This gene encodes one of the many ionotropic glutamate receptor (GluR) subunits that function as a ligand-gated ion channel. The specific GluR subunit encoded by this gene is of the kainate receptor subtype. Receptor assembly and intracellular trafficking of ionotropic glutamate receptors are regulated by RNA editing and alternative splicing. These receptors mediate excitatory neurotransmission and are critical for normal synaptic function. Two alternatively spliced transcript variants that encode different isoforms have been described. Exons of this gene are interspersed with exons from the C21orf41 gene, which is transcribed in the same orientation as this gene but does not seem to encode a protein.[5]
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines 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, whereas 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). ADARs bind interact directly with the dsRNA substrate via their double-stranded RNA binding domains. If an editing site occurs within a coding sequence, the result could be a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A to I editing occurs in a noncoding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs( especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus, among others.
Locationedit
The pre-mRNA of GluR-5 is edited at one position at the Q/R site located at membrane region 2 (M2). There is a codon change as a result of editing. The codon change is (CAG) Glutamine (Q) to (CGG) an Arginine (R).[7] Like GluR-6 the ECS is located about 2000 nucleotides downstream of the editing site.[8]
Regulationedit
Editing of the Q/R site is development- and tissue-regulated. Editing in the spinal cord, corpus callosum, cerebellum is 50%, while editing in the Thalamus, amygdala, hippocampus is about 70%.
Consequencesedit
Structureedit
Editing results in a change in amino acid in the second membrane domain of the receptor.
Functionedit
The editing site is found within the second intracellular domain. It is thought that editing affects the permeability of the receptor to CA2+. Editing of the Q/R site is thought to reduce the permeability of the channel to Ca2+[7]
RNA editing of the Q/R site can effect inhibition of the channel by membrane fatty acids such as arachidonic acid and docosahexaenoic acid[9] For Kainate receptors with only edited isoforms, these are strongly inhibited by these fatty acids. However, inclusion of just one nonedited subunit is enough to stop this inhibition(.[9]
^ abcHirbec, Hélène; Francis, Joanna C.; Lauri, Sari E.; Braithwaite, Steven P.; Coussen, Françoise; Mulle, Christophe; Dev, Kumlesh K.; Coutinho, Victoria; Meyer, Guido; Isaac, John T. R.; Collingridge, Graham L.; Henley, Jeremy M.; Couthino, Victoria (Feb 2003). "Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP". Neuron. 37 (4). United States: 625–38. doi:10.1016/S0896-6273(02)01191-1. ISSN 0896-6273. PMC3314502. PMID 12597860.
^ abSeeburg PH, Single F, Kuner T, Higuchi M, Sprengel R (July 2001). "Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse". Brain Res.907 (1–2): 233–43. doi:10.1016/S0006-8993(01)02445-3. PMID 11430906. S2CID 11969068.
^Herb A, Higuchi M, Sprengel R, Seeburg PH (March 1996). "Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences". Proc. Natl. Acad. Sci. U.S.A.93 (5): 1875–80. Bibcode:1996PNAS...93.1875H. doi:10.1073/pnas.93.5.1875. PMC39875. PMID 8700852.
^ abWilding TJ, Fulling E, Zhou Y, Huettner JE (July 2008). "Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids". J. Gen. Physiol.132 (1): 85–99. doi:10.1085/jgp.200810009. PMC2442176. PMID 18562501.
Further readingedit
Nutt SL, Kamboj RK (1995). "RNA editing of human kainate receptor subunits". NeuroReport. 5 (18): 2625–9. doi:10.1097/00001756-199412000-00055. PMID 7696618.
Roche KW, Raymond LA, Blackstone C, Huganir RL (1994). "Transmembrane topology of the glutamate receptor subunit GluR6". J. Biol. Chem. 269 (16): 11679–82. doi:10.1016/S0021-9258(17)32623-6. PMID 8163463.
