Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7H3ETA)

• DOT Name: Splicing factor, suppressor of white-apricot homolog (SFSWAP)
• Synonyms: Splicing factor, arginine/serine-rich 8; Suppressor of white apricot protein homolog
• Gene Name: SFSWAP
• Related Disease:
  Autism spectrum disorder
  Depression
  Late-onset Parkinson disease
  Schizophrenia
  Asthma
• UniProt ID: SFSWA_HUMAN
• PDB ID: 2E5Z; 2E60
• Pfam ID: PF09750 ; PF01805
• Sequence:
  MYGASGGRAKPERKSGAKEEAGPGGAGGGGSRVELLVFGYACKLFRDDERALAQEQGQHL
  IPWMGDHKILIDRYDGRGHLHDLSEYDAEYSTWNRDYQLSEEEARIEALCDEERYLALHT
  DLLEEEARQEEEYKRLSEALAEDGSYNAVGFTYGSDYYDPSEPTEEEEPSKQREKNEAEN
  LEENEEPFVAPLGLSVPSDVELPPTAKMHAIIERTASFVCRQGAQFEIMLKAKQARNSQF
  DFLRFDHYLNPYYKFIQKAMKEGRYTVLAENKSDEKKKSGVSSDNEDDDDEEDGNYLHPS
  LFASKKCNRLEELMKPLKVVDPDHPLAALVRKAQADSSTPTPHNADGAPVQPSQVEYTAD
  STVAAMYYSYYMLPDGTYCLAPPPPGIDVTTYYSTLPAGVTVSNSPGVTTTAPPPPGTTP
  LPPPTTAETSSGATSTTTTTSALAPVAAIIPPPPDVQPVIDKLAEYVARNGLKFETSVRA
  KNDQRFEFLQPWHQYNAYYEFKKQFFLQKEGGDSMQAVSAPEEAPTDSAPEKPSDAGEDG
  APEDAAEVGARAGSGGKKEASSSKTVPDGKLVKASFAPISFAIKAKENDLLPLEKNRVKL
  DDDSDDDEESKEGQESSSSAANTNPAVAPPCVVVEEKKPQLTQEELEAKQAKQKLEDRLA
  AAAREKLAQASKESKEKQLQAERKRKAALFLQTLKNPLPEAEAGKIEESPFSVEESSTTP
  CPLLTGGRPLPTLEVKPPDRPSSKSKDPPREEEKEKKKKKHKKRSRTRSRSPKYHSSSKS
  RSRSHSKAKHSLPSAYRTVRRSRSRSRSPRRRAHSPERRREERSVPTAYRVSRSPGASRK
  RTRSRSPHEKKKKRRSRSRTKSKARSQSVSPSKQAAPRPAAPAAHSAHSASVSPVESRGS
  SQERSRGVSQEKEAQISSAIVSSVQSKITQDLMAKVRAMLAASKNLQTSAS
• Function: Plays a role as an alternative splicing regulator. Regulate its own expression at the level of RNA processing. Also regulates the splicing of fibronectin and CD45 genes. May act, at least in part, by interaction with other R/S-containing splicing factors. Represses the splicing of MAPT/Tau exon 10.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Asthma	DISW9QNS	Limited	Genetic Variation	[5]

6 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, suppressor of white-apricot homolog (SFSWAP).	[6]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Splicing factor, suppressor of white-apricot homolog (SFSWAP).	[12]

References

• [1] Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders.J Physiol Pharmacol. 2014 Apr;65(2):257-72.
• [2] Personality Factors and Depressive Configurations. An Exploratory Study in an Italian Clinical Sample.Front Psychol. 2017 Mar 3;8:251. doi: 10.3389/fpsyg.2017.00251. eCollection 2017.
• [3] Personality and Personality Disorders in Medication-Overuse Headache: A Controlled Study by SWAP-200.Pain Res Manag. 2019 Jun 12;2019:1874078. doi: 10.1155/2019/1874078. eCollection 2019.
• [4] Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings.BMC Psychiatry. 2013 Oct 4;13:245. doi: 10.1186/1471-244X-13-245.
• [5] Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene.Thorax. 2006 Oct;61(10):874-9. doi: 10.1136/thx.2005.055475. Epub 2006 May 31.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.