Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZFS98)

• DOT Name: KN motif and ankyrin repeat domain-containing protein 3 (KANK3)
• Synonyms: Ankyrin repeat domain-containing protein 47
• Gene Name: KANK3
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: KANK3_HUMAN
• Pfam ID: PF12796 ; PF12075
• Sequence:
  MAKFALNQNLPDLGGPRLCPVPAAGGARSPSSPYSVETPYGFHLDLDFLKYIEELERGPA
  ARRAPGPPTSRRPRAPRPGLAGARSPGAWTSSESLASDDGGAPGILSQGAPSGLLMQPLS
  PRAPVRNPRVEHTLRETSRRLELAQTHERAPSPGRGVPRSPRGSGRSSPAPNLAPASPGP
  AQLQLVREQMAAALRRLRELEDQARTLPELQEQVRALRAEKARLLAGRAQPEPDGEAETR
  PDKLAQLRRLTERLATSERGGRARASPRADSPDGLAAGRSEGALQVLDGEVGSLDGTPQT
  REVAAEAVPETREAGAQAVPETREAGVEAAPETVEADAWVTEALLGLPAAAERELELLRA
  SLEHQRGVSELLRGRLRELEEAREAAEEAAAGARAQLREATTQTPWSCAEKAAQTESPAE
  APSLTQESSPGSMDGDRAVAPAGILKSIMKKRDGTPGAQPSSGPKSLQFVGVLNGEYESS
  SSEDASDSDGDSENGGAEPPGSSSGSGDDSGGGSDSGTPGPPSGGDIRDPEPEAEAEPQQ
  VAQGRCELSPRLREACVALQRQLSRPRGVASDGGAVRLVAQEWFRVSSQRRSQAEPVARM
  LEGVRRLGPELLAHVVNLADGNGNTALHYSVSHGNLAIASLLLDTGACEVNRQNRAGYSA
  LMLAALTSVRQEEEDMAVVQRLFCMGDVNAKASQTGQTALMLAISHGRQDMVATLLACGA
  DVNAQDADGATALMCASEYGRLDTVRLLLTQPGCDPAILDNEGTSALAIALEAEQDEVAA
  LLHAHLSSGQPDTQSESPPGSQTATPGEGECGDNGENPQVQ
• Function: May be involved in the control of cytoskeleton formation by regulating actin polymerization.
• Tissue Specificity: Strongly expressed in breast, liver, lung, skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[1]

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 KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of KN motif and ankyrin repeat domain-containing protein 3 (KANK3).	[8]

References

• [1] A novel HIF1AN substrate KANK3 plays a tumor-suppressive role in hepatocellular carcinoma.Cell Biol Int. 2018 Mar;42(3):303-312. doi: 10.1002/cbin.10895. Epub 2017 Nov 15.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] 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.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.