Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBQSOE6)

• DOT Name: Retinoblastoma-like protein 2 (RBL2)
• Synonyms: 130 kDa retinoblastoma-associated protein; p130; Retinoblastoma-related protein 2; RBR-2; pRb2
• Gene Name: RBL2
• Related Disease:
  Adenocarcinoma
  Atypical endometrial hyperplasia
  Breast cancer
  Ependymoma
  Glioma
  Retinoblastoma
  Acquired immune deficiency syndrome
  Adult T-cell leukemia/lymphoma
  Alzheimer disease
  Breast carcinoma
  Breast neoplasm
  Brunet-Wagner neurodevelopmental syndrome
  Burkitt lymphoma
  Carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Herpes simplex infection
  Intellectual disability
  Lung adenocarcinoma
  Lung neoplasm
  Malignant tumor of nasopharynx
  Martsolf syndrome
  Mesothelioma
  Nasopharyngeal carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Pancreatic adenocarcinoma
  Peters anomaly
  Precancerous condition
  Prostate neoplasm
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Warburg micro syndrome 1
  Head-neck squamous cell carcinoma
  Neuroblastoma
  Sarcoma
  Prostate cancer
  Prostate carcinoma
  Adult lymphoma
  Complex neurodevelopmental disorder
  Lymphoma
  Melanoma
  Pediatric lymphoma
  Squamous cell carcinoma
• UniProt ID: RBL2_HUMAN
• PDB ID: 4XI9; 5C1D
• Pfam ID: PF11934 ; PF01858 ; PF01857
• Sequence:
  MPSGGDQSPPPPPPPPAAAASDEEEEDDGEAEDAAPPAESPTPQIQQRFDELCSRLNMDE
  AARAEAWDSYRSMSESYTLEGNDLHWLACALYVACRKSVPTVSKGTVEGNYVSLTRILKC
  SEQSLIEFFNKMKKWEDMANLPPHFRERTERLERNFTVSAVIFKKYEPIFQDIFKYPQEE
  QPRQQRGRKQRRQPCTVSEIFHFCWVLFIYAKGNFPMISDDLVNSYHLLLCALDLVYGNA
  LQCSNRKELVNPNFKGLSEDFHAKDSKPSSDPPCIIEKLCSLHDGLVLEAKGIKEHFWKP
  YIRKLYEKKLLKGKEENLTGFLEPGNFGESFKAINKAYEEYVLSVGNLDERIFLGEDAEE
  EIGTLSRCLNAGSGTETAERVQMKNILQQHFDKSKALRISTPLTGVRYIKENSPCVTPVS
  TATHSLSRLHTMLTGLRNAPSEKLEQILRTCSRDPTQAIANRLKEMFEIYSQHFQPDEDF
  SNCAKEIASKHFRFAEMLYYKVLESVIEQEQKRLGDMDLSGILEQDAFHRSLLACCLEVV
  TFSYKPPGNFPFITEIFDVPLYHFYKVIEVFIRAEDGLCREVVKHLNQIEEQILDHLAWK
  PESPLWEKIRDNENRVPTCEEVMPPQNLERADEICIAGSPLTPRRVTEVRADTGGLGRSI
  TSPTTLYDRYSSPPASTTRRRLFVENDSPSDGGTPGRMPPQPLVNAVPVQNVSGETVSVT
  PVPGQTLVTMATATVTANNGQTVTIPVQGIANENGGITFFPVQVNVGGQAQAVTGSIQPL
  SAQALAGSLSSQQVTGTTLQVPGQVAIQQISPGGQQQKQGQSVTSSSNRPRKTSSLSLFF
  RKVYHLAAVRLRDLCAKLDISDELRKKIWTCFEFSIIQCPELMMDRHLDQLLMCAIYVMA
  KVTKEDKSFQNIMRCYRTQPQARSQVYRSVLIKGKRKRRNSGSSDSRSHQNSPTELNKDR
  TSRDSSPVMRSSSTLPVPQPSSAPPTPTRLTGANSDMEEEERGDLIQFYNNIYIKQIKTF
  AMKYSQANMDAPPLSPYPFVRTGSPRRIQLSQNHPVYISPHKNETMLSPREKIFYYFSNS
  PSKRLREINSMIRTGETPTKKRGILLEDGSESPAKRICPENHSALLRRLQDVANDRGSH
• Function: Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  PI3K-Akt sig.ling pathway (hsa04151)
  Cellular senescence (hsa04218)
  Human papillomavirus infection (hsa05165)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  G0 and Early G1 (R-HSA-1538133)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A (R-HSA-69656)
  FOXO-mediated transcription of cell cycle genes (R-HSA-9617828)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Atypical endometrial hyperplasia	DIS2POYG	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[2]
Ependymoma	DISUMRNZ	Definitive	Altered Expression	[3]
Glioma	DIS5RPEH	Definitive	Biomarker	[4]
Retinoblastoma	DISVPNPB	Definitive	Altered Expression	[5]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Genetic Variation	[6]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Brunet-Wagner neurodevelopmental syndrome	DISKRE24	Strong	Autosomal recessive	[9]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[10]
Carcinoma	DISH9F1N	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[12]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[13]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[14]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[15]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[18]
Malignant tumor of nasopharynx	DISTGIGF	Strong	Biomarker	[19]
Martsolf syndrome	DISF77WN	Strong	Genetic Variation	[16]
Mesothelioma	DISKWK9M	Strong	Altered Expression	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[21]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Therapeutic	[22]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Biomarker	[23]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[24]
Peters anomaly	DISERK0M	Strong	Genetic Variation	[25]
Precancerous condition	DISV06FL	Strong	Altered Expression	[5]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[26]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[27]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[28]
Warburg micro syndrome 1	DIS90EI2	Strong	Genetic Variation	[16]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Genetic Variation	[21]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[29]
Sarcoma	DISZDG3U	moderate	Biomarker	[30]
Prostate cancer	DISF190Y	Disputed	Biomarker	[31]
Prostate carcinoma	DISMJPLE	Disputed	Biomarker	[31]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[32]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[33]
Lymphoma	DISN6V4S	Limited	Altered Expression	[32]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[34]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[32]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[21]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Retinoblastoma-like protein 2 (RBL2) decreases the response to substance of Camptothecin.	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Retinoblastoma-like protein 2 (RBL2).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Retinoblastoma-like protein 2 (RBL2).	[40]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Retinoblastoma-like protein 2 (RBL2).	[43]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Retinoblastoma-like protein 2 (RBL2).	[44]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[45]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[47]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[48]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Retinoblastoma-like protein 2 (RBL2).	[49]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[51]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Retinoblastoma-like protein 2 (RBL2).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Retinoblastoma-like protein 2 (RBL2).	[55]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[56]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Retinoblastoma-like protein 2 (RBL2).	[42]
AHPN	DM8G6O4	Investigative	AHPN increases the expression of Retinoblastoma-like protein 2 (RBL2).	[49]
PD-158780	DMQXYE9	Investigative	PD-158780 increases the expression of Retinoblastoma-like protein 2 (RBL2).	[57]
NSC-654077	DMW3QAK	Investigative	NSC-654077 increases the expression of Retinoblastoma-like protein 2 (RBL2).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the ubiquitination of Retinoblastoma-like protein 2 (RBL2).	[22]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the phosphorylation of Retinoblastoma-like protein 2 (RBL2).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retinoblastoma-like protein 2 (RBL2).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Retinoblastoma-like protein 2 (RBL2).	[54]

References

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