Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPHT2QD)

• DOT Name: Switch-associated protein 70 (SWAP70)
• Synonyms: SWAP-70
• Gene Name: SWAP70
• Related Disease:
  Narcolepsy
  Adult glioblastoma
  Advanced cancer
  Cardiovascular disease
  Glioblastoma multiforme
  High blood pressure
  Ovarian cancer
  Benign prostatic hyperplasia
  Common variable immunodeficiency
  Coronary heart disease
  Hyper-IgM syndrome type 1
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SWP70_HUMAN
• PDB ID: 2DN6
• Pfam ID: PF00169
• Sequence:
  MGSLKEELLKAIWHAFTALDQDHSGKVSKSQLKVLSHNLCTVLKVPHDPVALEEHFRDDD
  EGPVSNQGYMPYLNRFILEKVQDNFDKIEFNRMCWTLCVKKNLTKNPLLITEEDAFKIWV
  IFNFLSEDKYPLIIVSEEIEYLLKKLTEAMGGGWQQEQFEHYKINFDDSKNGLSAWELIE
  LIGNGQFSKGMDRQTVSMAINEVFNELILDVLKQGYMMKKGHRRKNWTERWFVLKPNIIS
  YYVSEDLKDKKGDILLDENCCVESLPDKDGKKCLFLVKCFDKTFEISASDKKKKQEWIQA
  IHSTIHLLKLGSPPPHKEARQRRKELRKKQLAEQEELERQMKELQAANESKQQELEAVRK
  KLEEAASRAAEEEKKRLQTQVELQARFSTELEREKLIRQQMEEQVAQKSSELEQYLQRVR
  ELEDMYLKLQEALEDERQARQDEETVRKLQARLLEEESSKRAELEKWHLEQQQAIQTTEA
  EKQELENQRVLKEQALQEAMEQLEQLELERKQALEQYEEVKKKLEMATNKTKSWKDKVAH
  HEGLIRLIEPGSKNPHLITNWGPAAFTEAELEEREKNWKEKKTTE
• Function: Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion.
• Tissue Specificity: Expressed only in mature B-cells including those associated with mucosa-associated tissue and bronchus-associated tissue . Widely expressed. Abundant in spleen, and fairly abundant in kidney, lung and liver. Also found in monocytes and macrophages .
• Reactome Pathway:
  RAC2 GTPase cycle (R-HSA-9013404)
  RAC3 GTPase cycle (R-HSA-9013423)
  RAC1 GTPase cycle (R-HSA-9013149)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[5]
Benign prostatic hyperplasia	DISI3CW2	moderate	Biomarker	[6]
Common variable immunodeficiency	DISHE7JQ	moderate	Biomarker	[7]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[8]
Hyper-IgM syndrome type 1	DISC91LV	moderate	Biomarker	[7]
Prostate cancer	DISF190Y	moderate	Biomarker	[6]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Switch-associated protein 70 (SWAP70).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Switch-associated protein 70 (SWAP70).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Switch-associated protein 70 (SWAP70).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Switch-associated protein 70 (SWAP70).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Switch-associated protein 70 (SWAP70).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Switch-associated protein 70 (SWAP70).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Switch-associated protein 70 (SWAP70).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Switch-associated protein 70 (SWAP70).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Switch-associated protein 70 (SWAP70).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Switch-associated protein 70 (SWAP70).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Switch-associated protein 70 (SWAP70).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Switch-associated protein 70 (SWAP70).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Switch-associated protein 70 (SWAP70).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Switch-associated protein 70 (SWAP70).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Switch-associated protein 70 (SWAP70).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Switch-associated protein 70 (SWAP70).	[26]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Switch-associated protein 70 (SWAP70).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Switch-associated protein 70 (SWAP70).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Switch-associated protein 70 (SWAP70).	[24]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] SWAP-70 promotes glioblastoma cellular migration and invasion by regulating the expression of CD44s.Cancer Cell Int. 2019 Nov 21;19:305. doi: 10.1186/s12935-019-1035-3. eCollection 2019.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Interethnic analyses of blood pressure loci in populations of East Asian and European descent.Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
• [5] SWAP-70: a new type of oncogene.PLoS One. 2013;8(3):e59245. doi: 10.1371/journal.pone.0059245. Epub 2013 Mar 12.
• [6] SWAP70, actin-binding protein, function as an oncogene targeting tumor-suppressive miR-145 in prostate cancer.Prostate. 2011 Oct 1;71(14):1559-67. doi: 10.1002/pros.21372. Epub 2011 Feb 25.
• [7] Analysis of SWAP-70 as a candidate gene for non-X-linked hyper IgM syndrome and common variable immunodeficiency.Clin Immunol. 2001 Dec;101(3):270-5. doi: 10.1006/clim.2001.5116.
• [8] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [11] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [12] 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.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] 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.
• [16] 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.
• [17] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [18] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [19] 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.
• [20] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [26] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [27] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.