Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEFHXG6)

• DOT Name: Nuclear RNA export factor 1 (NXF1)
• Synonyms: Tip-associated protein; Tip-associating protein; mRNA export factor TAP
• Gene Name: NXF1
• Related Disease:
  Behcet disease
  Psoriasis
  Alzheimer disease
  Analgesia
  Ankylosing spondylitis
  Autoimmune disease
  Bronchiectasis
  Carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Coeliac disease
  Crohn disease
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Herpes simplex infection
  Human papillomavirus infection
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  OPTN-related open angle glaucoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Schizophrenia
  Systemic lupus erythematosus
  Tuberculosis
  Type-1 diabetes
  Ulcerative colitis
  Metastatic malignant neoplasm
  Neuroblastoma
  Pulmonary tuberculosis
  Adult lymphoma
  Advanced cancer
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Dementia
  Hepatitis C virus infection
  Inflammatory bowel disease
  Lymphoma
  Melanoma
  Multiple sclerosis
  Parkinson disease
  Pediatric lymphoma
• UniProt ID: NXF1_HUMAN
• PDB ID: 1FO1; 1FT8; 1GO5; 1JKG; 1JN5; 1KOH; 1KOO; 1OAI; 2Z5K; 2Z5M; 3RW6; 3RW7; 4WYK; 6E5U
• Pfam ID: PF02136 ; PF09162 ; PF03943
• Sequence:
  MADEGKSYSEHDDERVNFPQRKKKGRGPFRWKYGEGNRRSGRGGSGIRSSRLEEDDGDVA
  MSDAQDGPRVRYNPYTTRPNRRGDTWHDRDRIHVTVRRDRAPPERGGAGTSQDGTSKNWF
  KITIPYGRKYDKAWLLSMIQSKCSVPFTPIEFHYENTRAQFFVEDASTASALKAVNYKIL
  DRENRRISIIINSSAPPHTILNELKPEQVEQLKLIMSKRYDGSQQALDLKGLRSDPDLVA
  QNIDVVLNRRSCMAATLRIIEENIPELLSLNLSNNRLYRLDDMSSIVQKAPNLKILNLSG
  NELKSERELDKIKGLKLEELWLDGNSLCDTFRDQSTYISAIRERFPKLLRLDGHELPPPI
  AFDVEAPTTLPPCKGSYFGTENLKSLVLHFLQQYYAIYDSGDRQGLLDAYHDGACCSLSI
  PFIPQNPARSSLAEYFKDSRNVKKLKDPTLRFRLLKHTRLNVVAFLNELPKTQHDVNSFV
  VDISAQTSTLLCFSVNGVFKEVDGKSRDSLRAFTRTFIAVPASNSGLCIVNDELFVRNAS
  SEEIQRAFAMPAPTPSSSPVPTLSPEQQEMLQAFSTQSGMNLEWSQKCLQDNNWDYTRSA
  QAFTHLKAKGEIPEVAFMK
• Function: Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex. ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export. Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export.
• Tissue Specificity: Expressed ubiquitously.
• 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 the SLBP Dependant Mature mRNA (R-HSA-159230)
  Transport of Mature mRNA Derived from an Intronless Transcript (R-HSA-159231)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)
  Transport of the SLBP independent Mature mRNA (R-HSA-159227)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Definitive	Biomarker	[1]
Psoriasis	DIS59VMN	Definitive	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Analgesia	DISK3TVI	Strong	Biomarker	[4]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Altered Expression	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[10]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[12]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[13]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[15]
Herpes simplex infection	DISL1SAV	Strong	Genetic Variation	[16]
Human papillomavirus infection	DISX61LX	Strong	Genetic Variation	[17]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
OPTN-related open angle glaucoma	DISDR98A	Strong	Genetic Variation	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[24]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[26]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[27]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[28]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[13]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[29]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[30]
Pulmonary tuberculosis	DIS6FLUM	moderate	Genetic Variation	[31]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[32]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[33]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[34]
Breast cancer	DIS7DPX1	Limited	Biomarker	[35]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[35]
Dementia	DISXL1WY	Limited	Biomarker	[36]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[37]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[13]
Lymphoma	DISN6V4S	Limited	Altered Expression	[32]
Melanoma	DIS1RRCY	Limited	Biomarker	[38]
Multiple sclerosis	DISB2WZI	Limited	Biomarker	[39]
Parkinson disease	DISQVHKL	Limited	Biomarker	[40]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[32]

13 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 RNA export factor 1 (NXF1).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear RNA export factor 1 (NXF1).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear RNA export factor 1 (NXF1).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear RNA export factor 1 (NXF1).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear RNA export factor 1 (NXF1).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear RNA export factor 1 (NXF1).	[46]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nuclear RNA export factor 1 (NXF1).	[41]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear RNA export factor 1 (NXF1).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Nuclear RNA export factor 1 (NXF1).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nuclear RNA export factor 1 (NXF1).	[50]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Nuclear RNA export factor 1 (NXF1).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nuclear RNA export factor 1 (NXF1).	[55]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Nuclear RNA export factor 1 (NXF1).	[56]

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 decreases the methylation of Nuclear RNA export factor 1 (NXF1).	[48]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear RNA export factor 1 (NXF1).	[51]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nuclear RNA export factor 1 (NXF1).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear RNA export factor 1 (NXF1).	[54]

References

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