GLRA2_RAT
ID GLRA2_RAT Reviewed; 452 AA.
AC P22771; Q91W28;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Glycine receptor subunit alpha-2;
DE AltName: Full=Glycine receptor strychnine-binding subunit;
DE Flags: Precursor;
GN Name=Glra2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*), FUNCTION, SUBCELLULAR
RP LOCATION, ACTIVITY REGULATION, DEVELOPMENTAL STAGE, VARIANT GLY-194, AND
RP CHARACTERIZATION OF VARIANT GLY-194.
RC TISSUE=Brain;
RX PubMed=2176511; DOI=10.1016/0896-6273(90)90346-h;
RA Kuhse J., Schmieden V., Betz H.;
RT "A single amino acid exchange alters the pharmacology of neonatal rat
RT glycine receptor subunit.";
RL Neuron 5:867-873(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*), AND DEVELOPMENTAL STAGE.
RC STRAIN=Wistar; TISSUE=Spinal cord;
RX PubMed=1707830; DOI=10.1016/0014-5793(91)80383-e;
RA Akagi H., Hirai K., Hishinuma F.;
RT "Cloning of a glycine receptor subtype expressed in rat brain and spinal
RT cord during a specific period of neuronal development.";
RL FEBS Lett. 281:160-166(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-2* AND ALPHA-2B), AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=1645300; DOI=10.1016/0014-5793(91)80557-j;
RA Kuhse J., Kuryatov A., Maulet Y., Malosio M.L., Schmieden V., Betz H.;
RT "Alternative splicing generates two isoforms of the alpha 2 subunit of the
RT inhibitory glycine receptor.";
RL FEBS Lett. 283:73-77(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Beato M., Groot Kormelink P.J., Colquhoun D., Sivilotti L.G.;
RT "Concentration dependence of single channel currents through rat
RT recombinant alpha 1 glycine receptors.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
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 (PubMed:2176511). Plays a role in
CC the down-regulation of neuronal excitability. Contributes to the
CC generation of inhibitory postsynaptic currents. Plays a role in
CC cellular responses to ethanol. {ECO:0000250|UniProtKB:P23416,
CC ECO:0000269|PubMed:2176511}.
CC -!- ACTIVITY REGULATION: Inhibited by strychnine.
CC {ECO:0000269|PubMed:2176511}.
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:0000250|UniProtKB:Q7TNC8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7TNC8}. Synapse {ECO:0000250|UniProtKB:Q7TNC8}.
CC Cell membrane {ECO:0000269|PubMed:2176511}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P23415}. Cell projection
CC {ECO:0000250|UniProtKB:Q7TNC8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha-2*;
CC IsoId=P22771-1; Sequence=Displayed;
CC Name=Alpha-2B;
CC IsoId=P22771-2; Sequence=VSP_000083;
CC -!- DEVELOPMENTAL STAGE: The alpha-2* subunit isoform is present in
CC neonatal rats, but not in older animals (PubMed:2176511,
CC PubMed:1707830). Isoform Alpha-2* and isoform Alpha-2B are detected in
CC embryonic and neonatal brain. At later postnatal stages, isoform Alpha-
CC 2* levels greatly decrease while isoform Alpha-2B is barely detectable
CC (PubMed:1645300). {ECO:0000269|PubMed:1707830,
CC ECO:0000269|PubMed:2176511}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000269|PubMed:2176511}.
CC -!- MISCELLANEOUS: Identical to the human subunit alpha-2, except for 5
CC substitutions at positions 18, 24, 37, 194 and 404. Substitution at
CC position 194 (G -> E) accounts for the lower strychnine sensitivity
CC observed in neonatal rats. {ECO:0000269|PubMed:2176511}.
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; X57281; CAA40549.1; -; mRNA.
DR EMBL; X61159; CAA43471.1; -; mRNA.
DR EMBL; AJ310837; CAC35981.1; -; mRNA.
DR PIR; S14816; S14816.
DR PIR; S18836; S18836.
DR RefSeq; NP_036700.1; NM_012568.3.
DR RefSeq; XP_003752087.1; XM_003752039.4.
DR RefSeq; XP_017457394.1; XM_017601905.1.
DR AlphaFoldDB; P22771; -.
DR SMR; P22771; -.
DR CORUM; P22771; -.
DR STRING; 10116.ENSRNOP00000004426; -.
DR BindingDB; P22771; -.
DR ChEMBL; CHEMBL2328; -.
DR GlyGen; P22771; 2 sites.
DR PaxDb; P22771; -.
DR PRIDE; P22771; -.
DR GeneID; 24397; -.
DR KEGG; rno:24397; -.
DR UCSC; RGD:2705; rat. [P22771-1]
DR CTD; 2742; -.
DR RGD; 2705; Glra2.
DR eggNOG; KOG3644; Eukaryota.
DR InParanoid; P22771; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; P22771; -.
DR TreeFam; TF315453; -.
DR Reactome; R-RNO-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR PRO; PR:P22771; -.
DR Proteomes; UP000002494; Unplaced.
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; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
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:RGD.
DR GO; GO:0016594; F:glycine binding; ISO:RGD.
DR GO; GO:0022852; F:glycine-gated chloride ion channel activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:0071361; P:cellular response to ethanol; ISO:RGD.
DR GO; GO:0071294; P:cellular response to zinc ion; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:RGD.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
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:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0007416; P:synapse assembly; IEP:RGD.
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 Alternative splicing; Cell membrane; Cell projection; Chloride;
KW Chloride channel; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Metal-binding;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..452
FT /note="Glycine receptor subunit alpha-2"
FT /id="PRO_0000000418"
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 194
FT /note="Important for glycine and strychnine binding"
FT /evidence="ECO:0000305|PubMed:2176511"
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"
FT VAR_SEQ 85..86
FT /note="VT -> IA (in isoform Alpha-2B)"
FT /evidence="ECO:0000305"
FT /id="VSP_000083"
FT VARIANT 194
FT /note="E -> G (increased sensitivity to strychnine)"
FT /evidence="ECO:0000269|PubMed:2176511"
SQ SEQUENCE 452 AA; 52053 MW; A9EBC6D1552A3A1C CRC64;
MNRQLVNILT ALFAFFLGTN HFREAFCKDH DSRSGKHPSQ TLSPSDFLDK LMGRTSGYDA
RIRPNFKGPP VNVTCNIFIN SFGSVTETTM DYRVNIFLRQ QWNDSRLAYS EYPDDSLDLD
PSMLDSIWKP DLFFANEKGA NFHDVTTDNK LLRISKNGKV LYSIRLTLTL SCPMDLKNFP
MDVQTCTMQL ESFEYTMNDL IFEWLSDGPV QVAEGLTLPQ FILKEEKELG YCTKHYNTGK
FTCIEVKFHL ERQMGYYLIQ MYIPSLLIVI LSWVSFWINM DAAPARVALG ITTVLTMTTQ
SSGSRASLPK VSYVKAIDIW MAVCLLFVFA ALLEYAAVNF VSRQHKEFLR LRRRQKRQNK
EEDVTRESRF NFSGYGMGHC LQVKDGTAVK ATPANPLPQP PKDADAIKKK FVDRAKRIDT
ISRAAFPLAF LIFNIFYWIT YKIIRHEDVH KK
