Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSLOX04)

• DOT Name: Proactivator polypeptide-like 1 (PSAPL1)
• Gene Name: PSAPL1
• UniProt ID: SAPL1_HUMAN
• Pfam ID: PF02199 ; PF05184 ; PF03489
• Sequence:
  MLCALLLLPSLLGATRASPTSGPQECAKGSTVWCQDLQTAARCGAVGYCQGAVWNKPTAK
  SLPCDVCQDIAAAAGNGLNPDATESDILALVMKTCEWLPSQESSAGCKWMVDAHSSAILS
  MLRGAPDSAPAQVCTALSLCEPLQRHLATLRPLSKEDTFEAVAPFMANGPLTFHPRQAPE
  GALCQDCVRQVSRLQEAVRSNLTLADLNIQEQCESLGPGLAVLCKNYLFQFFVPADQALR
  LLPPQELCRKGGFCEELGAPARLTQVVAMDGVPSLELGLPRKQSEMQMKAGVTCEVCMNV
  VQKLDHWLMSNSSELMITHALERVCSVMPASITKECIILVDTYSPSLVQLVAKITPEKVC
  KFIRLCGNRRRARAVHDAYAIVPSPEWDAENQGSFCNGCKRLLTVSSHNLESKSTKRDIL
  VAFKGGCSILPLPYMIQCKHFVTQYEPVLIESLKDMMDPVAVCKKVGACHGPRTPLLGTD
  QCALGPSFWCRSQEAAKLCNAVQHCQKHVWKEMHLHAGEHA
• Function: May activate the lysosomal degradation of sphingolipids.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Proactivator polypeptide-like 1 (PSAPL1).	[1]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Proactivator polypeptide-like 1 (PSAPL1).	[2]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Proactivator polypeptide-like 1 (PSAPL1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proactivator polypeptide-like 1 (PSAPL1).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Proactivator polypeptide-like 1 (PSAPL1).	[6]

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 Proactivator polypeptide-like 1 (PSAPL1).	[5]

References

• [1] 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.
• [2] 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.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.