Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0G3KEQ)

• DOT Name: Hyaluronan and proteoglycan link protein 2 (HAPLN2)
• Synonyms: Brain link protein 1
• Gene Name: HAPLN2
• Related Disease:
  Neoplasm
  Parkinson disease
  Schizophrenia
• UniProt ID: HPLN2_HUMAN
• Pfam ID: PF07686 ; PF00193
• Sequence:
  MPGWLTLPTLCRFLLWAFTIFHKAQGDPASHPGPHYLLPPIHEVIHSHRGATATLPCVLG
  TTPPSYKVRWSKVEPGELRETLILITNGLHARGYGPLGGRARMRRGHRLDASLVIAGVRL
  EDEGRYRCELINGIEDESVALTLSLEGVVFPYQPSRGRYQFNYYEAKQACEEQDGRLATY
  SQLYQAWTEGLDWCNAGWLLEGSVRYPVLTARAPCGGRGRPGIRSYGPRDRMRDRYDAFC
  FTSALAGQVFFVPGRLTLSEAHAACRRRGAVVAKVGHLYAAWKFSGLDQCDGGWLADGSV
  RFPITTPRPRCGGLPDPGVRSFGFPRPQQAAYGTYCYAEN
• Function: Mediates a firm binding of versican V2 to hyaluronic acid. May play a pivotal role in the formation of the hyaluronan-associated matrix in the central nervous system (CNS) which facilitates neuronal conduction and general structural stabilization. Binds to hyaluronic acid.
• Tissue Specificity: Expressed only in adult brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]

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 Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hyaluronan and proteoglycan link protein 2 (HAPLN2).	[8]

References

• [1] Reduced expression of the hyaluronan and proteoglycan link proteins in malignant gliomas.J Biol Chem. 2009 Sep 25;284(39):26547-56. doi: 10.1074/jbc.M109.013185. Epub 2009 Jul 24.
• [2] Hapln2 in Neurological Diseases and Its Potential as Therapeutic Target.Front Aging Neurosci. 2019 Mar 21;11:60. doi: 10.3389/fnagi.2019.00060. eCollection 2019.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [7] 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.
• [8] 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.