Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDWIFQ2)

DOT Name Kinesin-like protein KIF16B (KIF16B)
Synonyms Sorting nexin-23
Gene Name KIF16B
Related Disease
Intellectual disability ( )
Congenital fibrosis of extraocular muscles ( )
Lung adenocarcinoma ( )
Mobius syndrome ( )
Non-small-cell lung cancer ( )
Asthma ( )
Carcinoid tumor ( )
UniProt ID
KI16B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2V14; 6EE0
Pfam ID
PF00498 ; PF00225 ; PF00787
Sequence
MASVKVAVRVRPMNRREKDLEAKFIIQMEKSKTTITNLKIPEGGTGDSGRERTKTFTYDF
SFYSADTKSPDYVSQEMVFKTLGTDVVKSAFEGYNACVFAYGQTGSGKSYTMMGNSGDSG
LIPRICEGLFSRINETTRWDEASFRTEVSYLEIYNERVRDLLRRKSSKTFNLRVREHPKE
GPYVEDLSKHLVQNYGDVEELMDAGNINRTTAATGMNDVSSRSHAIFTIKFTQAKFDSEM
PCETVSKIHLVDLAGSERADATGATGVRLKEGGNINKSLVTLGNVISALADLSQDAANTL
AKKKQVFVPYRDSVLTWLLKDSLGGNSKTIMIATISPADVNYGETLSTLRYANRAKNIIN
KPTINEDANVKLIRELRAEIARLKTLLAQGNQIALLDSPTALSMEEKLQQNEARVQELTK
EWTNKWNETQNILKEQTLALRKEGIGVVLDSELPHLIGIDDDLLSTGIILYHLKEGQTYV
GRDDASTEQDIVLHGLDLESEHCIFENIGGTVTLIPLSGSQCSVNGVQIVEATHLNQGAV
ILLGRTNMFRFNHPKEAAKLREKRKSGLLSSFSLSMTDLSKSRENLSAVMLYNPGLEFER
QQREELEKLESKRKLIEEMEEKQKSDKAELERMQQEVETQRKETEIVQLQIRKQEESLKR
RSFHIENKLKDLLAEKEKFEEERLREQQEIELQKKRQEEETFLRVQEELQRLKELNNNEK
AEKFQIFQELDQLQKEKDEQYAKLELEKKRLEEQEKEQVMLVAHLEEQLREKQEMIQLLR
RGEVQWVEEEKRDLEGIRESLLRVKEARAGGDEDGEELEKAQLRFFEFKRRQLVKLVNLE
KDLVQQKDILKKEVQEEQEILECLKCEHDKESRLLEKHDESVTDVTEVPQDFEKIKPVEY
RLQYKERQLQYLLQNHLPTLLEEKQRAFEILDRGPLSLDNTLYQVEKEMEEKEEQLAQYQ
ANANQLQKLQATFEFTANIARQEEKVRKKEKEILESREKQQREALERALARLERRHSALQ
RHSTLGMEIEEQRQKLASLNSGSREQSGLQASLEAEQEALEKDQERLEYEIQQLKQKIYE
VDGVQKDHHGTLEGKVASSSLPVSAEKSHLVPLMDARINAYIEEEVQRRLQDLHRVISEG
CSTSADTMKDNEKLHNGTIQRKLKYERMVSRSLGANPDDLKDPIKISIPRYVLCGQGKDA
HFEFEVKITVLDETWTVFRRYSRFREMHKTLKLKYAELAALEFPPKKLFGNKDERVIAER
RSHLEKYLRDFFSVMLQSATSPLHINKVGLTLSKHTICEFSPFFKKGVFDYSSHGTG
Function
Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. Regulates the plus end motility of early endosomes and the balance between recycling and degradation of receptors such as EGF receptor (EGFR) and FGF receptor (FGFR). Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development.
Tissue Specificity Primarily expressed in brain. Also present in kidney, liver, intestine, placenta, leukocytes, heart and skeletal muscle (at protein level).
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

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual disability DISMBNXP Definitive Biomarker [1]
Congenital fibrosis of extraocular muscles DISE84PU Strong Genetic Variation [2]
Lung adenocarcinoma DISD51WR Strong Biomarker [3]
Mobius syndrome DIS9YXP5 Strong Genetic Variation [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [4]
Asthma DISW9QNS Limited Genetic Variation [5]
Carcinoid tumor DISMNRDC Limited Genetic Variation [6]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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-like protein KIF16B (KIF16B). [7]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Kinesin-like protein KIF16B (KIF16B). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Kinesin-like protein KIF16B (KIF16B). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Kinesin-like protein KIF16B (KIF16B). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Kinesin-like protein KIF16B (KIF16B). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Kinesin-like protein KIF16B (KIF16B). [12]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Kinesin-like protein KIF16B (KIF16B). [13]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Kinesin-like protein KIF16B (KIF16B). [14]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Kinesin-like protein KIF16B (KIF16B). [15]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Kinesin-like protein KIF16B (KIF16B). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Kinesin-like protein KIF16B (KIF16B). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Kinesin-like protein KIF16B (KIF16B). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Kinesin-like protein KIF16B (KIF16B). [20]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Kinesin-like protein KIF16B (KIF16B). [21]
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⏷ Show the Full List of 14 Drug(s)
1 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 Kinesin-like protein KIF16B (KIF16B). [18]
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References

1 KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.Am J Med Genet A. 2018 Jul;176(7):1602-1609. doi: 10.1002/ajmg.a.38723. Epub 2018 May 7.
2 A novel de novo KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Mbius syndrome.Mol Vis. 2014 Mar 28;20:368-75. eCollection 2014.
3 Therapeutic Targeting of the Premetastatic Stage in Human Lung-to-Brain Metastasis.Cancer Res. 2018 Sep 1;78(17):5124-5134. doi: 10.1158/0008-5472.CAN-18-1022. Epub 2018 Jul 9.
4 Novel genetic variants in KIF16B and NEDD4L in the endosome-related genes are associated with nonsmall cell lung cancer survival.Int J Cancer. 2020 Jul 15;147(2):392-403. doi: 10.1002/ijc.32739. Epub 2019 Dec 19.
5 Identification of Four Novel Loci in Asthma in European American and African American Populations.Am J Respir Crit Care Med. 2017 Feb 15;195(4):456-463. doi: 10.1164/rccm.201604-0861OC.
6 A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.Endocr Relat Cancer. 2011 Jan 13;18(1):171-80. doi: 10.1677/ERC-10-0248. Print 2011 Feb.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 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.
9 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.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 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.
13 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
14 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
15 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
16 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
17 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
18 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.
19 Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
20 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.
21 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.