Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWR7WGU)

• DOT Name: Dystrophin-related protein 2 (DRP2)
• Synonyms: DRP-2
• Gene Name: DRP2
• Related Disease:
  Polyneuropathy
  Charcot marie tooth disease
  Schizophrenia
  Bipolar disorder
  Psychotic disorder
• UniProt ID: DRP2_HUMAN
• Pfam ID: PF09068 ; PF09069 ; PF00435 ; PF00397 ; PF00569
• Sequence:
  MQPMVMQGCPYTLPRCHDWQAADQFHHSSSLRSTCPHPQVRAAVTSPAPPQDGAGVPCLS
  LKLLNGSVGASGPLEPPAMNLCWNEIKKKSHNLRARLEAFSDHSGKLQLPLQEIIDWLSQ
  KDEELSAQLPLQGDVALVQQEKETHAAFMEEVKSRGPYIYSVLESAQAFLSQHPFEELEE
  PHSESKDTSPKQRIQNLSRFVWKQATVASELWEKLTARCVDQHRHIERTLEQLLEIQGAM
  EELSTTLSQAEGVRATWEPIGDLFIDSLPEHIQAIKLFKEEFSPMKDGVKLVNDLAHQLA
  ISDVHLSMENSQALEQINVRWKQLQASVSERLKQLQDAHRDFGPGSQHFLSSSVQVPWER
  AISPNKVPYYINHQAQTTCWDHPKMTELYQTLADLNNIKFSAYRTAMKLRRVQKALRLDL
  VTLTTALEIFNEHDLQASEHVMDVVEVIHCLTALYERLEEERGILVNVPLCVDMSLNWLL
  NVFDSGRSGKMRALSFKTGIACLCGTEVKEKLQYLFSQVANSGSQCDQRHLGVLLHEAIQ
  VPRQLGEVAAFGGSNVEPSVRSCFRFSTGKPVIEASQFLEWVNLEPQSMVWLAVLHRVTI
  AEQVKHQTKCSICRQCPIKGFRYRSLKQFNVDICQTCFLTGRASKGNKLHYPIMEYYTPT
  TSSENMRDFATTLKNKFRSKHYFSKHPQRGYLPVQSVLEADYSETPASSPMWPHADTHSR
  IEHFASRLAEMESQNCSFFNDSLSPDDSIDEDQYLLRHSSPITDREPAFGQQAPCSVATE
  SKGELQKILAHLEDENRILQGELRRLKWQHEEAAEAPSLADGSTEAATDHRNEELLAEAR
  ILRQHKSRLETRMQILEDHNKQLESQLQRLRELLLQPPTESDGSGSAGSSLASSPQQSEG
  SHPREKGQTTPDTEAADDVGSKSQDVSLCLEDIMEKLRHAFPSVRSSDVTANTLLAS
• Function: Required for normal myelination and for normal organization of the cytoplasm and the formation of Cajal bands in myelinating Schwann cells. Required for normal PRX location at appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane. Possibly involved in membrane-cytoskeleton interactions of the central nervous system.
• Tissue Specificity: Detected in fetal brain.
• Reactome Pathway: EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polyneuropathy	DISB9G3W	Strong	Genetic Variation	[1]
Charcot marie tooth disease	DIS3BT2L	Moderate	X-linked	[2]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[3]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[3]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dystrophin-related protein 2 (DRP2).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Dystrophin-related protein 2 (DRP2).	[5]
Cocaine	DMSOX7I	Approved	Cocaine affects the expression of Dystrophin-related protein 2 (DRP2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dystrophin-related protein 2 (DRP2).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dystrophin-related protein 2 (DRP2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dystrophin-related protein 2 (DRP2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dystrophin-related protein 2 (DRP2).	[11]

1 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 Dystrophin-related protein 2 (DRP2).	[8]

References

• [1] Whole exome sequencing revealed a novel dystrophin-related protein-2 (DRP2) deletion in an Iranian family with symptoms of polyneuropathy.Iran J Basic Med Sci. 2019 May;22(5):576-580. doi: 10.22038/ijbms.2019.30754.7414.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis.Ann N Y Acad Sci. 2006 Aug;1074:90-6. doi: 10.1196/annals.1369.008.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [6] Proteomic analysis of the nucleus accumbens of rats with different vulnerability to cocaine addiction. Neuropharmacology. 2009 Jul;57(1):41-8. doi: 10.1016/j.neuropharm.2009.04.005. Epub 2009 Apr 22.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] 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.
• [11] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.