Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ5XKYY)

DOT Name Plexin-C1 (PLXNC1)
Synonyms Virus-encoded semaphorin protein receptor; CD antigen CD232
Gene Name PLXNC1
Related Disease
Melanoma ( )
Thyroid gland papillary carcinoma ( )
Advanced cancer ( )
Autoimmune disease ( )
Autoimmune disease, susceptibility to, 6 ( )
Hypothyroidism ( )
Metastatic melanoma ( )
Pneumonia ( )
Pneumonitis ( )
Pulmonary fibrosis ( )
STAT3-related early-onset multisystem autoimmune disease ( )
Endometriosis ( )
Neoplasm ( )
UniProt ID
PLXC1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3KUZ; 3NVN; 3NVQ; 6VXK
Pfam ID
PF08337 ; PF20170 ; PF01437 ; PF01833
Sequence
MEVSRRKAPPRPPRPAAPLPLLAYLLALAAPGRGADEPVWRSEQAIGAIAASQEDGVFVA
SGSCLDQLDYSLEHSLSRLYRDQAGNCTEPVSLAPPARPRPGSSFSKLLLPYREGAAGLG
GLLLTGWTFDRGACEVRPLGNLSRNSLRNGTEVVSCHPQGSTAGVVYRAGRNNRWYLAVA
ATYVLPEPETASRCNPAASDHDTAIALKDTEGRSLATQELGRLKLCEGAGSLHFVDAFLW
NGSIYFPYYPYNYTSGAATGWPSMARIAQSTEVLFQGQASLDCGHGHPDGRRLLLSSSLV
EALDVWAGVFSAAAGEGQERRSPTTTALCLFRMSEIQARAKRVSWDFKTAESHCKEGDQP
ERVQPIASSTLIHSDLTSVYGTVVMNRTVLFLGTGDGQLLKVILGENLTSNCPEVIYEIK
EETPVFYKLVPDPVKNIYIYLTAGKEVRRIRVANCNKHKSCSECLTATDPHCGWCHSLQR
CTFQGDCVHSENLENWLDISSGAKKCPKIQIIRSSKEKTTVTMVGSFSPRHSKCMVKNVD
SSRELCQNKSQPNRTCTCSIPTRATYKDVSVVNVMFSFGSWNLSDRFNFTNCSSLKECPA
CVETGCAWCKSARRCIHPFTACDPSDYERNQEQCPVAVEKTSGGGRPKENKGNRTNQALQ
VFYIKSIEPQKVSTLGKSNVIVTGANFTRASNITMILKGTSTCDKDVIQVSHVLNDTHMK
FSLPSSRKEMKDVCIQFDGGNCSSVGSLSYIALPHCSLIFPATTWISGGQNITMMGRNFD
VIDNLIISHELKGNINVSEYCVATYCGFLAPSLKSSKVRTNVTVKLRVQDTYLDCGTLQY
REDPRFTGYRVESEVDTELEVKIQKENDNFNISKKDIEITLFHGENGQLNCSFENITRNQ
DLTTILCKIKGIKTASTIANSSKKVRVKLGNLELYVEQESVPSTWYFLIVLPVLLVIVIF
AAVGVTRHKSKELSRKQSQQLELLESELRKEIRDGFAELQMDKLDVVDSFGTVPFLDYKH
FALRTFFPESGGFTHIFTEDMHNRDANDKNESLTALDALICNKSFLVTVIHTLEKQKNFS
VKDRCLFASFLTIALQTKLVYLTSILEVLTRDLMEQCSNMQPKLMLRRTESVVEKLLTNW
MSVCLSGFLRETVGEPFYLLVTTLNQKINKGPVDVITCKALYTLNEDWLLWQVPEFSTVA
LNVVFEKIPENESADVCRNISVNVLDCDTIGQAKEKIFQAFLSKNGSPYGLQLNEIGLEL
QMGTRQKELLDIDSSSVILEDGITKLNTIGHYEISNGSTIKVFKKIANFTSDVEYSDDHC
HLILPDSEAFQDVQGKRHRGKHKFKVKEMYLTKLLSTKVAIHSVLEKLFRSIWSLPNSRA
PFAIKYFFDFLDAQAENKKITDPDVVHIWKTNSLPLRFWVNILKNPQFVFDIKKTPHIDG
CLSVIAQAFMDAFSLTEQQLGKEAPTNKLLYAKDIPTYKEEVKSYYKAIRDLPPLSSSEM
EEFLTQESKKHENEFNEEVALTEIYKYIVKYFDEILNKLERERGLEEAQKQLLHVKVLFD
EKKKCKWM
Function
Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8.
