Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOPD4QO)

• DOT Name: Kinesin-like protein KIFC3 (KIFC3)
• Gene Name: KIFC3
• Related Disease:
  Amyotrophic lateral sclerosis type 1
  Bardet biedl syndrome
  Intrahepatic cholestasis of pregnancy
• UniProt ID: KIFC3_HUMAN
• PDB ID: 5WDE
• Pfam ID: PF00225
• Sequence:
  MVPSRRTWNLGATPSLRGLWRVGRAPEPEPGMARPAPAPASPAARPFPHTGPGRLRTGRG
  KDTPVCGDEDSSARSAARPALAQCRALSVDWAGPGSPHGLYLTLQVEHLKEKLISQAQEV
  SRLRSELGGTDLEKHRDLLMVENERLRQEMRRCEAELQELRTKPAGPCPGCEHSQESAQL
  RDKLSQLQLEMAESKGMLSELNLEVQQKTDRLAEVELRLKDCLAEKAQEEERLSRRLRDS
  HETIASLRAQSPPVKYVIKTVEVESSKTKQALSESQARNQHLQEQVAMQRQVLKEMEQQL
  QSSHQLTARLRAQIAMYESELERAHGQMLEEMQSLEEDKNRAIEEAFARAQVEMKAVHEN
  LAGVRTNLLTLQPALRTLTNDYNGLKRQVRGFPLLLQEALRSVKAEIGQAIEEVNSNNQE
  LLRKYRRELQLRKKCHNELVRLKGNIRVIARVRPVTKEDGEGPEATNAVTFDADDDSIIH
  LLHKGKPVSFELDKVFSPQASQQDVFQEVQALVTSCIDGFNVCIFAYGQTGAGKTYTMEG
  TAENPGINQRALQLLFSEVQEKASDWEYTITVSAAEIYNEVLRDLLGKEPQEKLEIRLCP
  DGSGQLYVPGLTEFQVQSVDDINKVFEFGHTNRTTEFTNLNEHSSRSHALLIVTVRGVDC
  STGLRTTGKLNLVDLAGSERVGKSGAEGSRLREAQHINKSLSALGDVIAALRSRQGHVPF
  RNSKLTYLLQDSLSGDSKTLMVVQVSPVEKNTSETLYSLKFAERVRSVELGPGLRRAELG
  SWSSQEHLEWEPACQTPQPSARAHSAPSSGTSSRPGSIRRKLQPSGKSRPLPV
• Function: Minus-end microtubule-dependent motor protein. Involved in apically targeted transport. Required for zonula adherens maintenance.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

3 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]
Bardet biedl syndrome	DISTBNZW	Strong	Genetic Variation	[2]
Intrahepatic cholestasis of pregnancy	DISMHS5F	Strong	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Docetaxel	DMDI269	Approved	Kinesin-like protein KIFC3 (KIFC3) decreases the response to substance of Docetaxel.	[13]

6 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 Kinesin-like protein KIFC3 (KIFC3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Kinesin-like protein KIFC3 (KIFC3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kinesin-like protein KIFC3 (KIFC3).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kinesin-like protein KIFC3 (KIFC3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinesin-like protein KIFC3 (KIFC3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kinesin-like protein KIFC3 (KIFC3).	[12]

3 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-like protein KIFC3 (KIFC3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Kinesin-like protein KIFC3 (KIFC3).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Kinesin-like protein KIFC3 (KIFC3).	[11]

References

• [1] Kinesin expression in the central nervous system of humans and transgenic hSOD1G93A mice with amyotrophic lateral sclerosis.Neurodegener Dis. 2013;12(2):71-80. doi: 10.1159/000339529. Epub 2012 Sep 21.
• [2] Cloning of a novel C-terminal kinesin (KIFC3) that maps to human chromosome 16q13-q21 and thus is a candidate gene for Bardet-Biedl syndrome.Genomics. 1998 Sep 1;52(2):219-22. doi: 10.1006/geno.1998.5431.
• [3] Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis.J Matern Fetal Neonatal Med. 2013 Sep;26(14):1410-5. doi: 10.3109/14767058.2013.783810. Epub 2013 Apr 22.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Breast Cancer Res Treat. 2012 Feb;131(3):849-58. doi: 10.1007/s10549-011-1500-8. Epub 2011 Apr 9.