Details of Drug Off-Target (DOT)

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

• DOT Name: Plasmalemma vesicle-associated protein (PLVAP)
• Synonyms: Fenestrated endothelial-linked structure protein; Plasmalemma vesicle protein 1; PV-1
• Gene Name: PLVAP
• Related Disease:
  Hepatocellular carcinoma
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Brain neoplasm
  Breast cancer
  Diabetic macular edema
  Diabetic retinopathy
  Diarrhea 10, protein-losing enteropathy type
  Protein-losing enteropathy
  Retinopathy
  Congenital diarrhea 7 with exudative enteropathy
  Kaposi sarcoma
• UniProt ID: PLVAP_HUMAN
• Pfam ID: PF06637
• Sequence:
  MGLAMEHGGSYARAGGSSRGCWYYLRYFFLFVSLIQFLIILGLVLFMVYGNVHVSTESNL
  QATERRAEGLYSQLLGLTASQSNLTKELNFTTRAKDAIMQMWLNARRDLDRINASFRQCQ
  GDRVIYTNNQRYMAAIILSEKQCRDQFKDMNKSCDALLFMLNQKVKTLEVEIAKEKTICT
  KDKESVLLNKRVAEEQLVECVKTRELQHQERQLAKEQLQKVQALCLPLDKDKFEMDLRNL
  WRDSIIPRSLDNLGYNLYHPLGSELASIRRACDHMPSLMSSKVEELARSLRADIERVARE
  NSDLQRQKLEAQQGLRASQEAKQKVEKEAQAREAKLQAECSRQTQLALEEKAVLRKERDN
  LAKELEEKKREAEQLRMELAIRNSALDTCIKTKSQPMMPVSRPMGPVPNPQPIDPASLEE
  FKRKILESQRPPAGIPVAPSSG
• Function: Endothelial cell-specific membrane protein involved in the formation of the diaphragms that bridge endothelial fenestrae. It is also required for the formation of stomata of caveolae and transendothelial channels. Functions in microvascular permeability, endothelial fenestrae contributing to the passage of water and solutes and regulating transcellular versus paracellular flow in different organs. Plays a specific role in embryonic development.
• Tissue Specificity: Expressed in lung, kidney, heart, aorta, placenta, muscle, pituitary gland, adrenals, mammary gland, bladder, lymph node, bone marrow, trachea, digestive tract, liver and tumor-associated endothelium.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Diabetic macular edema	DIS162FN	Strong	Biomarker	[6]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[3]
Diarrhea 10, protein-losing enteropathy type	DISXHSNJ	Strong	Autosomal recessive	[7]
Protein-losing enteropathy	DISM3WQO	Strong	Genetic Variation	[8]
Retinopathy	DISB4B0F	Strong	Altered Expression	[6]
Congenital diarrhea 7 with exudative enteropathy	DISNANDK	Supportive	Autosomal recessive	[8]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Plasmalemma vesicle-associated protein (PLVAP).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Plasmalemma vesicle-associated protein (PLVAP).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Plasmalemma vesicle-associated protein (PLVAP).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Plasmalemma vesicle-associated protein (PLVAP).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Plasmalemma vesicle-associated protein (PLVAP).	[12]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Plasmalemma vesicle-associated protein (PLVAP).	[13]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] Production of a recombinant human T-cell leukemia virus type-I trans-activator (tax1) antigen and its utilization for generation of monoclonal antibodies against various epitopes on the tax1 antigen.Int J Cancer. 1991 Jun 19;48(4):623-30. doi: 10.1002/ijc.2910480423.
• [3] The role of plasmalemma vesicle-associated protein in pathological breakdown of blood-brain and blood-retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema.Fluids Barriers CNS. 2018 Sep 20;15(1):24. doi: 10.1186/s12987-018-0109-2.
• [4] Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain tumor angiogenesis.Clin Cancer Res. 2005 Nov 1;11(21):7643-50. doi: 10.1158/1078-0432.CCR-05-1099.
• [5] A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.Nat Genet. 2010 Oct;42(10):885-92. doi: 10.1038/ng.669. Epub 2010 Sep 19.
• [6] An anti-PLVAP antibody suppresses laser-induced choroidal neovascularization in monkeys.Eur J Pharmacol. 2019 Jul 5;854:240-246. doi: 10.1016/j.ejphar.2019.04.035. Epub 2019 Apr 23.
• [7] Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype. J Med Genet. 2018 Nov;55(11):779-784. doi: 10.1136/jmedgenet-2018-105299. Epub 2018 Jun 6.
• [8] Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy. J Med Genet. 2018 Sep;55(9):637-640. doi: 10.1136/jmedgenet-2018-105262. Epub 2018 Apr 16.
• [9] Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Szary syndrome and Kaposi's sarcoma.Cancer Res. 1992 Aug 15;52(16):4391-5.
• [10] 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.
• [11] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [14] 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.
• [15] 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.