Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFXFIU3)

DOT Name Kinesin-like protein KIF21B (KIF21B)
Gene Name KIF21B
Related Disease
Alzheimer disease ( )
Alzheimer disease 3 ( )
Ankylosing spondylitis ( )
Autism spectrum disorder ( )
Autoimmune disease ( )
Crohn disease ( )
Inflammatory bowel disease ( )
Multiple sclerosis ( )
Ulcerative colitis ( )
UniProt ID
KI21B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00225 ; PF00400
Sequence
MAGQGDCCVKVAVRIRPQLSKEKIEGCHICTSVTPGEPQVLLGKDKAFTYDFVFDLDTWQ
EQIYSTCVSKLIEGCFEGYNATVLAYGQTGAGKTYTMGTGFDMATSEEEQGIIPRAIAHL
FGGIAERKRRAQEQGVAGPEFKVSAQFLELYNEEILDLFDSTRDPDTRHRRSNIKIHEDA
NGGIYTTGVTSRLIHSQEELIQCLKQGALSRTTASTQMNVQSSRSHAIFTIHLCQMRMCT
QPDLVNEAVTGLPDGTPPSSEYETLTAKFHFVDLAGSERLKRTGATGERAKEGISINCGL
LALGNVISALGDQSKKVVHVPYRDSKLTRLLQDSLGGNSQTIMIACVSPSDRDFMETLNT
LKYANRARNIKNKVVVNQDKTSQQISALRAEIARLQMELMEYKAGKRVIGEDGAEGYSDL
FRENAMLQKENGALRLRVKAMQEAIDAINNRVTQLMSQEANLLLAKAGDGNEAIGALIQN
YIREIEELRTKLLESEAMNESLRRSLSRASARSPYSLGASPAAPAFGGSPASSMEDASEV
IRRAKQDLERLKKKEVRQRRKSPEKEAFKKRAKLQQENSEETDENEAEEEEEERDESGCE
EEEGREDEDEDSGSEESLVDSDSDPEEKEVNFQADLADLTCEIEIKQKLIDELENSQRRL
QTLKHQYEEKLILLQNKIRDTQLERDRVLQNLSTMECYTEEKANKIKADYEKRLREMNRD
LQKLQAAQKEHARLLKNQSRYERELKKLQAEVAEMKKAKVALMKQMREEQQRRRLVETKR
NREIAQLKKEQRRQEFQIRALESQKRQQEMVLRRKTQEVSALRRLAKPMSERVAGRAGLK
PPMLDSGAEVSASTTSSEAESGARSVSSIVRQWNRKINHFLGDHPAPTVNGTRPARKKFQ
KKGASQSFSKAARLKWQSLERRIIDIVMQRMTIVNLEADMERLIKKREELFLLQEALRRK
RERLQAESPEEEKGLQELAEEIEVLAANIDYINDGITDCQATIVQLEETKEELDSTDTSV
VISSCSLAEARLLLDNFLKASIDKGLQVAQKEAQIRLLEGRLRQTDMAGSSQNHLLLDAL
REKAEAHPELQALIYNVQQENGYASTDEEISEFSEGSFSQSFTMKGSTSHDDFKFKSEPK
LSAQMKAVSAECLGPPLDISTKNITKSLASLVEIKEDGVGFSVRDPYYRDRVSRTVSLPT
RGSTFPRQSRATETSPLTRRKSYDRGQPIRSTDVGFTPPSSPPTRPRNDRNVFSRLTSNQ
SQGSALDKSDDSDSSLSEVLRGIISPVGGAKGARTAPLQCVSMAEGHTKPILCLDATDEL
LFTGSKDRSCKMWNLVTGQEIAALKGHPNNVVSIKYCSHSGLVFSVSTSYIKVWDIRDSA
KCIRTLTSSGQVISGDACAATSTRAITSAQGEHQINQIALSPSGTMLYAASGNAVRIWEL
SRFQPVGKLTGHIGPVMCLTVTQTASQHDLVVTGSKDHYVKMFELGECVTGTIGPTHNFE
PPHYDGIECLAIQGDILFSGSRDNGIKKWDLDQQELIQQIPNAHKDWVCALAFIPGRPML
LSACRAGVIKVWNVDNFTPIGEIKGHDSPINAICTNAKHIFTASSDCRVKLWNYVPGLTP
CLPRRVLAIKGRATTLP
Function
Plus-end directed microtubule-dependent motor protein which displays processive activity. Is involved in regulation of microtubule dynamics, synapse function and neuronal morphology, including dendritic tree branching and spine formation. Plays a role in lerning and memory. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptor to cell surface.
