Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZIPB7)

• DOT Name: Ras association domain-containing protein 1 (RASSF1)
• Gene Name: RASSF1
• Related Disease:
  Breast neoplasm
  Breast carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Cholangiocarcinoma
  Colorectal neoplasm
  Ductal breast carcinoma in situ
  Endometrial carcinoma
  Esophageal cancer
  Familial adenomatous polyposis
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hypertrophic cardiomyopathy
  Inflammatory bowel disease
  Liver cirrhosis
  Lung adenocarcinoma
  Lung neoplasm
  Medulloblastoma
  Melanoma
  Neoplasm of esophagus
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Schizophrenia
  Stomach cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Uveal Melanoma
  Glioma
  Neuroendocrine neoplasm
  Epithelial ovarian cancer
  Ovarian cancer
  Bladder disease
  Carcinoma
  Colon cancer
  Colon carcinoma
  Endometrial cancer
  Esophageal squamous cell carcinoma
  Schistosomiasis
  Thyroid cancer
• UniProt ID: RASF1_HUMAN
• PDB ID: 2KZU
• Pfam ID: PF00130 ; PF16517 ; PF00788
• Sequence:
  MSGEPELIELRELAPAGRAGKGRTRLERANALRIARGTACNPTRQLVPGRGHRFQPAGPA
  THTWCDLCGDFIWGVVRKGLQCARLSADCKFTCHYRCRALVCLDCCGPRDLGWEPAVERD
  TNVDEPVEWETPDLSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSV
  PSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKDAVKHLHVLSRTRAREVIEALLRKFLVV
  DDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKENDSGEVNWDAF
  SMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHACPLG
• Function: Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage.
• Tissue Specificity: Isoform A and isoform C are ubiquitously expressed in all tissues tested, however isoform A is absent in many corresponding cancer cell lines. Isoform B is mainly expressed in hematopoietic cells.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Hippo sig.ling pathway (hsa04390)
  Hippo sig.ling pathway - multiple species (hsa04392)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Bladder cancer (hsa05219)
  Non-small cell lung cancer (hsa05223)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Posttranslational Modification	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Cervical cancer	DISFSHPF	Strong	Posttranslational Modification	[4]
Cervical carcinoma	DIST4S00	Strong	Posttranslational Modification	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Posttranslational Modification	[5]
Colorectal neoplasm	DISR1UCN	Strong	Posttranslational Modification	[6]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Posttranslational Modification	[7]
Endometrial carcinoma	DISXR5CY	Strong	Posttranslational Modification	[8]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Posttranslational Modification	[11]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Therapeutic	[12]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Posttranslational Modification	[15]
Lung neoplasm	DISVARNB	Strong	Biomarker	[16]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[17]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Posttranslational Modification	[21]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[22]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Thyroid gland carcinoma	DISMNGZ0	Strong	Posttranslational Modification	[23]
Thyroid tumor	DISLVKMD	Strong	Posttranslational Modification	[23]
Uveal Melanoma	DISA7ZGL	Strong	Posttranslational Modification	[24]
Glioma	DIS5RPEH	moderate	Genetic Variation	[25]
Neuroendocrine neoplasm	DISNPLOO	moderate	Posttranslational Modification	[26]
Epithelial ovarian cancer	DIS56MH2	Disputed	Biomarker	[27]
Ovarian cancer	DISZJHAP	Disputed	Biomarker	[27]
Bladder disease	DISTVIQI	Limited	Biomarker	[28]
Carcinoma	DISH9F1N	Limited	Posttranslational Modification	[29]
Colon cancer	DISVC52G	Limited	Biomarker	[30]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[30]
Endometrial cancer	DISW0LMR	Limited	Posttranslational Modification	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[31]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[28]
Thyroid cancer	DIS3VLDH	Limited	Posttranslational Modification	[23]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Ras association domain-containing protein 1 (RASSF1) increases the response to substance of Etoposide.	[17]
Mitomycin	DMH0ZJE	Approved	Ras association domain-containing protein 1 (RASSF1) increases the response to substance of Mitomycin.	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Ras association domain-containing protein 1 (RASSF1).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras association domain-containing protein 1 (RASSF1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras association domain-containing protein 1 (RASSF1).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras association domain-containing protein 1 (RASSF1).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras association domain-containing protein 1 (RASSF1).	[36]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ras association domain-containing protein 1 (RASSF1).	[38]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ras association domain-containing protein 1 (RASSF1).	[41]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ras association domain-containing protein 1 (RASSF1).	[42]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ras association domain-containing protein 1 (RASSF1).	[43]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Ras association domain-containing protein 1 (RASSF1).	[44]
Procainamide	DMNMXR8	Approved	Procainamide increases the expression of Ras association domain-containing protein 1 (RASSF1).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras association domain-containing protein 1 (RASSF1).	[46]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ras association domain-containing protein 1 (RASSF1).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras association domain-containing protein 1 (RASSF1).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras association domain-containing protein 1 (RASSF1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras association domain-containing protein 1 (RASSF1).	[50]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Ras association domain-containing protein 1 (RASSF1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Ras association domain-containing protein 1 (RASSF1).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Ras association domain-containing protein 1 (RASSF1).	[39]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Ras association domain-containing protein 1 (RASSF1).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras association domain-containing protein 1 (RASSF1).	[47]

References

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