GRIN2C glutamate ionotropic receptor NMDA type subunit 2C [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIN2Cprovided by HGNC
Official Full Name: glutamate ionotropic receptor NMDA type subunit 2Cprovided by HGNC
Primary source: HGNC:HGNC:4587
See related: Ensembl:ENSG00000161509 MIM:138254; AllianceGenome:HGNC:4587
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NR2C; GluN2C; NMDAR2C
Summary: This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
Expression: Biased expression in thyroid (RPKM 3.2), brain (RPKM 2.5) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.1

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (74842023..74861532, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (75733798..75753286, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (72838162..72856966, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
Title: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
Amyloid-beta (1-42) peptide induces rapid NMDA receptor-dependent alterations at glutamatergic synapses in the entorhinal cortex.
Title: Amyloid-β (1-42) peptide induces rapid NMDA receptor-dependent alterations at glutamatergic synapses in the entorhinal cortex.
Positions in the N-methyl-D-aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics.
Title: Positions in the N-methyl-D-aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics.
ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes like GRIN2C and GRIN2D may contribute to possible risk of schizophrenia
Title: Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility.
Findings indicate that SNPs in the GRIN2C gene is associated with altered cue-induced brain activation that is related to craving for alcohol and relapse risk.
Title: The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving.
these findings highlight the isoform-specific structural and functional differences within the 14-3-3 family of proteins, which determine GluN2C binding and its essential role in targeting the receptor to the cell surface
Title: Identification of Novel 14-3-3 Residues That Are Critical for Isoform-specific Interaction with GluN2C to Regulate N-Methyl-D-aspartate (NMDA) Receptor Trafficking.
NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells.
Title: Functional plasticity of the N-methyl-d-aspartate receptor in differentiating human erythroid precursor cells.
The major depression subjects exhibited significantly higher expression levels of the NMDA receptor subunit genes GRIN2C.
Title: Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression.
Reduction in NR1 and NR2C in the DLPFC of people with schizophrenia may lead to altered NMDAR stoichiometry and provides compelling evidence for an endogenous NMDAR deficit in schizophrenia.
Title: Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia.
TNFalpha significantly upregulates NMDA-R2C mRNA expression, in differentiated, confluent, normal keratinocytes but not in involved or uninvolved psoriatic keratinocyte monolayers
Title: Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction of mRNA for the NMDA-R2C subunit.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin	PubMed
	env	HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896	PubMed
	env	HIV-1 gp120-induced synapse loss requires sequential activation of CXCR4, IL-1beta receptor, and NMDA receptor	PubMed
	env	HIV-1 clade B gp120 significantly downregulates NMDA receptor gene and protein expression and levels of glutamine compared to clade C gp120	PubMed
	env	HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells	PubMed
	env	HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects	PubMed
	env	HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor	PubMed
	env	HIV-1 gp120 binds to cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit	PubMed
Tat	tat	The gene expression of GRIN2C is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells	PubMed
	tat	Ca(2+) influx through the NMDA receptor is necessary for HIV-1 Tat-induced synapse loss	PubMed
	tat	HIV-1 Tat upregulates the expression of NMDARs for the apoptosis of retinal pigmen epithelium (RPE) cells. Silencing of NMDARs by siRNA abolishes Tat-induced RPE apoptosis	PubMed
	tat	HIV-1 Tat-induced activation of spermine oxidase (SMO) activity involves NMDAR stimulation in human neuroblastoma	PubMed
	tat	HIV-1 Tat and methamphetamine inhibit the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death	PubMed
	tat	HIV-1 Tat interacts with NMDA receptors in primary neuronal-glial cultures and in hippocampal slice cultures	PubMed
	tat	HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface	PubMed
	tat	Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors	PubMed
	tat	HIV-1 Tat-induced NMDA receptor activation is clade dependent. The Cys 30-Cys 31 motif in Tat is critical for the NMDA receptor activation	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NMDA glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables NMDA glutamate receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables NMDA glutamate receptor activity	TAS Traceable Author Statement more info	PubMed
enables glutamate-gated calcium ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in brain development	NAS Non-traceable Author Statement more info	PubMed
involved_in calcium ion transmembrane import into cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in directional locomotion	IEA Inferred from Electronic Annotation more info
involved_in excitatory chemical synaptic transmission	NAS Non-traceable Author Statement more info	PubMed
involved_in excitatory postsynaptic potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutamate receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in ionotropic glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in long-term synaptic potentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic cation transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in protein localization to postsynaptic membrane	IEA Inferred from Electronic Annotation more info
involved_in regulation of monoatomic cation transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of neuronal synaptic plasticity	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of synaptic plasticity	NAS Non-traceable Author Statement more info	PubMed
involved_in response to wounding	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of NMDA selective glutamate receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of NMDA selective glutamate receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of NMDA selective glutamate receptor complex	ISS Inferred from Sequence or Structural Similarity more info
part_of NMDA selective glutamate receptor complex	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in postsynaptic density membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic membrane	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: glutamate receptor ionotropic, NMDA 2C