KEGG Pathway
Motor proteins (hsa04814 )
Reactome Pathway
Kinesins (R-HSA-983189 )
COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Alzheimer disease 3 DISVT69G Strong Biomarker [2]
Ankylosing spondylitis DISRC6IR Strong Genetic Variation [3]
Autism spectrum disorder DISXK8NV Strong Biomarker [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Crohn disease DIS2C5Q8 Strong Biomarker [3]
Inflammatory bowel disease DISGN23E Strong Genetic Variation [6]
Multiple sclerosis DISB2WZI Strong Biomarker [2]
Ulcerative colitis DIS8K27O Strong Biomarker [3]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Kinesin-like protein KIF21B (KIF21B). [7]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Kinesin-like protein KIF21B (KIF21B). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Kinesin-like protein KIF21B (KIF21B). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Kinesin-like protein KIF21B (KIF21B). [10]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Kinesin-like protein KIF21B (KIF21B). [11]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Kinesin-like protein KIF21B (KIF21B). [12]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Kinesin-like protein KIF21B (KIF21B). [13]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Kinesin-like protein KIF21B (KIF21B). [14]
Triclosan DMZUR4N Approved Triclosan increases the expression of Kinesin-like protein KIF21B (KIF21B). [15]
Nicotine DMWX5CO Approved Nicotine increases the expression of Kinesin-like protein KIF21B (KIF21B). [16]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide decreases the expression of Kinesin-like protein KIF21B (KIF21B). [17]
Lindane DMB8CNL Approved Lindane increases the expression of Kinesin-like protein KIF21B (KIF21B). [17]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Kinesin-like protein KIF21B (KIF21B). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Kinesin-like protein KIF21B (KIF21B). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Kinesin-like protein KIF21B (KIF21B). [7]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Kinesin-like protein KIF21B (KIF21B). [17]
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⏷ Show the Full List of 16 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Kinesin-like protein KIF21B (KIF21B). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Kinesin-like protein KIF21B (KIF21B). [21]
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References

1 Overexpression of Kinesin Superfamily Motor Proteins in Alzheimer's Disease.J Alzheimers Dis. 2017;60(4):1511-1524. doi: 10.3233/JAD-170094.
2 Abundant kif21b is associated with accelerated progression in neurodegenerative diseases.Acta Neuropathol Commun. 2014 Oct 3;2:144. doi: 10.1186/s40478-014-0144-4.
3 Association of KIF21B genetic polymorphisms with ankylosing spondylitis in a Chinese Han population of Shandong Province.Clin Rheumatol. 2015 Oct;34(10):1729-36. doi: 10.1007/s10067-014-2761-5. Epub 2014 Aug 23.
4 Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior.Cell Rep. 2018 May 29;23(9):2705-2717. doi: 10.1016/j.celrep.2018.04.112.
5 Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C.PLoS Genet. 2012;8(12):e1003140. doi: 10.1371/journal.pgen.1003140. Epub 2012 Dec 27.
6 Replication of KIF21B as a susceptibility locus for multiple sclerosis.J Med Genet. 2010 Nov;47(11):775-6. doi: 10.1136/jmg.2009.075911. Epub 2010 Jun 28.
7 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.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
12 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.
13 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
14 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
15 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
16 Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
17 Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
21 Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.