Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1TTYK1)

• DOT Name: Vacuolar fusion protein CCZ1 homolog B (CCZ1B)
• Synonyms: Vacuolar fusion protein CCZ1 homolog-like
• Gene Name: CCZ1B
• Related Disease: Retinitis pigmentosa
• UniProt ID: CCZ1B_HUMAN
• Pfam ID: PF19031 ; PF19032 ; PF19033
• Sequence:
  MAAAAAGAGSGPWAAQEKQFPPALLSFFIYNPRFGPREGQEENKILFYHPNEVEKNEKIR
  NVGLCEAIVQFTRTFSPSKPAKSLHTQKNRQFFNEPEENFWMVMVVRNPIIEKQSKDGKP
  VIEYQEEELLDKVYSSVLRQCYSMYKLFNGTFLKAMEDGGVKLLKERLEKFFHRYLQTLH
  LQSCDLLDIFGGISFFPLDKMTYLKIQSFINRMEESLNIVKYTAFLYNDQLIWSGLEQDD
  MRILYKYLTTSLFPRHIEPELAGRDSPIRAEMPGNLQHYGRFLTGPLNLNDPDAKCRFPK
  IFVNTDDTYEELHLIVYKAMSAAVCFMIDASVHPTLDFCRRLDSIVGPQLTVLASDICEQ
  FNINKRMSGSEKEPQFKFIYFNHMNLAEKSTVHMRKTPSVSLTSVHPDLMKILGDINSDF
  TRVDEDEEIIVKAMSDYWVVGKKSDRRELYVILNQKNANLIEVNEEVKKLCATQFNNIFF
  LD
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway: RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	moderate	Biomarker	[1]

5 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 Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[5]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[6]

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 increases the methylation of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Vacuolar fusion protein CCZ1 homolog B (CCZ1B).	[8]

References

• [1] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] 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.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [7] 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.
• [8] 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.