Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQUY6BV)

• DOT Name: Tight junction protein ZO-2 (TJP2)
• Synonyms: Tight junction protein 2; Zona occludens protein 2; Zonula occludens protein 2
• Gene Name: TJP2
• Related Disease:
  Carcinoma
  Cholestasis
  Cholestasis, progressive familial intrahepatic, 4
  Colorectal carcinoma
  Ductal carcinoma
  Friedreich ataxia 1
  Friedreich's ataxia
  Hepatobiliary disorder
  Hypercholesterolemia, familial, 1
  Intrahepatic cholestasis
  Intrahepatic cholestasis of pregnancy
  Neoplasm
  Pancreatic adenocarcinoma
  Refractive error
  Tuberculosis
  leukaemia
  Leukemia
  Autosomal dominant nonsyndromic hearing loss
  Obsolete familial hypercholanemia
  High blood pressure
  Deafness
  Hypercholanemia, familial
  Hypercholanemia, familial 1
  Myopia
  Non-insulin dependent diabetes
  Nonsyndromic genetic hearing loss
  Progressive familial intrahepatic cholestasis
  Progressive familial intrahepatic cholestasis type 1
• UniProt ID: ZO2_HUMAN
• PDB ID: 2OSG; 3E17
• Pfam ID: PF00625 ; PF00595 ; PF07653
• Sequence:
  MPVRGDRGFPPRRELSGWLRAPGMEELIWEQYTVTLQKDSKRGFGIAVSGGRDNPHFENG
  ETSIVISDVLPGGPADGLLQENDRVVMVNGTPMEDVLHSFAVQQLRKSGKVAAIVVKRPR
  KVQVAALQASPPLDQDDRAFEVMDEFDGRSFRSGYSERSRLNSHGGRSRSWEDSPERGRP
  HERARSRERDLSRDRSRGRSLERGLDQDHARTRDRSRGRSLERGLDHDFGPSRDRDRDRS
  RGRSIDQDYERAYHRAYDPDYERAYSPEYRRGARHDARSRGPRSRSREHPHSRSPSPEPR
  GRPGPIGVLLMKSRANEEYGLRLGSQIFVKEMTRTGLATKDGNLHEGDIILKINGTVTEN
  MSLTDARKLIEKSRGKLQLVVLRDSQQTLINIPSLNDSDSEIEDISEIESNRSFSPEERR
  HQYSDYDYHSSSEKLKERPSSREDTPSRLSRMGATPTPFKSTGDIAGTVVPETNKEPRYQ
  EDPPAPQPKAAPRTFLRPSPEDEAIYGPNTKMVRFKKGDSVGLRLAGGNDVGIFVAGIQE
  GTSAEQEGLQEGDQILKVNTQDFRGLVREDAVLYLLEIPKGEMVTILAQSRADVYRDILA
  CGRGDSFFIRSHFECEKETPQSLAFTRGEVFRVVDTLYDGKLGNWLAVRIGNELEKGLIP
  NKSRAEQMASVQNAQRDNAGDRADFWRMRGQRSGVKKNLRKSREDLTAVVSVSTKFPAYE
  RVLLREAGFKRPVVLFGPIADIAMEKLANELPDWFQTAKTEPKDAGSEKSTGVVRLNTVR
  QIIEQDKHALLDVTPKAVDLLNYTQWFPIVIFFNPDSRQGVKTMRQRLNPTSNKSSRKLF
  DQANKLKKTCAHLFTATINLNSANDSWFGSLKDTIQHQQGEAVWVSEGKMEGMDDDPEDR
  MSYLTAMGADYLSCDSRLISDFEDTDGEGGAYTDNELDEPAEEPLVSSITRSSEPVQHEE
  SIRKPSPEPRAQMRRAASSDQLRDNSPPPAFKPEPPKAKTQNKEESYDFSKSYEYKSNPS
  AVAGNETPGASTKGYPPPVAAKPTFGRSILKPSTPIPPQEGEEVGESSEEQDNAPKSVLG
  KVKIFEKMDHKARLQRMQELQEAQNARIEIAQKHPDIYAVPIKTHKPDPGTPQHTSSRPP
  EPQKAPSRPYQDTRGSYGSDAEEEEYRQQLSEHSKRGYYGQSARYRDTEL
• Function: Plays a role in tight junctions and adherens junctions. Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity.
• Tissue Specificity: This protein is found in epithelial cell junctions. Isoform A1 is abundant in the heart and brain. Detected in brain and skeletal muscle. It is present almost exclusively in normal tissues. Isoform C1 is expressed at high level in the kidney, pancreas, heart and placenta. Not detected in brain and skeletal muscle. Found in normal as well as in most neoplastic tissues.
• KEGG Pathway:
  Tight junction (hsa04530)
  Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  Apoptotic cleavage of cell adhesion proteins (R-HSA-351906)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  Signaling by Hippo (R-HSA-2028269)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Cholestasis	DISDJJWE	Strong	Genetic Variation	[2]
Cholestasis, progressive familial intrahepatic, 4	DISEUKLI	Strong	Autosomal recessive	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Ductal carcinoma	DIS15EA5	Strong	Altered Expression	[1]
Friedreich ataxia 1	DIS285GE	Strong	Genetic Variation	[5]
Friedreich's ataxia	DIS5DV35	Strong	Genetic Variation	[5]
Hepatobiliary disorder	DISEW817	Strong	Biomarker	[6]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Genetic Variation	[7]
Intrahepatic cholestasis	DISHITDZ	Strong	Genetic Variation	[6]
Intrahepatic cholestasis of pregnancy	DISMHS5F	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[9]
Refractive error	DISWNEQ1	Strong	Genetic Variation	[10]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[11]
leukaemia	DISS7D1V	moderate	Biomarker	[12]
Leukemia	DISNAKFL	moderate	Biomarker	[12]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[13]
Obsolete familial hypercholanemia	DISMGYNC	Supportive	Autosomal recessive	[7]
High blood pressure	DISY2OHH	Disputed	Biomarker	[14]
Deafness	DISKCLH4	Limited	Biomarker	[15]
Hypercholanemia, familial	DIS3MHVP	Limited	Biomarker	[15]
Hypercholanemia, familial 1	DISHF4Z3	Limited	Unknown	[7]
Myopia	DISK5S60	Limited	Genetic Variation	[16]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[17]
Nonsyndromic genetic hearing loss	DISZX61P	Limited	Autosomal dominant	[18]
Progressive familial intrahepatic cholestasis	DIS3J8HT	Limited	Genetic Variation	[19]
Progressive familial intrahepatic cholestasis type 1	DISU0AJE	Limited	Genetic Variation	[19]

