Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3TX3N)

• DOT Name: Protein kinase C-binding protein NELL1 (NELL1)
• Synonyms: NEL-like protein 1; Nel-related protein 1
• Gene Name: NELL1
• UniProt ID: NELL1_HUMAN
• PDB ID: 6POL
• Pfam ID: PF12947 ; PF07645 ; PF02210 ; PF00093
• Sequence:
  MPMDLILVVWFCVCTARTVVGFGMDPDLQMDIVTELDLVNTTLGVAQVSGMHNASKAFLF
  QDIEREIHAAPHVSEKLIQLFRNKSEFTILATVQQKPSTSGVILSIRELEHSYFELESSG
  LRDEIRYHYIHNGKPRTEALPYRMADGQWHKVALSVSASHLLLHVDCNRIYERVIDPPDT
  NLPPGINLWLGQRNQKHGLFKGIIQDGKIIFMPNGYITQCPNLNHTCPTCSDFLSLVQGI
  MDLQELLAKMTAKLNYAETRLSQLENCHCEKTCQVSGLLYRDQDSWVDGDHCRNCTCKSG
  AVECRRMSCPPLNCSPDSLPVHIAGQCCKVCRPKCIYGGKVLAEGQRILTKSCRECRGGV
  LVKITEMCPPLNCSEKDHILPENQCCRVCRGHNFCAEGPKCGENSECKNWNTKATCECKS
  GYISVQGDSAYCEDIDECAAKMHYCHANTVCVNLPGLYRCDCVPGYIRVDDFSCTEHDEC
  GSGQHNCDENAICTNTVQGHSCTCKPGYVGNGTICRAFCEEGCRYGGTCVAPNKCVCPSG
  FTGSHCEKDIDECSEGIIECHNHSRCVNLPGWYHCECRSGFHDDGTYSLSGESCIDIDEC
  ALRTHTCWNDSACINLAGGFDCLCPSGPSCSGDCPHEGGLKHNGQVWTLKEDRCSVCSCK
  DGKIFCRRTACDCQNPSADLFCCPECDTRVTSQCLDQNGHKLYRSGDNWTHSCQQCRCLE
  GEVDCWPLTCPNLSCEYTAILEGECCPRCVSDPCLADNITYDIRKTCLDSYGVSRLSGSV
  WTMAGSPCTTCKCKNGRVCCSVDFECLQNN
• Function: Plays a role in the control of cell growth and differentiation. Promotes osteoblast cell differentiation and terminal mineralization.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenytoin	DMNOKBV	Approved	Protein kinase C-binding protein NELL1 (NELL1) increases the Hypersensitivity ADR of Phenytoin.	[13]
Chlorothiazide	DMLHESP	Approved	Protein kinase C-binding protein NELL1 (NELL1) increases the Metabolic disorder ADR of Chlorothiazide.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein kinase C-binding protein NELL1 (NELL1).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Protein kinase C-binding protein NELL1 (NELL1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein kinase C-binding protein NELL1 (NELL1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Protein kinase C-binding protein NELL1 (NELL1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[7]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[9]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Protein kinase C-binding protein NELL1 (NELL1).	[12]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma. Oncogene. 2007 Sep 20;26(43):6332-40. doi: 10.1038/sj.onc.1210461. Epub 2007 Apr 23.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [9] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [10] 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.
• [11] 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.
• [12] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [13] Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. Pharmacogenomics. 2012 Mar;13(4):399-405. doi: 10.2217/pgs.11.165.
• [14] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.