Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI7B18G)

• DOT Name: Metalloprotease TIKI2 (TRABD2B)
• Synonyms: EC 3.4.-.-; Heart, kidney and adipose-enriched transmembrane protein homolog; TRAB domain-containing protein 2B
• Gene Name: TRABD2B
• Related Disease:
  Glioma
  Malignant glioma
• UniProt ID: TIKI2_HUMAN
• EC Number: 3.4.-.-
• Pfam ID: PF01963
• Sequence:
  MHAALAGPLLAALLATARARPQPPDGGQCRPPGSQRDLNSFLWTIRRDPPAYLFGTIHVP
  YTRVWDFIPDNSKAAFQASTRVYFELDLTDPYTISALASCQLLPHGENLQDVLPHELYWR
  LKRHLDYVKLMMPSWMTPAQRGKGLYADYLFNAIAGNWERKRPVWVMLMVNSLTERDVRF
  RGVPVLDLYLAQQAEKMKKTTGAVEQVEEQCHPLNNGLNFSQVLFALNQTLLQQESVRAG
  SLQASYTTEDLIKHYNCGDLSAVIFNHDTSQLPNFINTTLPPHEQVTAQEIDSYFRQELI
  YKRNERMGKRVMALLRENEDKICFFAFGAGHFLGNNTVIDILRQAGLEVDHTPAGQAIHS
  PAPQSPAPSPEGTSTSPAPVTPAAAVPEAPSVTPTAPPEDEDPALSPHLLLPDSLSQLEE
  FGRQRKWHKRQSTHQRPRQFNDLWVRIEDSTTASPPPLPLQPTHSSGTAKPPFQLSDQLQ
  QQDPPGPASSSAPTLGLLPAIATTIAVCFLLHSLGPS
• Function: Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required for head formation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Metalloprotease TIKI2 (TRABD2B).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Metalloprotease TIKI2 (TRABD2B).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Metalloprotease TIKI2 (TRABD2B).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Metalloprotease TIKI2 (TRABD2B).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Metalloprotease TIKI2 (TRABD2B).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Metalloprotease TIKI2 (TRABD2B).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Metalloprotease TIKI2 (TRABD2B).	[6]

References

• [1] microRNA response elementregulated TIKI2 expression suppresses the tumorigencity of malignant gliomas.Mol Med Rep. 2014 Oct;10(4):2079-86. doi: 10.3892/mmr.2014.2412. Epub 2014 Jul 22.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [6] 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.