Details of Drug Off-Target (DOT)

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

• DOT Name: Kinesin-like protein KIF13A (KIF13A)
• Synonyms: Kinesin-like protein RBKIN
• Gene Name: KIF13A
• Related Disease:
  Fuchs' endothelial dystrophy
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Retinoblastoma
  Schizophrenia
  Advanced cancer
• UniProt ID: KI13A_HUMAN
• Pfam ID: PF12473 ; PF00498 ; PF12423 ; PF00225 ; PF16183
• Sequence:
  MSDTKVKVAVRVRPMNRRELELNTKCVVEMEGNQTVLHPPPSNTKQGERKPPKVFAFDYC
  FWSMDESNTTKYAGQEVVFKCLGEGILEKAFQGYNACIFAYGQTGSGKSFSMMGHAEQLG
  LIPRLCCALFKRISLEQNESQTFKVEVSYMEIYNEKVRDLLDPKGSRQSLKVREHKVLGP
  YVDGLSQLAVTSFEDIESLMSEGNKSRTVAATNMNEESSRSHAVFNIIITQTLYDLQSGN
  SGEKVSKVSLVDLAGSERVSKTGAAGERLKEGSNINKSLTTLGLVISSLADQAAGKGKSK
  FVPYRDSVLTWLLKDNLGGNSQTSMIATISPAADNYEETLSTLRYADRAKRIVNHAVVNE
  DPNAKVIRELREEVEKLREQLSQAEAMKAPELKEKLEESEKLIKELTVTWEEKLRKTEEI
  AQERQRQLESMGISLEMSGIKVGDDKCYLVNLNADPALNELLVYYLKDHTRVGADTSQDI
  QLFGIGIQPQHCEIDIASDGDVTLTPKENARSCVNGTLVCSTTQLWHGDRILWGNNHFFR
  INLPKRKRRDWLKDFEKETGPPEHDLDAASEASSEPDYNYEFAQMEVIMKTLNSNDPVQN
  VVQVLEKQYLEEKRSALEEQRLMYERELEQLRQQLSPDRQPQSSGPDRLAYSSQTAQQKV
  TQWAEERDELFRQSLAKLREQLVKANTLVREANFLAEEMSKLTDYQVTLQIPAANLSANR
  KRGAIVSEPAIQVRRKGKSTQVWTIEKLENKLIDMRDLYQEWKEKVPEAKRLYGKRGDPF
  YEAQENHNLIGVANVFLECLFCDVKLQYAVPIISQQGEVAGRLHVEVMRVTGAVPERVVE
  DDSSENSSESGSLEVVDSSGEIIHRVKKLTCRVKIKEATGLPLNLSNFVFCQYTFWDQCE
  STVAAPVVDPEVPSPQSKDAQYTVTFSHCKDYVVNVTEEFLEFISDGALAIEVWGHRCAG
  NGSSIWEVDSLHAKTRTLHDRWNEVTRRIEMWISILELNELGEYAAVELHQAKDVNTGGI
  FQLRQGHSRRVQVTVKPVQHSGTLPLMVEAILSVSIGCVTARSTKLQRGLDSYQRDDEDG
  DDMDSYQEEDLNCVRERWSDALIKRREYLDEQIKKVSNKTEKTEDDVEREAQLVEQWVGL
  TEERNAVLVPAPGSGIPGAPADWIPPPGMETHIPVLFLDLNADDLSANEQLVGPHASGVN
  SILPKEHGSQFFYLPIIKHSDDEVSATASWDSSVHDSVHLNRVTPQNERIYLIVKTTVQL
  SHPAAMELVLRKRIAANIYNKQSFTQSLKRRISLKNIFYSCGVTYEIVSNIPKATEEIED
  RETLALLAARSENEGTSDGETYIEKYTRGVLQVENILSLERLRQAVTVKEALSTKARHIR
  RSLSTPNVHNVSSSRPDLSGFDEDDKGWPENQLDMSDYSSSYQDVACYGTLPRDSPRRNK
  EGCTSETPHALTVSPFKAFSPQPPKFFKPLMPVKEEHKKRIALEARPLLSQESMPPPQAH
  NPGCIVPSGSNGSSMPVEHNSKREKKIDSEEEENELEAINRKLISSQPYVPVEFADFSVY
  NASLENREWFSSKVDLSNSRVLEKEVSRSPTTSSITSGYFSHSASNATLSDMVVPSSDSS
  DQLAIQTKDADSTEHSTPSLVHDFRPSSNKELTEVEKGLVKDKIIVVPLKENSALAKGSP
  SSQSIPEKNSKSLCRTGSCSELDACPSKISQPARGFCPREVTVEHTTNILEDHSFTEFMG
  VSEGKDFDGLTDSSAGELSSRRSLPNKTGGKTVSDGLHHPSQLHSKLENDQVIIPEAAFW
  VLCCQ
• Function: Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abcission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis.
• Tissue Specificity: Widely expressed, with highest levels in heart, brain and skeletal muscle.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway: Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[2]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[2]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]

12 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 KIF13A (KIF13A).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kinesin-like protein KIF13A (KIF13A).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kinesin-like protein KIF13A (KIF13A).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Kinesin-like protein KIF13A (KIF13A).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Kinesin-like protein KIF13A (KIF13A).	[18]

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 affects the methylation of Kinesin-like protein KIF13A (KIF13A).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Kinesin-like protein KIF13A (KIF13A).	[13]

References

• [1] Gene Expression and Missplicing in the Corneal Endothelium of Patients With a TCF4 Trinucleotide Repeat Expansion Without Fuchs' Endothelial Corneal Dystrophy.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3636-3643. doi: 10.1167/iovs.19-27689.
• [2] Identification of a novel KIF13A-RET fusion in lung adenocarcinoma by next-generation sequencing.Lung Cancer. 2018 Apr;118:27-29. doi: 10.1016/j.lungcan.2017.08.019. Epub 2017 Sep 4.
• [3] Genomic amplification in retinoblastoma narrowed to 0.6 megabase on chromosome 6p containing a kinesin-like gene, RBKIN.Cancer Res. 2002 Feb 15;62(4):967-71.
• [4] Identification of the human KIF13A gene homologous to Drosophila kinesin-73 and candidate for schizophrenia.Genomics. 2001 May 15;74(1):36-44. doi: 10.1006/geno.2001.6535.
• [5] mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability to regulatory T cells by controlling kinesin KIF13A.Cell Discov. 2017 Apr 25;3:17011. doi: 10.1038/celldisc.2017.11. eCollection 2017.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] 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.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.