Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTB4VFQ)

DOT Name Protein cordon-bleu (COBL)
Gene Name COBL
Related Disease
Lung squamous cell carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Acute lymphocytic leukaemia ( )
Generalized anxiety disorder ( )
leukaemia ( )
Leukemia ( )
Non-insulin dependent diabetes ( )
Type-1 diabetes ( )
UniProt ID
COBL_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4PL8
Pfam ID
PF09469 ; PF02205
Sequence
MDAPRASAAKPPTGRKMKARAPPPPGKAATLHVHSDQKPPHDGALGSQQNLVRMKEALRA
STMDVTVVLPSGLEKRSVLNGSHAMMDLLVELCLQNHLNPSHHALEIRSSETQQPLSFKP
NTLIGTLNVHTVFLKEKVPEEKVKPGPPKVPEKSVRLVVNYLRTQKAVVRVSPEVPLQNI
LPVICAKCEVSPEHVVLLRDNIAGEELELSKSLNELGIKELYAWDNRRETFRKSSLGNDE
TDKEKKKFLGFFKVNKRSNSKGCLTTPNSPSMHSRSLTLGPSLSLGSISGVSVKSEMKKR
RAPPPPGSGPPVQDKASEKVSLGSQIDLQKKKRRAPAPPPPQPPPPSPLIPNRTEDKEEN
RKSTMVSLPLGSGSHCSPDGAPQVLSEAEETVSVGSCFASEDTTEDSGVMSSPSDIVSLD
SQQDSMKYKDKWATDQEDCSDQDLAGTPDLGPQKSPLWEKNGSENSHLRTEKAVTASNDE
EDLLIAGEFRKTLAELDEDLEEMEDSYETDTSSLTSSIHGASNHCPQDAMIPHGDTDAIP
VTFIGEVSDDPVDSGLFSNRNNNAGSFDSEGVASRRDSLAPLQAEHSQPHEKAREEVPAL
HPASHDVGKGIRVALSNISKDGNLMETAPRVTSFASNLHTDNLNAKVKDKVYGCADGERT
QATERVNSQPVNEKDSNDKNAALAPTSWHQRGQNPGKSYRLKHGLTTYKIIPPKSEMRCY
DRDVSLSTGAIKIDELGNLVSPHATGIRIISLSSSVPEAESQPIGKVREFWRCNSVEKHL
GRPSESSARGPPSTPVPTQTQNPESRLQADPKPISPQQKSAHHEGRNPLGEGRNQPPTMG
MGHVRVPAAHTTEVTFLKPQRRTSSQYVASAIAKRIGAPKVHADVVRPHGYAEKGYAGKA
PVLAAPPVTVKDDRTSSPHSETQGWKDGAQWPCVTPPNNHGEDLAVGAPPRGEVIGPHRK
LSTQDRPAAIHRSSCFSLVQSSQRDRVSVGQSCGFSGKQSTSSQEASSASEPRRAPDGTD
PPPPHTSDTQACSRELVNGSVRAPGHGEPSHPPGGSGTESHILLEREEKPSVFSTDGNET
DSIWPPSIFGPKKKFKPVVQRPVPKDTSLHSALMEAIHSAGGKDRLRKTAEHTGEGRPAK
LSYTEAEGERSALLAAIRGHSGTCSLRKVASSASEELQSFRDAALSAQGSESPLLEDLGL
LSPPAIPPPPPPPSQALSAPRTASRFSTGTLSNTADARQALMDAIRSGTGAARLRKVPLL
V
Function
Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells. Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung squamous cell carcinoma DISXPIBD Definitive Genetic Variation [1]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [2]
Acute lymphocytic leukaemia DISPX75S Limited Genetic Variation [3]
Generalized anxiety disorder DISPSQCW Limited Genetic Variation [4]
leukaemia DISS7D1V Limited Biomarker [3]
Leukemia DISNAKFL Limited Biomarker [3]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [5]
Type-1 diabetes DIS7HLUB Limited Biomarker [4]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Protein cordon-bleu (COBL). [6]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Protein cordon-bleu (COBL). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein cordon-bleu (COBL). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein cordon-bleu (COBL). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Protein cordon-bleu (COBL). [10]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Protein cordon-bleu (COBL). [11]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein cordon-bleu (COBL). [12]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Protein cordon-bleu (COBL). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Protein cordon-bleu (COBL). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Protein cordon-bleu (COBL). [15]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Protein cordon-bleu (COBL). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Protein cordon-bleu (COBL). [16]
Fenfluramine DM0762O Phase 3 Fenfluramine increases the expression of Protein cordon-bleu (COBL). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Protein cordon-bleu (COBL). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Protein cordon-bleu (COBL). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein cordon-bleu (COBL). [21]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Protein cordon-bleu (COBL). [22]
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⏷ Show the Full List of 17 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Protein cordon-bleu (COBL). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Protein cordon-bleu (COBL). [20]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Protein cordon-bleu (COBL). [19]
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References

1 TRIM58/cg26157385 methylation is associated with eight prognostic genes in lung squamous cell carcinoma.Oncol Rep. 2018 Jul;40(1):206-216. doi: 10.3892/or.2018.6426. Epub 2018 May 8.
2 COBL is a novel hotspot for IKZF1 deletions in childhood acute lymphoblastic leukemia.Oncotarget. 2016 Aug 16;7(33):53064-53073. doi: 10.18632/oncotarget.10590.
3 IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia.Transl Oncol. 2019 May;12(5):726-732. doi: 10.1016/j.tranon.2019.02.002. Epub 2019 Mar 13.
4 Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children.Diabetologia. 2013 Jul;56(7):1615-22. doi: 10.1007/s00125-013-2896-y. Epub 2013 Mar 29.
5 Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls.Nat Genet. 2015 Jul;47(7):839-46. doi: 10.1038/ng.3330. Epub 2015 Jun 8.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 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.
8 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
12 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
13 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 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.
16 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.
17 Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
18 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.
19 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.
20 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.
21 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.
22 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.