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Gene Review

NDOR1  -  NADPH dependent diflavin oxidoreductase 1

Homo sapiens

Synonyms: NADPH-dependent FMN and FAD-containing oxidoreductase, NADPH-dependent diflavin oxidoreductase 1, NR1, Novel reductase 1, bA350O14.9
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Disease relevance of NDOR1


Psychiatry related information on NDOR1

  • Recently, a mouse deficient in expression of the NR1 subunit gene (NMDAR1) of the heteromeric receptor has been developed and shown to display aberrant behaviors, with reduced social and sexual interactions as well as increased stereotypic motor activity [4].

High impact information on NDOR1

  • NMDAR activation failed to induce Ca(2+) responses in hippocampal neurons lacking the mandatory NMDAR subunit NR1, and no EGFP-CaMKIIalpha translocation was observed [5].
  • The discovery of a novel RNA editing mechanism for AMPA receptors and a revised view of the transmembrane topology of the NMDA receptor subunit, NR1, are particularly noteworthy [6].
  • The K(actNR1) is 1.27 +/- 0.16 microm, and a 20-fold higher stoichiometry of reductase to methionine synthase is required for NR1 versus methionine synthase reductase, suggesting that it may represent a minor pathway in the cell, assuming that the two proteins are present at similar levels [7].
  • This indicates that the S1 and S2 domains of the NR1 subunit are sufficient for the formation of a glycine binding site that displays pharmacological properties similar to those of the NMDA receptor in vivo [8].
  • The activity of the more slowly migrating nitrate reductase isozyme (NR1) was induced by NO3- in green seedlings and cycloheximide inhibited induction [9].

Chemical compound and disease context of NDOR1


Biological context of NDOR1


Anatomical context of NDOR1

  • In NMDA receptor (NMDAR) channels, where the influx is much greater, the extracellular vestibule, specifically the M3 segment and regions C-terminal to it in the NR1 subunit, contains elements critical to their high Ca2+ influx under physiological conditions [15].
  • NR1 mRNA was significantly increased in the gracile and inferior olivary nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH exposure, and in three of seven nuclei after nicotine+IHH [16].
  • Thus, NR1 in tufted and mitral cells in the gerbil MOB is changed after transient forebrain ischemia [2].
  • Using immunohistochemistry and RTPCR normal and OA chondrocytes are shown to express NR1 and NR2a subunits of the NMDA receptor [17].
  • NR1 positive neuron densities were significantly greater in females than males in the nucleus tractus solitarius (NTS), commissural nucleus of the NTS and hypoglossal nucleus due to higher counts [18].

Associations of NDOR1 with chemical compounds

  • However, further analysis of NDOR1 revealed a polymorphic c.1564G>A transition (NDOR1*1), detected in 24/200 Caucasian and 1/49 Japanese individuals, producing a valine to isoleucine substitution at codon 522 in the NADPH binding region [19].
  • Determination of the redox potentials and electron transfer properties of the FAD- and FMN-binding domains of the human oxidoreductase NR1 [20].
  • Despite overall structural resemblance of NR1 and CPR, our studies reveal thermodynamic similarities but major kinetic differences in the electron transfer reactions catalysed by the flavin-binding domains [20].
  • Stopped-flow studies indicate that hydride transfer from the FAD/NADPH domain of NR1 to NADP+ is faster than hydride transfer in the physiological direction (NADPH to FAD), consistent with the measured reduction potentials of the FAD couples [midpoint potential for FAD redox couples is -340 mV, cf-320 mV for NAD(P)H] [20].
  • Utilizing piglet models of early postnatal nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the hypothesis that these exposures, separately or combined, increase N-methyl-d-aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla [16].

Physical interactions of NDOR1

  • The FAD/NADPH- and FMN-binding domains of NR1 have been expressed and purified and their redox properties studied by stopped-flow and steady-state kinetic methods, and by potentiometry [20].

Analytical, diagnostic and therapeutic context of NDOR1

  • That GIIbeta is indeed a trans-acting protein and binds specifically to 3'-UTR of NR1 mRNA was confirmed by RNA gel mobility supershift assays and immuno RT-PCR [13].
  • Non-radioactive in situ hybridization and immunohistochemistry were performed for NR1 mRNA and protein expression, respectively, and were quantified in seven nuclei of the brainstem medulla [16].


