GLRA1_RAT
ID GLRA1_RAT Reviewed; 457 AA.
AC P07727; Q546L6;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 08-DEC-2000, sequence version 4.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Glycine receptor subunit alpha-1;
DE AltName: Full=Glycine receptor 48 kDa subunit;
DE AltName: Full=Glycine receptor strychnine-binding subunit;
DE Flags: Precursor;
GN Name=Glra1; Synonyms=Glyr;
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 B), FUNCTION, SUBCELLULAR LOCATION, AND
RP ACTIVITY REGULATION.
RX PubMed=1716350; DOI=10.1016/0168-0102(91)90064-6;
RA Akagi H., Hirai K., Hishinuma F.;
RT "Functional properties of strychnine-sensitive glycine receptors expressed
RT in Xenopus oocytes injected with a single mRNA.";
RL Neurosci. Res. 11:28-40(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND ALTERNATIVE SPLICING.
RC STRAIN=Wistar; TISSUE=Spinal cord;
RX PubMed=1703526; DOI=10.1016/s0021-9258(18)52207-9;
RA Malosio M.L., Grenningloh G., Kuhse J., Schmieden V., Schmitt B., Prior P.,
RA Betz H.;
RT "Alternative splicing generates two variants of the alpha 1 subunit of the
RT inhibitory glycine receptor.";
RL J. Biol. Chem. 266:2048-2053(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=11981023; DOI=10.1085/jgp.20028530;
RA Beato M., Groot-Kormelink P.J., Colquhoun D., Sivilotti L.G.;
RT "Openings of the rat recombinant alpha 1 homomeric glycine receptor as a
RT function of the number of agonist molecules bound.";
RL J. Gen. Physiol. 119:443-466(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-30, FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=2483325; DOI=10.1016/0896-6273(89)90195-5;
RA Sontheimer H., Becker C.M., Pritchett D.B., Schofield P.R., Grenningloh G.,
RA Kettenmann H., Betz H., Seeburg P.H.;
RT "Functional chloride channels by mammalian cell expression of rat glycine
RT receptor subunit.";
RL Neuron 2:1491-1497(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-457 (ISOFORM B), PROTEIN SEQUENCE OF
RP 29-49, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Wistar;
RX PubMed=3037383; DOI=10.1038/328215a0;
RA Grenningloh G., Rienitz A., Schmitt B., Methfessel C., Zensen M.,
RA Beyreuther K., Gundelfinger E.D., Betz H.;
RT "The strychnine-binding subunit of the glycine receptor shows homology with
RT nicotinic acetylcholine receptors.";
RL Nature 328:215-220(1987).
RN [6]
RP SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=6286620; DOI=10.1016/s0021-9258(18)34082-1;
RA Pfeiffer F., Graham D., Betz H.;
RT "Purification by affinity chromatography of the glycine receptor of rat
RT spinal cord.";
RL J. Biol. Chem. 257:9389-9393(1982).
RN [7]
RP STRYCHNINE BINDING SITE.
RX PubMed=2171639; DOI=10.1021/bi00482a012;
RA Ruiz-Gomez A., Morato E., Garcia-Calvo M., Valdivieso F., Mayor F. Jr.;
RT "Localization of the strychnine binding site on the 48-kilodalton subunit
RT of the glycine receptor.";
RL Biochemistry 29:7033-7040(1990).
RN [8]
RP INTERACTION WITH GLRB.
RX PubMed=14551753; DOI=10.1007/s00249-003-0286-y;
RA Mohammadi B., Krampfl K., Cetinkaya C., Moschref H., Grosskreutz J.,
RA Dengler R., Bufler J.;
RT "Kinetic analysis of recombinant mammalian alpha(1) and alpha(1)beta
RT glycine receptor channels.";
RL Eur. Biophys. J. 32:529-536(2003).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel
CC opening is triggered by extracellular glycine (PubMed:1716350,
CC PubMed:11981023, PubMed:2483325, PubMed:3037383). Channel opening is
CC also triggered by taurine and beta-alanine (PubMed:1716350). Channel
CC characteristics depend on the subunit composition; heteropentameric
CC channels are activated by lower glycine levels and display faster
CC desensitization. Plays an important role in the down-regulation of
CC neuronal excitability. Contributes to the generation of inhibitory
CC postsynaptic currents. Channel activity is potentiated by ethanol (By
CC similarity). Potentiation of channel activity by intoxicating levels of
CC ethanol contribute to the sedative effects of ethanol (By similarity).
CC {ECO:0000250|UniProtKB:P23415, ECO:0000250|UniProtKB:Q64018,
CC ECO:0000269|PubMed:11981023, ECO:0000269|PubMed:1716350,
CC ECO:0000269|PubMed:2483325, ECO:0000269|PubMed:3037383}.
CC -!- ACTIVITY REGULATION: Inhibited by strychnine (PubMed:1716350,
CC PubMed:2483325, PubMed:3037383). Inhibited by picrotoxin
CC (PubMed:2483325). {ECO:0000269|PubMed:1716350,
CC ECO:0000269|PubMed:2483325, ECO:0000269|PubMed:3037383}.
CC -!- SUBUNIT: Homopentamer (in vitro). Interacts with GLRB to form
CC heteropentameric channels; this is probably the predominant form in
CC vivo. Heteropentamer composed of two GLRA1 and three GLRB.