Gregor P, O'Hara BF, Yang X, Uhl GR (1994). "Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6". NeuroReport. 4 (12): 1343–6. doi:10.1097/00001756-199309150-00014. PMID 8260617.
Eubanks JH, Puranam RS, Kleckner NW, et al. (1993). "The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis". Proc. Natl. Acad. Sci. U.S.A. 90 (1): 178–82. Bibcode:1993PNAS...90..178E. doi:10.1073/pnas.90.1.178. PMC45623. PMID 8419920.
Potier MC, Dutriaux A, Lambolez B, et al. (1993). "Assignment of the human glutamate receptor gene GLUR5 to 21q22 by screening a chromosome 21 YAC library". Genomics. 15 (3): 696–7. doi:10.1006/geno.1993.1131. PMID 8468067.
Korczak B, Nutt SL, Fletcher EJ, et al. (1996). "cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration". Recept. Channels. 3 (1): 41–9. PMID 8589992.
Brakeman PR, Lanahan AA, O'Brien R, et al. (1997). "Homer: a protein that selectively binds metabotropic glutamate receptors". Nature. 386 (6622): 284–8. Bibcode:1997Natur.386..284B. doi:10.1038/386284a0. PMID 9069287. S2CID 4346579.
Sander T, Hildmann T, Kretz R, et al. (1997). "Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism". Am. J. Med. Genet. 74 (4): 416–21. doi:10.1002/(SICI)1096-8628(19970725)74:4<416::AID-AJMG13>3.0.CO;2-L. PMID 9259378.
Xiao B, Tu JC, Petralia RS, et al. (1998). "Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins". Neuron. 21 (4): 707–16. doi:10.1016/S0896-6273(00)80588-7. PMID 9808458. S2CID 16431031.
Montague AA, Greer CA (1999). "Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb". J. Comp. Neurol. 405 (2): 233–46. doi:10.1002/(SICI)1096-9861(19990308)405:2<233::AID-CNE7>3.0.CO;2-A. PMID 10023812. S2CID 1317987.
Bortolotto ZA, Clarke VR, Delany CM, et al. (1999). "Kainate receptors are involved in synaptic plasticity". Nature. 402 (6759): 297–301. Bibcode:1999Natur.402..297B. doi:10.1038/46290. PMID 10580501. S2CID 205051834.
Barbon A, Barlati S (2000). "Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1". Cytogenet. Cell Genet. 88 (3–4): 236–9. doi:10.1159/000015558. PMID 10828597. S2CID 5850944.
Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
Ango F, Prézeau L, Muller T, et al. (2001). "Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer". Nature. 411 (6840): 962–5. Bibcode:2001Natur.411..962A. doi:10.1038/35082096. PMID 11418862. S2CID 4417727.
Shibata H, Joo A, Fujii Y, et al. (2002). "Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia". Psychiatr. Genet. 11 (3): 139–44. doi:10.1097/00041444-200109000-00005. PMID 11702055. S2CID 38356907.
Hirbec H, Perestenko O, Nishimune A, et al. (2002). "The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs" (PDF). J. Biol. Chem. 277 (18): 15221–4. doi:10.1074/jbc.C200112200. PMID 11891216. S2CID 13732968.
Enz R (2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Lett. 514 (2–3): 184–8. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148. S2CID 44474808.
Hirbec H, Francis JC, Lauri SE, et al. (2003). "Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP". Neuron. 37 (4): 625–38. doi:10.1016/S0896-6273(02)01191-1. PMC3314502. PMID 12597860.
