Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWA6M5K)

• DOT Name: PDZK1-interacting protein 1 (PDZK1IP1)
• Synonyms: 17 kDa membrane-associated protein; Protein DD96
• Gene Name: PDZK1IP1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Adenocarcinoma
  Adenoma
  Atopic dermatitis
  Atrial fibrillation
  Breast neoplasm
  Intrahepatic cholangiocarcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Mantle cell lymphoma
  Neoplasm
  Ovarian cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate neoplasm
  Psoriasis
  Rectal neoplasm
  Skin disease
  Advanced cancer
  Colon adenoma
  Ductal breast carcinoma in situ
  Hepatocellular carcinoma
  Precancerous condition
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Carcinoma
  Dental caries
  Mesothelioma
  Ulcerative colitis
• UniProt ID: PDZ1I_HUMAN
• PDB ID: 7VSI; 7WMV; 7YNI; 7YNJ; 7YNK; 8HB0; 8HDH; 8HEZ; 8HG7; 8HIN
• Pfam ID: PF15807
• Sequence:
  MSALSLLILGLLTAVPPASCQQGLGNLQPWMQGLIAVAVFLVLVAIAFAVNHFWCQEEPE
  PAHMILTVGNKADGVLVGTDGRYSSMAASFRSSEHENAYENVPEEEGKVRSTPM
• Function: May play an important role in tumor biology.
• Tissue Specificity: Expressed at significant levels only in a single epithelial cell population, the proximal tubular epithelial cells of the kidney. Diffusely expressed in various carcinomas originating from kidney, colon, lung and breast.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[4]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Altered Expression	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Lung neoplasm	DISVARNB	Strong	Biomarker	[2]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[12]
Psoriasis	DIS59VMN	Strong	Altered Expression	[13]
Rectal neoplasm	DISB4UZ0	Strong	Biomarker	[14]
Skin disease	DISDW8R6	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[8]
Colon adenoma	DISPMZ3U	moderate	Altered Expression	[15]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[16]
Precancerous condition	DISV06FL	moderate	Altered Expression	[15]
Thyroid cancer	DIS3VLDH	moderate	Altered Expression	[17]
Thyroid gland carcinoma	DISMNGZ0	moderate	Altered Expression	[18]
Thyroid tumor	DISLVKMD	moderate	Altered Expression	[17]
Carcinoma	DISH9F1N	Limited	Altered Expression	[14]
Dental caries	DISRBCMD	Limited	Genetic Variation	[19]
Mesothelioma	DISKWK9M	Limited	Genetic Variation	[20]
Ulcerative colitis	DIS8K27O	Limited	Altered Expression	[21]

16 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 PDZK1-interacting protein 1 (PDZK1IP1).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[28]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[28]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[29]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[30]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[31]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[33]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[35]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of PDZK1-interacting protein 1 (PDZK1IP1).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of PDZK1-interacting protein 1 (PDZK1IP1).	[34]

References

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• [2] MAP17 predicts sensitivity to platinum-based therapy, EGFR inhibitors and the proteasome inhibitor bortezomib in lung adenocarcinoma.J Exp Clin Cancer Res. 2018 Aug 17;37(1):195. doi: 10.1186/s13046-018-0871-7.
• [3] Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.Am J Surg Pathol. 2006 Dec;30(12):1491-501. doi: 10.1097/01.pas.0000213313.36306.85.
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• [7] Overexpression of PDZK1IP1, EEF1A2 and RPL41 genes in intrahepatic cholangiocarcinoma.Mol Med Rep. 2016 Jun;13(6):4786-90. doi: 10.3892/mmr.2016.5110. Epub 2016 Apr 12.
• [8] EGFR-TKI resistance and MAP17 are associated with cancer stem cell like properties.Oncol Lett. 2018 May;15(5):6655-6665. doi: 10.3892/ol.2018.8129. Epub 2018 Feb 27.
• [9] MAP17 (PDZKIP1) Expression Determines Sensitivity to the Proteasomal Inhibitor Bortezomib by Preventing Cytoprotective Autophagy and NFB Activation in Breast Cancer.Mol Cancer Ther. 2015 Jun;14(6):1454-65. doi: 10.1158/1535-7163.MCT-14-1053. Epub 2015 Apr 2.
• [10] PDZK1-interacting protein 1 (PDZK1IP1) traps Smad4 protein and suppresses transforming growth factor- (TGF-) signaling.J Biol Chem. 2019 Mar 29;294(13):4966-4980. doi: 10.1074/jbc.RA118.004153. Epub 2019 Feb 4.
• [11] MAP17 overexpression is a common characteristic of carcinomas.Carcinogenesis. 2007 Aug;28(8):1646-52. doi: 10.1093/carcin/bgm083. Epub 2007 Apr 9.
• [12] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [13] The cargo protein MAP17 (PDZK1IP1) regulates the immune microenvironment.Oncotarget. 2017 Oct 6;8(58):98580-98597. doi: 10.18632/oncotarget.21651. eCollection 2017 Nov 17.
• [14] MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy.Oncotarget. 2018 Aug 31;9(68):32958-32971. doi: 10.18632/oncotarget.26010. eCollection 2018 Aug 31.
• [15] Identification of a novel gene, selectively up-regulated in human carcinomas, using the differential display technique.Clin Cancer Res. 1995 Oct;1(10):1209-15.
• [16] Elevation of MAP17 enhances the malignant behavior of cells via the Akt/mTOR pathway in hepatocellular carcinoma.Oncotarget. 2017 Oct 4;8(54):92589-92603. doi: 10.18632/oncotarget.21506. eCollection 2017 Nov 3.
• [17] DNA methylation signatures identify biologically distinct thyroid cancer subtypes.J Clin Endocrinol Metab. 2013 Jul;98(7):2811-21. doi: 10.1210/jc.2012-3566. Epub 2013 May 10.
• [18] Identification of targets of Twist1 transcription factor in thyroid cancer cells.J Clin Endocrinol Metab. 2014 Sep;99(9):E1617-26. doi: 10.1210/jc.2013-3799. Epub 2014 May 21.
• [19] Detection of Streptococcus mutans by PCR amplification of the spaP gene in teeth rendered caries free.J Dent. 1998 Jul-Aug;26(5-6):443-5. doi: 10.1016/s0300-5712(97)00058-4.
• [20] Transcriptome sequencing of malignant pleural mesothelioma tumors.Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3521-6. doi: 10.1073/pnas.0712399105. Epub 2008 Feb 26.
• [21] Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes.Hum Mol Genet. 2001 Mar 1;10(5):445-56. doi: 10.1093/hmg/10.5.445.
• [22] 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.
• [23] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [24] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [27] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [28] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [29] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [30] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [31] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [32] Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res. 2007 Apr;138(2):163-9. doi: 10.1016/j.jss.2006.05.037. Epub 2007 Jan 25.
• [33] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [34] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [35] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [36] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.