Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMHH14H)

DOT Name Dynamin-binding protein (DNMBP)
Synonyms Scaffold protein Tuba
Gene Name DNMBP
Related Disease
Cataract ( )
Cataract 48 ( )
Hepatocellular carcinoma ( )
Plasma cell myeloma ( )
Total early-onset cataract ( )
UniProt ID
DNMBP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1UG1; 1UHC; 4CC2; 4CC3; 4CC4; 4CC7; 4GLM
Pfam ID
PF03114 ; PF00621 ; PF00018 ; PF07653 ; PF14604
Sequence
MEAGSVVRAIFDFCPSVSEELPLFVGDIIEVLAVVDEFWLLGKKEDVTGQFPSSFVEIVT
IPSLKEGERLFVCICEFTSQELDNLPLHRGDLVILDGIPTAGWLQGRSCWGARGFFPSSC
VRELCLSSQSRQWHSQSALFQIPEYSMGQARALMGLSAQLDEELDFREGDVITIIGVPEP
GWFEGELEGRRGIFPEGFVELLGPLRTVDESVSSGNQDDCIVNGEVDTPVGEEEIGPDED
EEEPGTYGVALYRFQALEPNELDFEVGDKIRILATLEDGWLEGSLKGRTGIFPYRFVKLC
PDTRVEETMALPQEGSLARIPETSLDCLENTLGVEEQRHETSDHEAEEPDCIISEAPTSP
LGHLTSEYDTDRNSYQDEDTAGGPPRSPGVEWEMPLATDSPTSDPTEVVNGISSQPQVPF
HPNLQKSQYYSTVGGSHPHSEQYPDLLPLEARTRDYASLPPKRMYSQLKTLQKPVLPLYR
GSSVSASRVVKPRQSSPQLHNLASYTKKHHTSSVYSISERLEMKPGPQAQGLVMEAATHS
QGDGSTDLDSKLTQQLIEFEKSLAGPGTEPDKILRHFSIMDFNSEKDIVRGSSKLITEQE
LPERRKALRPPPPRPCTPVSTSPHLLVDQNLKPAPPLVVRPSRPAPLPPSAQQRTNAVSP
KLLSRHRPTCETLEKEGPGHMGRSLDQTSPCPLVLVRIEEMERDLDMYSRAQEELNLMLE
EKQDESSRAETLEDLKFCESNIESLNMELQQLREMTLLSSQSSSLVAPSGSVSAENPEQR
MLEKRAKVIEELLQTERDYIRDLEMCIERIMVPMQQAQVPNIDFEGLFGNMQMVIKVSKQ
LLAALEISDAVGPVFLGHRDELEGTYKIYCQNHDEAIALLEIYEKDEKIQKHLQDSLADL
KSLYNEWGCTNYINLGSFLIKPVQRVMRYPLLLMELLNSTPESHPDKVPLTNAVLAVKEI
NVNINEYKRRKDLVLKYRKGDEDSLMEKISKLNIHSIIKKSNRVSSHLKHLTGFAPQIKD
EVFEETEKNFRMQERLIKSFIRDLSLYLQHIRESACVKVVAAVSMWDVCMERGHRDLEQF
ERVHRYISDQLFTNFKERTERLVISPLNQLLSMFTGPHKLVQKRFDKLLDFYNCTERAEK
LKDKKTLEELQSARNNYEALNAQLLDELPKFHQYAQGLFTNCVHGYAEAHCDFVHQALEQ
LKPLLSLLKVAGREGNLIAIFHEEHSRVLQQLQVFTFFPESLPATKKPFERKTIDRQSAR
KPLLGLPSYMLQSEELRASLLARYPPEKLFQAERNFNAAQDLDVSLLEGDLVGVIKKKDP
MGSQNRWLIDNGVTKGFVYSSFLKPYNPRRSHSDASVGSHSSTESEHGSSSPRFPRQNSG
STLTFNPSSMAVSFTSGSCQKQPQDASPPPKECDQGTLSASLNPSNSESSPSRCPSDPDS
TSQPRSGDSADVARDVKQPTATPRSYRNFRHPEIVGYSVPGRNGQSQDLVKGCARTAQAP
EDRSTEPDGSEAEGNQVYFAVYTFKARNPNELSVSANQKLKILEFKDVTGNTEWWLAEVN
GKKGYVPSNYIRKTEYT
Function
Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells. Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation. Plays a role in ciliogenesis. May play a role in membrane trafficking between the cell surface and the Golgi.
Tissue Specificity Detected in heart, brain, lung, liver, skeletal muscle, kidney and pancreas.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cataract DISUD7SL Strong Genetic Variation [1]
Cataract 48 DISBRXRN Strong Autosomal recessive [1]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [2]
Plasma cell myeloma DIS0DFZ0 moderate Genetic Variation [3]
Total early-onset cataract DISACMEZ Supportive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Dynamin-binding protein (DNMBP). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Dynamin-binding protein (DNMBP). [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Dynamin-binding protein (DNMBP). [6]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Dynamin-binding protein (DNMBP). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Dynamin-binding protein (DNMBP). [4]
Marinol DM70IK5 Approved Marinol decreases the expression of Dynamin-binding protein (DNMBP). [9]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Dynamin-binding protein (DNMBP). [10]
Ifosfamide DMCT3I8 Approved Ifosfamide increases the expression of Dynamin-binding protein (DNMBP). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Dynamin-binding protein (DNMBP). [12]
PD-0325901 DM27D4J Phase 2 PD-0325901 decreases the expression of Dynamin-binding protein (DNMBP). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dynamin-binding protein (DNMBP). [15]
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⏷ Show the Full List of 11 Drug(s)
4 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 Dynamin-binding protein (DNMBP). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Dynamin-binding protein (DNMBP). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Dynamin-binding protein (DNMBP). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Dynamin-binding protein (DNMBP). [17]
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References

1 Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts. Am J Hum Genet. 2018 Oct 4;103(4):568-578. doi: 10.1016/j.ajhg.2018.09.004.
2 Different molecular pathways determining extrahepatic and intrahepatic recurrences of hepatocellular carcinoma.Oncol Rep. 2006 Nov;16(5):1137-42.
3 Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study).Hematol Oncol. 2018 Feb;36(1):202-209. doi: 10.1002/hon.2452. Epub 2017 Jul 6.
4 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.
5 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
7 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.
8 Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
9 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
10 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
11 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
14 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.
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 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.
17 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.