Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7SRHV3)

• DOT Name: RNA-binding protein EWS (EWSR1)
• Synonyms: EWS oncogene; Ewing sarcoma breakpoint region 1 protein
• Gene Name: EWSR1
• Related Disease:
  Central nervous system neoplasm
  Melanoma
  Advanced cancer
  Bone cancer
  Carcinoma
  Childhood kidney Wilms tumor
  Chondrosarcoma
  Chromosomal disorder
  Clear cell adenocarcinoma
  Clear cell sarcoma
  Colorectal carcinoma
  Ewing sarcoma/peripheral primitive neuroectodermal tumor
  leukaemia
  Leukemia
  Liposarcoma
  Lung neoplasm
  Metastatic malignant neoplasm
  Neuroblastoma
  Osteosarcoma
  Prostate neoplasm
  Rhabdomyosarcoma
  Soft tissue neoplasm
  Soft tissue sarcoma
  Wilms tumor
  Amyotrophic lateral sclerosis
  Frontotemporal dementia
  Linear skin defects with multiple congenital anomalies 1
  Synovial sarcoma
  Bone osteosarcoma
  Fibrosarcoma
  Kidney neoplasm
  Prostate cancer
• UniProt ID: EWS_HUMAN
• PDB ID: 2CPE
• Pfam ID: PF00076 ; PF00641
• Sequence:
  MASTDYSTYSQAAAQQGYSAYTAQPTQGYAQTTQAYGQQSYGTYGQPTDVSYTQAQTTAT
  YGQTAYATSYGQPPTGYTTPTAPQAYSQPVQGYGTGAYDTTTATVTTTQASYAAQSAYGT
  QPAYPAYGQQPAATAPTRPQDGNKPTETSQPQSSTGGYNQPSLGYGQSNYSYPQVPGSYP
  MQPVTAPPSYPPTSYSSTQPTSYDQSSYSQQNTYGQPSSYGQQSSYGQQSSYGQQPPTSY
  PPQTGSYSQAPSQYSQQSSSYGQQSSFRQDHPSSMGVYGQESGGFSGPGENRSMSGPDNR
  GRGRGGFDRGGMSRGGRGGGRGGMGSAGERGGFNKPGGPMDEGPDLDLGPPVDPDEDSDN
  SAIYVQGLNDSVTLDDLADFFKQCGVVKMNKRTGQPMIHIYLDKETGKPKGDATVSYEDP
  PTAKAAVEWFDGKDFQGSKLKVSLARKKPPMNSMRGGLPPREGRGMPPPLRGGPGGPGGP
  GGPMGRMGGRGGDRGGFPPRGPRGSRGNPSGGGNVQHRAGDWQCPNPGCGNQNFAWRTEC
  NQCKAPKPEGFLPPPFPPPGGDRGRGGPGGMRGGRGGLMDRGGPGGMFRGGRGGDRGGFR
  GGRGMDRGGFGGGRRGGPGGPPGPLMEQMGGRRGGRGGPGKMDKGEHRQERRDRPY
• Function: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Central nervous system neoplasm	DISFC18W	Definitive	Genetic Variation	[1]
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Bone cancer	DIS38NA0	Strong	Genetic Variation	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[6]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[7]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[8]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Genetic Variation	[9]
Clear cell sarcoma	DIS1MTE6	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Ewing sarcoma/peripheral primitive neuroectodermal tumor	DISD4VQC	Strong	Biomarker	[12]
leukaemia	DISS7D1V	Strong	Biomarker	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[13]
Liposarcoma	DIS8IZVM	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[16]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[17]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Rhabdomyosarcoma	DISNR7MS	Strong	Genetic Variation	[20]
Soft tissue neoplasm	DISP2OHE	Strong	Biomarker	[21]
Soft tissue sarcoma	DISSN8XB	Strong	Biomarker	[22]
Wilms tumor	DISB6T16	Strong	Biomarker	[23]
Amyotrophic lateral sclerosis	DISF7HVM	Moderate	Autosomal dominant	[24]
Frontotemporal dementia	DISKYHXL	moderate	Genetic Variation	[25]
Linear skin defects with multiple congenital anomalies 1	DISNYKBT	moderate	Genetic Variation	[26]
Synovial sarcoma	DISEZJS7	moderate	Genetic Variation	[27]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[18]
Fibrosarcoma	DISWX7MU	Limited	Genetic Variation	[28]
Kidney neoplasm	DISBNZTN	Limited	Genetic Variation	[29]
Prostate cancer	DISF190Y	Limited	Biomarker	[19]

21 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 RNA-binding protein EWS (EWSR1).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding protein EWS (EWSR1).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein EWS (EWSR1).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of RNA-binding protein EWS (EWSR1).	[33]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein EWS (EWSR1).	[34]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RNA-binding protein EWS (EWSR1).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RNA-binding protein EWS (EWSR1).	[35]
Selenium	DM25CGV	Approved	Selenium increases the expression of RNA-binding protein EWS (EWSR1).	[36]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of RNA-binding protein EWS (EWSR1).	[37]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of RNA-binding protein EWS (EWSR1).	[38]
Propofol	DMB4OLE	Approved	Propofol increases the expression of RNA-binding protein EWS (EWSR1).	[39]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of RNA-binding protein EWS (EWSR1).	[39]
Romidepsin	DMT5GNL	Approved	Romidepsin decreases the expression of RNA-binding protein EWS (EWSR1).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of RNA-binding protein EWS (EWSR1).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RNA-binding protein EWS (EWSR1).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RNA-binding protein EWS (EWSR1).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein EWS (EWSR1).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RNA-binding protein EWS (EWSR1).	[45]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of RNA-binding protein EWS (EWSR1).	[46]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of RNA-binding protein EWS (EWSR1).	[47]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of RNA-binding protein EWS (EWSR1).	[48]

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 RNA-binding protein EWS (EWSR1).	[41]

References

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