Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB853Z1)

• DOT Name: Hyaluronan and proteoglycan link protein 3 (HAPLN3)
• Gene Name: HAPLN3
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: HPLN3_HUMAN
• Pfam ID: PF07686 ; PF00193
• Sequence:
  MGLLLLVPLLLLPGSYGLPFYNGFYYSNSANDQNLGNGHGKDLLNGVKLVVETPEETLFT
  YQGASVILPCRYRYEPALVSPRRVRVKWWKLSENGAPEKDVLVAIGLRHRSFGDYQGRVH
  LRQDKEHDVSLEIQDLRLEDYGRYRCEVIDGLEDESGLVELELRGVVFPYQSPNGRYQFN
  FHEGQQVCAEQAAVVASFEQLFRAWEEGLDWCNAGWLQDATVQYPIMLPRQPCGGPGLAP
  GVRSYGPRHRRLHRYDVFCFATALKGRVYYLEHPEKLTLTEAREACQEDDATIAKVGQLF
  AAWKFHGLDRCDAGWLADGSVRYPVVHPHPNCGPPEPGVRSFGFPDPQSRLYGVYCYRQH
• Function: May function in hyaluronic acid binding.
• Tissue Specificity: Widely expressed with highest levels in spleen and placenta.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]

2 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 Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[6]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Hyaluronan and proteoglycan link protein 3 (HAPLN3).	[13]

References

• [1] Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer.Oncol Rep. 2010 Sep;24(3):759-66. doi: 10.3892/or_00000918.
• [2] 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.
• [3] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [7] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.