Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ1EZDJ)

• DOT Name: Leucine rich adaptor protein 1 (LURAP1)
• Synonyms: Leucine repeat adapter protein 35A
• Gene Name: LURAP1
• Related Disease:
  Neoplasm
  Bladder cancer
  Pneumocystis pneumonia
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: LURA1_HUMAN
• Pfam ID: PF14854
• Sequence:
  MEGTVESQTPDLRDVEGKVGRKTPEGLLRGLRGECELGTSGALLLPGASSTGHDLGDKIM
  ALKMELAYLRAIDVKILQQLVTLNEGIEAVRWLLEERGTLTSHCSSLTSSQYSLTGGSPG
  RSRRGSWDSLPDTSTTDRLDSVSIGSFLDTVAPSELDEQGPPGAPRSEMDWAKVIAGGER
  ARTEVDVAATRLGSLRAVWKPPGERLQGGPPESPEDESAKLGFEAHWFWEQCQDDVTFL
• Function: Acts as an activator of the canonical NF-kappa-B pathway and drive the production of pro-inflammatory cytokines. Promotes the antigen (Ag)-presenting and priming function of dendritic cells via the canonical NF-kappa-B pathway. In concert with MYO18A and CDC42BPA/CDC42BPB, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Activates CDC42BPA/CDC42BPB and targets it to actomyosin through its interaction with MYO18A, leading to MYL9/MLC2 phosphorylation and MYH9/MYH10-dependent actomyosin assembly in the lamella.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Limited	Genetic Variation	[2]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Limited	Genetic Variation	[2]
Urinary bladder neoplasm	DIS7HACE	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine rich adaptor protein 1 (LURAP1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leucine rich adaptor protein 1 (LURAP1).	[5]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Leucine rich adaptor protein 1 (LURAP1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine rich adaptor protein 1 (LURAP1).	[8]

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 Leucine rich adaptor protein 1 (LURAP1).	[7]

References

• [1] Chromosome 1 open reading frame 190 promotes activation of NF-B canonical pathway and resistance of dendritic cells to tumor-associated inhibition in vitro.J Immunol. 2010 Dec 1;185(11):6719-27. doi: 10.4049/jimmunol.0903869. Epub 2010 Nov 3.
• [2] A six-gene prognostic model predicts overall survival in bladder cancer patients.Cancer Cell Int. 2019 Sep 5;19:229. doi: 10.1186/s12935-019-0950-7. eCollection 2019.
• [3] Leucine repeat adaptor protein 1 interacts with Dishevelled to regulate gastrulation cell movements in zebrafish.Nat Commun. 2017 Nov 7;8(1):1353. doi: 10.1038/s41467-017-01552-x.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [7] 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.
• [8] 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.