Functions as transcriptional activator (PubMed:25765647). 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 activity. 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 (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728).

Uniprot Accession IDs

• P23246
• P30808
• Q5SZ71

Gene Name

• SFPQ

Ensembl ID

• ENST00000357214
• ENSP00000349748
• ENSG00000116560

Symbol

• PSF
• PSF
• POMP100
• PPP1R140

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
interacting protein	1
disease perturbation	0.99
kinase perturbation	0.97
transcription factor binding site profile	0.94

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Mrna Processing Factor / Mrna Splicing Factor / Splicing Factor, Proline- And Glutamine-rich

DTO Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Mrna Processing Factor / Mrna Splicing Factor / Splicing Factor, Proline- And Glutamine-rich

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 86.28   (req: < 5)

Gene RIFs: 54   (req: <= 3)

Antibodies: 288   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 86.28   (req: >= 5)

Gene RIFs: 54   (req: > 3)

Antibodies: 288   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (229)

Explore Interacting Targets

1 – 10 of 229

• See Interactions on String-DB

RBMXL1

Tdark

Novelty:  0.81422952

p_int:  0.999987701

p_ni:  0.000012299

Score:  0.549

Data Source:  BioPlex,STRINGDB

PSPC1

Tbio

Novelty:  0.01002246

p_int:  0.999976162

p_ni:  0.000023838

Score:  0.991

Data Source:  BioPlex,STRINGDB

NONO

Tbio

Novelty:  0.00501502

p_int:  0.999931729

p_ni:  0.000068271

Score:  0.999

Data Source:  BioPlex,STRINGDB

DIDO1

Tbio

Family:  Epigenetic

Novelty:  0.0492858

p_int:  0.999931434

p_ni:  0.000068566

Score:  0.421

Data Source:  BioPlex,STRINGDB

MMADHC

Tbio

Novelty:  0.02299238

p_int:  0.999918674

p_ni:  0.000081325

p_wrong:  1e-9

Data Source:  BioPlex

PRRC2A

Tbio

Novelty:  0.01493149

p_int:  0.99983284

p_ni:  0.000167151

p_wrong:  9e-9

Score:  0.161

Data Source:  BioPlex,STRINGDB

EWSR1

Tbio

Novelty:  0.00068411

p_int:  0.998663764

p_ni:  0.001336236

Score:  0.61

Data Source:  BioPlex,STRINGDB

LSM14A

Tbio

Novelty:  0.04728617

p_int:  0.993864477

p_ni:  0.006135523

Score:  0.244

Data Source:  BioPlex,STRINGDB

FAM98A

Tdark

Novelty:  0.30067413

p_int:  0.988658485

p_ni:  0.011341515

Score:  0.259

Data Source:  BioPlex,STRINGDB

DHPS

Tchem

Family:  Enzyme

Novelty:  0.00776893

p_int:  0.985136351

p_ni:  0.014862906

p_wrong:  7.43e-7

Score:  0.185

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (8)

Reactome (4)

PathwayCommons (1)

WikiPathways (3)

PTK6 Regulates Proteins Involved in RNA Processing (R-HSA-8849468)

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5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	PTK6 Regulates Proteins Involved in RNA Processing	5 targets	R-HSA-8849468
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by Non-Receptor Tyrosine Kinases	54 targets	R-HSA-9006927
Reactome	Signaling by PTK6	54 targets	R-HSA-8848021

Name	Explore in Pharos	Explore in Source
PTK6 Regulates Proteins Involved in RNA Processing	5 targets	R-HSA-8849468
Signal Transduction	2704 targets	R-HSA-162582
Signaling by Non-Receptor Tyrosine Kinases	54 targets	R-HSA-9006927
Signaling by PTK6	54 targets	R-HSA-8848021

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (34)

Functions (10)

Components (8)

Processes (16)

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10

1 – 10 of 10

GO Term	Evidence	Assigned by
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
histone deacetylase binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
chromatin binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
E-box binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
RNA polymerase II distal enhancer sequence-specific DNA binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
transcription regulatory region sequence-specific DNA binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB

Disease Associations (null)

No disease associations found

GWAS Traits (3)

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1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cigarettes per day measurement	EFO_0006525	1	1	1		6.7
monocyte percentage of leukocytes	EFO_0007989	1	1	1		5.9
allergy	EFO_0003785	1	1	0	1.1	1.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cigarettes per day measurement	EFO_0006525	1		6.7
monocyte percentage of leukocytes	EFO_0007989	1		5.9
allergy	EFO_0003785	0	1.1	1.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Alternative splicing
Biological rhythms
Chromosomal rearrangement
Coiled coil
Complete proteome
Cytoplasm
Direct protein sequencing

GWAS Trait Find Similar Targets

No Header	No Header
allergy
cigarettes per day measurement
monocyte percentage of leukocytes

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	splicing factor proline and glutamine rich	VGNC:9516	469274
Macaque	splicing factor proline and glutamine rich		712439
Mouse	splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated)	MGI:1918764	71514
Rat	splicing factor proline and glutamine rich	RGD:727923	252855
Dog	splicing factor proline and glutamine rich		100688260

Species	Name	OMA	EggNOG	Inparanoid
Chimp	splicing factor proline and glutamine rich
Macaque	splicing factor proline and glutamine rich
Mouse	splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated)
Rat	splicing factor proline and glutamine rich
Dog	splicing factor proline and glutamine rich

Publication Statistics

PubMed Score 86.28

PubMed score by year

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PubTator Score 119.83

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Related Publications

Text Mined References (103)

GeneRif Annotations (54)

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PMID	Year	Title