Details of Drug Off-Target (DOT)

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

• DOT Name: Anthrax toxin receptor 2 (ANTXR2)
• Synonyms: Capillary morphogenesis gene 2 protein; CMG-2
• Gene Name: ANTXR2
• Related Disease:
  Hyaline fibromatosis syndrome
  Infantile systemic hyalinosis
  Juvenile hyaline fibromatosis
• UniProt ID: ANTR2_HUMAN
• PDB ID: 1SHT; 1SHU; 1T6B; 1TZN; 7N1O; 8FT6; 8FT8; 8FZ4; 8FZU; 8FZV
• Pfam ID: PF05586 ; PF05587 ; PF00092
• Sequence:
  MVAERSPARSPGSWLFPGLWLLVLSGPGGLLRAQEQPSCRRAFDLYFVLDKSGSVANNWI
  EIYNFVQQLAERFVSPEMRLSFIVFSSQATIILPLTGDRGKISKGLEDLKRVSPVGETYI
  HEGLKLANEQIQKAGGLKTSSIIIALTDGKLDGLVPSYAEKEAKISRSLGASVYCVGVLD
  FEQAQLERIADSKEQVFPVKGGFQALKGIINSILAQSCTEILELQPSSVCVGEEFQIVLS
  GRGFMLGSRNGSVLCTYTVNETYTTSVKPVSVQLNSMLCPAPILNKAGETLDVSVSFNGG
  KSVISGSLIVTATECSNGIAAIIVILVLLLLLGIGLMWWFWPLCCKVVIKDPPPPPAPAP
  KEEEEEPLPTKKWPTVDASYYGGRGVGGIKRMEVRWGDKGSTEEGARLEKAKNAVVKIPE
  ETEEPIRPRPPRPKPTHQPPQTKWYTPIKGRLDALWALLRRQYDRVSLMRPQEGDEVCIW
  ECIEKELTA
• Function: Necessary for cellular interactions with laminin and the extracellular matrix; (Microbial infection) Receptor for the protective antigen (PA) of B.anthracis. Binding of PA leads to heptamerization of the receptor-PA complex. Upon binding of the PA of B.anthracis, the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway. In the endosomal membrane, at pH under 7, the complex then rearranges and forms a pore allowing the other components of anthrax toxin to escape to the cytoplasm.
• Tissue Specificity: Expressed in prostate, thymus, ovary, testis, pancreas, colon, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, skeletal muscle, small intestine and spleen.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway: Uptake and function of anthrax toxins (R-HSA-5210891)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyaline fibromatosis syndrome	DISZAHF9	Definitive	Autosomal recessive	[1]
Infantile systemic hyalinosis	DISECEE3	Supportive	Autosomal recessive	[2]
Juvenile hyaline fibromatosis	DISQP8V9	Supportive	Autosomal recessive	[2]

20 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 Anthrax toxin receptor 2 (ANTXR2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Anthrax toxin receptor 2 (ANTXR2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Anthrax toxin receptor 2 (ANTXR2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Anthrax toxin receptor 2 (ANTXR2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Anthrax toxin receptor 2 (ANTXR2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Anthrax toxin receptor 2 (ANTXR2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Anthrax toxin receptor 2 (ANTXR2).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Anthrax toxin receptor 2 (ANTXR2).	[17]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Anthrax toxin receptor 2 (ANTXR2).	[23]

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 Anthrax toxin receptor 2 (ANTXR2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Anthrax toxin receptor 2 (ANTXR2).	[19]

References

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• [2] Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):791-800. doi: 10.1086/378418. Epub 2003 Aug 21.
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• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] 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.
• [13] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
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• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder. BMC Syst Biol. 2010 Nov 19;4:158. doi: 10.1186/1752-0509-4-158.
• [19] 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.
• [20] 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.
• [21] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [22] 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.
• [23] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.