GRIA3
Encyclopedia
Glutamate receptor 3 is a protein
that in humans is encoded by the GRIA3 gene
.
s are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternative splicing at this locus results in several different isoforms which may vary in their signal transduction properties.
with GRIP1
and PICK1
.
as substrates for ADAR
s. This includes 5 subunits of the glutamate receptor ionotropic AMPA glutamate receptor subunits (Glur2
, Glur3
, Glur4
) and kainate receptor
subunits (Glur5
, Glur6
). Glutamate gated ion channels are made up of four subunits per channel with each subunit contributing to the pore loop structure. The pore loop structure is related to that found in K+ channels (e.g., human Kv1.1 channel). The human Kv1.1 channel pre mRNA is also subject to A to I RNA editing. The function of the glutamate receptors is in the mediation of fast neurotransmission to the brain. The diversity of the subunits is determined, as well as rna splicing by RNA editing events of the individual subunits. This give rise to the necessarily high diversity of these receptors. GluR3 is a gene product of the GRIA3 gene and its pre-mRNA is subject to RNA editing.
s acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine
. Inosine
s are recognised as guanosine
by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1
and ADAR2
being the only enzymatically active members. ADAR3
is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS)
13 between the M3 and M4 regions. Editing results in a codon change from an arginine
(AGA) to a glycine
(GGA). The location of editing corresponds to a bipartite ligand interaction domain of the receptor. The R/G site is found at amino acid 769 immediately before the 38-amino-acid-long flip and flop modules introduced by alternative splicing. Flip and Flop forms are present in both edited and nonedited versions of this protein. The editing complimentary sequence (ECS) is found in an intronic sequence close to the exon. The intronic sequence includes a 5' splice site. The predicted double stranded region is 30 base pairs in length. The adenosine residue is mismatched in genomically encoded transcript, however this is not the case following editing. Despite similar sequences to the Q/R site of GluR-B, editing a this site does not occur in GluR-3 pre-mRNA. Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become matched after editing. The intronic sequence involved contains a 5' donor splice site.
Editing results in a codon change from (AGA) to (GGA), an R to a G change at the editing site.
Editing at R/G site allows for faster recovery from desensitisation. Unedited Glu-R at this site have slower recovery rates. Editing, therefore, allow sustained response to rapid stimuli. A crosstalk between editing and splicing is likely to occur here. Editing takes place before splicing. All AMPA receptors occur in flip and flop alternatively spliced variants. AMPA receptors that occur in the Flop form desenstise faster than the flip form. Editing is also thought to affect splicing at this site.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the GRIA3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Glutamate receptorGlutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternative splicing at this locus results in several different isoforms which may vary in their signal transduction properties.
Interactions
GRIA3 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with GRIP1
GRIP1 (gene)
Glutamate receptor-interacting protein 1 is a protein that in humans is encoded by the GRIP1 gene.-Interactions:GRIP1 has been shown to interact with GRIA4, Metabotropic glutamate receptor 3, GRIK2, GRIK3, GRIPAP1, GRIA2 and GRIA3....
and PICK1
PICK1
PRKCA-binding protein is a protein that in humans is encoded by the PICK1 gene.-Interactions:PICK1 has been shown to interact with HER2/neu, ACCN2, Metabotropic glutamate receptor 7, BNC1, Metabotropic glutamate receptor 3, GRIA4, Dopamine transporter, GRIK1, GRIK2, GRIK3, GRIA2 and GRIA3.-Further...
.
RNA editing
Several ion channels and neurotransmitters receptors pre-mRNAMessenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
as substrates for ADAR
ADAR
Double-stranded RNA-specific adenosine deaminase is an enzyme that in humans is encoded by the ADAR gene.-Further reading:...
s. This includes 5 subunits of the glutamate receptor ionotropic AMPA glutamate receptor subunits (Glur2
Metabotropic glutamate receptor 2
Metabotropic glutamate receptor 2 is a protein that in humans is encoded by the GRM2 gene.-PAMs:The development of subtype-2-selective positive allosteric modulators experienced steady advance in recent years...
