Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX1HKM7)

• DOT Name: Dystrobrevin beta (DTNB)
• Synonyms: DTN-B; Beta-dystrobrevin
• Gene Name: DTNB
• Related Disease:
  Classic Hodgkin lymphoma
  Hypertrophic cardiomyopathy
  Plasma cell myeloma
  Schizophrenia
  Small lymphocytic lymphoma
• UniProt ID: DTNB_HUMAN
• Pfam ID: PF09068 ; PF09069 ; PF00569
• Sequence:
  MIEESGNKRKTMAEKRQLFIEMRAQNFDVIRLSTYRTACKLRFVQKRCNLHLVDIWNMIE
  AFRDNGLNTLDHTTEISVSRLETVISSIYYQLNKRLPSTHQISVEQSISLLLNFMIAAYD
  SEGRGKLTVFSVKAMLATMCGGKMLDKLRYVFSQMSDSNGLMIFSKFDQFLKEVLKLPTA
  VFEGPSFGYTEHSVRTCFPQQRKIMLNMFLDTMMADPPPQCLVWLPLMHRLAHVENVFHP
  VECSYCRCESMMGFRYRCQQCHNYQLCQNCFWRGHAGGPHSNQHQMKEHSSWKSPAKKLS
  HAISKSLGCVPTREPPHPVFPEQPEKPLDLAHIVPPRPLTNMNDTMVSHMSSGVPTPTKR
  LQYSQDIPSHLADEHALIASYVARLQHCARVLDSPSRLDEEHRLIARYAARLAAEAGNVT
  RPPTDLSFNFDANKQQRQLIAELENKNREILQEIQRLRLEHEQASQPTPEKAQQNPTLLA
  ELRLLRQRKDELEQRMSALQESRRELMVQLEELMKLLKEEEQKQAAQATGSPHTSPTHGG
  GRPMPMPVRSTSAGSTPTHCPQDSLSGVGGDVQEAFAQGTRRNLRNDLLVAADSITNTMS
  SLVKELHSAEEGAEEEEEKMQNGKDRG
• Function: Scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids. May function as a repressor of the SYN1 promoter through the binding of repressor element-1 (RE-1), in turn regulates SYN1 expression and may be involved in cell proliferation regulation during the early phase of neural differentiation. May be required for proper maturation and function of a subset of inhibitory synapses.
• Tissue Specificity: Highly expressed in brain, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[1]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[1]

5 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 Dystrobrevin beta (DTNB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dystrobrevin beta (DTNB).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dystrobrevin beta (DTNB).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dystrobrevin beta (DTNB).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dystrobrevin beta (DTNB).	[8]

2 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 decreases the methylation of Dystrobrevin beta (DTNB).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Dystrobrevin beta (DTNB).	[10]

References

• [1] Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.Sci Rep. 2017 Jan 23;7:41071. doi: 10.1038/srep41071.
• [2] Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure.Physiol Genomics. 2002 Jul 12;10(1):31-44. doi: 10.1152/physiolgenomics.00122.2001.
• [3] Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain.Arch Gen Psychiatry. 2004 Jun;61(6):544-55. doi: 10.1001/archpsyc.61.6.544.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.