Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI99KAZ)

• DOT Name: RNA-binding protein 6 (RBM6)
• Synonyms: Lung cancer antigen NY-LU-12; Protein G16; RNA-binding motif protein 6; RNA-binding protein DEF-3
• Gene Name: RBM6
• Related Disease:
  Acute megakaryoblastic leukemia
  Advanced cancer
  Childhood acute megakaryoblastic leukemia
  Leukemia
  Lung carcinoma
  Non-insulin dependent diabetes
  Obesity
  Osteoarthritis
  Schizophrenia
  Lung cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Neoplasm
• UniProt ID: RBM6_HUMAN
• Pfam ID: PF01585 ; PF17780
• Sequence:
  MWGDSRPANRTGPFRGSQEERFAPGWNRDYPPPPLKSHAQERHSGNFPGRDSLPFDFQGH
  SGPPFANVEEHSFSYGARDGPHGDYRGGEGPGHDFRGGDFSSSDFQSRDSSQLDFRGRDI
  HSGDFRDREGPPMDYRGGDGTSMDYRGREAPHMNYRDRDAHAVDFRGRDAPPSDFRGRGT
  YDLDFRGRDGSHADFRGRDLSDLDFRAREQSRSDFRNRDVSDLDFRDKDGTQVDFRGRGS
  GTTDLDFRDRDTPHSDFRGRHRSRTDQDFRGREMGSCMEFKDREMPPVDPNILDYIQPST
  QDREHSGMNVNRREESTHDHTIERPAFGIQKGEFEHSETREGETQGVAFEHESPADFQNS
  QSPVQDQDKSQLSGREEQSSDAGLFKEEGGLDFLGRQDTDYRSMEYRDVDHRLPGSQMFG
  YGQSKSFPEGKTARDAQRDLQDQDYRTGPSEEKPSRLIRLSGVPEDATKEEILNAFRTPD
  GMPVKNLQLKEYNTGYDYGYVCVEFSLLEDAIGCMEANQGTLMIQDKEVTLEYVSSLDFW
  YCKRCKANIGGHRSSCSFCKNPREVTEAKQELITYPQPQKTSIPAPLEKQPNQPLRPADK
  EPEPRKREEGQESRLGHQKREAERYLPPSRREGPTFRRDRERESWSGETRQDGESKTIML
  KRIYRSTPPEVIVEVLEPYVRLTTANVRIIKNRTGPMGHTYGFIDLDSHAEALRVVKILQ
  NLDPPFSIDGKMVAVNLATGKRRNDSGDHSDHMHYYQGKKYFRDRRGGGRNSDWSSDTNR
  QGQQSSSDCYIYDSATGYYYDPLAGTYYDPNTQQEVYVPQDPGLPEEEEIKEKKPTSQGK
  SSSKKEMSKRDGKEKKDRGVTRFQENASEGKAPAEDVFKKPLPPTVKKEESPPPPKVVNP
  LIGLLGEYGGDSDYEEEEEEEQTPPPQPRTAQPQKREEQTKKENEEDKLTDWNKLACLLC
  RRQFPNKEVLIKHQQLSDLHKQNLEIHRKIKQSEQELAYLERREREGKFKGRGNDRREKL
  QSFDSPERKRIKYSRETDSDRKLVDKEDIDTSSKGGCVQQATGWRKGTGLGYGHPGLASS
  EEAEGRMRGPSVGASGRTSKRQSNETYRDAVRRVMFARYKELD
• Function: Specifically binds poly(G) RNA homopolymers in vitro.
• Tissue Specificity: Ubiquitous in adults.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[3]
Pancreatic cancer	DISJC981	moderate	Biomarker	[7]
Prostate cancer	DISF190Y	moderate	Biomarker	[8]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

9 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 6 (RBM6).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA-binding protein 6 (RBM6).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein 6 (RBM6).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RNA-binding protein 6 (RBM6).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 6 (RBM6).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RNA-binding protein 6 (RBM6).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of RNA-binding protein 6 (RBM6).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of RNA-binding protein 6 (RBM6).	[18]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of RNA-binding protein 6 (RBM6).	[19]

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 increases the sumoylation of RNA-binding protein 6 (RBM6).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of RNA-binding protein 6 (RBM6).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of RNA-binding protein 6 (RBM6).	[14]

References

• [1] A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia.Blood. 2007 Jul 1;110(1):323-33. doi: 10.1182/blood-2006-10-052282. Epub 2007 Mar 14.
• [2] RNA-binding protein RBM6 as a tumor suppressor gene represses the growth and progression in laryngocarcinoma.Gene. 2019 May 20;697:26-34. doi: 10.1016/j.gene.2019.02.025. Epub 2019 Feb 15.
• [3] RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation.Mol Cell. 2013 Dec 12;52(5):720-33. doi: 10.1016/j.molcel.2013.11.010.
• [4] Physical Interactions and Expression Quantitative Traits Loci Identify Regulatory Connections for Obesity and Type 2 Diabetes Associated SNPs.Front Genet. 2017 Oct 13;8:150. doi: 10.3389/fgene.2017.00150. eCollection 2017.
• [5] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [6] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [7] RNA-Binding Motif Protein 6 is a Candidate Serum Biomarker for Pancreatic Cancer.Proteomics Clin Appl. 2019 Sep;13(5):e1900048. doi: 10.1002/prca.201900048. Epub 2019 Jul 3.
• [8] AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy.Prostate. 2012 Jul 1;72(10):1133-9. doi: 10.1002/pros.22461. Epub 2011 Nov 29.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [19] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.