Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWZO0DW)

• DOT Name: WAS/WASL-interacting protein family member 1
• Synonyms: Protein PRPL-2; Wiskott-Aldrich syndrome protein-interacting protein; WASP-interacting protein
• Gene Name: WIPF1
• Related Disease:
  Wiskott-Aldrich syndrome 2
  Wiskott-Aldrich syndrome
• UniProt ID: WIPF1_HUMAN
• PDB ID: 2A41
• Pfam ID: PF02205
• Sequence:
  MPVPPPPAPPPPPTFALANTEKPTLNKTEQAGRNALLSDISKGKKLKKTVTNDRSAPILD
  KPKGAGAGGGGGGFGGGGGFGGGGGGGGGGSFGGGGPPGLGGLFQAGMPKLRSTANRDND
  SGGSRPPLLPPGGRSTSAKPFSPPSGPGRFPVPSPGHRSGPPEPQRNRMPPPRPDVGSKP
  DSIPPPVPSTPRPIQSSPHNRGSPPVPGGPRQPSPGPTPPPFPGNRGTALGGGSIRQSPL
  SSSSPFSNRPPLPPTPSRALDDKPPPPPPPVGNRPSIHREAVPPPPPQNNKPPVPSTPRP
  SASSQAPPPPPPPSRPGPPPLPPSSSGNDETPRLPQRNLSLSSSTPPLPSPGRSGPLPPP
  PSERPPPPVRDPPGRSGPLPPPPPVSRNGSTSRALPATPQLPSRSGVDSPRSGPRPPLPP
  DRPSAGAPPPPPPSTSIRNGFQDSPCEDEWESRFYFHPISDLPPPEPYVQTTKSYPSKLA
  RNESRSGSNRRERGAPPLPPIPR
• Function: Plays a role in the reorganization of the actin cytoskeleton. Contributes with NCK1 and GRB2 in the recruitment and activation of WASL. May participate in regulating the subcellular localization of WASL, resulting in the disassembly of stress fibers in favor of filopodia formation. Plays a role in the formation of cell ruffles. Plays an important role in the intracellular motility of vaccinia virus by functioning as an adapter for recruiting WASL to vaccinia virus.
• Tissue Specificity: Highly expressed in peripheral blood mononuclear cells, spleen, placenta, small intestine, colon and thymus. Lower expression in ovary, heart, brain, lung, liver, skeletal muscle, kidney, pancreas, prostate and testis.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Pathogenic Escherichia coli infection (hsa05130)
  Yersinia infection (hsa05135)
• Reactome Pathway:
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Wiskott-Aldrich syndrome 2	DIS3SZFH	Definitive	Autosomal recessive	[1]
Wiskott-Aldrich syndrome	DISATMDB	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of WAS/WASL-interacting protein family member 1.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of WAS/WASL-interacting protein family member 1.	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of WAS/WASL-interacting protein family member 1.	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of WAS/WASL-interacting protein family member 1.	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of WAS/WASL-interacting protein family member 1.	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of WAS/WASL-interacting protein family member 1.	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of WAS/WASL-interacting protein family member 1.	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of WAS/WASL-interacting protein family member 1.	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of WAS/WASL-interacting protein family member 1.	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of WAS/WASL-interacting protein family member 1.	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of WAS/WASL-interacting protein family member 1.	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of WAS/WASL-interacting protein family member 1.	[15]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of WAS/WASL-interacting protein family member 1.	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of WAS/WASL-interacting protein family member 1.	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of WAS/WASL-interacting protein family member 1.	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of WAS/WASL-interacting protein family member 1.	[20]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of WAS/WASL-interacting protein family member 1.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of WAS/WASL-interacting protein family member 1.	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of WAS/WASL-interacting protein family member 1.	[17]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J Exp Med. 2012 Jan 16;209(1):29-34. doi: 10.1084/jem.20110896. Epub 2012 Jan 9.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [14] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [17] 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.
• [18] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [21] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.