Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR0Z4U5)

• DOT Name: Sesquipedalian-2 (PHETA2)
• Synonyms: Ses2; 27 kDa inositol polyphosphate phosphatase interacting protein B; IPIP27B; PH domain-containing endocytic trafficking adaptor 2
• Gene Name: PHETA2
• Related Disease:
  Oculocerebrorenal syndrome
  Obesity
• UniProt ID: SESQ2_HUMAN
• Pfam ID: PF00169
• Sequence:
  MKLNERSVAHYALSDSPADHMGFLRTWGGPGTPPTPSGTGRRCWFVLKGNLLFSFESREG
  RAPLSLVVLEGCTVELAEAPVPEEFAFAICFDAPGVRPHLLAAEGPAAQEAWVKVLSRAS
  FGYMRLVVRELESQLQDARQSLALQRRSSWKSVASRCKPQAPNHRAAGLENGHCLSKDSS
  PVGLVEEAGSRSAGWGLAEWELQGPASLLLGKGQSPVSPETSCFSTLHDWYGQEIVELRQ
  CWQKRAQGSHSKCEEQDRP
• Function: Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[1]
Obesity	DIS47Y1K	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sesquipedalian-2 (PHETA2).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sesquipedalian-2 (PHETA2).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sesquipedalian-2 (PHETA2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sesquipedalian-2 (PHETA2).	[6]

References

• [1] Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3511-6. doi: 10.1073/pnas.0914658107. Epub 2010 Feb 2.
• [2] The association between obesity and race among Brazilian adults is dependent on sex and socio-economic status.Public Health Nutr. 2018 Aug;21(11):2096-2102. doi: 10.1017/S1368980018000307. Epub 2018 Mar 4.
• [3] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [6] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.