Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11J9HL)

• DOT Name: Leucine repeat adapter protein 25 (FAM89B)
• Gene Name: FAM89B
• UniProt ID: LRA25_HUMAN
• Pfam ID: PF14854
• Sequence:
  MNGLPSAEAPGGAGCALAGLPPLPRGLSGLLNASGGSWRELERVYSQRSRIHDELSRAAR
  APDGPRHAAGAANAGPAAGPRRPVNLDSALAALRKEMVGLRQLDMSLLCQLWGLYESIQD
  YKHLCQDLSFCQDLSSSLHSDSSYPPDAGLSDDEEPPDASLPPDPPPLTVPQTHNARDQW
  LQDAFHISL
• Function: Negatively regulates TGF-beta-induced signaling; in cooperation with SKI prevents the translocation of SMAD2 from the nucleus to the cytoplasm in response to TGF-beta. Acts as an adapter that mediates the specific recognition of LIMK1 by CDC42BPA and CDC42BPB in the lamellipodia. LRAP25-mediated CDC42BPA/CDC42BPB targeting to LIMK1 and the lamellipodium results in LIMK1 activation and the subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation.

Molecular Interaction Atlas (MIA) of This DOT

10 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 Leucine repeat adapter protein 25 (FAM89B).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leucine repeat adapter protein 25 (FAM89B).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Leucine repeat adapter protein 25 (FAM89B).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine repeat adapter protein 25 (FAM89B).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Leucine repeat adapter protein 25 (FAM89B).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Leucine repeat adapter protein 25 (FAM89B).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Leucine repeat adapter protein 25 (FAM89B).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Leucine repeat adapter protein 25 (FAM89B).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Leucine repeat adapter protein 25 (FAM89B).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Leucine repeat adapter protein 25 (FAM89B).	[9]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.