Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSR6DEJ)

• DOT Name: U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48)
• Synonyms: U11/U12 snRNP 48 kDa protein; U11/U12-48K
• Gene Name: SNRNP48
• UniProt ID: SNR48_HUMAN
• PDB ID: 2VY4; 2VY5
• Pfam ID: PF05253
• Sequence:
  MEGEPPPVEERRRLQEELNEFVESGCRTLEEVTASLGWDLDSLDPGEEEAAEDEVVICPY
  DSNHHMPKSSLAKHMASCRLRKMGYTKEEEDEMYNPEFFYENVKIPSITLNKDSQFQIIK
  QARTAVGKDSDCYNQRIYSSLPVEVPLNHKRFVCDLTQADRLALYDFVVEETKKKRSDSQ
  IIENDSDLFVDLAAKINQDNSRKSPKSYLEILAEVRDYKRRRQSYRAKNVHITKKSYTEV
  IRDVINVHMEELSNHWQEEQEKAEDDAEKNEERRSASVDSRQSGGSYLDAECSRHRRDRS
  RSPHKRKRNKDKDKNCESRRRKERDGERHHSHKRRKQKI
• Function: Likely involved in U12-type 5' splice site recognition.
• Reactome Pathway: mRNA Splicing - Minor Pathway (R-HSA-72165)

Molecular Interaction Atlas (MIA) of This DOT

8 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 U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[4]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[10]

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 decreases the methylation of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of U11/U12 small nuclear ribonucleoprotein 48 kDa protein (SNRNP48).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [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] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] 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.
• [8] 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.
• [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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.