Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEG5Q2G)

• DOT Name: A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19)
• Synonyms: ADAM-TS 19; ADAM-TS19; ADAMTS-19; EC 3.4.24.-
• Gene Name: ADAMTS19
• Related Disease:
  Heart valve disorder
  Cardiac valvular dysplasia 2
  Female hypogonadism
  Chronic obstructive pulmonary disease
  Polycystic ovarian syndrome
• UniProt ID: ATS19_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF17771 ; PF05986 ; PF01421 ; PF19030 ; PF00090
• Sequence:
  MRLTHICCCCLLYQLGFLSNGIVSELQFAPDREEWEVVFPALWRREPVDPAGGSGGSADP
  GWVRGVGGGGSARAQAAGSSREVRSVAPVPLEEPVEGRSESRLRPPPPSEGEEDEELESQ
  ELPRGSSGAAALSPGAPASWQPPPPPQPPPSPPPAQHAEPDGDEVLLRIPAFSRDLYLLL
  RRDGRFLAPRFAVEQRPNPGPGPTGAASAPQPPAPPDAGCFYTGAVLRHPGSLASFSTCG
  GGLMGFIQLNEDFIFIEPLNDTMAITGHPHRVYRQKRSMEEKVTEKSALHSHYCGIISDK
  GRPRSRKIAESGRGKRYSYKLPQEYNIETVVVADPAMVSYHGADAARRFILTILNMVFNL
  FQHKSLSVQVNLRVIKLILLHETPPELYIGHHGEKMLESFCKWQHEEFGKKNDIHLEMST
  NWGEDMTSVDAAILITRKDFCVHKDEPCDTVGIAYLSGMCSEKRKCIIAEDNGLNLAFTI
  AHEMGHNMGINHDNDHPSCADGLHIMSGEWIKGQNLGDVSWSRCSKEDLERFLRSKASNC
  LLQTNPQSVNSVMVPSKLPGMTYTADEQCQILFGPLASFCQEMQHVICTGLWCKVEGEKE
  CRTKLDPPMDGTDCDLGKWCKAGECTSRTSAPEHLAGEWSLWSPCSRTCSAGISSRERKC
  PGLDSEARDCNGPRKQYRICENPPCPAGLPGFRDWQCQAYSVRTSSPKHILQWQAVLDEE
  KPCALFCSPVGKEQPILLSEKVMDGTSCGYQGLDICANGRCQKVGCDGLLGSLAREDHCG
  VCNGNGKSCKIIKGDFNHTRGAGYVEVLVIPAGARRIKVVEEKPAHSYLALRDAGKQSIN
  SDWKIEHSGAFNLAGTTVHYVRRGLWEKISAKGPTTAPLHLLVLLFQDQNYGLHYEYTIP
  SDPLPENQSSKAPEPLFMWTHTSWEDCDATCGGGERKTTVSCTKIMSKNISIVDNEKCKY
  LTKPEPQIRKCNEQPCQTRWMMTEWTPCSRTCGKGMQSRQVACTQQLSNGTLIRARERDC
  IGPKPASAQRCEGQDCMTVWEAGVWSECSVKCGKGIRHRTVRCTNPRKKCVLSTRPREAE
  DCEDYSKCYVWRMGDWSKCSITCGKGMQSRVIQCMHKITGRHGNECFSSEKPAAYRPCHL
  QPCNEKINVNTITSPRLAALTFKCLGDQWPVYCRVIREKNLCQDMRWYQRCCETCRDFYA
  QKLQQKS
• Tissue Specificity: Expressed in fetal lung, but not in any adult tissues examined. Expression was detected in an osteosarcoma cDNA library.
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Heart valve disorder	DIS84O7T	Definitive	Biomarker	[1]
Cardiac valvular dysplasia 2	DISB5WX8	Strong	Autosomal recessive	[2]
Female hypogonadism	DISWASB4	Strong	Biomarker	[3]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS19).	[13]

1 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 19 (ADAMTS19).	[11]

References

• [1] Loss of ADAMTS19 causes progressive non-syndromic heart valve disease.Nat Genet. 2020 Jan;52(1):40-47. doi: 10.1038/s41588-019-0536-2. Epub 2019 Dec 16.
• [2] [Myocardial hypertrophy caused by hypobaric hypoxia. Studies in male and female rats of various ages]. Boll Soc Ital Cardiol. 1975;20(12):1860-6.
• [3] Comparison of Serum A Disintegrin and Metalloproteinase with Thrombospondin Motifs-19 Levels in Different Fertility Situations: Could It Be a Serum Marker of Ovarian Function and Oocyte Pool?.Gynecol Obstet Invest. 2019;84(1):6-11. doi: 10.1159/000490665. Epub 2018 Jul 6.
• [4] Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.Am J Respir Crit Care Med. 2012 Oct 1;186(7):622-32. doi: 10.1164/rccm.201202-0366OC. Epub 2012 Jul 26.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.