Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHGHV6D)

• DOT Name: Tubby-related protein 1
• Synonyms: Tubby-like protein 1
• Gene Name: TULP1
• Related Disease:
  Retinitis pigmentosa 14
  Leber congenital amaurosis 15
  Leber congenital amaurosis
  Retinitis pigmentosa
• UniProt ID: TULP1_HUMAN
• PDB ID: 2FIM; 3C5N
• Pfam ID: PF01167
• Sequence:
  MPLRDETLREVWASDSGHEEESLSPEAPRRPKQRPAPAQRLRKKRTEAPESPCPTGSKPR
  KPGAGRTGRPREEPSPDPAQARAPQTVYARFLRDPEAKKRDPRETFLVARAPDAEDEEEE
  EEEDEEDEEEEAEEKKEKILLPPKKPLREKSSADLKERRAKAQGPRGDLGSPDPPPKPLR
  VRNKEAPAGEGTKMRKTKKKGSGEADKDPSGSPASARKSPAAMFLVGEGSPDKKALKKKG
  TPKGARKEEEEEEEAATVIKKSNQKGKAKGKGKKKAKEERAPSPPVEVDEPREFVLRPAP
  QGRTVRCRLTRDKKGMDRGMYPSYFLHLDTEKKVFLLAGRKRKRSKTANYLISIDPTNLS
  RGGENFIGKLRSNLLGNRFTVFDNGQNPQRGYSTNVASLRQELAAVIYETNVLGFRGPRR
  MTVIIPGMSAENERVPIRPRNASDGLLVRWQNKTLESLIELHNKPPVWNDDSGSYTLNFQ
  GRVTQASVKNFQIVHADDPDYIVLQFGRVAEDAFTLDYRYPLCALQAFAIALSSFDGKLA
  CE
• Function: Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells. Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages.
• Tissue Specificity: Retina-specific.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa 14	DIS6AY6F	Definitive	Autosomal recessive	[1]
Leber congenital amaurosis 15	DISJW5JU	Strong	Autosomal recessive	[2]
Leber congenital amaurosis	DISMGH8F	Supportive	Autosomal dominant	[3]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tubby-related protein 1.	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tubby-related protein 1.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tubby-related protein 1.	[6]

References

• [1] Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa. Arch Ophthalmol. 2007 Jul;125(7):932-5. doi: 10.1001/archopht.125.7.932.
• [2] Retinal degeneration in tulp1-/- mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci. 1999 Nov;40(12):2795-802.
• [3] Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5160-7. doi: 10.1167/iovs.06-1013.
• [4] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [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.