GRID2

Protein identityUniProt · HPA

UniProt accession

O43424

Gene

GRID2

Ensembl

ENSG00000152208

Chromosome

4

Canonical length

1007 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

The protein encoded by this gene is a member of the family of ionotropic glutamate receptors which are the predominant excitatory neurotransmitter receptors in the mammalian brain. The encoded protein is a multi-pass membrane protein that is expressed selectively in cerebellar Purkinje cells. A point mutation in the mouse ortholog, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. This protein also plays a role in synapse organization between parallel fibers and Purkinje cells. Alternate splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause cerebellar ataxia in humans. [provided by RefSeq, Apr 2014]

Canonical amino-acid sequenceUniProt

1007 residues, UniProt reviewed canonical sequence.

>O43424|GRID2
     1  MEVFPFLLVL SVWWSRTWDS ANADSIIHIG AIFDESAKKD DEVFRTAVGD LNQNEEILQT
    61  EKITFSVTFV DGNNPFQAVQ EACELMNQGI LALVSSIGCT SAGSLQSLAD AMHIPHLFIQ
   121  RSTAGTPRSG CGLTRSNRND DYTLSVRPPV YLHDVILRVV TEYAWQKFII FYDSEYDIRG
   181  IQEFLDKVSQ QGMDVALQKV ENNINKMITT LFDTMRIEEL NRYRDTLRRA ILVMNPATAK
   241  SFITEVVETN LVAFDCHWII INEEINDVDV QELVRRSIGR LTIIRQTFPV PQNISQRCFR
   301  GNHRISSTLC DPKDPFAQNM EISNLYIYDT VLLLANAFHK KLEDRKWHSM ASLSCIRKNS
   361  KPWQGGRSML ETIKKGGVSG LTGELEFGEN GGNPNVHFEI LGTNYGEELG RGVRKLGCWN
   421  PVTGLNGSLT DKKLENNMRG VVLRVVTVLE EPFVMVSENV LGKPKKYQGF SIDVLDALSN
   481  YLGFNYEIYV APDHKYGSPQ EDGTWNGLVG ELVFKRADIG ISALTITPDR ENVVDFTTRY
   541  MDYSVGVLLR RAEKTVDMFA CLAPFDLSLW ACIAGTVLLV GLLVYLLNWL NPPRLQMGSM
   601  TSTTLYNSMW FVYGSFVQQG GEVPYTTLAT RMMMGAWWLF ALIVISSYTA NLAAFLTITR
   661  IESSIQSLQD LSKQTEIPYG TVLDSAVYEH VRMKGLNPFE RDSMYSQMWR MINRSNGSEN
   721  NVLESQAGIQ KVKYGNYAFV WDAAVLEYVA INDPDCSFYT IGNTVADRGY GIALQHGSPY
   781  RDVFSQRILE LQQNGDMDIL KHKWWPKNGQ CDLYSSVDTK QKGGALDIKS FAGVFCILAA
   841  GIVLSCFIAM LETWWNKRKG SRVPSKEDDK EIDLEHLHRR VNSLCTDDDS PHKQFSTSSI
   901  DLTPLDIDTL PTRQALEQIS DFRNTHITTT TFIPEQIQTL SRTLSAKAAS GFTFGNVPEH
   961  RTGPFRHRAP NGGFFRSPIK TMSSIPYQPT PTLGLNLGND PDRGTSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRID2 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)

0.35

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRID2.

Disease | AllUniProt

Conditions GRID2 is implicated in, by any mechanism.

• Spinocerebellar ataxia, autosomal recessive, 18 (SCAR18) MIM:616204

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 342 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive spinocerebellar ataxia 18
• See cases
• Schizophrenia
• Inborn genetic diseases

Disease | AutoantibodyPubMed

Conditions in which antibodies against GRID2 are reported. Each links to that disease's full target list.

• Cerebellar Ataxia 4

ReferencesPubMed · IEDB

Publications for GRID2 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. 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)

0.17

gnomAD pLI

1

gnomAD missense Z

0.71

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cerebellar granule cell differentiation
• excitatory postsynaptic potential
• excitatory synapse assembly
• glutamate receptor signaling pathway
• heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
• intracellular protein localization
• modulation of chemical synaptic transmission
• positive regulation of long-term synaptic depression
• positive regulation of synapse assembly
• prepulse inhibition
• regulation of neuron apoptotic process
• regulation of neuron projection development
• regulation of postsynaptic density assembly
• regulation of postsynaptic membrane neurotransmitter receptor levels
• regulation of presynapse assembly
• synaptic signaling via neuropeptide
• synaptic transmission, glutamatergic

Molecular functions

• AMPA glutamate receptor activity
• glutamate receptor activity
• identical protein binding
• metal ion binding
• PDZ domain binding
• scaffold protein binding
• transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential

Cellular components

• AMPA glutamate receptor complex
• dendritic spine
• glutamatergic synapse
• ionotropic glutamate receptor complex
• parallel fiber to Purkinje cell synapse
• plasma membrane
• postsynaptic density membrane
• synapse
• trans-synaptic protein complex

Protein domainsUniProt · Pfam · InterPro

• Ionotropic glutamate receptor, C-terminal
• Ionotropic glutamate receptor, metazoa
• Receptor, ligand binding region
• Ionotropic glutamate receptor
• Ionotropic glutamate receptor, L-glutamate and glycine-binding domain
• Periplasmic binding protein-like I
• Ligand-gated ion channel
• Receptor family ligand binding region
• Ligated ion channel L-glutamate- and glycine-binding site

KeywordsUniProt

• Calcium
• Cell membrane
• Disulfide bond
• Glycoprotein
• Ion channel
• Ion transport
• Ligand-gated ion channel
• Membrane
• Metal-binding
• Neurodegeneration
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of GRID2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BECN1
• CBLN1
• CBLN2
• EML2
• GOPC
• GRID2IP
• MAGI2
• SHANK1
• SHANK2