GRID2 Membrane Protein Introduction

Introduction of GRID2

Glutamate receptor ionotropic, delta-2 (GRID2), also known as GluR delta-2 subunit (GluD2), is a protein that is encoded by the GRID2 gene. The protein belongs to the family of ionotropic glutamate receptors. It is a multi-pass membrane protein which is expressed selectively in cerebellar Purkinje cells. Ionotropic glutamate receptors are the major excitatory neurotransmitter receptors in the mammalian brain. Point mutations in mouse ortholog are related to the phenotype known as 'lurcher'. Mutations are in the heterozygous state, resulting in ataxia caused by selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. This mutant homozygous mouse dies shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. In addition, this protein is essential in synapse organization between Purkinje cells and parallel fibers. Alternate splicing leads to multiple transcript variants encoding distinct isoforms. Mutations in this gene cause cerebellar ataxia in humans.

Basic Information of GRID2
Protein Name	Glutamate receptor ionotropic, delta-2
Gene Name	GRID2
Aliases	GluD2, GluR delta-2 subunit, GLURD2
Organism	Homo sapiens (Human)
UniProt ID	O43424
Transmembrane Times	3
Length (aa)	1007
Sequence	MEVFPFLLVLSVWWSRTWDSANADSIIHIGAIFDESAKKDDEVFRTAVGDLNQNEEILQTEKITFSVTFVDGNNPFQAVQEACELMNQGILALVSSIGCTSAGSLQSLADAMHIPHLFIQRSTAGTPRSGCGLTRSNRNDDYTLSVRPPVYLHDVILRVVTEYAWQKFIIFYDSEYDIRGIQEFLDKVSQQGMDVALQKVENNINKMITTLFDTMRIEELNRYRDTLRRAILVMNPATAKSFITEVVETNLVAFDCHWIIINEEINDVDVQELVRRSIGRLTIIRQTFPVPQNISQRCFRGNHRISSTLCDPKDPFAQNMEISNLYIYDTVLLLANAFHKKLEDRKWHSMASLSCIRKNSKPWQGGRSMLETIKKGGVSGLTGELEFGENGGNPNVHFEILGTNYGEELGRGVRKLGCWNPVTGLNGSLTDKKLENNMRGVVLRVVTVLEEPFVMVSENVLGKPKKYQGFSIDVLDALSNYLGFNYEIYVAPDHKYGSPQEDGTWNGLVGELVFKRADIGISALTITPDRENVVDFTTRYMDYSVGVLLRRAEKTVDMFACLAPFDLSLWACIAGTVLLVGLLVYLLNWLNPPRLQMGSMTSTTLYNSMWFVYGSFVQQGGEVPYTTLATRMMMGAWWLFALIVISSYTANLAAFLTITRIESSIQSLQDLSKQTEIPYGTVLDSAVYEHVRMKGLNPFERDSMYSQMWRMINRSNGSENNVLESQAGIQKVKYGNYAFVWDAAVLEYVAINDPDCSFYTIGNTVADRGYGIALQHGSPYRDVFSQRILELQQNGDMDILKHKWWPKNGQCDLYSSVDTKQKGGALDIKSFAGVFCILAAGIVLSCFIAMLETWWNKRKGSRVPSKEDDKEIDLEHLHRRVNSLCTDDDSPHKQFSTSSIDLTPLDIDTLPTRQALEQISDFRNTHITTTTFIPEQIQTLSRTLSAKAASGFTFGNVPEHRTGPFRHRAPNGGFFRSPIKTMSSIPYQPTPTLGLNLGNDPDRGTSI

Function of GRID2 Membrane Protein

Several diseases are associated with GRID2, such as spinocerebellar ataxia, spinocerebellar ataxia and autosomal recessive. Among its related pathways are long-term depression and peptide ligand-binding receptors. Deletions involving the GRID2 gene, encoding the glutamate receptor subunit delta-2 protein, have been reported in families segregating autosomal recessive cerebellar syndrome with infantile onset. Affected individuals exhibit abnormal eye movements, developmental delay, slowly progressive hypotonia, ataxia, and dysarthria. Radiological investigation revealed cerebellar atrophy, in a small number of patients with pontine involvement. In addition, heterozygous GRID2 mutations have been identified, including three missense variants, ocular symptoms, cerebellar ataxia, and cognitive impairment.

Fig.1 Cartoon representation of the molecular structure of protein registered with 1hwx code.

Application of GRID2 Membrane Protein in Literature

Ali Z., et al. Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features. BMC Med Genet. 2017, 18(1): 144. PubMed ID: 29207948

The article reveals that a wide range of supratentorial brain abnormalities, increased peripheral muscle tone, loss of oculomotor symptoms, and new missense mutation increase the genetic and clinical variability in GRID2 related cerebellar syndrome.
Kotajima-Murakami H., et al. Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice. PLoS One. 2016, 11(11): e0166144. PubMed ID: 27820843

Authors in this group demonstrate that GluD2 is involved in the fear-conditioned bradycardia in mice. The results show that GluD2 mutation in the ho15J mice affects stable retention of the acquired conditioned bradycardia.
Li Q., et al. Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development. Proc Natl Acad Sci U S A. 2016, 113(19): 5358-63. PubMed ID: 27118840

The article demonstrates that GLUD2 affects carbon flux during early brain development and possibly supports lipid biosynthesis.
Kalkan Z., et al. Potential of GRID2 receptor gene for preventing TNF-induced neurodegeneration in autism. PLoS One. 2016, 620: 62-9. PubMed ID: 27019035

Authors in this group study the association between TNF-induced neurodegeneration and GRID2 expression levels. GRID2 gene may be an inhibitor of TNF-induced neurodegeneration and may be helpful in understanding the major factors leading to autism.
Coutelier M., et al. GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia. Neurology. 2015, 84(17): 1751-9. PubMed ID: 25841024

This article reports that GRID2 has only been involved in ataxia through complete loss-of-function mutations due to exon deletions in humans.

GRID2 Preparation Options

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