  1. Phosphorylation of NMDA NR1 subunits in the myenteric plexus during TNBS induced colitis. Zhou, Q., Caudle, R.M., Moshiree, B., Price, D.D., Verne, G.N. Neurosci. Lett. (2006) [Pubmed]
  2. N-methyl-d: -aspartate receptor type 1 immunoreactivity and protein level in the gerbil main olfactory bulb after transient forebrain ischemia. Her, Y., Yoo, K.Y., Hwang, I.K., Lee, J.S., Kang, T.C., Lee, B.H., Kim, d.o. .H., Won, M.H. Neurochem. Res. (2007) [Pubmed]
  3. Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats. Zhou, Q., Caudle, R.M., Price, D.D., Del Valle-Pinero, A.Y., Verne, G.N. Molecular pain [electronic resource] (2006) [Pubmed]
  4. Identification of single nucleotide polymorphisms (SNPs) and other sequence changes and estimation of nucleotide diversity in coding and flanking regions of the NMDAR1 receptor gene in schizophrenic patients. Rice, S.R., Niu, N., Berman, D.B., Heston, L.L., Sobell, J.L. Mol. Psychiatry (2001) [Pubmed]
  5. CaMKII translocation requires local NMDA receptor-mediated Ca(2+) signaling. Thalhammer, A., Rudhard, Y., Tigaret, C.M., Volynski, K.E., Rusakov, D.A., Schoepfer, R. EMBO J. (2006) [Pubmed]
  6. Glutamate receptor update. Westbrook, G.L. Curr. Opin. Neurobiol. (1994) [Pubmed]
  7. Redundancy in the pathway for redox regulation of mammalian methionine synthase: reductive activation by the dual flavoprotein, novel reductase 1. Olteanu, H., Banerjee, R. J. Biol. Chem. (2003) [Pubmed]
  8. Expression and initial characterization of a soluble glycine binding domain of the N-methyl-D-aspartate receptor NR1 subunit. Ivanovic, A., Reiländer, H., Laube, B., Kuhse, J. J. Biol. Chem. (1998) [Pubmed]
  9. Inheritance of nitrite reductase and regulation of nitrate reductase, nitrite reductase, and glutamine synthetase isozymes. Heath-Pagliuso, S., Huffaker, R.C., Allard, R.W. Plant Physiol. (1984) [Pubmed]
  10. Augmentation of locomotor activity by chronic phencyclidine is associated with an increase in striatal NMDA receptor function and an upregulation of the NR1 receptor subunit. Hanania, T., Hillman, G.R., Johnson, K.M. Synapse (1999) [Pubmed]
  11. Typical and atypical antipsychotic drug effects on locomotor hyperactivity and deficits in sensorimotor gating in a genetic model of NMDA receptor hypofunction. Duncan, G.E., Moy, S.S., Lieberman, J.A., Koller, B.H. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  12. Distinct mechanisms underlie distinct polyphenol-induced neuroprotection. Yazawa, K., Kihara, T., Shen, H., Shimmyo, Y., Niidome, T., Sugimoto, H. FEBS Lett. (2006) [Pubmed]
  13. A novel RNA binding protein that interacts with NMDA R1 mRNA: regulation by ethanol. Anji, A., Kumari, M. Eur. J. Neurosci. (2006) [Pubmed]
  14. Experience-dependent regulation of zif268 gene expression and spatial learning. Toscano, C.D., McGlothan, J.L., Guilarte, T.R. Exp. Neurol. (2006) [Pubmed]
  15. Extracellular vestibule determinants of Ca2+ influx in Ca2+-permeable AMPA receptor channels. Jatzke, C., Hernandez, M., Wollmuth, L.P. J. Physiol. (Lond.) (2003) [Pubmed]
  16. N-methyl-d-aspartate receptor 1 changes in the piglet braintem after nicotine and/or intermittent hypercapnic-hypoxia. Fanous, A.M., Machaalani, R., Waters, K.A. Neuroscience (2006) [Pubmed]
  17. NMDA receptor expression and roles in human articular chondrocyte mechanotransduction. Salter, D.M., Wright, M.O., Millward-Sadler, S.J. Biorheology. (2004) [Pubmed]
  18. Comparison of NMDA modulation of breathing and NR1 expression in medullary nuclei of weanling male and female rats. Schlenker, E.H., Hansen, S.N. Respiratory physiology & neurobiology (2007) [Pubmed]
  19. Identification of a functionally impaired allele of human novel oxidoreductase 1 (NDOR1), NDOR1*1. Finn, R.D., Wilkie, M., Smith, G., Paine, M.J. Pharmacogenet. Genomics (2005) [Pubmed]
  20. Determination of the redox potentials and electron transfer properties of the FAD- and FMN-binding domains of the human oxidoreductase NR1. Finn, R.D., Basran, J., Roitel, O., Wolf, C.R., Munro, A.W., Paine, M.J., Scrutton, N.S. Eur. J. Biochem. (2003) [Pubmed]
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