Details of Drug Off-Target (DOT)

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

• DOT Name: Nuclear speckle splicing regulatory protein 1 (NSRP1)
• Synonyms: Coiled-coil domain-containing protein 55; Nuclear speckle-related protein 70; NSrp70
• Gene Name: NSRP1
• Related Disease:
  Acute leukaemia
  Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
• UniProt ID: NSRP1_HUMAN
• Pfam ID: PF20427 ; PF09745
• Sequence:
  MAIPGRQYGLILPKKTQQLHPVLQKPSVFGNDSDDDDETSVSESLQREAAKKQAMKQTKL
  EIQKALAEDATVYEYDSIYDEMQKKKEENNPKLLLGKDRKPKYIHNLLKAVEIRKKEQEK
  RMEKKIQREREMEKGEFDDKEAFVTSAYKKKLQERAEEEEREKRAAALEACLDVTKQKDL
  SGFYRHLLNQAVGEEEVPKCSFREARSGIKEEKSRGFSNEVSSKNRIPQEKCILQTDVKV
  EENPDADSDFDAKSSADDEIEETRVNCRREKVIETPENDFKHHRSQNHSRSPSEERGHST
  RHHTKGSRTSRGHEKREDQHQQKQSRDQENHYTDRDYRKERDSHRHREASHRDSHWKRHE
  QEDKPRARDQRERSDRVWKREKDREKYSQREQERDRQQNDQNRPSEKGEKEEKSKAKEEH
  MKVRKERYENNDKYRDREKREVGVQSSERNQDRKESSPNSRAKDKFLDQERSNKMRNMAK
  DKERNQEKPSNSESSLGAKHRLTEEGQEKGKEQERPPEAVSKFAKRNNEETVMSARDRYL
  ARQMARVNAKTYIEKEDD
• Function: RNA-binding protein that mediates pre-mRNA alternative splicing regulation.
• Tissue Specificity: Expressed in dendritic cells, T-cells, B-cells and natural killer cells. Expressed in secondary lymphoid organs such as spleen and mesenteric, axillary and brachial lymph nodes.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[1]
Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities	DIS4IJAY	Strong	Autosomal recessive	[2]

6 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 Nuclear speckle splicing regulatory protein 1 (NSRP1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[6]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[11]

4 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 Nuclear speckle splicing regulatory protein 1 (NSRP1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear speckle splicing regulatory protein 1 (NSRP1).	[10]

References

• [1] Aberrant proteomic expression of NSRP70 and its clinical implications and connection to the transcriptional level in adult acute leukemia.Leuk Res. 2014 Oct;38(10):1252-9. doi: 10.1016/j.leukres.2014.08.001. Epub 2014 Aug 10.
• [2] Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy. Genet Med. 2021 Dec;23(12):2455-2460. doi: 10.1038/s41436-021-01291-x. Epub 2021 Aug 12.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.