Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

GRIN2B (Q13224) - Overview - Molecular Target Synopsis

Protein


GRIN2B, Glutamate receptor ionotropic, NMDA 2B
UniProt Q13224

Also Known as NMDE2_HUMAN, GRIN2B, NMDAR2B

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28126851). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:8768735, PubMed:26875626). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity. Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28126851, PubMed:26912815). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By similarity). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with HIP1 and NETO1 (By similarity). Interacts with MAGI3 (PubMed:10748157). Interacts with DAPK1 (By similarity). Found in a complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 (PubMed:27458189). Interacts with CAMK2A (PubMed:28130356).

5EWJ
CRYSTAL STRUCTURE OF AMINO TERMINAL DOMAINS OF THE NMDA RECEPTOR SUBUNIT GLUN1 AND GLUN2B IN COMPLEX WITH IFENPRODIL
RCSB/PDB
Inspect Structure
See all 3D Structures for GRIN2B

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1484ENSG00000273079ENST00000609686ENSP00000477455Q13224-1

Drugs


GRIN2B is targeted by Approved Drugs Felbamate, Amantadine, Esketamine. (see details)
Felbamate
Amantadine
Esketamine

Sub-cellular localization


UniProt: GRIN2B is active in the following subcellular-locations: cell junction, cell membrane, postsynaptic cell membrane, synapse.
GO terms: GRIN2B is active in the following subcellular-locations: cell junction, cell surface, cytoplasm, integral component of plasma membrane, neuron projection, NMDA selective glutamate receptor complex, plasma membrane, postsynaptic density, postsynaptic density membrane, postsynaptic membrane, synaptic membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GRIN2B has gain in 7 cell-lines, loss in 4 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SW_620, MCF7, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, NCI-H209, LN-18

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


GRIN2B was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)

3D Structures


For GRIN2B there are:
3 structures (6 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GRIN2B has been screened with 838 compounds (1348 bioactivities), 350 compounds have bioactivities that show binding affinity of <= 500nM (505 bioactivities). (see details)