Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSAU864)

• DOT Name: U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200)
• Synonyms: EC 3.6.4.13; Activating signal cointegrator 1 complex subunit 3-like 1; BRR2 homolog; U5 snRNP-specific 200 kDa protein; U5-200KD
• Gene Name: SNRNP200
• Related Disease:
  Retinitis pigmentosa 33
  SNRNP200-related dominant retinopathy
  Acute myelogenous leukaemia
  Influenza
  Retinopathy
  Retinitis pigmentosa
  Blindness
• UniProt ID: U520_HUMAN
• PDB ID: 2Q0Z ; 3JCR ; 4F91 ; 4F92 ; 4F93 ; 4KIT ; 5O9Z ; 5URJ ; 5URK ; 5URM ; 5XJC ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6AHD ; 6FF7 ; 6ICZ ; 6QDV ; 6QW6 ; 6QX9 ; 6S8O ; 6S8Q ; 6S9I ; 7A5P ; 7ABG ; 7ABI ; 7BDI ; 7BDJ ; 7BDK ; 7BDL ; 7DVQ ; 7OS1 ; 7OS2 ; 7PX3 ; 7W5B ; 8BC8 ; 8BC9 ; 8BCA ; 8BCB ; 8BCC ; 8BCD ; 8BCE ; 8BCF ; 8BCG ; 8BCH ; 8C6J ; 8CH6
• EC Number: 3.6.4.13
• Pfam ID: PF21188 ; PF00270 ; PF00271 ; PF18149 ; PF02889
• Sequence:
  MADVTARSLQYEYKANSNLVLQADRSLIDRTRRDEPTGEVLSLVGKLEGTRMGDKAQRTK
  PQMQEERRAKRRKRDEDRHDINKMKGYTLLSEGIDEMVGIIYKPKTKETRETYEVLLSFI
  QAALGDQPRDILCGAADEVLAVLKNEKLRDKERRKEIDLLLGQTDDTRYHVLVNLGKKIT
  DYGGDKEIQNMDDNIDETYGVNVQFESDEEEGDEDVYGEVREEASDDDMEGDEAVVRCTL
  SANLVASGELMSSKKKDLHPRDIDAFWLQRQLSRFYDDAIVSQKKADEVLEILKTASDDR
  ECENQLVLLLGFNTFDFIKVLRQHRMMILYCTLLASAQSEAEKERIMGKMEADPELSKFL
  YQLHETEKEDLIREERSRRERVRQSRMDTDLETMDLDQGGEALAPRQVLDLEDLVFTQGS
  HFMANKRCQLPDGSFRRQRKGYEEVHVPALKPKPFGSEEQLLPVEKLPKYAQAGFEGFKT
  LNRIQSKLYRAALETDENLLLCAPTGAGKTNVALMCMLREIGKHINMDGTINVDDFKIIY
  IAPMRSLVQEMVGSFGKRLATYGITVAELTGDHQLCKEEISATQIIVCTPEKWDIITRKG
  GERTYTQLVRLIILDEIHLLHDDRGPVLEALVARAIRNIEMTQEDVRLIGLSATLPNYED
  VATFLRVDPAKGLFYFDNSFRPVPLEQTYVGITEKKAIKRFQIMNEIVYEKIMEHAGKNQ
  VLVFVHSRKETGKTARAIRDMCLEKDTLGLFLREGSASTEVLRTEAEQCKNLELKDLLPY
  GFAIHHAGMTRVDRTLVEDLFADKHIQVLVSTATLAWGVNLPAHTVIIKGTQVYSPEKGR
  WTELGALDILQMLGRAGRPQYDTKGEGILITSHGELQYYLSLLNQQLPIESQMVSKLPDM
  LNAEIVLGNVQNAKDAVNWLGYAYLYIRMLRSPTLYGISHDDLKGDPLLDQRRLDLVHTA
  ALMLDKNNLVKYDKKTGNFQVTELGRIASHYYITNDTVQTYNQLLKPTLSEIELFRVFSL
  SSEFKNITVREEEKLELQKLLERVPIPVKESIEEPSAKINVLLQAFISQLKLEGFALMAD
  MVYVTQSAGRLMRAIFEIVLNRGWAQLTDKTLNLCKMIDKRMWQSMCPLRQFRKLPEEVV
  KKIEKKNFPFERLYDLNHNEIGELIRMPKMGKTIHKYVHLFPKLELSVHLQPITRSTLKV
  ELTITPDFQWDEKVHGSSEAFWILVEDVDSEVILHHEYFLLKAKYAQDEHLITFFVPVFE
  PLPPQYFIRVVSDRWLSCETQLPVSFRHLILPEKYPPPTELLDLQPLPVSALRNSAFESL
  YQDKFPFFNPIQTQVFNTVYNSDDNVFVGAPTGSGKTICAEFAILRMLLQSSEGRCVYIT
  PMEALAEQVYMDWYEKFQDRLNKKVVLLTGETSTDLKLLGKGNIIISTPEKWDILSRRWK
