Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT56I2VD)

• DOT Name: Plexin-B2 (PLXNB2)
• Synonyms: MM1
• Gene Name: PLXNB2
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Al amyloidosis
  Atopic dermatitis
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Psoriasis
• UniProt ID: PLXB2_HUMAN
• PDB ID: 4.00E+71
• Pfam ID: PF08337 ; PF20170 ; PF01437 ; PF01403 ; PF01833 ; PF17960
• Sequence:
  MALQLWALTLLGLLGAGASLRPRKLDFFRSEKELNHLAVDEASGVVYLGAVNALYQLDAK
  LQLEQQVATGPALDNKKCTPPIEASQCHEAEMTDNVNQLLLLDPPRKRLVECGSLFKGIC
  ALRALSNISLRLFYEDGSGEKSFVASNDEGVATVGLVSSTGPGGDRVLFVGKGNGPHDNG
  IIVSTRLLDRTDSREAFEAYTDHATYKAGYLSTNTQQFVAAFEDGPYVFFVFNQQDKHPA
  RNRTLLARMCREDPNYYSYLEMDLQCRDPDIHAAAFGTCLAASVAAPGSGRVLYAVFSRD
  SRSSGGPGAGLCLFPLDKVHAKMEANRNACYTGTREARDIFYKPFHGDIQCGGHAPGSSK
  SFPCGSEHLPYPLGSRDGLRGTAVLQRGGLNLTAVTVAAENNHTVAFLGTSDGRILKVYL
  TPDGTSSEYDSILVEINKRVKRDLVLSGDLGSLYAMTQDKVFRLPVQECLSYPTCTQCRD
  SQDPYCGWCVVEGRCTRKAECPRAEEASHWLWSRSKSCVAVTSAQPQNMSRRAQGEVQLT
  VSPLPALSEEDELLCLFGESPPHPARVEGEAVICNSPSSIPVTPPGQDHVAVTIQLLLRR
  GNIFLTSYQYPFYDCRQAMSLEENLPCISCVSNRWTCQWDLRYHECREASPNPEDGIVRA
  HMEDSCPQFLGPSPLVIPMNHETDVNFQGKNLDTVKGSSLHVGSDLLKFMEPVTMQESGT
  FAFRTPKLSHDANETLPLHLYVKSYGKNIDSKLHVTLYNCSFGRSDCSLCRAANPDYRCA
  WCGGQSRCVYEALCNTTSECPPPVITRIQPETGPLGGGIRITILGSNLGVQAGDIQRISV
  AGRNCSFQPERYSVSTRIVCVIEAAETPFTGGVEVDVFGKLGRSPPNVQFTFQQPKPLSV
  EPQQGPQAGGTTLTIHGTHLDTGSQEDVRVTLNGVPCKVTKFGAQLQCVTGPQATRGQML
  LEVSYGGSPVPNPGIFFTYRENPVLRAFEPLRSFASGGRSINVTGQGFSLIQRFAMVVIA
  EPLQSWQPPREAESLQPMTVVGTDYVFHNDTKVVFLSPAVPEEPEAYNLTVLIEMDGHRA
  LLRTEAGAFEYVPDPTFENFTGGVKKQVNKLIHARGTNLNKAMTLQEAEAFVGAERCTMK
  TLTETDLYCEPPEVQPPPKRRQKRDTTHNLPEFIVKFGSREWVLGRVEYDTRVSDVPLSL
  ILPLVIVPMVVVIAVSVYCYWRKSQQAEREYEKIKSQLEGLEESVRDRCKKEFTDLMIEM
  EDQTNDVHEAGIPVLDYKTYTDRVFFLPSKDGDKDVMITGKLDIPEPRRPVVEQALYQFS
  NLLNSKSFLINFIHTLENQREFSARAKVYFASLLTVALHGKLEYYTDIMHTLFLELLEQY
  VVAKNPKLMLRRSETVVERMLSNWMSICLYQYLKDSAGEPLYKLFKAIKHQVEKGPVDAV
  QKKAKYTLNDTGLLGDDVEYAPLTVSVIVQDEGVDAIPVKVLNCDTISQVKEKIIDQVYR
  GQPCSCWPRPDSVVLEWRPGSTAQILSDLDLTSQREGRWKRVNTLMHYNVRDGATLILSK
  VGVSQQPEDSQQDLPGERHALLEEENRVWHLVRPTDEVDEGKSKRGSVKEKERTKAITEI
  YLTRLLSVKGTLQQFVDNFFQSVLAPGHAVPPAVKYFFDFLDEQAEKHNIQDEDTIHIWK
  TNSLPLRFWVNILKNPHFIFDVHVHEVVDASLSVIAQTFMDACTRTEHKLSRDSPSNKLL
  YAKEISTYKKMVEDYYKGIRQMVQVSDQDMNTHLAEISRAHTDSLNTLVALHQLYQYTQK
  YYDEIINALEEDPAAQKMQLAFRLQQIAAALENKVTDL
• Function: Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling. Plays a role in glutamatergic synapse development and is required for SEMA4A-mediated excitatory synapse development. Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development. Regulates the migration of cerebellar granule cells in the developing brain. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. May modulate the activity of RAC1 and CDC42.
• KEGG Pathway: Axon guidance (hsa04360)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Al amyloidosis	DISMHVSL	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Psoriasis	DIS59VMN	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Plexin-B2 (PLXNB2) decreases the response to substance of Arsenic trioxide.	[21]

15 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 Plexin-B2 (PLXNB2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Plexin-B2 (PLXNB2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Plexin-B2 (PLXNB2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Plexin-B2 (PLXNB2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Plexin-B2 (PLXNB2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Plexin-B2 (PLXNB2).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Plexin-B2 (PLXNB2).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Plexin-B2 (PLXNB2).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Plexin-B2 (PLXNB2).	[15]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Plexin-B2 (PLXNB2).	[16]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Plexin-B2 (PLXNB2).	[17]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Plexin-B2 (PLXNB2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Plexin-B2 (PLXNB2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Plexin-B2 (PLXNB2).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Plexin-B2 (PLXNB2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Plexin-B2 (PLXNB2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Plexin-B2 (PLXNB2).	[18]

References

• [1] Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction.JCI Insight. 2017 Sep 7;2(17):e93344. doi: 10.1172/jci.insight.93344. eCollection 2017 Sep 7.
• [2] Plexin-B2 Mediates Physiologic and Pathologic Functions of Angiogenin.Cell. 2017 Nov 2;171(4):849-864.e25. doi: 10.1016/j.cell.2017.10.005.
• [3] Hyperdiploidy is less frequent in AL amyloidosis compared with monoclonal gammopathy of undetermined significance and inversely associated with translocation t(11;14).Blood. 2011 Apr 7;117(14):3809-15. doi: 10.1182/blood-2010-02-268987. Epub 2011 Feb 10.
• [4] CD100-Plexin-B2 Promotes the Inflammation in Psoriasis by Activating NF-B and the Inflammasome inKeratinocytes.J Invest Dermatol. 2018 Feb;138(2):375-383. doi: 10.1016/j.jid.2017.09.005. Epub 2017 Sep 18.
• [5] MiR-126-3p inhibits ovarian cancer proliferation and invasion via targeting PLXNB2.Reprod Biol. 2018 Sep;18(3):218-224. doi: 10.1016/j.repbio.2018.07.005. Epub 2018 Jul 24.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] 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.
• [9] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [17] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [18] Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1. Mol Neurobiol. 2017 Jul;54(5):3798-3812. doi: 10.1007/s12035-016-9898-y. Epub 2016 Jun 7.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [21] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.