22 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 Tight junction protein ZO-2 (TJP2).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tight junction protein ZO-2 (TJP2).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tight junction protein ZO-2 (TJP2).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tight junction protein ZO-2 (TJP2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tight junction protein ZO-2 (TJP2).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tight junction protein ZO-2 (TJP2).	[25]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tight junction protein ZO-2 (TJP2).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tight junction protein ZO-2 (TJP2).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tight junction protein ZO-2 (TJP2).	[28]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tight junction protein ZO-2 (TJP2).	[29]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tight junction protein ZO-2 (TJP2).	[30]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tight junction protein ZO-2 (TJP2).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Tight junction protein ZO-2 (TJP2).	[32]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tight junction protein ZO-2 (TJP2).	[33]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Tight junction protein ZO-2 (TJP2).	[34]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Tight junction protein ZO-2 (TJP2).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tight junction protein ZO-2 (TJP2).	[37]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Tight junction protein ZO-2 (TJP2).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tight junction protein ZO-2 (TJP2).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tight junction protein ZO-2 (TJP2).	[41]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tight junction protein ZO-2 (TJP2).	[42]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Tight junction protein ZO-2 (TJP2).	[43]

3 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 Tight junction protein ZO-2 (TJP2).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Tight junction protein ZO-2 (TJP2).	[38]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Tight junction protein ZO-2 (TJP2).	[38]

References

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