Details of Drug Off-Target (DOT)

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

DOT Name Plexin-B3 (PLXNB3)
Gene Name PLXNB3
Related Disease
Advanced cancer ( )
Glioma ( )
Schizophrenia ( )
Stomach cancer ( )
UniProt ID
PLXB3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF08337 ; PF20170 ; PF01437 ; PF01403 ; PF01833 ; PF18020 ; PF17960
Sequence
MCHAAQETPLLHHFMAPVMARWPPFGLCLLLLLLSPPPLPLTGAHRFSAPNTTLNHLALA
PGRGTLYVGAVNRLFQLSPELQLEAVAVTGPVIDSPDCVPFRDPAECPQAQLTDNANQLL
LVSSRAQELVACGQVRQGVCETRRLGDVAEVLYQAEDPGDGQFVAANTPGVATVGLVVPL
PGRDLLLVARGLAGKLSAGVPPLAIRQLAGSQPFSSEGLGRLVVGDFSDYNNSYVGAFAD
ARSAYFVFRRRGARAQAEYRSYVARVCLGDTNLYSYVEVPLACQGQGLIQAAFLAPGTLL
GVFAAGPRGTQAALCAFPMVELGASMEQARRLCYTAGGRGPSGAEEATVEYGVTSRCVTL
PLDSPESYPCGDEHTPSPIAGRQPLEVQPLLKLGQPVSAVAALQADGHMIAFLGDTQGQL
YKVFLHGSQGQVYHSQQVGPPGSAISPDLLLDSSGSHLYVLTAHQVDRIPVAACPQFPDC
ASCLQAQDPLCGWCVLQGRCTRKGQCGRAGQLNQWLWSYEEDSHCLHIQSLLPGHHPRQE
QGQVTLSVPRLPILDADEYFHCAFGDYDSLAHVEGPHVACVTPPQDQVPLNPPGTDHVTV
PLALMFEDVTVAATNFSFYDCSAVQALEAAAPCRACVGSIWRCHWCPQSSHCVYGEHCPE
GERTIYSAQEVDIQVRGPGACPQVEGLAGPHLVPVGWESHLALRVRNLQHFRGLPASFHC
WLELPGELRGLPATLEETAGDSGLIHCQAHQFYPSMSQRELPVPIYVTQGEAQRLDNTHA
LYVILYDCAMGHPDCSHCQAANRSLGCLWCADGQPACRYGPLCPPGAVELLCPAPSIDAV
EPLTGPPEGGLALTILGSNLGRAFADVQYAVSVASRPCNPEPSLYRTSARIVCVTSPAPN
GTTGPVRVAIKSQPPGISSQHFTYQDPVLLSLSPRWGPQAGGTQLTIRGQHLQTGGNTSA
FVGGQPCPILEPVCPEAIVCRTRPQAAPGEAAVLVVFGHAQRTLLASPFRYTANPQLVAA
EPSASFRGGGRLIRVRGTGLDVVQRPLLSVWLEADAEVQASRAQPQDPQPRRSCGAPAAD
PQACIQLGGGLLQCSTVCSVNSSSLLLCRSPAVPDRAHPQRVFFTLDNVQVDFASASGGQ
GFLYQPNPRLAPLSREGPARPYRLKPGHVLDVEGEGLNLGISKEEVRVHIGRGECLVKTL
TRTHLYCEPPAHAPQPANGSGLPQFVVQMGNVQLALGPVQYEAEPPLSAFPVEAQAGVGM
GAAVLIAAVLLLTLMYRHKSKQALRDYQKVLVQLESLETGVGDQCRKEFTDLMTEMTDLS
SDLEGSGIPFLDYRTYAERAFFPGHGGCPLQPKPEGPGEDGHCATVRQGLTQLSNLLNSK
LFLLTLIHTLEEQPSFSQRDRCHVASLLSLALHGKLEYLTDIMRTLLGDLAAHYVHRNPK
LMLRRTETMVEKLLTNWLSICLYAFLREVAGEPLYMLFRAIQYQVDKGPVDAVTGKAKRT
LNDSRLLREDVEFQPLTLMVLVGPGAGGAAGSSEMQRVPARVLDTDTITQVKEKVLDQVY
KGTPFSQRPSVHALDLEWRSGLAGHLTLSDEDLTSVTQNHWKRLNTLQHYKVPDGATVGL
VPQLHRGSTISQSLAQRCPLGENIPTLEDGEEGGVCLWHLVKATEEPEGAKVRCSSLRER
EPARAKAIPEIYLTRLLSMKGTLQKFVDDTFQAILSVNRPIPIAVKYLFDLLDELAEKHG
IEDPGTLHIWKTNSLLLRFWVNALKNPQLIFDVRVSDNVDAILAVIAQTFIDSCTTSEHK
VGRDSPVNKLLYAREIPRYKQMVERYYADIRQSSPASYQEMNSALAELSGNYTSAPHCLE
ALQELYNHIHRYYDQIISALEEDPVGQKLQLACRLQQVAALVENKVTDL
Function
Receptor for SEMA5A that plays a role in axon guidance, invasive growth and cell migration. Stimulates neurite outgrowth and mediates Ca(2+)/Mg(2+)-dependent cell aggregation. In glioma cells, SEMA5A stimulation of PLXNB3 results in the disassembly of F-actin stress fibers, disruption of focal adhesions and cellular collapse as well as inhibition of cell migration and invasion through ARHGDIA-mediated inactivation of RAC1.
Tissue Specificity
Expression detected in Purkinje and granular cells in cerebellum, and in brain neocortex but not in corpus callosum. Expressed in glioma cells and embryonic kidney cells (at protein level). Expressed in brain, liver, pancreas and placenta, with weak expression detected also in lung and kidney. Expressed in several glioma cell lines.
KEGG Pathway
Axon guidance (hsa04360 )
Reactome Pathway
Other semaphorin interactions (R-HSA-416700 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Glioma DIS5RPEH Strong Biomarker [2]
Schizophrenia DISSRV2N Strong Biomarker [3]
Stomach cancer DISKIJSX Strong Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Plexin-B3 (PLXNB3). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Plexin-B3 (PLXNB3). [12]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Plexin-B3 (PLXNB3). [6]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Plexin-B3 (PLXNB3). [7]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Plexin-B3 (PLXNB3). [8]
Triclosan DMZUR4N Approved Triclosan increases the expression of Plexin-B3 (PLXNB3). [9]
Marinol DM70IK5 Approved Marinol increases the expression of Plexin-B3 (PLXNB3). [10]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Plexin-B3 (PLXNB3). [11]
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⏷ Show the Full List of 6 Drug(s)

References

1 Molecular profiling of the "plexinome" in melanoma and pancreatic cancer.Hum Mutat. 2009 Aug;30(8):1167-74. doi: 10.1002/humu.21017.
2 Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton.Oncogene. 2012 Feb 2;31(5):595-610. doi: 10.1038/onc.2011.256. Epub 2011 Jun 27.
3 Plexin B3 is genetically associated with verbal performance and white matter volume in human brain.Mol Psychiatry. 2007 Feb;12(2):190-4, 115. doi: 10.1038/sj.mp.4001903. Epub 2006 Oct 10.
4 Expression of semaphorin 5A and its receptor plexin B3 contributes to invasion and metastasis of gastric carcinoma.World J Gastroenterol. 2009 Jun 14;15(22):2800-4. doi: 10.3748/wjg.15.2800.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
8 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
9 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
11 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
12 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.