Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTVG4HU)

• DOT Name: E3 ubiquitin-protein ligase RBBP6 (RBBP6)
• Synonyms: EC 2.3.2.27; Proliferation potential-related protein; Protein P2P-R; RING-type E3 ubiquitin transferase RBBP6; Retinoblastoma-binding Q protein 1; RBQ-1; Retinoblastoma-binding protein 6; p53-associated cellular protein of testis
• Gene Name: RBBP6
• Related Disease:
  Ebola virus infection
  Alzheimer disease
  Arterial disorder
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Dystonia
  Epithelial ovarian cancer
  Esophageal cancer
  Gastric cancer
  Glioma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Mental disorder
  Neoplasm
  Neoplasm of esophagus
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Colorectal carcinoma
  Dystonia 16
  Movement disorder
  Peripheral arterial disease
  Autoimmune disease
  Encephalitis
  Adenocarcinoma
  Advanced cancer
  Herpes simplex infection
  Minimally invasive lung adenocarcinoma
  Retinoblastoma
  Squamous cell carcinoma
• UniProt ID: RBBP6_HUMAN
• PDB ID: 2C7H; 2YSA; 2YUR; 3ZTG; 6E5X
• EC Number: 2.3.2.27
• Pfam ID: PF08783 ; PF04564 ; PF13696
• Sequence:
  MSCVHYKFSSKLNYDTVTFDGLHISLCDLKKQIMGREKLKAADCDLQITNAQTKEEYTDD
  NALIPKNSSVIVRRIPIGGVKSTSKTYVISRTEPAMATTKAIDDSSASISLAQLTKTANL
  AEANASEEDKIKAMMSQSGHEYDPINYMKKPLGPPPPSYTCFRCGKPGHYIKNCPTNGDK
  NFESGPRIKKSTGIPRSFMMEVKDPNMKGAMLTNTGKYAIPTIDAEAYAIGKKEKPPFLP
  EEPSSSSEEDDPIPDELLCLICKDIMTDAVVIPCCGNSYCDECIRTALLESDEHTCPTCH
  QNDVSPDALIANKFLRQAVNNFKNETGYTKRLRKQLPPPPPPIPPPRPLIQRNLQPLMRS
  PISRQQDPLMIPVTSSSTHPAPSISSLTSNQSSLAPPVSGNPSSAPAPVPDITATVSISV
  HSEKSDGPFRDSDNKILPAAALASEHSKGTSSIAITALMEEKGYQVPVLGTPSLLGQSLL
  HGQLIPTTGPVRINTARPGGGRPGWEHSNKLGYLVSPPQQIRRGERSCYRSINRGRHHSE
  RSQRTQGPSLPATPVFVPVPPPPLYPPPPHTLPLPPGVPPPQFSPQFPPGQPPPAGYSVP
  PPGFPPAPANLSTPWVSSGVQTAHSNTIPTTQAPPLSREEFYREQRRLKEEEKKKSKLDE
  FTNDFAKELMEYKKIQKERRRSFSRSKSPYSGSSYSRSSYTYSKSRSGSTRSRSYSRSFS
  RSHSRSYSRSPPYPRRGRGKSRNYRSRSRSHGYHRSRSRSPPYRRYHSRSRSPQAFRGQS
  PNKRNVPQGETEREYFNRYREVPPPYDMKAYYGRSVDFRDPFEKERYREWERKYREWYEK
  YYKGYAAGAQPRPSANRENFSPERFLPLNIRNSPFTRGRREDYVGGQSHRSRNIGSNYPE
  KLSARDGHNQKDNTKSKEKESENAPGDGKGNKHKKHRKRRKGEESEGFLNPELLETSRKS
  REPTGVEENKTDSLFVLPSRDDATPVRDEPMDAESITFKSVSEKDKRERDKPKAKGDKTK
  RKNDGSAVSKKENIVKPAKGPQEKVDGERERSPRSEPPIKKAKEETPKTDNTKSSSSSQK
  DEKITGTPRKAHSKSAKEHQETKPVKEEKVKKDYSKDVKSEKLTTKEEKAKKPNEKNKPL
  DNKGEKRKRKTEEKGVDKDFESSSMKISKLEVTEIVKPSPKRKMEPDTEKMDRTPEKDKI
  SLSAPAKKIKLNRETGKKIGSTENISNTKEPSEKLESTSSKVKQEKVKGKVRRKVTGTEG
  SSSTLVDYTSTSSTGGSPVRKSEEKTDTKRTVIKTMEEYNNDNTAPAEDVIIMIQVPQSK
  WDKDDFESEEEDVKSTQPISSVGKPASVIKNVSTKPSNIVKYPEKESEPSEKIQKFTKDV
  SHEIIQHEVKSSKNSASSEKGKTKDRDYSVLEKENPEKRKNSTQPEKESNLDRLNEQGNF
  KSLSQSSKEARTSDKHDSTRASSNKDFTPNRDKKTDYDTREYSSSKRRDEKNELTRRKDS
  PSRNKDSASGQKNKPREERDLPKKGTGDSKKSNSSPSRDRKPHDHKATYDTKRPNEETKS
  VDKNPCKDREKHVLEARNNKESSGNKLLYILNPPETQVEKEQITGQIDKSTVKPKPQLSH
  SSRLSSDLTRETDEAAFEPDYNESDSESNVSVKEEESSGNISKDLKDKIVEKAKESLDTA
  AVVQVGISRNQSHSSPSVSPSRSHSPSGSQTRSHSSSASSAESQDSKKKKKKKEKKKHKK
  HKKHKKHKKHAGTEVELEKSQKHKHKKKKSKKNKDKEKEKEKDDQKVKSVTV
• Function: E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome. May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth. Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication ; (Microbial infection) [Isoform 1]: Restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription.
• Tissue Specificity: Highly expressed in the placenta and testis. Expressed at lower levels in the brain, heart, kidney, liver and lung. Overexpressed in esophageal cancer.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  RHOBTB1 GTPase cycle (R-HSA-9013422)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ebola virus infection	DISJAVM1	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Arterial disorder	DISLG4XS	Strong	Genetic Variation	[3]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Dystonia	DISJLFGW	Strong	Genetic Variation	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Genetic Variation	[13]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[13]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[13]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[6]
Mental disorder	DIS3J5R8	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[15]
Dystonia 16	DISJY7JE	moderate	Genetic Variation	[16]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[16]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[17]
Autoimmune disease	DISORMTM	Disputed	Biomarker	[18]
Encephalitis	DISLD1RL	Disputed	Biomarker	[18]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[19]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[20]
Herpes simplex infection	DISL1SAV	Limited	Biomarker	[21]
Minimally invasive lung adenocarcinoma	DIS4W83X	Limited	Altered Expression	[19]
Retinoblastoma	DISVPNPB	Limited	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[19]

24 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 E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[26]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[30]
Selenium	DM25CGV	Approved	Selenium decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[29]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[32]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[33]
Menthol	DMG2KW7	Approved	Menthol increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[34]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[35]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[36]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[37]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[38]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[40]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of E3 ubiquitin-protein ligase RBBP6 (RBBP6).	[42]

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