Details of Drug Off-Target (DOT)

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

• DOT Name: Protein crumbs homolog 3 (CRB3)
• Gene Name: CRB3
• Related Disease:
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Estrogen-receptor positive breast cancer
  Neoplasm
  Pineoblastoma
  Triple negative breast cancer
  Small lymphocytic lymphoma
• UniProt ID: CRUM3_HUMAN
• PDB ID: 5I7Z
• Sequence:
  MANPGLGLLLALGLPFLLARWGRAWGQIQTTSANENSTVLPSSTSSSSDGNLRPEAITAI
  IVVFSLLAALLLAVGLALLVRKLREKRQTEGTYRPSSEEQVGARVPPTPNLKLPPEERLI
• Function: Involved in the establishment of cell polarity in mammalian epithelial cells. Regulates the morphogenesis of tight junctions. Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7.
• Tissue Specificity: Preferentially expressed in epithelial tissues . Expressed at high levels in lung, kidney, and colon . Expressed at high levels in retina, colon and mammary glands . Moderately expressed in liver, spleen, pancreas and prostate . Moderately to weakly expressed in the placenta . Weakly expressed in skeletal muscle and small intestine .
• KEGG Pathway:
  Tight junction (hsa04530)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  SARS-CoV-2 targets PDZ proteins in cell-cell junction (R-HSA-9705677)
  Tight junction interactions (R-HSA-420029)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[3]
Colon adenocarcinoma	DISDRE0J	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pineoblastoma	DISQK8F3	Strong	Altered Expression	[5]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[2]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[6]

5 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 Protein crumbs homolog 3 (CRB3).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein crumbs homolog 3 (CRB3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein crumbs homolog 3 (CRB3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein crumbs homolog 3 (CRB3).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein crumbs homolog 3 (CRB3).	[12]

1 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 affects the methylation of Protein crumbs homolog 3 (CRB3).	[9]

References

• [1] Crumbs3 is a critical factor that regulates invasion and metastasis of colon adenocarcinoma via the specific interaction with FGFR1.Int J Cancer. 2019 Nov 15;145(10):2740-2753. doi: 10.1002/ijc.32336. Epub 2019 Apr 29.
• [2] Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.Clin Exp Pharmacol Physiol. 2019 Sep;46(9):837-844. doi: 10.1111/1440-1681.13104. Epub 2019 Jun 10.
• [3] DNA methylation of CRB3 is a prognostic biomarker in clear cell renal cell carcinoma.Mol Biol Rep. 2019 Aug;46(4):4377-4383. doi: 10.1007/s11033-019-04892-7. Epub 2019 May 30.
• [4] Crumbs3 regulates the expression of glycosphingolipids on the plasma membrane to promote colon cancer cell migration.Biochem Biophys Res Commun. 2019 Nov 5;519(2):287-293. doi: 10.1016/j.bbrc.2019.08.161. Epub 2019 Sep 26.
• [5] Microarray analysis reveals differential gene expression patterns in tumors of the pineal region.J Neuropathol Exp Neurol. 2006 Jul;65(7):675-84. doi: 10.1097/01.jnen.0000225907.90052.e3.
• [6] KIBRA gene methylation is associated with unfavorable biological prognostic parameters in chronic lymphocytic leukemia.Epigenetics. 2012 Mar;7(3):211-5. doi: 10.4161/epi.7.3.19222.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] 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.