Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGZ43YI)

• DOT Name: Partitioning defective 3 homolog B (PARD3B)
• Synonyms: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 19 protein; PAR3-beta; Partitioning defective 3-like protein; PAR3-L protein
• Gene Name: PARD3B
• Related Disease:
  Autism
  Neurodevelopmental disorder
  Acquired immune deficiency syndrome
  Advanced cancer
  Craniofacial microsomia
  Neoplasm
  Acute myelogenous leukaemia
  Asthma
  Colorectal carcinoma
• UniProt ID: PAR3L_HUMAN
• Pfam ID: PF12053 ; PF00595
• Sequence:
  MKVTVCFGRTGIVVPCKEGQLRVGELTQQALQRYLKTREKGPGYWVKIHHLEYTDGGILD
  PDDVLADVVEDKDKLIAVFEEQEPLHKIESPSGNPADRQSPDAFETEVAAQLAAFKPIGG
  EIEVTPSALKLGTPLLVRRSSDPVPGPPADTQPSASHPGGQSLKLVVPDSTQNLEDREVL
  NGVQTELLTSPRTKDTLSDMTRTVEISGEGGPLGIHVVPFFSSLSGRILGLFIRGIEDNS
  RSKREGLFHENECIVKINNVDLVDKTFAQAQDVFRQAMKSPSVLLHVLPPQNREQYEKSV
  IGSLNIFGNNDGVLKTKVPPPVHGKSGLKTANLTGTDSPETDASASLQQNKSPRVPRLGG
  KPSSPSLSPLMGFGSNKNAKKIKIDLKKGPEGLGFTVVTRDSSIHGPGPIFVKNILPKGA
  AIKDGRLQSGDRILEVNGRDVTGRTQEELVAMLRSTKQGETASLVIARQEGHFLPRELKG
  EPDCCALSLETSEQLTFEIPLNDSGSAGLGVSLKGNKSRETGTDLGIFIKSIIHGGAAFK
  DGRLRMNDQLIAVNGESLLGKSNHEAMETLRRSMSMEGNIRGMIQLVILRRPERPMEDPA
  ECGAFSKPCFENCQNAVTTSRRNDNSILHPLGTCSPQDKQKGLLLPNDGWAESEVPPSPT
  PHSALGLGLEDYSHSSGVDSAVYFPDQHINFRSVTPARQPESINLKASKSMDLVPDESKV
  HSLAGQKSESPSKDFGPTLGLKKSSSLESLQTAVAEVRKNDLPFHRPRPHMVRGRGCNES
  FRAAIDKSYDGPEEIEADGLSDKSSHSGQGALNCESAPQGNSELEDMENKARKVKKTKEK
  EKKKEKGKLKVKEKKRKEENEDPERKIKKKGFGAMLRFGKKKEDKGGKAEQKGTLKHGGL
  REEELEKMKEERERIGAKHQELREKQARGLLDYATGAIGSVYDMDDDEMDPNYARVNHFR
  EPCTSANVFRSPSPPRAGPFGYPRDGHPLSPERDHLEGLYAKVNKPYHPLVPADSGRPTG
  GSTDRIQKLRKEYYQARREGFPLYEDDEGRARPSEYDLLWVPGRGPDGNAHNLRFEGMER
  QYASLPRGGPADPVDYLPAAPRGLYKERELPYYPGAHPMHPPKGSYPRPTELRVADLRYP
  QHYPPPPAPQHKGPFRQDVPPSPPQHQRMPAYQETGRPGPRGGSPDQYPYRTQDSRQKNP
  MTAAV
• Function: Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions.
• Tissue Specificity: Highly expressed in kidney, lung and skeletal muscle. Expressed at intermediate levels in brain, heart, placenta, liver and pancreas. Isoform 1 is predominant, while isoform 2 and isoform 3 are expressed at lower levels.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Neurodevelopmental disorder	DIS372XH	Definitive	Biomarker	[2]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Craniofacial microsomia	DISYHJ2P	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[6]
Asthma	DISW9QNS	Limited	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[4]

8 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 Partitioning defective 3 homolog B (PARD3B).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Partitioning defective 3 homolog B (PARD3B).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Partitioning defective 3 homolog B (PARD3B).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Partitioning defective 3 homolog B (PARD3B).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Partitioning defective 3 homolog B (PARD3B).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Partitioning defective 3 homolog B (PARD3B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Partitioning defective 3 homolog B (PARD3B).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Partitioning defective 3 homolog B (PARD3B).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Partitioning defective 3 homolog B (PARD3B).	[16]

References

• [1] Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet. 2012 Nov 1;21(21):4781-92. doi: 10.1093/hmg/dds301. Epub 2012 Jul 26.
• [2] Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
• [3] Genome-wide association study implicates PARD3B-based AIDS restriction.J Infect Dis. 2011 May 15;203(10):1491-502. doi: 10.1093/infdis/jir046.
• [4] High expression of partitioning defective 3-like protein is associated with malignancy in colorectal cancer.Tumour Biol. 2017 Apr;39(4):1010428317698393. doi: 10.1177/1010428317698393.
• [5] Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia.Nat Commun. 2016 Feb 8;7:10605. doi: 10.1038/ncomms10605.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [15] 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.
• [16] 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.