Details of Drug Off-Target (DOT)

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

• DOT Name: Death-associated protein-like 1 (DAPL1)
• Synonyms: Early epithelial differentiation-associated protein
• Gene Name: DAPL1
• Related Disease: Age-related macular degeneration
• UniProt ID: DAPL1_HUMAN
• Pfam ID: PF15228
• Sequence:
  MANEVQDLLSPRKGGHPPAVKAGGMRISKKQEIGTLERHTKKTGFEKTSAIANVAKIQTL
  DALNDALEKLNYKFPATVHMAHQKPTPALEKVVPLKRIYIIQQPRKC
• Function: May play a role in the early stages of epithelial differentiation or in apoptosis.
• Tissue Specificity: Expressed in hair follicle (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Death-associated protein-like 1 (DAPL1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Death-associated protein-like 1 (DAPL1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Death-associated protein-like 1 (DAPL1).	[3]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Death-associated protein-like 1 (DAPL1).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Death-associated protein-like 1 (DAPL1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Death-associated protein-like 1 (DAPL1).	[7]

References

• [1] DAPL1, a susceptibility locus for age-related macular degeneration, acts as a novel suppressor of cell proliferation in the retinal pigment epithelium.Hum Mol Genet. 2017 May 1;26(9):1612-1621. doi: 10.1093/hmg/ddx063.
• [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] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [4] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [5] 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.
• [6] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.