Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOQ5W67)

DOT Name Angiopoietin-related protein 6 (ANGPTL6)
Synonyms Angiopoietin-like protein 6; Angiopoietin-related growth factor; Angiopoietin-related protein 5
Gene Name ANGPTL6
Related Disease
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Advanced cancer ( )
Anorexia nervosa cachexia ( )
Bladder cancer ( )
Gastric cancer ( )
Non-alcoholic fatty liver disease ( )
Polycystic ovarian syndrome ( )
Psoriasis ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Obesity ( )
Peripheral arterial disease ( )
Intracranial berry aneurysm ( )
High blood pressure ( )
Intermittent claudication ( )
Neoplasm ( )
Peripheral vascular disease ( )
UniProt ID
ANGL6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6Y43
Pfam ID
PF00147
Sequence
MGKPWLRALQLLLLLGASWARAGAPRCTYTFVLPPQKFTGAVCWSGPASTRATPEAANAS
ELAALRMRVGRHEELLRELQRLAAADGAVAGEVRALRKESRGLSARLGQLRAQLQHEAGP
GAGPGADLGAEPAAALALLGERVLNASAEAQRAAARFHQLDVKFRELAQLVTQQSSLIAR
LERLCPGGAGGQQQVLPPPPLVPVVPVRLVGSTSDTSRMLDPAPEPQRDQTQRQQEPMAS
PMPAGHPAVPTKPVGPWQDCAEARQAGHEQSGVYELRVGRHVVSVWCEQQLEGGGWTVIQ
RRQDGSVNFFTTWQHYKAGFGRPDGEYWLGLEPVYQLTSRGDHELLVLLEDWGGRGARAH
YDGFSLEPESDHYRLRLGQYHGDAGDSLSWHNDKPFSTVDRDRDSYSGNCALYQRGGWWY
HACAHSNLNGVWHHGGHYRSRYQDGVYWAEFRGGAYSLRKAAMLIRPLKL
Function
May play a role in the wound healing process. May promote epidermal proliferation, remodeling and regeneration. May promote the chemotactic activity of endothelial cells and induce neovascularization. May counteract high-fat diet-induced obesity and related insulin resistance through increased energy expenditure.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Definitive Biomarker [1]
Hepatocellular carcinoma DIS0J828 Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Anorexia nervosa cachexia DISFO5RQ Strong Altered Expression [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Gastric cancer DISXGOUK Strong Biomarker [3]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [6]
Polycystic ovarian syndrome DISZ2BNG Strong Altered Expression [7]
Psoriasis DIS59VMN Strong Biomarker [8]
Stomach cancer DISKIJSX Strong Biomarker [3]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Obesity DIS47Y1K moderate Biomarker [9]
Peripheral arterial disease DIS78WFB moderate Biomarker [10]
Intracranial berry aneurysm DISJYQ0R Supportive Autosomal dominant [11]
High blood pressure DISY2OHH Limited Biomarker [11]
Intermittent claudication DISGY3B0 Limited Altered Expression [10]
Neoplasm DISZKGEW Limited Biomarker [3]
Peripheral vascular disease DISXSU1Y Limited Biomarker [10]
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⏷ Show the Full List of 19 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Angiopoietin-related protein 6 (ANGPTL6). [12]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Angiopoietin-related protein 6 (ANGPTL6). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Angiopoietin-related protein 6 (ANGPTL6). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Angiopoietin-related protein 6 (ANGPTL6). [15]
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References

1 A complex of 6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6.EMBO Mol Med. 2012 Nov;4(11):1156-75. doi: 10.1002/emmm.201101164. Epub 2012 Oct 16.
2 Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
3 ANGPTL6-mediated angiogenesis promotes alpha fetoprotein-producing gastric cancer progression.Pathol Res Pract. 2019 Aug;215(8):152454. doi: 10.1016/j.prp.2019.152454. Epub 2019 May 23.
4 Angiopoietin-like protein 6 in patients with obesity, type 2 diabetes mellitus, and anorexia nervosa: The influence of very low-calorie diet, bariatric surgery, and partial realimentation.Endocr Res. 2017 Feb;42(1):22-30. doi: 10.3109/07435800.2016.1169544. Epub 2016 May 2.
5 Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.Oncotarget. 2017 Apr 11;8(15):24262-24274. doi: 10.18632/oncotarget.10529.
6 Angiopoietin-like protein 2 and angiopoietin-like protein 6 levels in patients with nonalcoholic fatty liver disease.Arch Med Sci. 2018 Jun;14(4):781-787. doi: 10.5114/aoms.2016.61811. Epub 2016 Aug 16.
7 Evaluation of cardiac risk marker levels in obese and non-obese patients with polycystic ovaries.Gynecol Endocrinol. 2017 Jan;33(1):43-47. doi: 10.1080/09513590.2016.1203893. Epub 2016 Jul 16.
8 Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis.Sci Rep. 2016 Oct 4;6:34690. doi: 10.1038/srep34690.
9 Intron retention as an alternative splice variant of the cattle ANGPTL6 gene.Gene. 2019 Aug 15;709:17-24. doi: 10.1016/j.gene.2019.05.031. Epub 2019 May 15.
10 Angiopoietin-related growth factor is independently associated with lower extremity peripheral arterial disease.J Diabetes Complications. 2017 Feb;31(2):433-438. doi: 10.1016/j.jdiacomp.2016.10.019. Epub 2016 Oct 27.
11 Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm. Am J Hum Genet. 2018 Jan 4;102(1):133-141. doi: 10.1016/j.ajhg.2017.12.006.
12 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.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.