GLRA2_MOUSE
ID GLRA2_MOUSE Reviewed; 452 AA.
AC Q7TNC8;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Glycine receptor subunit alpha-2;
DE Flags: Precursor;
GN Name=Glra2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15329889; DOI=10.1002/cne.20267;
RA Haverkamp S., Mueller U., Zeilhofer H.U., Harvey R.J., Waessle H.;
RT "Diversity of glycine receptors in the mouse retina: localization of the
RT alpha2 subunit.";
RL J. Comp. Neurol. 477:399-411(2004).
RN [3]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=16847326; DOI=10.1128/mcb.00237-06;
RA Young-Pearse T.L., Ivic L., Kriegstein A.R., Cepko C.L.;
RT "Characterization of mice with targeted deletion of glycine receptor alpha
RT 2.";
RL Mol. Cell. Biol. 26:5728-5734(2006).
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=21924294; DOI=10.1016/j.bbr.2011.09.002;
RA Kallenborn-Gerhardt W., Lu R., Lorenz J., Gao W., Weiland J., Del Turco D.,
RA Deller T., Laube B., Betz H., Geisslinger G., Schmidtko A.;
RT "Prolonged zymosan-induced inflammatory pain hypersensitivity in mice
RT lacking glycine receptor alpha2.";
RL Behav. Brain Res. 226:106-111(2012).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel
CC opening is triggered by extracellular glycine. Channel opening is also
CC triggered by taurine and beta-alanine. Plays a role in the down-
CC regulation of neuronal excitability. Contributes to the generation of
CC inhibitory postsynaptic currents. Plays a role in cellular responses to
CC ethanol. {ECO:0000250|UniProtKB:P23416}.
CC -!- SUBUNIT: Homopentamer (in vitro). Interacts with GLRB. Heteropentamer
CC composed of GLRA2 and GLRB. Both homopentamers and heteropentamers form
CC functional ion channels, but their characteristics are subtly
CC different. {ECO:0000250|UniProtKB:P23416}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:15329889}; Multi-pass membrane protein
CC {ECO:0000305}. Synapse {ECO:0000269|PubMed:15329889}. Cell membrane;
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P23415}. Cell
CC projection {ECO:0000269|PubMed:15329889}.
CC -!- TISSUE SPECIFICITY: Detected in the retina inner plexiform layer (at
CC protein level) (PubMed:15329889). Detected in neonate retina. Detected
CC in brain (PubMed:21924294). Detected in spinal cord, with higher levels
CC in the dorsal horn (PubMed:16847326, PubMed:21924294).
CC {ECO:0000269|PubMed:15329889, ECO:0000269|PubMed:16847326,
CC ECO:0000269|PubMed:21924294}.
CC -!- DISRUPTION PHENOTYPE: Loss of glycine-induced currents in cortical
CC neurons from 17 dpc embryos. Still, mutant mice are born at the
CC expected Mendelian rate, are healthy and fertile. No effect on glycine-
CC induced currents in cortical neurons from seven day old mice
CC (PubMed:16847326). Baseline nociception is not changed, but mutant mice
CC show increased hyperalgesia in response to mechanical stimuli during
CC later stages of inflammation caused by zymosan injection
CC (PubMed:21924294). {ECO:0000269|PubMed:16847326}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000250|UniProtKB:P23416}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glycine receptor (TC 1.A.9.3) subfamily. GLRA2 sub-subfamily.
CC {ECO:0000305}.
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DR EMBL; BC056342; AAH56342.1; -; mRNA.
DR EMBL; BC068987; AAH68987.1; -; mRNA.
DR CCDS; CCDS41206.1; -.
DR RefSeq; NP_906272.1; NM_183427.4.
DR RefSeq; XP_006528897.1; XM_006528834.1.
DR RefSeq; XP_006528898.1; XM_006528835.3.
DR AlphaFoldDB; Q7TNC8; -.
DR SMR; Q7TNC8; -.
DR BioGRID; 231850; 1.
DR STRING; 10090.ENSMUSP00000060827; -.
DR GlyGen; Q7TNC8; 2 sites.
DR iPTMnet; Q7TNC8; -.