Ren Z, Riley NJ, Needleman LA, et al. (2004). "Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal". J. Biol. Chem. 278 (52): 52700–9. doi:10.1074/jbc.M309585200. PMID 14527949.
grik1, glutamate, receptor, ionotropic, kainate, also, known, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2zns, 2znt, 2znu, 3fuz, 3fv1, 3fv2, 3fvg, 3fvk, 3fvn, 3fvo, 4mf3identifiersaliases, eaa3, eea3, g. Glutamate receptor ionotropic kainate 1 also known as GRIK1 is a protein that in humans is encoded by the GRIK1 gene 5 GRIK1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2ZNS 2ZNT 2ZNU 3FUZ 3FV1 3FV2 3FVG 3FVK 3FVN 3FVO 4MF3IdentifiersAliasesGRIK1 EAA3 EEA3 GLR5 GLUR5 GluK1 gluR 5 glutamate ionotropic receptor kainate type subunit 1External IDsOMIM 138245 MGI 95814 HomoloGene 68992 GeneCards GRIK1Gene location Human Chr Chromosome 21 human 1 Band21q21 3Start29 536 933 bp 1 End29 940 033 bp 1 Gene location Mouse Chr Chromosome 16 mouse 2 Band16 C3 3 16 50 23 cMStart87 692 788 bp 2 End88 087 153 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incingulate gyrusamygdalaprefrontal cortexdorsolateral prefrontal cortexfrontal polehypothalamusBrodmann area 9ponshippocampus properBrodmann area 10Top expressed inlateral hypothalamusmedial geniculate nucleussuprachiasmatic nucleuspontine nucleiretinal pigment epitheliumbarrel cortexlateral geniculate nucleussupraoptic nucleusparaventricular nucleus of hypothalamussuperior colliculusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionion channel activity kainate selective glutamate receptor activity extracellularly glutamate gated ion channel activity ionotropic glutamate receptor activity ligand gated ion channel activity signaling receptor activity glutamate receptor activity transmitter gated ion channel activity involved in regulation of postsynaptic membrane potentialCellular componentintegral component of membrane cell junction plasma membrane postsynaptic membrane integral component of plasma membrane synapse membrane kainate selective glutamate receptor complex presynaptic membraneBiological processglutamate receptor signaling pathway central nervous system development ion transmembrane transport regulation of synaptic transmission glutamatergic ion transport nervous system development chemical synaptic transmission ionotropic glutamate receptor signaling pathway excitatory postsynaptic potential synaptic transmission glutamatergic modulation of chemical synaptic transmission regulation of postsynaptic membrane potentialSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez289714805EnsemblENSG00000171189ENSMUSG00000022935UniProtP39086Q60934RefSeq mRNA NM 000830NM 175611NM 001320616NM 001320618NM 001320621NM 001320630NM 001330993NM 001330994NM 001393424NM 001393425NM 001393426NM 010348NM 146072NM 001346964RefSeq protein NP 000821NP 001307545NP 001307547NP 001307550NP 001307559NP 001317922NP 001317923NP 783300n aLocation UCSC Chr 21 29 54 29 94 MbChr 16 87 69 88 09 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 RNA editing 3 1 Type 3 2 Location 3 3 Regulation 3 4 Consequences 3 4 1 Structure 3 4 2 Function 4 See also 5 References 6 Further reading 7 External linksFunction editThis gene encodes one of the many ionotropic glutamate receptor GluR subunits that function as a ligand gated ion channel The specific GluR subunit encoded by this gene is of the kainate receptor subtype Receptor assembly and intracellular trafficking of ionotropic glutamate receptors are regulated by RNA editing and alternative splicing These receptors mediate excitatory neurotransmission and are critical for normal synaptic function Two alternatively spliced transcript variants that encode different isoforms have been described Exons of this gene are interspersed with exons from the C21orf41 gene which is transcribed in the same orientation as this gene but does not seem to encode a