Details of Drug Off-Target (DOT)

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

• DOT Name: Kinesin-like protein KIF3C (KIF3C)
• Gene Name: KIF3C
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Amyotrophic lateral sclerosis type 1
  Atrial fibrillation
  Familial amyotrophic lateral sclerosis
  Neuroblastoma
  Familial atrial fibrillation
• UniProt ID: KIF3C_HUMAN
• PDB ID: 3B6V
• Pfam ID: PF00225
• Sequence:
  MASKTKASEALKVVARCRPLSRKEEAAGHEQILTMDVKLGQVTLRNPRAAPGELPKTFTF
  DAVYDASSKQADLYDETVRPLIDSVLQGFNGTVFAYGQTGTGKTYTMQGTWVEPELRGVI
  PNAFEHIFTHISRSQNQQYLVRASYLEIYQEEIRDLLSKEPGKRLELKENPETGVYIKDL
  SSFVTKNVKEIEHVMNLGNQTRAVGSTHMNEVSSRSHAIFIITVECSERGSDGQDHIRVG
  KLNLVDLAGSERQNKAGPNTAGGAATPSSGGGGGGGGSGGGAGGERPKEASKINLSLSAL
  GNVIAALAGNRSTHIPYRDSKLTRLLQDSLGGNAKTIMVATLGPASHSYDESLSTLRFAN
  RAKNIKNKPRVNEDPKDTLLREFQEEIARLKAQLEKRGMLGKRPRRKSSRRKKAVSAPPG
  YPEGPVIEAWVAEEEDDNNNNHRPPQPILESALEKNMENYLQEQKERLEEEKAAIQDDRS
  LVSEEKQKLLEEKEKMLEDLRREQQATELLAAKYKAMESKLLIGGRNIMDHTNEQQKMLE
  LKRQEIAEQKRREREMQQEMMLRDEETMELRGTYTSLQQEVEVKTKKLKKLYAKLQAVKA
  EIQDQHDEYIRVRQDLEEAQNEQTRELKLKYLIIENFIPPEEKNKIMNRLFLDCEEEQWK
  FQPLVPAGVSSSQMKKRPTSAVGYKRPISQYARVAMAMGSHPRYRAENIMFLELDVSPPA
  VFEMEFSHDQEQDPRALHMERLMRLDSFLERPSTSKVRKSRSWCQSPQRPPPSTTHASLA
  SASLRPATVADHE
• Function: Microtubule-based anterograde translocator for membranous organelles.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  Intraflagellar transport (R-HSA-5620924)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Kinesins (R-HSA-983189)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[3]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[2]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[4]
Familial atrial fibrillation	DISL4AGF	Limited	Biomarker	[3]

2 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 Kinesin-like protein KIF3C (KIF3C).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Kinesin-like protein KIF3C (KIF3C).	[13]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kinesin-like protein KIF3C (KIF3C).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Kinesin-like protein KIF3C (KIF3C).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kinesin-like protein KIF3C (KIF3C).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinesin-like protein KIF3C (KIF3C).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kinesin-like protein KIF3C (KIF3C).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kinesin-like protein KIF3C (KIF3C).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kinesin-like protein KIF3C (KIF3C).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Kinesin-like protein KIF3C (KIF3C).	[14]

References

• [1] Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF- signaling.Cancer Lett. 2015 Nov 1;368(1):105-114. doi: 10.1016/j.canlet.2015.07.037. Epub 2015 Aug 10.
• [2] Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.J Neurochem. 2002 Jan;80(1):158-67. doi: 10.1046/j.0022-3042.2001.00683.x.
• [3] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [4] Expression of KIF3C kinesin during neural development and in vitro neuronal differentiation.J Neurochem. 2001 May;77(3):741-53. doi: 10.1046/j.1471-4159.2001.00277.x.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.