Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDDKT8R)

• DOT Name: Battenin (CLN3)
• Synonyms: Batten disease protein; Protein CLN3
• Gene Name: CLN3
• Related Disease:
  CLN2 Batten disease
  Neuronal ceroid lipofuscinosis
• UniProt ID: CLN3_HUMAN
• Pfam ID: PF02487
• Sequence:
  MGGCAGSRRRFSDSEGEETVPEPRLPLLDHQGAHWKNAVGFWLLGLCNNFSYVVMLSAAH
  DILSHKRTSGNQSHVDPGPTPIPHNSSSRFDCNSVSTAAVLLADILPTLVIKLLAPLGLH
  LLPYSPRVLVSGICAAGSFVLVAFSHSVGTSLCGVVFASISSGLGEVTFLSLTAFYPRAV
  ISWWSSGTGGAGLLGALSYLGLTQAGLSPQQTLLSMLGIPALLLASYFLLLTSPEAQDPG
  GEEEAESAARQPLIRTEAPESKPGSSSSLSLRERWTVFKGLLWYIVPLVVVYFAEYFINQ
  GLFELLFFWNTSLSHAQQYRWYQMLYQAGVFASRSSLRCCRIRFTWALALLQCLNLVFLL
  ADVWFGFLPSIYLVFLIILYEGLLGGAAYVNTFHNIALETSDEHREFAMAATCISDTLGI
  SLSGLLALPLHDFLCQLS
• Function: Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission. Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing. Moreover regulates CTSD activity in response to osmotic stress. Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis. At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex. Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory. Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process. Participates also in cellular homeostasis of compounds such as, water, ions, amino acids, proteins and lipids in several tissue namely in brain and kidney through regulation of their transport and synthesis.
• Tissue Specificity: Expressed in the cortical brain, pancreas, spleen, and testis with weaker expression in the peripheral nerve (at protein level). Highly expressed in gray matter (at protein level).
• KEGG Pathway: Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CLN2 Batten disease	DISZC5YB	Definitive	Autosomal recessive	[1]
Neuronal ceroid lipofuscinosis	DIS9A4K4	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Battenin (CLN3) decreases the response to substance of Arsenic trioxide.	[16]
Methotrexate	DM2TEOL	Approved	Battenin (CLN3) affects the response to substance of Methotrexate.	[17]

3 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 Battenin (CLN3).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Battenin (CLN3).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Battenin (CLN3).	[9]

14 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 Battenin (CLN3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Battenin (CLN3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Battenin (CLN3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Battenin (CLN3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Battenin (CLN3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Battenin (CLN3).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Battenin (CLN3).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Battenin (CLN3).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Battenin (CLN3).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Battenin (CLN3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Battenin (CLN3).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Battenin (CLN3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Battenin (CLN3).	[14]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Battenin (CLN3).	[15]

References

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• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] 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.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] 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.
• [15] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [16] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.