DR PhosphoSitePlus; Q7TNC8; -.
DR SwissPalm; Q7TNC8; -.
DR MaxQB; Q7TNC8; -.
DR PaxDb; Q7TNC8; -.
DR PRIDE; Q7TNC8; -.
DR ProteomicsDB; 270997; -.
DR Antibodypedia; 54675; 53 antibodies from 17 providers.
DR DNASU; 237213; -.
DR Ensembl; ENSMUST00000058787; ENSMUSP00000060827; ENSMUSG00000018589.
DR GeneID; 237213; -.
DR KEGG; mmu:237213; -.
DR UCSC; uc009uwb.1; mouse.
DR CTD; 2742; -.
DR MGI; MGI:95748; Glra2.
DR VEuPathDB; HostDB:ENSMUSG00000018589; -.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000158730; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; Q7TNC8; -.
DR OMA; ENMFLRI; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; Q7TNC8; -.
DR TreeFam; TF315453; -.
DR Reactome; R-MMU-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR BioGRID-ORCS; 237213; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q7TNC8; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q7TNC8; protein.
DR Bgee; ENSMUSG00000018589; Expressed in cortical plate and 60 other tissues.
DR ExpressionAtlas; Q7TNC8; baseline and differential.
DR Genevisible; Q7TNC8; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0098690; C:glycinergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0016934; F:extracellularly glycine-gated chloride channel activity; ISO:MGI.
DR GO; GO:0016594; F:glycine binding; ISO:MGI.
DR GO; GO:0022852; F:glycine-gated chloride ion channel activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:MGI.
DR GO; GO:0071361; P:cellular response to ethanol; ISO:MGI.
DR GO; GO:0071294; P:cellular response to zinc ion; ISO:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:MGI.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0043200; P:response to amino acid; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060012; P:synaptic transmission, glycinergic; IBA:GO_Central.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR008127; Glycine_rcpt_A.
DR InterPro; IPR008129; Glycine_rcpt_A2.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR PANTHER; PTHR18945:SF28; PTHR18945:SF28; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR01673; GLYRALPHA.
DR PRINTS; PR01675; GLYRALPHA2.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Chloride; Chloride channel; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW Membrane; Metal-binding; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport; Zinc.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..452
FT /note="Glycine receptor subunit alpha-2"
FT /id="PRO_0000000417"
FT TOPO_DOM 28..256
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TRANSMEM 257..278
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TOPO_DOM 279..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TRANSMEM 284..304
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TOPO_DOM 305..315
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TRANSMEM 316..336
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TOPO_DOM 337..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TRANSMEM 421..441
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TOPO_DOM 442..452
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 228
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 236..241
FT /ligand="strychnine"
FT /ligand_id="ChEBI:CHEBI:90700"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT SITE 295
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 172..186
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT DISULFID 232..243
FT /evidence="ECO:0000250|UniProtKB:P23415"
SQ SEQUENCE 452 AA; 52062 MW; C8962DFD7D6D8A61 CRC64;
MYRQLVNILT ALFAFFLGTN HFREAFCKDH DSRSGKHPSQ TLSPSDFLDK LMGRTSGYDA
RIRPNFKGPP VNVTCNIFIN SFGSVTETTM DYRVNIFLRQ QWNDSRLAYS EYPDDSLDLD
PSMLDSIWKP DLFFANEKGA NFHDVTTDNK LLRISKNGKV LYSIRLTLTL SCPMDLKNFP
MDVQTCTMQL ESFGYTMNDL IFEWLSDGPV QVAEGLTLPQ FILKEEKELG YCTKHYNTGK
FTCIEVKFHL ERQMGYYLIQ MYIPSLLIVI LSWVSFWINM DAAPARVALG ITTVLTMTTQ
SSGSRASLPK VSYVKAIDIW MAVCLLFVFA ALLEYAAVNF VSRQHKEFLR LRRRQKRQNK
EEDVTRESRF NFSGYGMGHC LQMKDGTAVK ATPANPLPQP PKDADAIKKK FVDRAKRIDT
ISRAAFPLAF LIFNIFYWIT YKIIRHEDVH KK
