Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62YCDZ)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2)
• Synonyms: ADAM 2; Cancer/testis antigen 15; CT15; Fertilin subunit beta; PH-30; PH30; PH30-beta
• Gene Name: ADAM2
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Testicular cancer
• UniProt ID: ADAM2_HUMAN
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MWRVLFLLSGLGGLRMDSNFDSLPVQITVPEKIRSIIKEGIESQASYKIVIEGKPYTVNL
  MQKNFLPHNFRVYSYSGTGIMKPLDQDFQNFCHYQGYIEGYPKSVVMVSTCTGLRGVLQF
  ENVSYGIEPLESSVGFEHVIYQVKHKKADVSLYNEKDIESRDLSFKLQSVEPQQDFAKYI
  EMHVIVEKQLYNHMGSDTTVVAQKVFQLIGLTNAIFVSFNITIILSSLELWIDENKIATT
  GEANELLHTFLRWKTSYLVLRPHDVAFLLVYREKSNYVGATFQGKMCDANYAGGVVLHPR
  TISLESLAVILAQLLSLSMGITYDDINKCQCSGAVCIMNPEAIHFSGVKIFSNCSFEDFA
  HFISKQKSQCLHNQPRLDPFFKQQAVCGNAKLEAGEECDCGTEQDCALIGETCCDIATCR
  FKAGSNCAEGPCCENCLFMSKERMCRPSFEECDLPEYCNGSSASCPENHYVQTGHPCGLN
  QWICIDGVCMSGDKQCTDTFGKEVEFGPSECYSHLNSKTDVSGNCGISDSGYTQCEADNL
  QCGKLICKYVGKFLLQIPRATIIYANISGHLCIAVEFASDHADSQKMWIKDGTSCGSNKV
  CRNQRCVSSSYLGYDCTTDKCNDRGVCNNKKHCHCSASYLPPDCSVQSDLWPGGSIDSGN
  FPPVAIPARLPERRYIENIYHSKPMRWPFFLFIPFFIIFCVLIAIMVKVNFQRKKWRTED
  YSSDEQPESESEPKG
• Function: Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. Could have a direct role in sperm-zona binding or migration of sperm from the uterus into the oviduct. Interactions with egg membrane could be mediated via binding between its disintegrin-like domain to one or more integrins receptors on the egg. This is a non catalytic metalloprotease-like protein.
• Tissue Specificity: Expressed specifically in spermatogenic cells in the seminiferous cells. Not detected in fetal tissues.
• Reactome Pathway: Interaction With Cumulus Cells And The Zona Pellucida (R-HSA-2534343)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Disintegrin and metalloproteinase domain-containing protein 2 (ADAM2).	[7]

References

• [1] Novel biomarkers for prostate cancer including noncoding transcripts.Am J Pathol. 2009 Dec;175(6):2264-76. doi: 10.2353/ajpath.2009.080868. Epub 2009 Nov 5.
• [2] Identification of cancer/testis genes by database mining and mRNA expression analysis.Int J Cancer. 2002 Apr 1;98(4):485-92. doi: 10.1002/ijc.10276.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] 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.