Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLCIAPJ)

• DOT Name: Splicing factor, proline- and glutamine-rich (SFPQ)
• Synonyms: 100 kDa DNA-pairing protein; hPOMp100; DNA-binding p52/p100 complex, 100 kDa subunit; Polypyrimidine tract-binding protein-associated-splicing factor; PSF; PTB-associated-splicing factor
• Gene Name: SFPQ
• Related Disease:
  Acne vulgaris
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Androgen insensitivity syndrome
  Bacterial meningitis
  Breast neoplasm
  Cerebral palsy
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Dementia
  Dermatomyositis
  Epithelial neoplasm
  Hepatocellular carcinoma
  HIV infectious disease
  Kidney cancer
  Kidney neoplasm
  Neoplasm
  Neoplasm with perivascular epithelioid cell differentiation
  Neuroblastoma
  Obesity
  Papillary renal cell carcinoma
  Pick disease
  Pituitary gland disorder
  Renal carcinoma
  Renal cell carcinoma
  Skin disease
  Stroke
  Triple negative breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Frontotemporal dementia
  Liver cancer
  Aplasia cutis congenita
  Castration-resistant prostate carcinoma
  Corpus callosum, agenesis of
  Hepatitis
  Melanoma
  Tauopathy
• UniProt ID: SFPQ_HUMAN
• PDB ID: 4WII; 4WIJ; 4WIK; 5WPA; 6NCQ; 6OWJ; 6WMZ; 7LRQ; 7LRU; 7PU5; 7SP0; 7UJ1; 7UK1
• Pfam ID: PF08075 ; PF00076
• Sequence:
  MSRDRFRSRGGGGGGFHRRGGGGGRGGLHDFRSPPPGMGLNQNRGPMGPGPGQSGPKPPI
  PPPPPHQQQQQPPPQQPPPQQPPPHQPPPHPQPHQQQQPPPPPQDSSKPVVAQGPGPAPG
  VGSAPPASSSAPPATPPTSGAPPGSGPGPTPTPPPAVTSAPPGAPPPTPPSSGVPTTPPQ
  AGGPPPPPAAVPGPGPGPKQGPGPGGPKGGKMPGGPKPGGGPGLSTPGGHPKPPHRGGGE
  PRGGRQHHPPYHQQHHQGPPPGGPGGRSEEKISDSEGFKANLSLLRRPGEKTYTQRCRLF
  VGNLPADITEDEFKRLFAKYGEPGEVFINKGKGFGFIKLESRALAEIAKAELDDTPMRGR
  QLRVRFATHAAALSVRNLSPYVSNELLEEAFSQFGPIERAVVIVDDRGRSTGKGIVEFAS
  KPAARKAFERCSEGVFLLTTTPRPVIVEPLEQLDDEDGLPEKLAQKNPMYQKERETPPRF
  AQHGTFEYEYSQRWKSLDEMEKQQREQVEKNMKDAKDKLESEMEDAYHEHQANLLRQDLM
  RRQEELRRMEELHNQEMQKRKEMQLRQEEERRRREEEMMIRQREMEEQMRRQREESYSRM
  GYMDPRERDMRMGGGGAMNMGDPYGSGGQKFPPLGGGGGIGYEANPGVPPATMSGSMMGS
  DMRTERFGQGGAGPVGGQGPRGMGPGTPAGYGRGREEYEGPNKKPRF
• 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 binds DNA. 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 a transcriptional activator. 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 a 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-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Required for the assembly of nuclear speckles. 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.
• Reactome Pathway:
  Suppression of apoptosis (R-HSA-9635465)
  PTK6 Regulates Proteins Involved in RNA Processing (R-HSA-8849468)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[5]
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[6]
Bacterial meningitis	DISRP9SL	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cerebral palsy	DIS82ODL	Strong	Altered Expression	[9]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Dementia	DISXL1WY	Strong	Biomarker	[14]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[15]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
HIV infectious disease	DISO97HC	Strong	Biomarker	[17]
Kidney cancer	DISBIPKM	Strong	Genetic Variation	[18]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[20]
Neoplasm with perivascular epithelioid cell differentiation	DIS8V0NT	Strong	Biomarker	[21]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Altered Expression	[22]
Papillary renal cell carcinoma	DIS25HBV	Strong	Genetic Variation	[23]
Pick disease	DISP6X50	Strong	Biomarker	[24]
Pituitary gland disorder	DIS7XB48	Strong	Altered Expression	[25]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[26]
Skin disease	DISDW8R6	Strong	Biomarker	[27]
Stroke	DISX6UHX	Strong	Biomarker	[28]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[29]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[16]
Frontotemporal dementia	DISKYHXL	moderate	Biomarker	[24]
Liver cancer	DISDE4BI	moderate	Biomarker	[16]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[30]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[31]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[30]
Hepatitis	DISXXX35	Limited	Biomarker	[32]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[33]
Tauopathy	DISY2IPA	Limited	Biomarker	[34]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Splicing factor, proline- and glutamine-rich (SFPQ).	[35]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[42]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[44]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[45]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[41]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[46]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[47]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[37]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[49]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[50]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[49]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[51]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[54]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[55]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Splicing factor, proline- and glutamine-rich (SFPQ).	[56]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Splicing factor, proline- and glutamine-rich (SFPQ).	[48]

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