  QRKNVQNINLFVVDEVHLIGGENGPVLEVICSRMRYISSQIERPIRIVALSSSLSNAKDV
  AHWLGCSATSTFNFHPNVRPVPLELHIQGFNISHTQTRLLSMAKPVYHAITKHSPKKPVI
  VFVPSRKQTRLTAIDILTTCAADIQRQRFLHCTEKDLIPYLEKLSDSTLKETLLNGVGYL
  HEGLSPMERRLVEQLFSSGAIQVVVASRSLCWGMNVAAHLVIIMDTQYYNGKIHAYVDYP
  IYDVLQMVGHANRPLQDDEGRCVIMCQGSKKDFFKKFLYEPLPVESHLDHCMHDHFNAEI
  VTKTIENKQDAVDYLTWTFLYRRMTQNPNYYNLQGISHRHLSDHLSELVEQTLSDLEQSK
  CISIEDEMDVAPLNLGMIAAYYYINYTTIELFSMSLNAKTKVRGLIEIISNAAEYENIPI
  RHHEDNLLRQLAQKVPHKLNNPKFNDPHVKTNLLLQAHLSRMQLSAELQSDTEEILSKAI
  RLIQACVDVLSSNGWLSPALAAMELAQMVTQAMWSKDSYLKQLPHFTSEHIKRCTDKGVE
  SVFDIMEMEDEERNALLQLTDSQIADVARFCNRYPNIELSYEVVDKDSIRSGGPVVVLVQ
  LEREEEVTGPVIAPLFPQKREEGWWVVIGDAKSNSLISIKRLTLQQKAKVKLDFVAPATG
  AHNYTLYFMSDAYMGCDQEYKFSVDVKEAETDSDSD
• Function: Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome. Plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa 33	DISYCSFY	Definitive	Autosomal dominant	[1]
SNRNP200-related dominant retinopathy	DISW3PXJ	Definitive	Autosomal dominant	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Influenza	DIS3PNU3	Strong	Biomarker	[4]
Retinopathy	DISB4B0F	moderate	Biomarker	[5]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[6]
Blindness	DISTIM10	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[14]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[15]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[8]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200).	[17]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] AML-specific cytotoxic antibodies in patients with durable graft-versus-leukemia responses.Blood. 2018 Jan 4;131(1):131-143. doi: 10.1182/blood-2017-02-768762. Epub 2017 Oct 23.
• [4] Human interactome of the influenza B virus NS1 protein.J Gen Virol. 2017 Sep;98(9):2267-2273. doi: 10.1099/jgv.0.000909. Epub 2017 Sep 4.
• [5] Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans.RNA Biol. 2014;11(4):298-312. doi: 10.4161/rna.28353. Epub 2014 Mar 5.
• [6] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [7] Prp8 retinitis pigmentosa mutants cause defects in the transition between the catalytic steps of splicing.RNA. 2016 May;22(5):793-809. doi: 10.1261/rna.055459.115. Epub 2016 Mar 11.
• [8] 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.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] 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.
• [17] 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.
• [18] 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.