Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ1V33O)

• DOT Name: Nuclear exosome regulator NRDE2 (NRDE2)
• Synonyms: Protein NRDE2 homolog
• Gene Name: NRDE2
• Related Disease: Melanoma
• UniProt ID: NRDE2_HUMAN
• PDB ID: 6IEH
• Pfam ID: PF08424
• Sequence:
  MALFPAFAGLSEAPDGGSSRKELDWLSNPSFCVGSITSLSQQTEAAPAHVSEGLPLTRSH
  LKSESSDESDTNKKLKQTSRKKKKEKKKKRKHQHHKKTKRKHGPSSSSRSETDTDSEKDK
  PSRGVGGSKKESEEPNQGNNAAADTGHRFVWLEDIQAVTGETFRTDKKPDPANWEYKSLY
  RGDIARYKRKGDSCLGINPKKQCISWEGTSTEKKHSRKQVERYFTKKSVGLMNIDGVAIS
  SKTEPPSSEPISFIPVKDLEDAAPVTTWLNPLGIYDQSTTHWLQGQGPPEQESKQPDAQP
  DSESAALKAKVEEFNRRVRENPRDTQLWMAFVAFQDEVMKSPGLYAIEEGEQEKRKRSLK
  LILEKKLAILERAIESNQSSVDLKLAKLKLCTEFWEPSTLVKEWQKLIFLHPNNTALWQK
  YLLFCQSQFSTFSISKIHSLYGKCLSTLSAVKDGSILSHPALPGTEEAMFALFLQQCHFL
  RQAGHSEKAISLFQAMVDFTFFKPDSVKDLPTKGQVEFFEPFWDSGEPRAGEKGARGWKA
  WMHQQERGGWVVINPDEDDDEPEEDDQEIKDKTLPRWQIWLAAERSRDQRHWRPWRPDKT
  KKQTEEDCEDPERQVLFDDIGQSLIRLSSHDLQFQLVEAFLQFLGVPSGFTPPASCLYLA
  MDENSIFDNGLYDEKPLTFFNPLFSGASCVGRMDRLGYPRWTRGQNREGEEFIRNVFHLV
  MPLFSGKEKSQLCFSWLQYEIAKVIWCLHTKNKKRLKSQGKNCKKLAKNLLKEPENCNNF
  CLWKQYAHLEWLLGNTEDARKVFDTALGMAGSRELKDSDLCELSLLYAELEVELSPEVRR
  AATARAVHILTKLTESSPYGPYTGQVLAVHILKARKAYEHALQDCLGDSCVSNPAPTDSC
  SRLISLAKCFMLFQYLTIGIDAAVQIYEQVFAKLNSSVFPEGSGEGDSASSQSWTSVLEA
  ITLMHTSLLRFHMKVSVYPLAPLREALSQALKLYPGNQVLWRSYVQIQNKSHSASKTRRF
  FDTITRSAKPLEPWLFAIEAEKLRKRLVETVQRLDGREIHATIPETGLMHRIQALFENAM
  RSDSGSQCPLLWRMYLNFLVSLGNKERSKGVFYKALQNCPWAKVLYLDAVEYFPDEMQEI
  LDLMTEKELRVRLPLEELELLLED
• Function: Protein of the nuclear speckles that regulates RNA degradation and export from the nucleus through its interaction with MTREX an essential factor directing various RNAs to exosomal degradation. Changes the conformation of MTREX, precluding its association with the nuclear exosome and interaction with proteins required for its function in RNA exosomal degradation. Negatively regulates, for instance, the degradation of mRNAs and lncRNAs by inhibiting their MTREX-mediated recruitment to nuclear exosome. By preventing the degradation of RNAs in the nucleus, it promotes their export to the cytoplasm. U5 snRNP-associated RNA splicing factor which is required for efficient splicing of CEP131 pre-mRNA and plays an important role in centrosome maturation, integrity and function during mitosis. Suppresses intron retention in a subset of pre-mRNAs containing short, GC-rich introns with relatively weak 5' and 3' splice sites. Plays a role in DNA damage response.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	moderate	Biomarker	[1]

6 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 Nuclear exosome regulator NRDE2 (NRDE2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear exosome regulator NRDE2 (NRDE2).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Nuclear exosome regulator NRDE2 (NRDE2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear exosome regulator NRDE2 (NRDE2).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nuclear exosome regulator NRDE2 (NRDE2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear exosome regulator NRDE2 (NRDE2).	[8]

1 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 affects the methylation of Nuclear exosome regulator NRDE2 (NRDE2).	[6]

References

• [1] Genome-wide characterization of circulating tumor cells identifies novel prognostic genomic alterations in systemic melanoma metastasis.Clin Chem. 2014 Jun;60(6):873-85. doi: 10.1373/clinchem.2013.213611. Epub 2014 Apr 9.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.