Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJS5KTH)

• DOT Name: Nuclear RNA export factor 2 (NXF2)
• Synonyms: Cancer/testis antigen 39; CT39; TAP-like protein 2; TAPL-2
• Gene Name: NXF2
• Related Disease:
  Acute leukaemia
  Carcinoma
  Cleft palate
  Colorectal carcinoma
  Isolated cleft palate
  Seminoma
  Testicular cancer
  Small lymphocytic lymphoma
• UniProt ID: NXF2_HUMAN
• Pfam ID: PF02136 ; PF09162 ; PF03943
• Sequence:
  MCSTLKKCGTYRTEVAECHDHGSTFQGRKKGGSSFRDNFDKRSCHYEHGGYERPPSHCQE
  NDGSVEMRDVHKDQQLRHTPYSIRCERRMKWHSEDEIRITTWRNRKPPERKMSQNTQDGY
  TRNWFKVTIPYGIKYDKAWLMNSIQSHCSDRFTPVDFHYVRNRACFFVQDASAASALKDV
  SYKIYDDENQKICIFVNHSTAPYSVKNKLKPGQMEMLKLTMNKRYNVSQQALDLQNLRFD
  PDLMGRDIDIILNRRNCMAATLKIIERNFPELLSLNLCNNKLYQLDGLSDITEKAPKVKT
  LNLSKNKLESAWELGKVKGLKLEELWLEGNPLCSTFSDQSAYVSAIRDCFPKLLRLDGRE
  LSAPVIVDIDSSETMKPCKENFTGSETLKHLVLQFLQQYYSIYDSGDRQGLLGAYHDEAC
  FSLAIPFDPKDSAPSSLCKYFEDSRNMKTLKDPYLKGELLRRTKRDIVDSLSALPKTQHD
  LSSILVDVWCQTERMLCFSVNGVFKEVEGQSQGSVLAFTRTFIATPGSSSSLCIVNDELF
  VRDASPQETQSAFSIPVSTLSSSSEPSLSQEQQEMVQAFSAQSGMKLEWSQKCLQDNEWN
  YTRAGQAFTMLQTEGKIPAEAFKQIS
• Function: Involved in the export of mRNA from the nucleus to the cytoplasm.
• Tissue Specificity: Expressed almost exclusively in testis. Also expressed in several cancers.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)
  Amyotrophic lateral sclerosis (hsa05014)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway: Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Cleft palate	DIS6G5TF	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[3]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[4]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[1]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nuclear RNA export factor 2 (NXF2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Nuclear RNA export factor 2 (NXF2).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Nuclear RNA export factor 2 (NXF2).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Nuclear RNA export factor 2 (NXF2).	[9]

References

• [1] The cancertestis antigen NXF2 is activated by the hypomethylating agent decitabine in acute leukemia cells in vitro and in vivo.Mol Med Rep. 2013 Nov;8(5):1549-55. doi: 10.3892/mmr.2013.1659. Epub 2013 Aug 28.
• [2] Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.Cancer Immunol Res. 2014 May;2(5):480-6. doi: 10.1158/2326-6066.CIR-13-0124. Epub 2013 Nov 11.
• [3] Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1 deletion syndrome.Hum Mol Genet. 2014 Jul 15;23(14):3823-9. doi: 10.1093/hmg/ddu095. Epub 2014 Feb 25.
• [4] Chromosome X-encoded cancer/testis antigens show distinctive expression patterns in developing gonads and in testicular seminoma.Hum Reprod. 2011 Dec;26(12):3232-43. doi: 10.1093/humrep/der330. Epub 2011 Oct 20.
• [5] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [6] 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.
• [7] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [8] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.