Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMT7ZMG)

• DOT Name: ADAM DEC1 (ADAMDEC1)
• Synonyms: EC 3.4.24.-; A disintegrin and metalloproteinase domain-like protein decysin-1; ADAM-like protein decysin-1
• Gene Name: ADAMDEC1
• Related Disease:
  Glioblastoma multiforme
  Craniosynostosis
  Inflammatory bowel disease
  Nasal polyp
  Pulmonary sarcoidosis
  Sarcoidosis
  Systemic lupus erythematosus
  Carcinoma
  Ovarian cancer
  Dermatitis
  Rosacea
  Venous thromboembolism
• UniProt ID: ADEC1_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF01562 ; PF01421
• Sequence:
  MLRGISQLPAVATMSWVLLPVLWLIVQTQAIAIKQTPELTLHEIVCPKKLHILHKREIKN
  NQTEKHGKEERYEPEVQYQMILNGEEIILSLQKTKHLLGPDYTETLYSPRGEEITTKPEN
  MEHCYYKGNILNEKNSVASISTCDGLRGYFTHHHQRYQIKPLKSTDEKEHAVFTSNQEEQ
  DPANHTCGVKSTDGKQGPIRISRSLKSPEKEDFLRAQKYIDLYLVLDNAFYKNYNENLTL
  IRSFVFDVMNLLNVIYNTIDVQVALVGMEIWSDGDKIKVVPSASTTFDNFLRWHSSNLGK
  KIHDHAQLLSGISFNNRRVGLAASNSLCSPSSVAVIEAKKKNNVALVGVMSHELGHVLGM
  PDVPFNTKCPSGSCVMNQYLSSKFPKDFSTSCRAHFERYLLSQKPKCLLQAPIPTNIMTT
  PVCGNHLLEVGEDCDCGSPKECTNLCCEALTCKLKPGTDCGGDAPNHTTE
• Function: May play an important role in the control of the immune response and during pregnancy.
• Tissue Specificity: Expressed highly in the small intestine and appendix, moderately in lymph node, mucosal lining of the colon, thymus, spleen and very weakly in the bone marrow. Predominantly expressed in dendritic cells (DC) of the germinal center. Weakly expressed in monocyte and highly expressed in macrophage. Absent in immature DC.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Craniosynostosis	DIS6J405	Strong	Altered Expression	[2]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[3]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[2]
Pulmonary sarcoidosis	DIS1XQCN	Strong	Altered Expression	[4]
Sarcoidosis	DISE5B8Z	Strong	Altered Expression	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	moderate	Altered Expression	[6]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[6]
Dermatitis	DISY5SZC	Limited	Biomarker	[7]
Rosacea	DIS02PWG	Limited	Biomarker	[7]
Venous thromboembolism	DISUR7CR	Limited	Altered Expression	[8]

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 ADAM DEC1 (ADAMDEC1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ADAM DEC1 (ADAMDEC1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ADAM DEC1 (ADAMDEC1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ADAM DEC1 (ADAMDEC1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ADAM DEC1 (ADAMDEC1).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of ADAM DEC1 (ADAMDEC1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ADAM DEC1 (ADAMDEC1).	[15]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of ADAM DEC1 (ADAMDEC1).	[16]

References

• [1] ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells.Cancer Discov. 2019 Nov;9(11):1574-1589. doi: 10.1158/2159-8290.CD-18-1308. Epub 2019 Aug 21.
• [2] The role of ADAM-like decysin 1 in non-eosinophilic chronic rhinosinusitis with nasal polyps.Acta Otolaryngol. 2018 Sep;138(9):830-836. doi: 10.1080/00016489.2018.1481296. Epub 2018 Jun 23.
• [3] Infliximab restores the dysfunctional matrix remodeling protein and growth factor gene expression in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2014 Feb;20(2):339-52. doi: 10.1097/01.MIB.0000438430.15553.90.
• [4] Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.Am J Respir Crit Care Med. 2009 May 15;179(10):929-38. doi: 10.1164/rccm.200803-490OC. Epub 2009 Feb 12.
• [5] Enhancer RNA and NFB-dependent P300 regulation of ADAMDEC1.Mol Immunol. 2018 Nov;103:312-321. doi: 10.1016/j.molimm.2018.09.019. Epub 2018 Oct 20.
• [6] ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death.Cancer Sci. 2018 Feb;109(2):471-482. doi: 10.1111/cas.13469.
• [7] ADAMDEC1 promotes skin inflammation in rosacea via modulating the polarization of M1 macrophages.Biochem Biophys Res Commun. 2020 Jan 1;521(1):64-71. doi: 10.1016/j.bbrc.2019.10.073. Epub 2019 Oct 16.
• [8] Association of ADAMDEC1 haplotype with high factor VIII levels in venous thromboembolism.Thromb Haemost. 2008 May;99(5):905-8. doi: 10.1160/TH08-01-0059.
• [9] 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.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [12] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.