Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9A48WV)

• DOT Name: RNA-binding protein 28 (RBM28)
• Synonyms: RNA-binding motif protein 28
• Gene Name: RBM28
• Related Disease:
  Alopecia
  ANE syndrome
  Endocrine disease
  Panhypopituitarism
  Intellectual disability
• UniProt ID: RBM28_HUMAN
• Pfam ID: PF00076
• Sequence:
  MAGLTLFVGRLPPSARSEQLEELFSQVGPVKQCFVVTEKGSKACRGFGYVTFSMLEDVQR
  ALKEITTFEGCKINVTVAKKKLRNKTKEKGKNENSECPKKEPKAKKAKVADKKARLIIRN
  LSFKCSEDDLKTVFAQFGAVLEVNIPRKPDGKMRGFGFVQFKNLLEAGKALKGMNMKEIK
  GRTVAVDWAVAKDKYKDTQSVSAIGEEKSHESKHQESVKKKGREEEDMEEEENDDDDDDD
  DEEDGVFDDEDEEEENIESKVTKPVQIQKRAVKRPAPAKSSDHSEEDSDLEESDSIDDGE
  ELAQSDTSTEEQEDKAVQVSNKKKRKLPSDVNEGKTVFIRNLSFDSEEEELGELLQQFGE
  LKYVRIVLHPDTEHSKGCAFAQFMTQEAAQKCLLAASPENEAGGLKLDGRQLKVDLAVTR
  DEAAKLQTTKVKKPTGTRNLYLAREGLIRAGTKAAEGVSAADMAKRERFELLKHQKLKDQ
  NIFVSRTRLCLHNLPKAVDDKQLRKLLLSATSGEKGVRIKECRVMRDLKGVHGNMKGQSL
  GYAFAEFQEHEHALKALRLINNNPEIFGPLKRPIVEFSLEDRRKLKMKELRIQRSLQKMR
  SKPATGEPQKGQPEPAKDQQQKAAQHHTEEQSKVPPEQKRKAGSTSWTGFQTKAEVEQVE
  LPDGKKRRKVLALPSHRGPKIRLRDKGKVKPVHPKKPKPQINQWKQEKQQLSSEQVSRKK
  AKGNKTETRFNQLVEQYKQKLLGPSKGAPLAKRSKWFDS
• Function: Nucleolar component of the spliceosomal ribonucleoprotein complexes.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Strong	Genetic Variation	[1]
ANE syndrome	DISZFU6A	Strong	Autosomal recessive	[2]
Endocrine disease	DISRGY2N	Strong	Altered Expression	[3]
Panhypopituitarism	DISAKJ4T	Strong	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RNA-binding protein 28 (RBM28).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA-binding protein 28 (RBM28).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA-binding protein 28 (RBM28).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA-binding protein 28 (RBM28).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein 28 (RBM28).	[8]

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 RNA-binding protein 28 (RBM28).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of RNA-binding protein 28 (RBM28).	[10]

References

• [1] ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency.Eur J Endocrinol. 2010 Jun;162(6):1021-5. doi: 10.1530/EJE-10-0077. Epub 2010 Mar 15.
• [2] Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome. Proc Natl Acad Sci U S A. 2021 May 11;118(19):e2017777118. doi: 10.1073/pnas.2017777118.
• [3] Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis. Am J Hum Genet. 2008 May;82(5):1114-21. doi: 10.1016/j.ajhg.2008.03.014. Epub 2008 Apr 24.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.