Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZN6BMJ)

• DOT Name: Protein unc-119 homolog A
• Synonyms: Retinal protein 4; hRG4
• Gene Name: UNC119
• Related Disease:
  Cone-rod dystrophy
  Cone-rod dystrophy 24
• UniProt ID: U119A_HUMAN
• PDB ID: 3GQQ; 3RBQ; 4GOJ; 4GOK; 5L7K; 6H6A; 7UMO
• Pfam ID: PF05351
• Sequence:
  MKVKKGGGGAGTATESAPGPSGQSVAPIPQPPAESESGSESEPDAGPGPRPGPLQRKQPI
  GPEDVLGLQRITGDYLCSPEENIYKIDFVRFKIRDMDSGTVLFEIKKPPVSERLPINRRD
  LDPNAGRFVRYQFTPAFLRLRQVGATVEFTVGDKPVNNFRMIERHYFRNQLLKSFDFHFG
  FCIPSSKNTCEHIYDFPPLSEELISEMIRHPYETQSDSFYFVDDRLVMHNKADYSYSGTP
• Function: Involved in synaptic functions in photoreceptor cells, the signal transduction in immune cells as a Src family kinase activator, endosome recycling, the uptake of bacteria and endocytosis, protein trafficking in sensory neurons and as lipid-binding chaperone with specificity for a diverse subset of myristoylated proteins. Specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Probably plays a role in trafficking proteins in photoreceptor cells. Plays important roles in mediating Src family kinase signals for the completion of cytokinesis via RAB11A.
• Tissue Specificity: Abundantly expressed in retina, in photoreceptor synapses and inner segments. Expressed in a much lesser extent in several other tissues.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[1]
Cone-rod dystrophy 24	DISNP4QO	Limited	Unknown	[1]

9 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 Protein unc-119 homolog A.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein unc-119 homolog A.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein unc-119 homolog A.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein unc-119 homolog A.	[5]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Protein unc-119 homolog A.	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein unc-119 homolog A.	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein unc-119 homolog A.	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein unc-119 homolog A.	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein unc-119 homolog A.	[11]

1 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 Protein unc-119 homolog A.	[8]

References

• [1] HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3268-77.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [11] 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.