Details of Drug Off-Target (DOT)

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

DOT Name Molecule interacting with CasL protein 1 (MICAL-1)
Synonyms EC 1.14.13.225; EC 1.6.3.1; Molecule interacting with CasL protein 1; MICAL-1; NEDD9-interacting protein with calponin homology and LIM domains
Gene Name MICAL1
Related Disease
Breast carcinoma ( )
Cone-rod dystrophy 2 ( )
Advanced cancer ( )
Breast cancer ( )
Epilepsy ( )
Gastric cancer ( )
Major depressive disorder ( )
Stomach cancer ( )
Temporal lobe epilepsy ( )
Melanoma ( )
UniProt ID
MICA1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1WYL; 2CO8; 2DK9; 5LE0; 5LPN; 6KU0; 8HLO
EC Number
1.14.13.225; 1.6.3.1
Pfam ID
PF12130 ; PF00307 ; PF01494 ; PF00412
Sequence
MASPTSTNPAHAHFESFLQAQLCQDVLSSFQELCGALGLEPGGGLPQYHKIKDQLNYWSA
KSLWTKLDKRAGQPVYQQGRACTSTKCLVVGAGPCGLRVAVELALLGARVVLVEKRTKFS
RHNVLHLWPFTIHDLRALGAKKFYGRFCTGTLDHISIRQLQLLLLKVALLLGVEIHWGVT
FTGLQPPPRKGSGWRAQLQPNPPAQLANYEFDVLISAAGGKFVPEGFKVREMRGKLAIGI
TANFVNGRTVEETQVPEISGVARIYNQSFFQSLLKATGIDLENIVYYKDDTHYFVMTAKK
QCLLRLGVLRQDWPDTNRLLGSANVVPEALQRFTRAAADFATHGKLGKLEFAQDAHGQPD
VSAFDFTSMMRAESSARVQEKHGARLLLGLVGDCLVEPFWPLGTGVARGFLAAFDAAWMV
KRWAEGAESLEVLAERESLYQLLSQTSPENMHRNVAQYGLDPATRYPNLNLRAVTPNQVR
DLYDVLAKEPVQRNNDKTDTGMPATGSAGTQEELLRWCQEQTAGYPGVHVSDLSSSWADG
LALCALVYRLQPGLLEPSELQGLGALEATAWALKVAENELGITPVVSAQAVVAGSDPLGL
IAYLSHFHSAFKSMAHSPGPVSQASPGTSSAVLFLSKLQRTLQRSRAKENAEDAGGKKLR
LEMEAETPSTEVPPDPEPGVPLTPPSQHQEAGAGDLCALCGEHLYVLERLCVNGHFFHRS
CFRCHTCEATLWPGGYEQHPGDGHFYCLQHLPQTDHKAEGSDRGPESPELPTPSENSMPP
GLSTPTASQEGAGPVPDPSQPTRRQIRLSSPERQRLSSLNLTPDPEMEPPPKPPRSCSAL
ARHALESSFVGWGLPVQSPQALVAMEKEEKESPFSSEEEEEDVPLDSDVEQALQTFAKTS
GTMNNYPTWRRTLLRRAKEEEMKRFCKAQTIQRRLNEIEAALRELEAEGVKLELALRRQS
SSPEQQKKLWVGQLLQLVDKKNSLVAEEAELMITVQELNLEEKQWQLDQELRGYMNREEN
LKTAADRQAEDQVLRKLVDLVNQRDALIRFQEERRLSELALGTGAQG
Function
Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels. May act as Rab effector protein and play a role in vesicle trafficking. Promotes endosomal tubule extension by associating with RAB8 (RAB8A or RAB8B), RAB10 and GRAF (GRAF1/ARHGAP26 or GRAF2/ARHGAP10) on the endosomal membrane which may connect GRAFs to Rabs, thereby participating in neosynthesized Rab8-Rab10-Rab11-dependent protein export.
Tissue Specificity Expressed in the thymus, lung, spleen, kidney, testis and hematopoietic cells.
Reactome Pathway
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast carcinoma DIS2UE88 Definitive Biomarker [1]
Cone-rod dystrophy 2 DISX2RWY Definitive Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Biomarker [1]
Epilepsy DISBB28L Strong Biomarker [4]
Gastric cancer DISXGOUK Strong Biomarker [5]
Major depressive disorder DIS4CL3X Strong Genetic Variation [6]
Stomach cancer DISKIJSX Strong Biomarker [5]
Temporal lobe epilepsy DISNOPXX Strong Biomarker [4]
Melanoma DIS1RRCY moderate Altered Expression [7]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Molecule interacting with CasL protein 1 (MICAL-1). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Molecule interacting with CasL protein 1 (MICAL-1). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Molecule interacting with CasL protein 1 (MICAL-1). [20]
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14 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 Molecule interacting with CasL protein 1 (MICAL-1). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [10]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [12]
Quercetin DM3NC4M Approved Quercetin increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [13]
Testosterone DM7HUNW Approved Testosterone increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [13]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [14]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [15]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [9]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Molecule interacting with CasL protein 1 (MICAL-1). [21]
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⏷ Show the Full List of 14 Drug(s)

References

1 MICAL1 facilitates breast cancer cell proliferation via ROS-sensitive ERK/cyclin D pathway.J Cell Mol Med. 2018 Jun;22(6):3108-3118. doi: 10.1111/jcmm.13588. Epub 2018 Mar 10.
2 MICAL flavoprotein monooxygenases: expression during neural development and following spinal cord injuries in the rat.Mol Cell Neurosci. 2006 Jan;31(1):52-69. doi: 10.1016/j.mcn.2005.09.001. Epub 2005 Oct 17.
3 Identification of novel TGF- regulated genes with pro-migratory roles.Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165537. doi: 10.1016/j.bbadis.2019.165537. Epub 2019 Aug 23.
4 Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model.Synapse. 2011 Nov;65(11):1213-21. doi: 10.1002/syn.20961. Epub 2011 Jun 17.
5 NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation.Front Pharmacol. 2019 Apr 4;10:291. doi: 10.3389/fphar.2019.00291. eCollection 2019.
6 GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.J Affect Disord. 2019 Jan 15;243:16-22. doi: 10.1016/j.jad.2018.09.003. Epub 2018 Sep 7.
7 Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells.Oncotarget. 2015 Feb 20;6(5):2779-93. doi: 10.18632/oncotarget.2995.
8 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.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
12 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.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
15 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
16 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
17 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
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.