Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHF38RR)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 7 (ADAM7)
• Synonyms: ADAM 7; Sperm maturation-related glycoprotein GP-83
• Gene Name: ADAM7
• Related Disease: Chagas disease
• UniProt ID: ADAM7_HUMAN
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MLPGCIFLMILLIPQVKEKFILGVEGQQLVRPKKLPLIQKRDTGHTHDDDILKTYEEELL
  YEIKLNRKTLVLHLLRSREFLGSNYSETFYSMKGEAFTRHPQIMDHCFYQGSIVHEYDSA
  ASISTCNGLRGFFRINDQRYLIEPVKYSDEGEHLVFKYNLRVPYGANYSCTELNFTRKTV
  PGDNESEEDSKIKGIHDEKYVELFIVADDTVYRRNGHPHNKLRNRIWGMVNFVNMIYKTL
  NIHVTLVGIEIWTHEDKIELYSNIETTLLRFSFWQEKILKTRKDFDHVVLLSGKWLYSHV
  QGISYPGGMCLPYYSTSIIKDLLPDTNIIANRMAHQLGHNLGMQHDEFPCTCPSGKCVMD
  SDGSIPALKFSKCSQNQYHQYLKDYKPTCMLNIPFPYNFHDFQFCGNKKLDEGEECDCGP
  AQECTNPCCDAHTCVLKPGFTCAEGECCESCQIKKAGSICRPAKDECDFPEMCTGHSPAC
  PKDQFRVNGFPCKNSEGYCFMGKCPTREDQCSELFDDEAIESHDICYKMNTKGNKFGYCK
  NKENRFLPCEEKDVRCGKIYCTGGELSSLLGEDKTYHLKDPQKNATVKCKTIFLYHDSTD
  IGLVASGTKCGEGMVCNNGECLNMEKVYISTNCPSQCNENPVDGHGLQCHCEEGQAPVAC
  EETLHVTNITILVVVLVLVIVGIGVLILLVRYRKCIKLKQVQSPPTETLGVENKGYFGDE
  QQIRTEPILPEIHFLNKPASKDSRGIADPNQSAK
• Function: Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development. Plays a role in sperm motility, flagella morphology and tyrosine phosphorylation during sperm capacitance. Plays a role in normal expression levels of HSPA5, ITM2B and ADAM2 in sperm both prior to and post-capacitation. This is a non catalytic metalloprotease-like protein.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chagas disease	DIS8KNVF	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Disintegrin and metalloproteinase domain-containing protein 7 (ADAM7) affects the binding of PEITC.	[4]

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 affects the methylation of Disintegrin and metalloproteinase domain-containing protein 7 (ADAM7).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Disintegrin and metalloproteinase domain-containing protein 7 (ADAM7).	[3]

References

• [1] Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.PLoS Negl Trop Dis. 2014 Aug 21;8(8):e3089. doi: 10.1371/journal.pntd.0003089. eCollection 2014 Aug.
• [2] 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.
• [3] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [4] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.