Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT450PAO)

DOT Name Kinesin-associated protein 3 (KIFAP3)
Synonyms KAP-3; KAP3; Smg GDS-associated protein
Gene Name KIFAP3
Related Disease
Amyotrophic lateral sclerosis type 1 ( )
Burkitt lymphoma ( )
Colonic neoplasm ( )
Endometriosis ( )
Pancreatic cancer ( )
Venous thromboembolism ( )
Advanced cancer ( )
Neoplasm ( )
UniProt ID
KIFA3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF05804
Sequence
MQGEDARYLKRKVKGGNIDVHPSEKALIVHYEVEATILGEMGDPMLGERKECQKIIRLKS
LNANTDITSLARKVVEECKLIHPSKLNEVEQLLYYLQNRRDSLSGKEKKEKSSKPKDPPP
FEGMEIDEVANINDMDEYIELLYEDIPDKVRGSALILQLARNPDNLEELLLNETALGALA
RVLREDWKQSVELATNIIYIFFCFSSFSQFHGLITHYKIGALCMNIIDHELKRHELWQEE
LSKKKKAVDEDPENQTLRKDYEKTFKKYQGLVVKQEQLLRVALYLLLNLAEDTRTELKMR
NKNIVHMLVKALDRDNFELLILVVSFLKKLSIFMENKNDMVEMDIVEKLVKMIPCEHEDL
LNITLRLLLNLSFDTGLRNKMVQVGLLPKLTALLGNDNYKQIAMCVLYHISMDDRFKSMF
AYTDCIPQLMKMLFECSDERIDLELISFCINLAANKRNVQLICEGNGLKMLMKRALKFKD
PLLMKMIRNISQHDGPTKNLFIDYVGDLAAQISNDEEEEFVIECLGTLANLTIPDLDWEL
VLKEYKLVPYLKDKLKPGAAEDDLVLEVVIMIGTVSMDDSCAALLAKSGIIPALIELLNA
QQEDDEFVCQIIYVFYQMVFHQATRDVIIKETQAPAYLIDLMHDKNNEIRKVCDNTLDII
AEYDEEWAKKIQSEKFRWHNSQWLEMVESRQMDESEQYLYGDDRIEPYIHEGDILERPDL
FYNSDGLIASEGAISPDFFNDYHLQNGDVVGQHSFPGSLGMDGFGQPVGILGRPATAYGF
RPDEPYYYGYGS
Function
Involved in tethering the chromosomes to the spindle pole and in chromosome movement. Binds to the tail domain of the KIF3A/KIF3B heterodimer to form a heterotrimeric KIF3 complex and may regulate the membrane binding of this complex.
KEGG Pathway
Motor proteins (hsa04814 )
Reactome Pathway
MHC class II antigen presentation (R-HSA-2132295 )
Intraflagellar transport (R-HSA-5620924 )
COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434 )
Kinesins (R-HSA-983189 )
Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis type 1 DIS5A2M0 Strong Biomarker [1]
Burkitt lymphoma DIS9D5XU Strong Biomarker [2]
Colonic neoplasm DISSZ04P Strong Biomarker [3]
Endometriosis DISX1AG8 Strong Biomarker [4]
Pancreatic cancer DISJC981 Strong Biomarker [5]
Venous thromboembolism DISUR7CR Strong Genetic Variation [6]
Advanced cancer DISAT1Z9 Limited Biomarker [7]
Neoplasm DISZKGEW Limited Biomarker [7]
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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
13 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 Kinesin-associated protein 3 (KIFAP3). [8]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Kinesin-associated protein 3 (KIFAP3). [9]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Kinesin-associated protein 3 (KIFAP3). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Kinesin-associated protein 3 (KIFAP3). [11]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Kinesin-associated protein 3 (KIFAP3). [12]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Kinesin-associated protein 3 (KIFAP3). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Kinesin-associated protein 3 (KIFAP3). [15]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Kinesin-associated protein 3 (KIFAP3). [16]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Kinesin-associated protein 3 (KIFAP3). [17]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Kinesin-associated protein 3 (KIFAP3). [18]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Kinesin-associated protein 3 (KIFAP3). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Kinesin-associated protein 3 (KIFAP3). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Kinesin-associated protein 3 (KIFAP3). [22]
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⏷ Show the Full List of 13 Drug(s)
2 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 Kinesin-associated protein 3 (KIFAP3). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Kinesin-associated protein 3 (KIFAP3). [21]
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References

1 Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3.Hum Mol Genet. 2009 Mar 1;18(5):942-55. doi: 10.1093/hmg/ddn422. Epub 2008 Dec 16.
2 Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers.J Biol Chem. 2020 Jan 17;295(3):757-770. doi: 10.1074/jbc.RA119.011443. Epub 2019 Dec 10.
3 Tumor microsomal metabolism of the food toxicant, benzo(a)pyrene, in ApcMin mouse model of colon cancer.Tumour Biol. 2012 Aug;33(4):1255-60. doi: 10.1007/s13277-012-0375-6. Epub 2012 Mar 20.
4 Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.Hum Mol Genet. 2015 Feb 15;24(4):1185-99. doi: 10.1093/hmg/ddu516. Epub 2014 Oct 8.
5 KAP-1 is overexpressed and correlates with increased metastatic ability and tumorigenicity in pancreatic cancer.Med Oncol. 2014 Jul;31(7):25. doi: 10.1007/s12032-014-0025-5. Epub 2014 May 27.
6 Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
7 A SMAP in the face for cancer.J Clin Invest. 2017 Jun 1;127(6):2048-2050. doi: 10.1172/JCI94763. Epub 2017 May 15.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 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.
11 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.
12 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.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 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.
15 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.
16 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
17 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
18 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.
19 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
20 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.
21 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.
22 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.