Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI733D7)

• DOT Name: Splicing factor 3A subunit 1 (SF3A1)
• Synonyms: SF3a120; Spliceosome-associated protein 114; SAP 114
• Gene Name: SF3A1
• Related Disease:
  Acute myelogenous leukaemia
  Myelodysplastic syndrome
  Breast neoplasm
  Advanced cancer
  Pancreatic cancer
• UniProt ID: SF3A1_HUMAN
• PDB ID: 1ZKH; 2DT6; 2DT7; 5Z56; 5Z57; 5Z58; 6AH0; 6AHD; 6FF7; 6QX9; 6Y53; 6Y5Q; 7ABG; 7ABI; 7EVO; 7P08; 7P0V; 7VH9; 7VPX; 8CH6; 8HK1; 8ID2
• Pfam ID: PF12230 ; PF01805 ; PF00240
• Sequence:
  MPAGPVQAVPPPPPVPTEPKQPTEEEASSKEDSAPSKPVVGIIYPPPEVRNIVDKTASFV
  ARNGPEFEARIRQNEINNPKFNFLNPNDPYHAYYRHKVSEFKEGKAQEPSAAIPKVMQQQ
  QQTTQQQLPQKVQAQVIQETIVPKEPPPEFEFIADPPSISAFDLDVVKLTAQFVARNGRQ
  FLTQLMQKEQRNYQFDFLRPQHSLFNYFTKLVEQYTKILIPPKGLFSKLKKEAENPREVL
  DQVCYRVEWAKFQERERKKEEEEKEKERVAYAQIDWHDFVVVETVDFQPNEQGNFPPPTT
  PEELGARILIQERYEKFGESEEVEMEVESDEEDDKQEKAEEPPSQLDQDTQVQDMDEGSD
  DEEEGQKVPPPPETPMPPPLPPTPDQVIVRKDYDPKASKPLPPAPAPDEYLVSPITGEKI
  PASKMQEHMRIGLLDPRWLEQRDRSIREKQSDDEVYAPGLDIESSLKQLAERRTDIFGVE
  ETAIGKKIGEEEIQKPEEKVTWDGHSGSMARTQQAAQANITLQEQIEAIHKAKGLVPEDD
  TKEKIGPSKPNEIPQQPPPPSSATNIPSSAPPITSVPRPPTMPPPVRTTVVSAVPVMPRP
  PMASVVRLPPGSVIAPMPPIIHAPRINVVPMPPSAPPIMAPRPPPMIVPTAFVPAPPVAP
  VPAPAPMPPVHPPPPMEDEPTSKKLKTEDSLMPEEEFLRRNKGPVSIKVQVPNMQDKTEW
  KLNGQVLVFTLPLTDQVSVIKVKIHEATGMPAGKQKLQYEGIFIKDSNSLAYYNMANGAV
  IHLALKERGGRKK
• Function: Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing. Within the 17S U2 SnRNP complex, SF3A1 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex. Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Splicing factor 3A subunit 1 (SF3A1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Splicing factor 3A subunit 1 (SF3A1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Splicing factor 3A subunit 1 (SF3A1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Splicing factor 3A subunit 1 (SF3A1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor 3A subunit 1 (SF3A1).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Splicing factor 3A subunit 1 (SF3A1).	[9]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Splicing factor 3A subunit 1 (SF3A1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Splicing factor 3A subunit 1 (SF3A1).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Splicing factor 3A subunit 1 (SF3A1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Splicing factor 3A subunit 1 (SF3A1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Splicing factor 3A subunit 1 (SF3A1).	[12]

References

• [1] The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome.Mol Cancer Res. 2013 Aug;11(8):815-27. doi: 10.1158/1541-7786.MCR-12-0695. Epub 2013 May 3.
• [2] Statistical modeling for selecting housekeeper genes.Genome Biol. 2004;5(8):R59. doi: 10.1186/gb-2004-5-8-r59. Epub 2004 Jul 29.
• [3] SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer.Oncotarget. 2015 Nov 10;6(35):37750-7. doi: 10.18632/oncotarget.5647.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] 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.
• [12] 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.
• [13] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.