Glutamate receptor ionotropic, NMDA 3A
Also known as: GRIN3A, KIAA1973
Function
Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+) (By similarity). During the development of neural circuits, participates in the synaptic refinement period, restricting spine maturation and growth (By similarity). Forms glutamatergic receptor complexes with GluN1 and GluN2 subunits which are activated by glycine binding to the GluN1 and GluN3 subunits and L-glutamate binding to GluN2 subunits (By similarity). Forms excitatory glycinergic receptor complexes with GluN1 alone which are activated by glycine binding to the GluN1 and GluN3 subunits. GluN3A subunit also binds D-serine (By similarity). Each GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (By similarity). By competing with GIT1 interaction with ARHGEF7/beta-PIX, may reduce GIT1/ARHGEF7-regulated local activation of RAC1, hence affecting signaling and limiting the maturation and growth of inactive synapses (By similarity).
Classification
- Family (Pfam)
- PF01094 ANF_receptor, PF00060 Lig_chan, PF10613 Lig_chan-Glu_bd
- InterPro
- ANF_lig-bd_rcpt, Glu/Gly-bd, Iono_Glu_rcpt_met, Ionotropic_Glu_rcpt, Iontro_rcpt_C, Peripla_BP_I
- Functional cluster
- RNA Polymerase & tRNA Deacylases
Experimental structures · PDB · 3
A predicted model is available from AlphaFold.
Gene Ontology · 32
- GO:0005789 endoplasmic reticulum membrane
- GO:0098978 glutamatergic synapse
- GO:0016020 membrane
- GO:0043005 neuron projection
- GO:0043025 neuronal cell body
- GO:0098878 neurotransmitter receptor complex
- GO:0017146 NMDA selective glutamate receptor complex
- GO:0005886 plasma membrane
- GO:0098839 postsynaptic density membrane
- GO:0045211 postsynaptic membrane
- GO:0098793 presynapse
- GO:0045202 synapse
- GO:0005262 calcium channel activity
- GO:0008066 glutamate receptor activity
- GO:0016594 glycine binding
- GO:0160212 glycine-gated cation channel activity
- GO:0042802 identical protein binding
- GO:0004972 NMDA glutamate receptor activity
- GO:0051721 protein phosphatase 2A binding
- GO:0070905 serine binding
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0006816 calcium ion transport
- GO:0035235 ionotropic glutamate receptor signaling pathway
- GO:0050804 modulation of chemical synaptic transmission
- GO:0098655 monoatomic cation transmembrane transport
- GO:0061000 negative regulation of dendritic spine development
- GO:0048666 neuron development
- GO:0099171 presynaptic modulation of chemical synaptic transmission
- GO:0048167 regulation of synaptic plasticity
- GO:0045471 response to ethanol
- GO:0048511 rhythmic process
- GO:0035249 synaptic transmission, glutamatergic
Drugs targeting this protein · 20
- FELBAMATE antagonist
- ORPHENADRINE CITRATE antagonist
- ORPHENADRINE HYDROCHLORIDE antagonist
- GW468816 antagonist
- NEBOGLAMINE positive allosteric modulator
- AMANTADINE HYDROCHLORIDE antagonist
- MEMANTINE HYDROCHLORIDE negative allosteric modulator
- KETAMINE HYDROCHLORIDE negative allosteric modulator
- ACAMPROSATE CALCIUM antagonist
- NERAMEXANE MESYLATE antagonist
- RALFINAMIDE antagonist
- DELUCEMINE antagonist
- ESKETAMINE HYDROCHLORIDE negative allosteric modulator
- RAPASTINEL partial agonist
- AV-101 antagonist
- ESKETAMINE negative allosteric modulator
- APIMOSTINEL partial agonist
- CNS-5161 blocker
- PERZINFOTEL antagonist
- LANICEMINE blocker
Related proteins · sequence + function similarity
- Glutamate receptor ionotropic, NMDA 3A 0.99
- Glutamate receptor ionotropic, NMDA 3A 0.99
- Glutamate receptor ionotropic, NMDA 2C 0.86
- Glutamate receptor ionotropic, NMDA 2C 0.86
- Glutamate receptor ionotropic, NMDA 2C 0.86
- Glutamate receptor ionotropic, NMDA 2D 0.78
- Glutamate receptor ionotropic, NMDA 2D 0.77
- Glutamate receptor ionotropic, NMDA 2A 0.77
- Glutamate receptor ionotropic, NMDA 2A 0.77
- Glutamate receptor ionotropic, NMDA 2D 0.77
- Glutamate receptor ionotropic, NMDA 2A 0.76
- Glutamate receptor ionotropic, NMDA 2A 0.75
Co-cited proteins · studied together in the literature
- Glutamate receptor ionotropic, NMDA 3B 2 shared papers
- Glutamate receptor ionotropic, NMDA 1 2 shared papers
- Glutamate receptor ionotropic, NMDA 3B 1 shared papers
- Glutamate receptor ionotropic, NMDA 3B 1 shared papers
- Glutamate receptor ionotropic, NMDA 3A 1 shared papers
- Glutamate receptor ionotropic, NMDA 2C 1 shared papers
- Glutamate receptor ionotropic, NMDA 2D 1 shared papers
- Glutamate receptor ionotropic, NMDA 2B 1 shared papers
- Glutamate receptor ionotropic, NMDA 2A 1 shared papers
- Glutamate receptor ionotropic, NMDA 1 1 shared papers
- Glutamate receptor ionotropic, NMDA 2A 1 shared papers
- Glutamate receptor ionotropic, NMDA 2B 1 shared papers
Literature · 9 cited papers
- Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Sci. Adv. · 2024
- Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl. Psychiatry · 2011
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- DNA sequence and analysis of human chromosome 9. Nature · 2004
- Expression of the NR3A subunit of the NMDA receptor in human fetal brain. Ann. N. Y. Acad. Sci. · 2003
- Cloning and expression of the human NMDA receptor subunit NR3A. Neurosci. Lett. · 2002
- Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. DNA Res. · 2001
- Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Genomics · 2001
- An NMDA receptor signaling complex with protein phosphatase 2A. J. Neurosci. · 2001