Details of Drug Off-Target (DOT)

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

• DOT Name: Aminopeptidase NAALADL1 (NAALADL1)
• Synonyms: EC 3.4.11.-; 100 kDa ileum brush border membrane protein; I100; Ileal dipeptidylpeptidase; N-acetylated-alpha-linked acidic dipeptidase-like protein; NAALADase L
• Gene Name: NAALADL1
• Related Disease:
  Neuroblastoma
  Retinitis pigmentosa
  Thyroid gland papillary carcinoma
• UniProt ID: NALDL_HUMAN
• PDB ID: 4TWE
• EC Number: 3.4.11.-
• Pfam ID: PF02225 ; PF04389 ; PF04253
• Sequence:
  MQWTKVLGLGLGAAALLGLGIILGHFAIPKKANSLAPQDLDLEILETVMGQLDAHRIREN
  LRELSREPHLASSPRDEDLVQLLLQRWKDPESGLDSAEASTYEVLLSFPSQEQPNVVDIV
  GPTGGIIHSCHRTEENVTGEQGGPDVVQPYAAYAPSGTPQGLLVYANRGAEEDFKELQTQ
  GIKLEGTIALTRYGGVGRGAKAVNAAKHGVAGVLVYTDPADINDGLSSPDETFPNSWYLP
  PSGVERGSYYEYFGDPLTPYLPAVPSSFRVDLANVSGFPPIPTQPIGFQDARDLLCNLNG
  TLAPATWQGALGCHYRLGPGFRPDGDFPADSQVNVSVYNRLELRNSSNVLGIIRGAVEPD
  RYVLYGNHRDSWVHGAVDPSSGTAVLLELSRVLGTLLKKGTWRPRRSIVFASWGAEEFGL
  IGSTEFTEEFFNKLQERTVAYINVDISVFANATLRVQGTPPVQSVVFSATKEIRSPGPGD
  LSIYDNWIRYFNRSSPVYGLVPSLGSLGAGSDYAPFVHFLGISSMDIAYTYDRSKTSARI
  YPTYHTAFDTFDYVDKFLDPGFSSHQAVARTAGSVILRLSDSFFLPLKVSDYSETLRSFL
  QAAQQDLGALLEQHSISLGPLVTAVEKFEAEAAALGQRISTLQKGSPDPLQVRMLNDQLM
  LLERTFLNPRAFPEERYYSHVLWAPRTGSVVTFPGLSNACSRARDTASGSEAWAEVQRQL
  SIVVTALEGAAATLRPVADL
• Function: Aminopeptidase with broad substrate specificity. Has lower activity with substrates that have Asp or Glu in the P2' position, or Pro in the P3' position. Lacks activity with substrates that have both Pro in the P3' position and Asp or Glu in the P2' position. Lacks carboxypeptidase activity. Lacks dipeptidyl-peptidase IV type activity.
• Tissue Specificity: Detected in small intestine (at protein level) . Detected in ileum . Detected in small intestine, spleen and testis. Isoform 2 and isoform 3 are found in the small intestine and colon .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	moderate	Biomarker	[1]
Retinitis pigmentosa	DISCGPY8	moderate	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Aminopeptidase NAALADL1 (NAALADL1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Aminopeptidase NAALADL1 (NAALADL1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aminopeptidase NAALADL1 (NAALADL1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Aminopeptidase NAALADL1 (NAALADL1).	[7]

References

• [1] Insulin-like growth factor binding protein-2 binding to extracellular matrix plays a critical role in neuroblastoma cell proliferation, migration, and invasion.Endocrinology. 2005 Oct;146(10):4445-55. doi: 10.1210/en.2005-0467. Epub 2005 Jun 30.
• [2] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [3] Enduring remission of active and sight-threatening Graves' orbitopathy with rituximab: report of two cases.Endocr J. 2018 Sep 27;65(9):963-967. doi: 10.1507/endocrj.EJ18-0074. Epub 2018 Jun 22.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.