protein 5 Interactions editGRIK1 has been shown to interact with DLG4 6 PICK1 6 and SDCBP 6 RNA editing editType edit A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA ADARs that specifically recognize adenosines within double stranded regions of pre mRNAs and deaminate them to inosine Inosines 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 whereas 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 ADARs bind interact directly with the dsRNA substrate via their double stranded RNA binding domains If an editing site occurs within a coding sequence the result could be a codon change This can lead to translation of a protein isoform due to a change in its primary protein structure Therefore editing can also alter protein function A to I editing occurs in a noncoding RNA sequences such as introns untranslated regions UTRs LINEs SINEs especially Alu repeats The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus among others Location edit The pre mRNA of GluR 5 is edited at one position at the Q R site located at membrane region 2 M2 There is a codon change as a result of editing The codon change is CAG Glutamine Q to CGG an Arginine R 7 Like GluR 6 the ECS is located about 2000 nucleotides downstream of the editing site 8 Regulation edit Editing of the Q R site is development and tissue regulated Editing in the spinal cord corpus callosum cerebellum is 50 while editing in the Thalamus amygdala hippocampus is about 70 Consequences edit Structure edit Editing results in a change in amino acid in the second membrane domain of the receptor Function edit The editing site is found within the second intracellular domain It is thought that editing affects the permeability of the receptor to CA2 Editing of the Q R site is thought to reduce the permeability of the channel to Ca2 7 RNA editing of the Q R site can effect inhibition of the channel by membrane fatty acids such as arachidonic acid and docosahexaenoic acid 9 For Kainate receptors with only edited isoforms these are strongly inhibited by these fatty acids However inclusion of just one nonedited subunit is enough to stop this inhibition 9 See also editKainate receptor GRIK1 RNA editingReferences edit a b c GRCh38 Ensembl release 89 ENSG00000171189 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000022935 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene GRIK1 glutamate receptor ionotropic kainate 1 a b c Hirbec Helene Francis Joanna C Lauri Sari E Braithwaite Steven P Coussen Francoise Mulle Christophe Dev Kumlesh K Coutinho Victoria Meyer Guido Isaac John T R Collingridge Graham L Henley Jeremy M Couthino Victoria Feb 2003 Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP Neuron 37 4 United States 625 38 doi 10 1016 S0896 6273 02 01191 1 ISSN 0896 6273 PMC 3314502 PMID 12597860 a b Seeburg PH Single F Kuner T Higuchi M Sprengel R July 2001 Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse Brain Res 907 1 2 233 43 doi 10 1016 S0006 8993 01 02445 3 PMID 11430906 S2CID 11969068 Herb A Higuchi M Sprengel R Seeburg PH March 1996 Q R site editing in kainate receptor GluR5 and GluR6 pre mRNAs requires distant intronic sequences Proc Natl Acad Sci U S A 93 5 1875 80 Bibcode 1996PNAS 93 1875H doi 10 1073 pnas 93 5 1875 PMC 39875 PMID 8700852 a b Wilding TJ Fulling E Zhou Y Huettner JE July 2008 Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids J Gen Physiol 132 1 85 99 doi 10 1085 jgp 200810009 PMC 2442176 PMID 18562501 Further reading editNutt SL Kamboj RK 1995 RNA editing of human kainate receptor subunits NeuroReport 5 18 2625 9 doi 10 1097 00001756 199412000 00055 PMID 7696618 Roche KW Raymond LA Blackstone C Huganir RL 1994 Transmembrane topology of the glutamate receptor subunit GluR6 J Biol Chem 269 16 11679 82 doi 10 1016 S0021 9258 17 32623 6 PMID 8163463 Gregor P O Hara BF Yang X Uhl GR 1994 Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6 