Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA1Q07C)

• DOT Name: APC membrane recruitment protein 2 (AMER2)
• Synonyms: Amer2; Protein FAM123A
• Gene Name: AMER2
• Related Disease:
  Familial adenomatous polyposis
  Wilms tumor
• UniProt ID: AMER2_HUMAN
• Pfam ID: PF09422
• Sequence:
  METSRSRGGGGAVSERGGAGASVGVCRRKAEAGAGTGTLAADMDLHCDCAAETPAAEPPS
  GKINKAAFKLFKKRKSGGTMPSIFGVKNKGDGKSSGPTGLVRSRTHDGLAEVLVLESGRK
  EEPRGGGDSGGGGGGRPNPGPPRAAGPGGGSLASSSVAKSHSFFSLLKKNGRSENGKGEP
  VDASKAGGKQKRGLRGLFSGMRWHRKDKRAKAEAAEGRAPGGGLILPGSLTASLECVKEE
  TPRAAREPEEPSQDAPRDPAGEPAGGEEVPAPADRAPARSCREAEGLAHPGDTGARGEDA
  AGHRRAEPGPGEVRTAEDASRTGAVPVKTVPLVDSEGGSGRAPAAPDPASVDPPSDPSAD
  RICLMFSDVTSLKSFDSLTGCGDIIADQEEEAGPSCDKHVPGPGKPALSKKNPGVVAYQG
  GGEEMASPDEVDDTYLQEFWDMLSQTEEQGPEPQEGAAKVAAALETKVVPETPKDTRCVE
  AAKDASSVKRRRLNRIPIEPHPKEEPKHPEKEQQEGVPNSDEGYWDSTTPGPEEDSSSSG
  KKAGIPRDSYSGDALYDLYADPDGSPATLPGGKDNEETSSLSRLKPVSPGTITCPLRTPG
  SLLKDSKIPISIKHLTNLPSSHPVVHQQPSRSEMPRTKIPVSKVLVRRVSNRGLAGTTIR
  ATACHDSAKKL
• Function: Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[1]
Wilms tumor	DISB6T16	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of APC membrane recruitment protein 2 (AMER2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of APC membrane recruitment protein 2 (AMER2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of APC membrane recruitment protein 2 (AMER2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of APC membrane recruitment protein 2 (AMER2).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of APC membrane recruitment protein 2 (AMER2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of APC membrane recruitment protein 2 (AMER2).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of APC membrane recruitment protein 2 (AMER2).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of APC membrane recruitment protein 2 (AMER2).	[9]

References

• [1] Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt--catenin signalling.FEBS J. 2014 Feb;281(3):787-801. doi: 10.1111/febs.12624. Epub 2013 Dec 12.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.