Details of Drug Off-Target (DOT)

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

• DOT Name: Splicing factor 3A subunit 3 (SF3A3)
• Synonyms: SF3a60; Spliceosome-associated protein 61; SAP 61
• Gene Name: SF3A3
• Related Disease:
  HIV infectious disease
  Non-small-cell lung cancer
• UniProt ID: SF3A3_HUMAN
• PDB ID: 2DT7; 5Z56; 5Z57; 5Z58; 6AH0; 6AHD; 6FF7; 6QX9; 6Y50; 6Y53; 6Y5Q; 7ABG; 7ABH; 7ABI; 7EVO; 7ONB; 7Q3L; 7Q4O; 7Q4P; 7QTT; 7VPX; 8CH6; 8HK1
• Pfam ID: PF13297 ; PF16837 ; PF12108 ; PF11931
• Sequence:
  METILEQQRRYHEEKERLMDVMAKEMLTKKSTLRDQINSDHRTRAMQDRYMEVSGNLRDL
  YDDKDGLRKEELNAISGPNEFAEFYNRLKQIKEFHRKHPNEICVPMSVEFEELLKARENP
  SEEAQNLVEFTDEEGYGRYLDLHDCYLKYINLKASEKLDYITYLSIFDQLFDIPKERKNA
  EYKRYLEMLLEYLQDYTDRVKPLQDQNELFGKIQAEFEKKWENGTFPGWPKETSSALTHA
  GAHLDLSAFSSWEELASLGLDRLKSALLALGLKCGGTLEERAQRLFSTKGKSLESLDTSL
  FAKNPKSKGTKRDTERNKDIAFLEAQIYEYVEILGEQRHLTHENVQRKQARTGEEREEEE
  EEQISESESEDEENEIIYNPKNLPLGWDGKPIPYWLYKLHGLNINYNCEICGNYTYRGPK
  AFQRHFAEWRHAHGMRCLGIPNTAHFANVTQIEDAVSLWAKLKLQKASERWQPDTEEEYE
  DSSGNVVNKKTYEDLKRQGLL
• 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, SF3A3 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: Ubiquitous.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
HIV infectious disease	DISO97HC	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Splicing factor 3A subunit 3 (SF3A3) affects the binding of PEITC.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Splicing factor 3A subunit 3 (SF3A3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Splicing factor 3A subunit 3 (SF3A3).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor 3A subunit 3 (SF3A3).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Splicing factor 3A subunit 3 (SF3A3).	[6]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Splicing factor 3A subunit 3 (SF3A3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Splicing factor 3A subunit 3 (SF3A3).	[10]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Splicing factor 3A subunit 3 (SF3A3).	[11]

2 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 increases the methylation of Splicing factor 3A subunit 3 (SF3A3).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Splicing factor 3A subunit 3 (SF3A3).	[9]

References

• [1] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [2] A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.Mol Oncol. 2017 May;11(5):534-551. doi: 10.1002/1878-0261.12052. Epub 2017 Apr 11.
• [3] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [8] 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.
• [9] 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.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [12] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.