Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT658KRM)

• DOT Name: Cytosol aminopeptidase (LAP3)
• Synonyms: EC 3.4.11.1; Cysteinylglycine-S-conjugate dipeptidase; EC 3.4.13.23; Leucine aminopeptidase 3; LAP-3; Leucyl aminopeptidase; Peptidase S; Proline aminopeptidase; EC 3.4.11.5; Prolyl aminopeptidase
• Gene Name: LAP3
• UniProt ID: AMPL_HUMAN
• EC Number: 3.4.11.1; 3.4.11.5; 3.4.13.23
• Pfam ID: PF00883 ; PF02789
• Sequence:
  MFLLPLPAAGRVVVRRLAVRRFGSRSLSTADMTKGLVLGIYSKEKEDDVPQFTSAGENFD
  KLLAGKLRETLNISGPPLKAGKTRTFYGLHQDFPSVVLVGLGKKAAGIDEQENWHEGKEN
  IRAAVAAGCRQIQDLELSSVEVDPCGDAQAAAEGAVLGLYEYDDLKQKKKMAVSAKLYGS
  GDQEAWQKGVLFASGQNLARQLMETPANEMTPTRFAEIIEKNLKSASSKTEVHIRPKSWI
  EEQAMGSFLSVAKGSDEPPVFLEIHYKGSPNANEPPLVFVGKGITFDSGGISIKASANMD
  LMRADMGGAATICSAIVSAAKLNLPINIIGLAPLCENMPSGKANKPGDVVRAKNGKTIQV
  DNTDAEGRLILADALCYAHTFNPKVILNAATLTGAMDVALGSGATGVFTNSSWLWNKLFE
  ASIETGDRVWRMPLFEHYTRQVVDCQLADVNNIGKYRSAGACTAAAFLKEFVTHPKWAHL
  DIAGVMTNKDEVPYLRKGMTGRPTRTLIEFLLRFSQDNA
• Function: Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cytosol aminopeptidase (LAP3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytosol aminopeptidase (LAP3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytosol aminopeptidase (LAP3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytosol aminopeptidase (LAP3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Cytosol aminopeptidase (LAP3).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cytosol aminopeptidase (LAP3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytosol aminopeptidase (LAP3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cytosol aminopeptidase (LAP3).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.