NeuroReport 4 12 1343 6 doi 10 1097 00001756 199309150 00014 PMID 8260617 Eubanks JH Puranam RS Kleckner NW et al 1993 The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21 1 22 1 in the vicinity of the gene for familial amyotrophic lateral sclerosis Proc Natl Acad Sci U S A 90 1 178 82 Bibcode 1993PNAS 90 178E doi 10 1073 pnas 90 1 178 PMC 45623 PMID 8419920 Potier MC Dutriaux A Lambolez B et al 1993 Assignment of the human glutamate receptor gene GLUR5 to 21q22 by screening a chromosome 21 YAC library Genomics 15 3 696 7 doi 10 1006 geno 1993 1131 PMID 8468067 Korczak B Nutt SL Fletcher EJ et al 1996 cDNA cloning and functional properties of human glutamate receptor EAA3 GluR5 in homomeric and heteromeric configuration Recept Channels 3 1 41 9 PMID 8589992 Brakeman PR Lanahan AA O Brien R et al 1997 Homer a protein that selectively binds metabotropic glutamate receptors Nature 386 6622 284 8 Bibcode 1997Natur 386 284B doi 10 1038 386284a0 PMID 9069287 S2CID 4346579 Sander T Hildmann T Kretz R et al 1997 Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene GRIK1 polymorphism Am J Med Genet 74 4 416 21 doi 10 1002 SICI 1096 8628 19970725 74 4 lt 416 AID AJMG13 gt 3 0 CO 2 L PMID 9259378 Clarke VR Ballyk BA Hoo KH et al 1997 A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission Nature 389 6651 599 603 Bibcode 1997Natur 389 599C doi 10 1038 39315 PMID 9335499 S2CID 4426839 Xiao B Tu JC Petralia RS et al 1998 Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer related synaptic proteins Neuron 21 4 707 16 doi 10 1016 S0896 6273 00 80588 7 PMID 9808458 S2CID 16431031 Montague AA Greer CA 1999 Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb J Comp Neurol 405 2 233 46 doi 10 1002 SICI 1096 9861 19990308 405 2 lt 233 AID CNE7 gt 3 0 CO 2 A PMID 10023812 S2CID 1317987 Bortolotto ZA Clarke VR Delany CM et al 1999 Kainate receptors are involved in synaptic plasticity Nature 402 6759 297 301 Bibcode 1999Natur 402 297B doi 10 1038 46290 PMID 10580501 S2CID 205051834 Barbon A Barlati S 2000 Genomic organization proposed alternative splicing mechanisms and RNA editing structure of GRIK1 Cytogenet Cell Genet 88 3 4 236 9 doi 10 1159 000015558 PMID 10828597 S2CID 5850944 Hattori M Fujiyama A Taylor TD et al 2000 The DNA sequence of human chromosome 21 Nature 405 6784 311 9 Bibcode 2000Natur 405 311H doi 10 1038 35012518 PMID 10830953 Ango F Prezeau L Muller T et al 2001 Agonist independent activation of metabotropic glutamate receptors by the intracellular protein Homer Nature 411 6840 962 5 Bibcode 2001Natur 411 962A doi 10 1038 35082096 PMID 11418862 S2CID 4417727 Shibata H Joo A Fujii Y et al 2002 Association study of polymorphisms in the GluR5 kainate receptor gene GRIK1 with schizophrenia Psychiatr Genet 11 3 139 44 doi 10 1097 00041444 200109000 00005 PMID 11702055 S2CID 38356907 Hirbec H Perestenko O Nishimune A et al 2002 The PDZ proteins PICK1 GRIP and syntenin bind multiple glutamate receptor subtypes Analysis of PDZ binding motifs PDF J Biol Chem 277 18 15221 4 doi 10 1074 jbc C200112200 PMID 11891216 S2CID 13732968 Enz R 2002 The actin binding protein Filamin A interacts with the metabotropic glutamate receptor type 7 FEBS Lett 514 2 3 184 8 doi 10 1016 S0014 5793 02 02361 X PMID 11943148 S2CID 44474808 Hirbec H Francis JC Lauri SE et al 2003 Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP Neuron 37 4 625 38 doi 10 1016 S0896 6273 02 01191 1 PMC 3314502 PMID 12597860 Ren Z Riley NJ Needleman LA et al 2004 Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal J Biol Chem 278 52 52700 9 doi 10 1074 jbc M309585200 PMID 14527949 External links editGRIK1 protein human at the U S National Library of Medicine Medical Subject Headings MeSH This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title GRIK1 amp oldid 1178671991, wikipedia, wiki, book, books, library,
