Details of Drug Off-Target (DOT)

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

• DOT Name: Spliceosome RNA helicase DDX39B (DDX39B)
• Synonyms: EC 3.6.4.13; 56 kDa U2AF65-associated protein; ATP-dependent RNA helicase p47; DEAD box protein UAP56; HLA-B-associated transcript 1 protein
• Gene Name: DDX39B
• Related Disease:
  Alzheimer disease
  Atopic dermatitis
  Cardiac disease
  Endometrial cancer
  Endometrial carcinoma
  Graves disease
  Hepatitis C virus infection
  Influenza
  Malaria
  Multiple sclerosis
  Nephritis
  Periodontal disease
  Periodontitis
  Plasmodium vivax malaria
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Rheumatoid arthritis
  Stevens-Johnson syndrome
  Systemic lupus erythematosus
  Toxic epidermal necrolysis
  Type-1 diabetes
  Vitiligo
  Asthma
  Myocardial infarction
  Peripheral sensory neuropathies
  Type-1/2 diabetes
  Leprosy
  Advanced cancer
  Autoimmune disease
  Cystinuria
  Hematologic disease
  Myasthenia gravis
  Myositis disease
  Small lymphocytic lymphoma
• UniProt ID: DX39B_HUMAN
• PDB ID: 1T5I; 1T6N; 1XTI; 1XTJ; 1XTK; 7APK; 7ZNK; 7ZNL; 8ENK
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MAENDVDNELLDYEDDEVETAAGGDGAEAPAKKDVKGSYVSIHSSGFRDFLLKPELLRAI
  VDCGFEHPSEVQHECIPQAILGMDVLCQAKSGMGKTAVFVLATLQQLEPVTGQVSVLVMC
  HTRELAFQISKEYERFSKYMPNVKVAVFFGGLSIKKDEEVLKKNCPHIVVGTPGRILALA
  RNKSLNLKHIKHFILDECDKMLEQLDMRRDVQEIFRMTPHEKQVMMFSATLSKEIRPVCR
  KFMQDPMEIFVDDETKLTLHGLQQYYVKLKDNEKNRKLFDLLDVLEFNQVVIFVKSVQRC
  IALAQLLVEQNFPAIAIHRGMPQEERLSRYQQFKDFQRRILVATNLFGRGMDIERVNIAF
  NYDMPEDSDTYLHRVARAGRFGTKGLAITFVSDENDAKILNDVQDRFEVNISELPDEIDI
  SSYIEQTR
• Function: Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4 and the THO complex. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability; Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [PubMed:23299939] reporting a stimulatory effect; (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)
  Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA 3'-end processing (R-HSA-72187)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[2]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[3]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[4]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[4]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[6]
Influenza	DIS3PNU3	Strong	Biomarker	[7]
Malaria	DISQ9Y50	Strong	Genetic Variation	[8]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[9]
Nephritis	DISQZQ70	Strong	Genetic Variation	[10]
Periodontal disease	DISJQHVN	Strong	Biomarker	[11]
Periodontitis	DISI9JOI	Strong	Genetic Variation	[12]
Plasmodium vivax malaria	DISPU3H9	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[13]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[13]
Psoriasis	DIS59VMN	Strong	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[15]
Stevens-Johnson syndrome	DISZG4YX	Strong	Genetic Variation	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[10]
Toxic epidermal necrolysis	DISIWPFR	Strong	Genetic Variation	[16]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[17]
Vitiligo	DISR05SL	Strong	Genetic Variation	[18]
Asthma	DISW9QNS	moderate	Genetic Variation	[19]
Myocardial infarction	DIS655KI	moderate	Genetic Variation	[20]
Peripheral sensory neuropathies	DISYWI6M	moderate	Biomarker	[21]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[22]
Leprosy	DISAA4UI	Disputed	Biomarker	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[24]
Autoimmune disease	DISORMTM	Limited	Genetic Variation	[25]
Cystinuria	DISCU7CO	Limited	Altered Expression	[26]
Hematologic disease	DIS9XD9A	Limited	Biomarker	[24]
Myasthenia gravis	DISELRCI	Limited	Genetic Variation	[25]
Myositis disease	DISCIXF0	Limited	Genetic Variation	[27]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[24]

13 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 Spliceosome RNA helicase DDX39B (DDX39B).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[34]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[35]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[36]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[37]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[38]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[41]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Spliceosome RNA helicase DDX39B (DDX39B).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Spliceosome RNA helicase DDX39B (DDX39B).	[32]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Spliceosome RNA helicase DDX39B (DDX39B).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Spliceosome RNA helicase DDX39B (DDX39B).	[40]

References

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