Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHBF42S)

• DOT Name: Aminopeptidase Q (LVRN)
• Synonyms: AP-Q; APQ; EC 3.4.11.-; CHL2 antigen; Laeverin
• Gene Name: LVRN
• Related Disease:
  Melanoma
  Rheumatoid arthritis
• UniProt ID: AMPQ_HUMAN
• EC Number: 3.4.11.-
• Pfam ID: PF11838 ; PF01433 ; PF17900
• Sequence:
  MGPPSSSGFYVSRAVALLLAGLVAALLLALAVLAALYGHCERVPPSELPGLRDLEAESSP
  PLRQKPTPTPKPSSARELAVTTTPSNWRPPGPWDQLRLPPWLVPLHYDLELWPQLRPDEL
  PAGSLPFTGRVNITVRCTVATSRLLLHSLFQDCERAEVRGPLSPGTGNATVGRVPVDDVW
  FALDTEYMVLELSEPLKPGSSYELQLSFSGLVKEDLREGLFLNVYTDQGERRALLASQLE
  PTFARYVFPCFDEPALKATFNITMIHHPSYVALSNMPKLGQSEKEDVNGSKWTVTTFSTT
  PHMPTYLVAFVICDYDHVNRTERGKEIRIWARKDAIANGSADFALNITGPIFSFLEDLFN
  ISYSLPKTDIIALPSFDNHAMENWGLMIFDESGLLLEPKDQLTEKKTLISYVVSHEIGHQ
  WFGNLVTMNWWNNIWLNEGFASYFEFEVINYFNPKLPRNEIFFSNILHNILREDHALVTR
  AVAMKVENFKTSEIQELFDIFTYSKGASMARMLSCFLNEHLFVSALKSYLKTFSYSNAEQ
  DDLWRHFQMAIDDQSTVILPATIKNIMDSWTHQSGFPVITLNVSTGVMKQEPFYLENIKN
  RTLLTSNDTWIVPILWIKNGTTQPLVWLDQSSKVFPEMQVSDSDHDWVILNLNMTGYYRV
  NYDKLGWKKLNQQLEKDPKAIPVIHRLQLIDDAFSLSKNNYIEIETALELTKYLAEEDEI
  IVWHTVLVNLVTRDLVSEVNIYDIYSLLKRYLLKRLNLIWNIYSTIIRENVLALQDDYLA
  LISLEKLFVTACWLGLEDCLQLSKELFAKWVDHPENEIPYPIKDVVLCYGIALGSDKEWD
  ILLNTYTNTTNKEEKIQLAYAMSCSKDPWILNRYMEYAISTSPFTSNETNIIEVVASSEV
  GRYVAKDFLVNNWQAVSKRYGTQSLINLIYTIGRTVTTDLQIVELQQFFSNMLEEHQRIR
  VHANLQTIKNENLKNKKLSARIAAWLRRNT
• Function: Metalloprotease which may be important for placentation by regulating biological activity of key peptides at the embryo-maternal interface. On synthetic substrates it shows a marked preference for Leu-4-methylcoumaryl-7-amide (Leu-MCA) over Met-MCA, Arg-LCA and Lys-LCA. Cleaves the N-terminal amino acid of several peptides such as angiotensin-3, kisspeptin-10 and endokinin C.
• Tissue Specificity: Specifically expressed in placenta and not in other tissues. Mainly found at the cell surface region of the extravillous trophoblasts. Detected on extravillous trophoblasts in the outer layer of the chorion laeve in the fetal membrane Not detected on either fetal amnionic epithelial cells or maternal decidual cells. Also detected in the migrating extravillous trophoblasts in the maternal decidual tissues (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Limited	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Aminopeptidase Q (LVRN).	[3]

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 Aminopeptidase Q (LVRN).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Aminopeptidase Q (LVRN).	[5]

References

• [1] Aquaporins mediate the chemoresistance of human melanoma cells to arsenite.Mol Oncol. 2012 Feb;6(1):81-7. doi: 10.1016/j.molonc.2011.11.001. Epub 2011 Nov 13.
• [2] Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins.Arthritis Rheum. 2006 Jul;54(7):2047-60. doi: 10.1002/art.21953.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [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.