Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7T1OJP)

• DOT Name: Glutamate receptor ionotropic, NMDA 3B (GRIN3B)
• Synonyms: GluN3B; N-methyl-D-aspartate receptor subtype 3B; NMDAR3B; NR3B
• Gene Name: GRIN3B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Epilepsy
  Heroin dependence
  Schizophrenia
  Amyotrophic lateral sclerosis
• UniProt ID: NMD3B_HUMAN
• Pfam ID: PF00060 ; PF10613 ; PF00497
• Sequence:
  MEFVRALWLGLALALGPGSAGGHPQPCGVLARLGGSVRLGALLPRAPLARARARAALARA
  ALAPRLPHNLSLELVVAAPPARDPASLTRGLCQALVPPGVAALLAFPEARPELLQLHFLA
  AATETPVLSLLRREARAPLGAPNPFHLQLHWASPLETLLDVLVAVLQAHAWEDVGLALCR
  TQDPGGLVALWTSRAGRPPQLVLDLSRRDTGDAGLRARLAPMAAPVGGEAPVPAAVLLGC
  DIARARRVLEAVPPGPHWLLGTPLPPKALPTAGLPPGLLALGEVARPPLEAAIHDIVQLV
  ARALGSAAQVQPKRALLPAPVNCGDLQPAGPESPGRFLARFLANTSFQGRTGPVWVTGSS
  QVHMSRHFKVWSLRRDPRGAPAWATVGSWRDGQLDLEPGGASARPPPPQGAQVWPKLRVV
  TLLEHPFVFARDPDEDGQCPAGQLCLDPGTNDSATLDALFAALANGSAPRALRKCCYGYC
  IDLLERLAEDTPFDFELYLVGDGKYGALRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQ
  VVDFTSPFFSTSLGIMVRARDTASPIGAFMWPLHWSTWLGVFAALHLTALFLTVYEWRSP
  YGLTPRGRNRSTVFSYSSALNLCYAILFRRTVSSKTPKCPTGRLLMNLWAIFCLLVLSSY
  TANLAAVMVGDKTFEELSGIHDPKLHHPAQGFRFGTVWESSAEAYIKKSFPDMHAHMRRH
  SAPTTPRGVAMLTSDPPKLNAFIMDKSLLDYEVSIDADCKLLTVGKPFAIEGYGIGLPQN
  SPLTSNLSEFISRYKSSGFIDLLHDKWYKMVPCGKRVFAVTETLQMSIYHFAGLFVLLCL
  GLGSALLSSLGEHAFFRLALPRIRKGSRLQYWLHTSQKIHRALNTEPPEGSKEETAEAEP
  SGPEVEQQQQQQDQPTAPEGWKRARRAVDKERRVRFLLEPAVVVAPEADAEAEAAPREGP
  VWLCSYGRPPAARPTGAPQPGELQELERRIEVARERLRQALVRRGQLLAQLGDSARHRPR
  RLLQARAAPAEAPPHSGRPGSQE
• Function: NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Glutamatergic sy.pse (hsa04724)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Nicotine addiction (hsa05033)
  Alcoholism (hsa05034)
• Reactome Pathway: Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Epilepsy	DISBB28L	Strong	Altered Expression	[2]
Heroin dependence	DISQ1H57	Strong	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Glutamate receptor ionotropic, NMDA 3B (GRIN3B) affects the response to substance of Methotrexate.	[10]

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 Glutamate receptor ionotropic, NMDA 3B (GRIN3B).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutamate receptor ionotropic, NMDA 3B (GRIN3B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutamate receptor ionotropic, NMDA 3B (GRIN3B).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Glutamate receptor ionotropic, NMDA 3B (GRIN3B).	[8]

References

• [1] Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma.BMC Cancer. 2018 Jun 26;18(1):690. doi: 10.1186/s12885-018-4586-0.
• [2] Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy.Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):328-337. doi: 10.26355/eurrev_201901_16780.
• [3] Association between genetic variations of NMDA receptor NR3 subfamily genes and heroin addiction in male Han Chinese.Neurosci Lett. 2016 Sep 19;631:122-125. doi: 10.1016/j.neulet.2016.08.025. Epub 2016 Aug 16.
• [4] A naturally occurring null variant of the NMDA type glutamate receptor NR3B subunit is a risk factor of schizophrenia.PLoS One. 2015 Mar 13;10(3):e0116319. doi: 10.1371/journal.pone.0116319. eCollection 2015.
• [5] Motoneuron-specific NR3B gene: no association with ALS and evidence for a common null allele.Neurology. 2008 Feb 26;70(9):666-76. doi: 10.1212/01.wnl.0000271078.51280.17. Epub 2007 Aug 8.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [9] 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.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.