Tissue Specificity Detected in heart, brain, lung, spleen and placenta.
KEGG Pathway
Axon guidance (hsa04360 )
Reactome Pathway
Other semaphorin interactions (R-HSA-416700 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Melanoma DIS1RRCY Definitive Biomarker [1]
Thyroid gland papillary carcinoma DIS48YMM Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Autoimmune disease DISORMTM Strong Genetic Variation [4]
Autoimmune disease, susceptibility to, 6 DISHNUXI Strong Genetic Variation [4]
Hypothyroidism DISR0H6D Strong Genetic Variation [4]
Metastatic melanoma DISSL43L Strong Biomarker [5]
Pneumonia DIS8EF3M Strong Biomarker [6]
Pneumonitis DIS88E0K Strong Biomarker [6]
Pulmonary fibrosis DISQKVLA Strong Biomarker [7]
STAT3-related early-onset multisystem autoimmune disease DISAXTN7 Strong Genetic Variation [4]
Endometriosis DISX1AG8 Disputed Biomarker [8]
Neoplasm DISZKGEW Limited Altered Expression [9]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
21 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-C1 (PLXNC1). [10]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Plexin-C1 (PLXNC1). [11]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Plexin-C1 (PLXNC1). [12]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Plexin-C1 (PLXNC1). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Plexin-C1 (PLXNC1). [15]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Plexin-C1 (PLXNC1). [16]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Plexin-C1 (PLXNC1). [17]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Plexin-C1 (PLXNC1). [18]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Plexin-C1 (PLXNC1). [19]
Progesterone DMUY35B Approved Progesterone increases the expression of Plexin-C1 (PLXNC1). [8]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Plexin-C1 (PLXNC1). [18]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of Plexin-C1 (PLXNC1). [21]
Liothyronine DM6IR3P Approved Liothyronine increases the expression of Plexin-C1 (PLXNC1). [22]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Plexin-C1 (PLXNC1). [23]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Plexin-C1 (PLXNC1). [18]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Plexin-C1 (PLXNC1). [18]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Plexin-C1 (PLXNC1). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Plexin-C1 (PLXNC1). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Plexin-C1 (PLXNC1). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Plexin-C1 (PLXNC1). [28]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Plexin-C1 (PLXNC1). [29]
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⏷ Show the Full List of 21 Drug(s)
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-C1 (PLXNC1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Plexin-C1 (PLXNC1). [24]
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References

1 Long non-coding RNA CASC2 inhibits tumorigenesis via the miR-181a/PLXNC1 axis in melanoma.Acta Biochim Biophys Sin (Shanghai). 2018 Mar 1;50(3):263-272. doi: 10.1093/abbs/gmx148.
2 MiR-4500 Regulates PLXNC1 and Inhibits Papillary Thyroid Cancer Progression.Horm Cancer. 2019 Dec;10(4-6):150-160. doi: 10.1007/s12672-019-00366-1. Epub 2019 Jul 17.
3 Plexin C1 Marks Liver Cancer Cells with Epithelial Phenotype and Is Overexpressed in Hepatocellular Carcinoma.Can J Gastroenterol Hepatol. 2018 Sep 19;2018:4040787. doi: 10.1155/2018/4040787. eCollection 2018.
4 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
5 Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression.J Invest Dermatol. 2009 Apr;129(4):954-63. doi: 10.1038/jid.2008.329. Epub 2008 Nov 6.
6 Endothelial semaphorin 7A promotes seawater aspiration-induced acute lung injury through plexin C1 and 1 integrin.Mol Med Rep. 2017 Oct;16(4):4215-4221. doi: 10.3892/mmr.2017.7097. Epub 2017 Jul 27.
7 Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.FASEB J. 2016 Dec;30(12):4056-4070. doi: 10.1096/fj.201600373R. Epub 2016 Sep 8.
8 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
9 Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222.Mol Ther. 2015 Dec;23(12):1899-911. doi: 10.1038/mt.2015.170. Epub 2015 Sep 15.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
12 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
13 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
14 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.
15 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.
16 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
17 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
18 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
19 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
20 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
21 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
22 Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
23 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
24 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.
25 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
26 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.
27 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
28 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
29 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.