, Glur3
Metabotropic glutamate receptor 3
Metabotropic glutamate receptor 3 is a protein that in humans is encoded by the GRM3 gene.-Ligands:Though truly mGluR3 selective agents still await their discovery, mixed mGluR2/3 ligands with selectivity over other mGluR-subtypes are known...
, Glur4
Metabotropic glutamate receptor 4
Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.Activation of GRM4 has...
) and kainate receptor
Kainate receptor
Kainate receptors, or KARs, are non-NMDA ionotropic receptors which respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from red algae Digenea simplex. KARs are less well...
subunits (Glur5
Metabotropic glutamate receptor 5
Metabotropic glutamate receptor 5 is a protein that in humans is encoded by the GRM5 gene.- Function :The amino acid L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors...
, Glur6
Metabotropic glutamate receptor 6
Glutamate receptor, metabotropic 6, also known as GRM6, is a protein which in humans is encoded by the GRM6 gene.- Function :L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors...
). Glutamate gated ion channels are made up of four subunits per channel with each subunit contributing to the pore loop structure. The pore loop structure is related to that found in K+ channels (e.g., human Kv1.1 channel). The human Kv1.1 channel pre mRNA is also subject to A to I RNA editing. The function of the glutamate receptors is in the mediation of fast neurotransmission to the brain. The diversity of the subunits is determined, as well as rna splicing by RNA editing events of the individual subunits. This give rise to the necessarily high diversity of these receptors. GluR3 is a gene product of the GRIA3 gene and its pre-mRNA is subject to RNA editing.
Type
A to I RNA editing is catalyzed by a family of adenosine deaminaseAdenosine deaminase
Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.-Reactions:...
s acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine
Inosine
Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a β-N9-glycosidic bond....
. Inosine
Inosine
Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a β-N9-glycosidic bond....
s are recognised as guanosine
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1
ADAR
Double-stranded RNA-specific adenosine deaminase is an enzyme that in humans is encoded by the ADAR gene.-Further reading:...
and ADAR2
ADARB1
Double-stranded RNA-specific editase 1 is an enzyme that in humans is encoded by the ADARB1 gene.ADAR2 requires the small molecule inositol hexakisphosphate for proper function.-Further reading:...
being the only enzymatically active members. ADAR3
ADARB2
Double-stranded RNA-specific editase B2 is an enzyme that in humans is encoded by the ADARB2 gene.-Further reading:...
is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS)
Location
The pre-mRNA of this subunit is edited at one position. The R/G editing site is located in exonExon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
13 between the M3 and M4 regions. Editing results in a codon change from an arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
(AGA) to a glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
(GGA). The location of editing corresponds to a bipartite ligand interaction domain of the receptor. The R/G site is found at amino acid 769 immediately before the 38-amino-acid-long flip and flop modules introduced by alternative splicing. Flip and Flop forms are present in both edited and nonedited versions of this protein. The editing complimentary sequence (ECS) is found in an intronic sequence close to the exon. The intronic sequence includes a 5' splice site. The predicted double stranded region is 30 base pairs in length. The adenosine residue is mismatched in genomically encoded transcript, however this is not the case following editing. Despite similar sequences to the Q/R site of GluR-B, editing a this site does not occur in GluR-3 pre-mRNA. Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become matched after editing. The intronic sequence involved contains a 5' donor splice site.
Regulation
Editing of GluR-3 is regulated in rat brain from low levels in embryonic stage to a large increase in editing levels at birth. In humans, 80-90% of GRIA3 transcripts are edited. The absence of the Q/R site editing in this glutamate receptor subunit is due to the absence of necessary intronic sequence required to form a duplex.Structure
Editing results in a codon change from (AGA) to (GGA), an R to a G change at the editing site.
Function
Editing at R/G site allows for faster recovery from desensitisation. Unedited Glu-R at this site have slower recovery rates. Editing, therefore, allow sustained response to rapid stimuli. A crosstalk between editing and splicing is likely to occur here. Editing takes place before splicing. All AMPA receptors occur in flip and flop alternatively spliced variants. AMPA receptors that occur in the Flop form desenstise faster than the flip form. Editing is also thought to affect splicing at this site.