Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC6AFVO)

• DOT Name: Angiopoietin-related protein 5 (ANGPTL5)
• Synonyms: Angiopoietin-like protein 5
• Gene Name: ANGPTL5
• Related Disease:
  Juvenile idiopathic arthritis
  Non-small-cell lung cancer
  Non-insulin dependent diabetes
  Obesity
  Type-1/2 diabetes
• UniProt ID: ANGL5_HUMAN
• Pfam ID: PF00147
• Sequence:
  MMSPSQASLLFLNVCIFICGEAVQGNCVHHSTDSSVVNIVEDGSNAKDESKSNDTVCKED
  CEESCDVKTKITREEKHFMCRNLQNSIVSYTRSTKKLLRNMMDEQQASLDYLSNQVNELM
  NRVLLLTTEVFRKQLDPFPHRPVQSHGLDCTDIKDTIGSVTKTPSGLYIIHPEGSSYPFE
  VMCDMDYRGGGRTVIQKRIDGIIDFQRLWCDYLDGFGDLLGEFWLGLKKIFYIVNQKNTS
  FMLYVALESEDDTLAYASYDNFWLEDETRFFKMHLGRYSGNAGDAFRGLKKEDNQNAMPF
  STSDVDNDGCRPACLVNGQSVKSCSHLHNKTGWWFNECGLANLNGIHHFSGKLLATGIQW
  GTWTKNNSPVKIKSVSMKIRRMYNPYFK
• Tissue Specificity: Mainly expressed in adult heart.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Altered Expression	[3]
Obesity	DIS47Y1K	moderate	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Angiopoietin-related protein 5 (ANGPTL5).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Angiopoietin-related protein 5 (ANGPTL5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Angiopoietin-related protein 5 (ANGPTL5).	[6]

References

• [1] Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.Pharmacogenomics J. 2014 Aug;14(4):356-64. doi: 10.1038/tpj.2014.3. Epub 2014 Apr 8.
• [2] Co-expression of immunoglobulin-like transcript 4 and angiopoietin-like proteins in human non-small cell lung cancer.Mol Med Rep. 2015 Apr;11(4):2789-96. doi: 10.3892/mmr.2014.3029. Epub 2014 Dec 2.
• [3] Higher Levels of ANGPTL5 in the Circulation of Subjects With Obesity and Type 2 Diabetes Are Associated With Insulin Resistance.Front Endocrinol (Lausanne). 2019 Jul 24;10:495. doi: 10.3389/fendo.2019.00495. eCollection 2019.
• [4] 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.
• [5] 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.
• [6] 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.