Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB9KA3F)

• DOT Name: Astacin-like metalloendopeptidase (ASTL)
• Synonyms: EC 3.4.-.-; Oocyte astacin; Ovastacin; ZP2-proteinase
• Gene Name: ASTL
• Related Disease:
  Neoplasm
  Pancreatic cancer
• UniProt ID: ASTL_HUMAN
• PDB ID: 7ST8
• EC Number: 3.4.-.-
• Pfam ID: PF01400
• Sequence:
  MEGVGGLWPWVLGLLSLPGVILGAPLASSCAGACGTSFPDGLTPEGTQASGDKDIPAINQ
  GLILEETPESSFLIEGDIIRPSPFRLLSATSNKWPMGGSGVVEVPFLLSSKYDEPSRQVI
  LEALAEFERSTCIRFVTYQDQRDFISIIPMYGCFSSVGRSGGMQVVSLAPTCLQKGRGIV
  LHELMHVLGFWHEHTRADRDRYIRVNWNEILPGFEINFIKSQSSNMLTPYDYSSVMHYGR
  LAFSRRGLPTITPLWAPSVHIGQRWNLSASDITRVLKLYGCSPSGPRPRGRGSHAHSTGR
  SPAPASLSLQRLLEALSAESRSPDPSGSSAGGQPVPAGPGESPHGWESPALKKLSAEASA
  RQPQTLASSPRSRPGAGAPGVAQEQSWLAGVSTKPTVPSSEAGIQPVPVQGSPALPGGCV
  PRNHFKGMSED
• Function: Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. Plays a role in the polyspermy inhibition. Probably acts as a protease for the post-fertilization cleavage of ZP2. Cleaves the sperm-binding ZP2 at the surface of the zona pellucida after fertilization and cortical granule exocytosis, rendering the zona pellucida unable to support further sperm binding.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pancreatic cancer	DISJC981	moderate	Biomarker	[2]

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 decreases the methylation of Astacin-like metalloendopeptidase (ASTL).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Astacin-like metalloendopeptidase (ASTL).	[4]

References

• [1] Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors.Oncotarget. 2015 Oct 6;6(30):30194-211. doi: 10.18632/oncotarget.4734.
• [2] Evaluation of SAS1B as a target for antibody-drug conjugate therapy in the treatment of pancreatic cancer.Oncotarget. 2018 Jan 4;9(10):8972-8984. doi: 10.18632/oncotarget.23944. eCollection 2018 Feb 6.
• [3] 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.
• [4] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.