Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB71I02)

• DOT Name: Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2)
• Synonyms: CUB, LCCL and coagulation factor V/VIII-homology domains protein 1; Endothelial and smooth muscle cell-derived neuropilin-like protein
• Gene Name: DCBLD2
• Related Disease:
  Glioblastoma multiforme
  Neoplasm
  Arteriosclerosis
  Asthma
  Ataxia-telangiectasia
  Hypopharyngeal squamous cell carcinoma
  Immunodeficiency
  Lung cancer
  Nasal polyp
  Polycystic ovarian syndrome
  Stomach cancer
  Advanced cancer
  Hereditary diffuse gastric adenocarcinoma
  Gastric cancer
  Gastric neoplasm
  Marfan syndrome
  Neuroendocrine neoplasm
• UniProt ID: DCBD2_HUMAN
• Pfam ID: PF00431 ; PF00754 ; PF03815
• Sequence:
  MASRAVVRARRCPQCPQVRAAAAAPAWAALPLSRSLPPCSNSSSFSMPLFLLLLLVLLLL
  LEDAGAQQGDGCGHTVLGPESGTLTSINYPQTYPNSTVCEWEIRVKMGERVRIKFGDFDI
  EDSDSCHFNYLRIYNGIGVSRTEIGKYCGLGLQMNHSIESKGNEITLLFMSGIHVSGRGF
  LASYSVIDKQDLITCLDTASNFLEPEFSKYCPAGCLLPFAEISGTIPHGYRDSSPLCMAG
  VHAGVVSNTLGGQISVVISKGIPYYESSLANNVTSVVGHLSTSLFTFKTSGCYGTLGMES
  GVIADPQITASSVLEWTDHTGQENSWKPKKARLKKPGPPWAAFATDEYQWLQIDLNKEKK
  ITGIITTGSTMVEHNYYVSAYRILYSDDGQKWTVYREPGVEQDKIFQGNKDYHQDVRNNF
  LPPIIARFIRVNPTQWQQKIAMKMELLGCQFIPKGRPPKLTQPPPPRNSNDLKNTTAPPK
  IAKGRAPKFTQPLQPRSSNEFPAQTEQTTASPDIRNTTVTPNVTKDVALAAVLVPVLVMV
  LTTLILILVCAWHWRNRKKKTEGTYDLPYWDRAGWWKGMKQFLPAKAVDHEETPVRYSSS
  EVNHLSPREVTTVLQADSAEYAQPLVGGIVGTLHQRSTFKPEEGKEAGYADLDPYNSPGQ
  EVYHAYAEPLPITGPEYATPIIMDMSGHPTTSVGQPSTSTFKATGNQPPPLVGTYNTLLS
  RTDSCSSAQAQYDTPKAGKPGLPAPDELVYQVPQSTQEVSGAGRDGECDVFKEIL
• Tissue Specificity: Highly expressed in testis, heart, skeletal muscle and also in cultured vascular smooth muscle cells.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Genetic Variation	[4]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[5]
Hypopharyngeal squamous cell carcinoma	DISDDD65	Strong	Altered Expression	[6]
Immunodeficiency	DIS093I0	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Nasal polyp	DISLP3XE	Strong	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[7]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[8]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[9]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	moderate	Biomarker	[8]
Gastric cancer	DISXGOUK	Limited	Posttranslational Modification	[8]
Gastric neoplasm	DISOKN4Y	Limited	Posttranslational Modification	[8]
Marfan syndrome	DISVEUWZ	Limited	Biomarker	[9]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[29]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[29]

20 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[18]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[24]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[25]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[30]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[31]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2).	[32]

References

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• [2] Ensemble of gene signatures identifies novel biomarkers in colorectal cancer activated through PPAR and TNF signaling.PLoS One. 2013 Aug 19;8(8):e72638. doi: 10.1371/journal.pone.0072638. eCollection 2013.
• [3] ESDN is a marker of vascular remodeling and regulator of cell proliferation in graft arteriosclerosis.Am J Transplant. 2007 Sep;7(9):2098-105. doi: 10.1111/j.1600-6143.2007.01919.x.
• [4] DCBLD2 gene variations correlate with nasal polyposis in Korean asthma patients.Lung. 2012 Apr;190(2):199-207. doi: 10.1007/s00408-011-9354-8. Epub 2012 Jan 21.
• [5] Potential association of DCBLD2 polymorphisms with fall rates of FEV(1) by aspirin provocation in Korean asthmatics.J Korean Med Sci. 2012 Apr;27(4):343-9. doi: 10.3346/jkms.2012.27.4.343. Epub 2012 Mar 21.
• [6] Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature.Br J Cancer. 2014 Jul 15;111(2):386-94. doi: 10.1038/bjc.2014.293. Epub 2014 Jun 10.
• [7] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [8] Epigenetic down-regulation and suppressive role of DCBLD2 in gastric cancer cell proliferation and invasion.Mol Cancer Res. 2008 Feb;6(2):222-30. doi: 10.1158/1541-7786.MCR-07-0142.
• [9] Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling.Biochim Biophys Acta Proteins Proteom. 2017 Sep;1865(9):1160-1166. doi: 10.1016/j.bbapap.2017.06.023. Epub 2017 Jun 29.
• [10] Identification of novel neuroendocrine-specific tumour genes.Br J Cancer. 2008 Oct 21;99(8):1330-9. doi: 10.1038/sj.bjc.6604565. Epub 2008 Sep 30.
• [11] 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.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [22] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [23] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [24] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [25] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [26] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [27] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [28] 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.
• [29] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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• [32] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.