Details of Drug Off-Target (DOT)

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

• DOT Name: Ran-binding protein 3-like (RANBP3L)
• Gene Name: RANBP3L
• Related Disease: Benign prostatic hyperplasia
• UniProt ID: RNB3L_HUMAN
• Pfam ID: PF00638
• Sequence:
  MTTIPRKGSSHLPGSLHTCKLKLQEDRRQQEKSVIAQPIFVFEKGEQTFKRPAEDTLYEA
  AEPECNGFPTKRVRSSSFTFHITDSQSQGVRKNNVFMTSALVQSSVDIKSAEQGPVKHSK
  HVIRPAILQLPQARSCAKVRKTFGHKALESCKTKEKTNNKISEGNSYLLSENLSRARISV
  QLSTNQDFLGATSVGCQPNEDKCSFKSCSSNFVFGENMVERVLGTQKLTQPQLENDSYAK
  EKPFKSIPKFPVNFLSSRTDSIKNTSLIESAAAFSSQPSRKCLLEKIDVITGEETEHNVL
  KINCKLFIFNKTTQSWIERGRGTLRLNDTASTDCGTLQSRLIMRNQGSLRLILNSKLWAQ
  MKIQRANHKNVRITATDLEDYSIKIFLIQASAQDTAYLYAAIHHRLVALQSFNKQRDVNQ
  AESLSETAQQLNCESCDENEDDFIQVTKNGSDPSSWTHRQSVACS
• Function: Nuclear export factor for BMP-specific SMAD1/5/8 that plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation by blocking osteoblast differentiation to promote myogenic differention. Directly recognizes dephosphorylated SMAD1/5/8 and mediates their nuclear export in a Ran-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ran-binding protein 3-like (RANBP3L).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ran-binding protein 3-like (RANBP3L).	[3]

2 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 increases the methylation of Ran-binding protein 3-like (RANBP3L).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ran-binding protein 3-like (RANBP3L).	[5]

References

• [1] Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the -adrenergic receptor antagonist.Aging Male. 2017 Dec;20(4):250-256. doi: 10.1080/13685538.2017.1358261. Epub 2017 Aug 8.
• [2] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [3] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [4] 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.
• [5] 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.