Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUJR3Q3)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32)
• Synonyms: ADAM 32
• Gene Name: ADAM32
• Related Disease:
  Meningococcal disease
  Advanced cancer
  Neoplasm
• UniProt ID: ADA32_HUMAN
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MFRLWLLLAGLCGLLASRPGFQNSLLQIVIPEKIQTNTNDSSEIEYEQISYIIPIDEKLY
  TVHLKQRYFLADNFMIYLYNQGSMNTYSSDIQTQCYYQGNIEGYPDSMVTLSTCSGLRGI
  LQFENVSYGIEPLESAVEFQHVLYKLKNEDNDIAIFIDRSLKEQPMDDNIFISEKSEPAV
  PDLFPLYLEMHIVVDKTLYDYWGSDSMIVTNKVIEIVGLANSMFTQFKVTIVLSSLELWS
  DENKISTVGEADELLQKFLEWKQSYLNLRPHDIAYLLIYMDYPRYLGAVFPGTMCITRYS
  AGVALYPKEITLEAFAVIVTQMLALSLGISYDDPKKCQCSESTCIMNPEVVQSNGVKTFS
  SCSLRSFQNFISNVGVKCLQNKPQMQKKSPKPVCGNGRLEGNEICDCGTEAQCGPASCCD
  FRTCVLKDGAKCYKGLCCKDCQILQSGVECRPKAHPECDIAENCNGTSPECGPDITLING
  LSCKNNKFICYDGDCHDLDARCESVFGKGSRNAPFACYEEIQSQSDRFGNCGRDRNNKYV
  FCGWRNLICGRLVCTYPTRKPFHQENGDVIYAFVRDSVCITVDYKLPRTVPDPLAVKNGS
  QCDIGRVCVNRECVESRIIKASAHVCSQQCSGHGVCDSRNKCHCSPGYKPPNCQIRSKGF
  SIFPEEDMGSIMERASGKTENTWLLGFLIALPILIVTTAIVLARKQLKKWFAKEEEFPSS
  ESKSEGSTQTYASQSSSEGSTQTYASQTRSESSSQADTSKSKSEDSAEAYTSRSKSQDST
  QTQSSSN
• Function: May play a role in sperm development and fertilization This is a non-catalytic metalloprotease-like protein.
• Tissue Specificity: Testis specific.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meningococcal disease	DISGDM2Z	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32).	[4]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32).	[5]

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 32 (ADAM32).	[6]

References

• [1] Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
• [2] Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues.PLoS One. 2016 Jul 8;11(7):e0158995. doi: 10.1371/journal.pone.0158995. eCollection 2016.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.