Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2UM3M)

• DOT Name: Anoctamin-9 (ANO9)
• Synonyms: Transmembrane protein 16J; Tumor protein p53-inducible protein 5; p53-induced gene 5 protein
• Gene Name: ANO9
• Related Disease:
  Colorectal carcinoma
  Pancreatic cancer
  Tuberculosis
• UniProt ID: ANO9_HUMAN
• Pfam ID: PF04547
• Sequence:
  MQGEESLRILVEPEGDSFPLMEISTCETEASEQWDYVLVAQRHTQRDPRQARQQQFLEEL
  RRKGFHIKVIRDQKQVFFGIRADNSVFGLYRTLLLEPEGPAPHAELAAPTTIPVTTSLRI
  RIVNFVVMNNKTSAGETFEDLMKDGVFEARFPLHKGEGRLKKTWARWRHMFREQPVDEIR
  NYFGEKVALYFVWLGWYTYMLVPAALTGLLVFLSGFSLFEASQISKEICEAHDILMCPLG
  DHSRRYQRLSETCTFAKLTHLFDNDGTVVFAIFMALWATVFLEIWKRQRARVVLHWDLYV
  WDEEQEEMALQLINCPDYKLRPYQHSYLRSTVILVLTLLMICLMIGMAHVLVVYRVLASA
  LFSSSAVPFLEEQVTTAVVVTGALVHYVTIIIMTKINRCVALKLCDFEMPRTFSERESRF
  TIRFFTLQFFTHFSSLIYIAFILGRINGHPGKSTRLAGLWKLEECHASGCMMDLFVQMAI
  IMGLKQTLSNCVEYLVPWVTHKCRSLRASESGHLPRDPELRDWRRNYLLNPVNTFSLFDE
  FMEMMIQYGFTTIFVAAFPLAPLLALFSNLVEIRLDAIKMVWLQRRLVPRKAKDIGTWLQ
  VLETIGVLAVIANGMVIAFTSEFIPRVVYKYRYSPCLKEGNSTVDCLKGYVNHSLSVFHT
  KDFQDPDGIEGSENVTLCRYRDYRNPPDYNFSEQFWFLLAIRLAFVILFEHVALCIKLIA
  AWFVPDIPQSVKNKVLEVKYQRLREKMWHGRQRLGGVGAGSRPPMPAHPTPASIFSARST
  DV
• Function: Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Does not exhibit calcium-activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway:
  Induction of Cell-Cell Fusion (R-HSA-9733458)
  Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[3]

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 Anoctamin-9 (ANO9).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Anoctamin-9 (ANO9).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Anoctamin-9 (ANO9).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Anoctamin-9 (ANO9).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Anoctamin-9 (ANO9).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Anoctamin-9 (ANO9).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Anoctamin-9 (ANO9).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Anoctamin-9 (ANO9).	[11]

References

• [1] Identification and characterization of ANO9 in stage II and III colorectal carcinoma.Oncotarget. 2015 Oct 6;6(30):29324-34. doi: 10.18632/oncotarget.4979.
• [2] ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer.Br J Cancer. 2017 Dec 5;117(12):1798-1809. doi: 10.1038/bjc.2017.355. Epub 2017 Oct 12.
• [3] Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.PLoS One. 2016 Feb 12;11(2):e0148649. doi: 10.1371/journal.pone.0148649. eCollection 2016.
• [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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.