GRIN2B

Protein identityUniProt · HPA

UniProt accession

Q13224

Gene

GRIN2B

Ensembl

ENSG00000273079

Chromosome

12

Canonical length

1484 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, RAS pathway related proteins

OverviewNCBI Gene

This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

1484 residues, UniProt reviewed canonical sequence.

>Q13224|GRIN2B
     1  MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI KDAHEKDDFH
    61  HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL
   121  TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ
   181  DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI
   241  FEVANSVGLT GYGYTWIVPS LVAGDTDTVP AEFPTGLISV SYDEWDYGLP ARVRDGIAII
   301  TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP
   361  KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE
   421  SVDPLSGTCM RNTVPCQKRI VTENKTDEEP GYIKKCCKGF CIDILKKISK SVKFTYDLYL
   481  VTNGKHGKKI NGTWNGMIGE VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR
   541  SNGTVSPSAF LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF
   601  TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQEEYV
   661  DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA EMHAYMGKFN QRGVDDALLS
   721  LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKDS GWKRQVDLAI
   781  LQLFGDGEME ELEALWLTGI CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH
   841  LFYWQFRHCF MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR
   901  LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN NPPCEENLFS
   961  DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSASSI DGLYDCDNPP FTTQSRSISK
  1021  KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR
  1081  RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK
  1141  ENSPHWEHVD LTDIYKERSD DFKRDSVSGG GPCTNRSHIK HGTGDKHGVV SGVPAPWEKN
  1201  LTNVEWEDRS GGNFCRSCPS KLHNYSTTVT GQNSGRQACI RCEACKKAGN LYDISEDNSL
  1261  QELDQPAAPV AVTSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR
  1321  SVSLKDKGRF MDGSPYAHMF EMSAGESTFA NNKSSVPTAG HHHHNNPGGG YMLSKSLYPD
  1381  RVTQNPFIPT FGDDQCLLHG SKSYFFRQPT VAGASKARPD FRALVTNKPV VSALHGAVPA
  1441  RFQKDICIGN QSNPCVPNNK NPRAFNGSSN GHVYEKLSSI ESDV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIN2B can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

3

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

6.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIN2B.

Disease | AllUniProt

Conditions GRIN2B is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 6, with or without seizures (MRD6) MIM:613970
• Developmental and epileptic encephalopathy 27 (DEE27) MIM:616139

Disease | GeneticClinVar

280 pathogenic / likely-pathogenic of 1,818 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal dominant 6
• Developmental and epileptic encephalopathy, 27
• Complex neurodevelopmental disorder
• Inborn genetic diseases
• Intellectual disability

Disease | ImmuneIEDB

Conditions an epitope on GRIN2B was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

ReferencesPubMed · IEDB

Publications for GRIN2B from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.06

gnomAD pLI

1

gnomAD missense Z

5.42

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• calcium ion transmembrane import into cytosol
• chemical synaptic transmission
• excitatory chemical synaptic transmission
• excitatory postsynaptic potential
• glutamate receptor signaling pathway
• ionotropic glutamate receptor signaling pathway
• learning or memory
• long-term synaptic potentiation
• monoatomic cation transmembrane transport
• negative regulation of dendritic spine maintenance
• positive regulation of excitatory postsynaptic potential
• positive regulation of synaptic transmission, glutamatergic
• protein heterotetramerization
• regulation of monoatomic cation transmembrane transport
• regulation of neuronal synaptic plasticity
• regulation of synaptic plasticity
• response to ethanol
• synaptic transmission, glutamatergic

Molecular functions

• amyloid-beta binding
• glutamate binding
• glutamate-gated calcium ion channel activity
• glycine binding
• ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• NMDA glutamate receptor activity
• transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
• zinc ion binding

Cellular components

• cell surface
• cytoplasm
• cytoskeleton
• dendrite
• endoplasmic reticulum membrane
• late endosome
• lysosome
• neuron projection
• NMDA selective glutamate receptor complex
• plasma membrane
• postsynaptic density
• postsynaptic density membrane
• postsynaptic membrane
• synaptic membrane

Protein domainsUniProt · Pfam · InterPro

• Ionotropic glutamate receptor, C-terminal
• Ionotropic glutamate receptor, metazoa
• Receptor, ligand binding region
• Ionotropic glutamate receptor
• Glutamate [NMDA] receptor, epsilon subunit, C-terminal
• Ionotropic glutamate receptor, L-glutamate and glycine-binding domain
• Periplasmic binding protein-like I
• Ligand-gated ion channel
• Receptor family ligand binding region
• N-methyl D-aspartate receptor 2B3 C-terminus
• Ligated ion channel L-glutamate- and glycine-binding site

KeywordsUniProt

• Calcium
• Cell membrane
• Cell projection
• Chromosomal rearrangement
• Cytoplasm
• Cytoskeleton
• Disulfide bond
• Endosome
• Epilepsy
• Glycoprotein
• Intellectual disability
• Ion channel
• Ion transport
• Ligand-gated ion channel
• Lysosome
• Magnesium
• Membrane
• Metal-binding
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport
• Zinc

InteractionsUniProt · HPA

Protein binding partners of GRIN2B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARC
• CAMK2A
• DAPK1
• DLG3
• DLG4
• FAM81A
• HIP1
• MAGI3
• NETO1
• PRR7
• TMEM25
• TANC1
• LIN7A
• PATJ
• ARHGAP32
• DLG1