Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNZ0VVM)

• DOT Name: Protein GPR15LG (GPR15LG)
• Synonyms: Antimicrobial peptide with 57 amino acid residues; AP-57; Antimicrobial peptide-57; Colon-derived SUSD2 binding factor; CSBF; Protein GPR15 ligand; Protein GPR15L; Secreted protein C10orf99
• Gene Name: GPR15LG
• UniProt ID: GP15L_HUMAN
• Pfam ID: PF15854
• Sequence:
  MRLLVLSSLLCILLLCFSIFSTEGKRRPAKAWSGRRTRLCCHRVPSPNSTNLKGHHVRLC
  KPCKLEPEPRLWVVPGALPQV
• Function: Highly cationic protein that has multiple functions. Acts as a chemotactic factor that mediates lymphocytes recruitment to epithelia through binding and activation of the G-protein coupled receptor GPR15. May be a tumor suppressor; together with SUSD2 has a growth inhibitory effect on colon cancer cells which includes G1 cell cycle arrest. May regulate keratinocyte proliferation. In addition, through activation of Mas-related G protein-coupled receptors (MRGPRs) contributes to pruritogenesis by activating itch-selective sensory neurons and mast cells degranulation ; Has antimicrobial activity against Gram-positive bacteria, including Staphylococcus aureus and Actinomyces spec., and Mycoplasma hominis and lentivirus.
• Tissue Specificity: Expressed at high levels in colon, and cervix and at moderate level in tonsil . Highly reduced expression in primary colon cancer tissues compared with that in adjacent tissues . Highest levels of expression detected in stomach and colon; expressed in epithelium of skin and esophagus, and in some tumor and/or tumor adjacent tissues (TAT), including TAT of esophagus cancer, hepatocellular carcinoma (HCC), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and invasive ductal carcinoma (IDC) tissues (at protein level) . Highly expressed by inflammatory differentiated keratinocytese .

Molecular Interaction Atlas (MIA) of This DOT

1 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 Protein GPR15LG (GPR15LG).	[1]

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 decreases the methylation of Protein GPR15LG (GPR15LG).	[2]

References

• [1] 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.
• [2] 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.