Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTKUH99)

• DOT Name: A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16)
• Synonyms: ADAM-TS 16; ADAM-TS16; ADAMTS-16; EC 3.4.24.-
• Gene Name: ADAMTS16
• Related Disease:
  Chondrosarcoma
  Bipolar disorder
  Carcinoma of esophagus
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Esophageal cancer
  Esophageal squamous cell carcinoma
  High blood pressure
  Major depressive disorder
  Neoplasm
  Neoplasm of esophagus
  Open-angle glaucoma
  Osteoarthritis
  Ovarian neoplasm
  Schizophrenia
  Female hypogonadism
  Male infertility
• UniProt ID: ATS16_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF17771 ; PF19236 ; PF05986 ; PF01562 ; PF08686 ; PF01421 ; PF19030 ; PF00090
• Sequence:
  MKPRARGWRGLAALWMLLAQVAEQAPACAMGPAAAAPGSPSVPRPPPPAERPGWMEKGEY
  DLVSAYEVDHRGDYVSHEIMHHQRRRRAVPVSEVESLHLRLKGSRHDFHMDLRTSSSLVA
  PGFIVQTLGKTGTKSVQTLPPEDFCFYQGSLRSHRNSSVALSTCQGLSGMIRTEEADYFL
  RPLPSHLSWKLGRAAQGSSPSHVLYKRSTEPHAPGASEVLVTSRTWELAHQPLHSSDLRL
  GLPQKQHFCGRRKKYMPQPPKEDLFILPDEYKSCLRHKRSLLRSHRNEELNVETLVVVDK
  KMMQNHGHENITTYVLTILNMVSALFKDGTIGGNINIAIVGLILLEDEQPGLVISHHADH
  TLSSFCQWQSGLMGKDGTRHDHAILLTGLDICSWKNEPCDTLGFAPISGMCSKYRSCTIN
  EDTGLGLAFTIAHESGHNFGMIHDGEGNMCKKSEGNIMSPTLAGRNGVFSWSPCSRQYLH
  KFLSTAQAICLADQPKPVKEYKYPEKLPGELYDANTQCKWQFGEKAKLCMLDFKKDICKA
  LWCHRIGRKCETKFMPAAEGTICGHDMWCRGGQCVKYGDEGPKPTHGHWSDWSSWSPCSR
  TCGGGVSHRSRLCTNPKPSHGGKFCEGSTRTLKLCNSQKCPRDSVDFRAAQCAEHNSRRF
  RGRHYKWKPYTQVEDQDLCKLYCIAEGFDFFFSLSNKVKDGTPCSEDSRNVCIDGICERV
  GCDNVLGSDAVEDVCGVCNGNNSACTIHRGLYTKHHHTNQYYHMVTIPSGARSIRIYEMN
  VSTSYISVRNALRRYYLNGHWTVDWPGRYKFSGTTFDYRRSYNEPENLIATGPTNETLIV
  ELLFQGRNPGVAWEYSMPRLGTEKQPPAQPSYTWAIVRSECSVSCGGGQMTVREGCYRDL
  KFQVNMSFCNPKTRPVTGLVPCKVSACPPSWSVGNWSACSRTCGGGAQSRPVQCTRRVHY
  DSEPVPASLCPQPAPSSRQACNSQSCPPAWSAGPWAECSHTCGKGWRKRAVACKSTNPSA
  RAQLLPDAVCTSEPKPRMHEACLLQRCHKPKKLQWLVSAWSQCSVTCERGTQKRFLKCAE
  KYVSGKYRELASKKCSHLPKPSLELERACAPLPCPRHPPFAAAGPSRGSWFASPWSQCTA
  SCGGGVQTRSVQCLAGGRPASGCLLHQKPSASLACNTHFCPIAEKKDAFCKDYFHWCYLV
  PQHGMCSHKFYGKQCCKTCSKSNL
• Tissue Specificity: Expressed in fetal lung and kidney and in adult prostate and ovary.
• Reactome Pathway:
  Defective B3GALTL causes PpS (R-HSA-5083635)
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chondrosarcoma	DIS4I7JB	Definitive	Altered Expression	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[4]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
High blood pressure	DISY2OHH	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[7]
Osteoarthritis	DIS05URM	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[9]
Male infertility	DISY3YZZ	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16).	[14]

References

• [1] The Investigation of ADAMTS16 in Insulin-Induced Human Chondrosarcoma Cells.Cancer Biother Radiopharm. 2015 Aug;30(6):255-60. doi: 10.1089/cbr.2015.1840.
• [2] Genetic predictors of risk and resilience in psychiatric disorders: a cross-disorder genome-wide association study of functional impairment in major depressive disorder, bipolar disorder, and schizophrenia.Am J Med Genet B Neuropsychiatr Genet. 2013 Dec;162B(8):779-88. doi: 10.1002/ajmg.b.32190. Epub 2013 Sep 13.
• [3] Serial analysis of gene expression of esophageal squamous cell carcinoma: ADAMTS16 is upregulated in esophageal squamous cell carcinoma.Cancer Sci. 2010 Apr;101(4):1038-44. doi: 10.1111/j.1349-7006.2009.01477.x. Epub 2009 Dec 16.
• [4] ADAMTS16 activates latent TGF-, accentuating fibrosis and dysfunction of the pressure-overloaded heart.Cardiovasc Res. 2020 Apr 1;116(5):956-969. doi: 10.1093/cvr/cvz187.
• [5] Aberrant DNA methylation of ADAMTS16 in colorectal and other epithelial cancers.BMC Cancer. 2018 Aug 6;18(1):796. doi: 10.1186/s12885-018-4701-2.
• [6] Male mice lacking ADAMTS-16 are fertile but exhibit testes of reduced weight.Sci Rep. 2019 Nov 20;9(1):17195. doi: 10.1038/s41598-019-53900-0.
• [7] Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese.PLoS One. 2012;7(3):e33389. doi: 10.1371/journal.pone.0033389. Epub 2012 Mar 12.
• [8] Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1.PLoS One. 2018 Dec 17;13(12):e0209096. doi: 10.1371/journal.pone.0209096. eCollection 2018.
• [9] Epistasis between polymorphisms in TSHB and ADAMTS16 is associated with premature ovarian failure.Menopause. 2014 Aug;21(8):890-5. doi: 10.1097/GME.0000000000000172.
• [10] Cryptorchidism and infertility in rats with targeted disruption of the Adamts16 locus.PLoS One. 2014 Jul 1;9(7):e100967. doi: 10.1371/journal.pone.0100967. eCollection 2014.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] 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.
• [14] 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.