Names: GluN2C(alt_5'UTR_77nt); GluN2C(alt_5'UTR_87nt); GluN2C(del_e2); GluN2C-b alternative isoform; N-methyl D-aspartate receptor subtype 2C; N-methyl-D-aspartate receptor subunit 2C; glutamate [NMDA] receptor subunit epsilon-3; glutamate receptor, ionotropic, N-methyl D-aspartate 2C; putative NMDtranscript(altAcc_e11); putative NMDtranscript(altDon_e4); putative NMDtranscript(del_e4)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000835.6 → NP_000826.2 glutamate receptor ionotropic, NMDA 2C isoform 1 precursor

See identical proteins and their annotated locations for NP_000826.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC068874, AC087651

Consensus CDS

CCDS32724.1

UniProtKB/Swiss-Prot

B2RTT1, Q14957

UniProtKB/TrEMBL

A0A8D9PH81, O15398

Related

ENSP00000293190.5, ENST00000293190.10

Conserved Domains (3) summary

cd13718
Location:400 → 800

PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cd06378
Location:28 → 384

PBP1_iGluR_NMDA_NR2; N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family

pfam10565
Location:837 → 912

NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
NM_001278553.2 → NP_001265482.1 glutamate receptor ionotropic, NMDA 2C isoform 2 precursor

See identical proteins and their annotated locations for NP_001265482.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, includes an alternate terminal 3' exon, and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.

Source sequence(s)

AC087651, BC041128

Consensus CDS

CCDS62330.1

UniProtKB/TrEMBL

H0Y2V8, Q8IW23

Related

ENSP00000338645.4, ENST00000347612.4

Conserved Domains (3) summary

cd06378
Location:28 → 389

PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family

cd13718
Location:400 → 800

PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

pfam00060
Location:554 → 826

Lig_chan; Ligand-gated ion channel

RNA

NR_103735.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC068874, AC087651

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

74842023..74861532 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047435867.1 → XP_047291823.1 glutamate receptor ionotropic, NMDA 2C isoform X6

UniProtKB/Swiss-Prot

B2RTT1, Q14957

UniProtKB/TrEMBL

A0A8D9PH81
XM_011524689.3 → XP_011522991.1 glutamate receptor ionotropic, NMDA 2C isoform X5

See identical proteins and their annotated locations for XP_011522991.1

UniProtKB/TrEMBL

O15398

Conserved Domains (4) summary

cd06378
Location:28 → 389

PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family

cd13718
Location:400 → 829

PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

pfam00060
Location:554 → 855

Lig_chan; Ligand-gated ion channel

pfam10565
Location:866 → 946

NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
XM_006721846.5 → XP_006721909.2 glutamate receptor ionotropic, NMDA 2C isoform X4
XM_011524686.4 → XP_011522988.2 glutamate receptor ionotropic, NMDA 2C isoform X1
XM_011524688.4 → XP_011522990.2 glutamate receptor ionotropic, NMDA 2C isoform X3
XM_011524687.4 → XP_011522989.2 glutamate receptor ionotropic, NMDA 2C isoform X2
XM_011524692.4 → XP_011522994.2 glutamate receptor ionotropic, NMDA 2C isoform X7

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

75733798..75753286 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054315877.1 → XP_054171852.1 glutamate receptor ionotropic, NMDA 2C isoform X6
XM_054315876.1 → XP_054171851.1 glutamate receptor ionotropic, NMDA 2C isoform X5
XM_054315875.1 → XP_054171850.1 glutamate receptor ionotropic, NMDA 2C isoform X4
XM_054315872.1 → XP_054171847.1 glutamate receptor ionotropic, NMDA 2C isoform X1
XM_054315874.1 → XP_054171849.1 glutamate receptor ionotropic, NMDA 2C isoform X3
XM_054315873.1 → XP_054171848.1 glutamate receptor ionotropic, NMDA 2C isoform X2
XM_054315878.1 → XP_054171853.1 glutamate receptor ionotropic, NMDA 2C isoform X7