CC Heteropentamer composed of three GLRA1 and two GLRB. Both homopentamers
CC and heteropentamers form functional ion channels, but their
CC characteristics are subtly different. {ECO:0000250|UniProtKB:P23415,
CC ECO:0000269|PubMed:6286620}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:6286620}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q64018}. Synapse {ECO:0000269|PubMed:6286620}.
CC Perikaryon {ECO:0000250|UniProtKB:Q64018}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q64018}. Cell membrane
CC {ECO:0000269|PubMed:11981023, ECO:0000269|PubMed:1716350,
CC ECO:0000269|PubMed:2483325, ECO:0000269|PubMed:3037383}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P23415}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a; Synonyms=Long;
CC IsoId=P07727-1; Sequence=Displayed;
CC Name=b; Synonyms=Short;
CC IsoId=P07727-2; Sequence=VSP_000081;
CC -!- TISSUE SPECIFICITY: Detected in spinal cord (at protein level)
CC (PubMed:2483325, PubMed:6286620). Detected in spinal cord and brain
CC stem (PubMed:3037383). {ECO:0000269|PubMed:2483325,
CC ECO:0000269|PubMed:3037383, ECO:0000269|PubMed:6286620}.
CC -!- DOMAIN: The channel pore is formed by pentameric assembly of the second
CC transmembrane domain from all five subunits. Channel opening is
CC effected by an outward rotation of the transmembrane domains that
CC increases the diameter of the pore. {ECO:0000250|UniProtKB:O93430}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000269|PubMed:2171639, ECO:0000269|PubMed:3037383,
CC ECO:0000269|PubMed:6286620}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily.
CC {ECO:0000305}.
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DR EMBL; D00833; BAA00707.1; -; mRNA.
DR EMBL; X55246; CAA38987.1; -; mRNA.
DR EMBL; M63915; AAA63490.1; -; mRNA.
DR EMBL; AJ310835; CAC35979.1; -; mRNA.
DR EMBL; Y00276; CAA68378.1; -; mRNA.
DR PIR; JN0014; JN0014.
DR PIR; S20662; S20662.
DR RefSeq; NP_037265.1; NM_013133.1. [P07727-2]
DR RefSeq; XP_006246440.1; XM_006246378.3. [P07727-1]
DR AlphaFoldDB; P07727; -.
DR BMRB; P07727; -.
DR SMR; P07727; -.
DR CORUM; P07727; -.
DR DIP; DIP-48879N; -.
DR IntAct; P07727; 2.
DR STRING; 10116.ENSRNOP00000063384; -.
DR BindingDB; P07727; -.
DR ChEMBL; CHEMBL3246; -.
DR GlyGen; P07727; 1 site.
DR iPTMnet; P07727; -.
DR PRIDE; P07727; -.
DR Ensembl; ENSRNOT00000063889; ENSRNOP00000063384; ENSRNOG00000013588. [P07727-2]
DR GeneID; 25674; -.
DR KEGG; rno:25674; -.
DR UCSC; RGD:2704; rat. [P07727-1]
DR CTD; 2741; -.
DR RGD; 2704; Glra1.
DR VEuPathDB; HostDB:ENSRNOG00000013588; -.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000159047; -.
DR InParanoid; P07727; -.
DR OMA; FNFAYGM; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; P07727; -.
DR Reactome; R-RNO-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR PRO; PR:P07727; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000013588; Expressed in cerebellum and 3 other tissues.
DR ExpressionAtlas; P07727; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0044305; C:calyx of Held; IDA:SynGO.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0098690; C:glycinergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
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; IDA:RGD.
DR GO; GO:0016933; F:extracellularly glycine-gated ion channel activity; IDA:RGD.
DR GO; GO:0016594; F:glycine binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0030977; F:taurine binding; ISS:UniProtKB.
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:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007340; P:acrosome reaction; ISO:RGD.
DR GO; GO:0001508; P:action potential; ISO:RGD.
DR GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR GO; GO:0006820; P:anion transport; IDA:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0071361; P:cellular response to ethanol; ISS:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0006821; P:chloride transport; IDA:RGD.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; ISS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR GO; GO:0051970; P:negative regulation of transmission of nerve impulse; ISS:UniProtKB.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISS:UniProtKB.
DR GO; GO:2000344; P:positive regulation of acrosome reaction; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; ISO:RGD.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; ISO:RGD.
DR GO; GO:0097305; P:response to alcohol; ISS:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IBA:GO_Central.
DR GO; GO:0060013; P:righting reflex; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001964; P:startle response; ISS:UniProtKB.
DR GO; GO:0060012; P:synaptic transmission, glycinergic; IDA:RGD.
DR GO; GO:0007601; P:visual perception; ISO:RGD.
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; IPR008128; Glycine_rcpt_A1.
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 Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR01673; GLYRALPHA.
DR PRINTS; PR01674; GLYRALPHA1.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Metal-binding; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:3037383"
FT CHAIN 29..457
FT /note="Glycine receptor subunit alpha-1"
FT /id="PRO_0000000414"
FT TOPO_DOM 29..250
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TRANSMEM 251..272
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TOPO_DOM 273..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TRANSMEM 278..298
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TOPO_DOM 299..309
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TRANSMEM 310..330
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TOPO_DOM 331..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TRANSMEM 426..446
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT TOPO_DOM 447..457
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 230..235
FT /ligand="strychnine"
FT /ligand_id="ChEBI:CHEBI:90700"
FT /evidence="ECO:0000250|UniProtKB:O93430,
FT ECO:0000305|PubMed:2171639"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT SITE 289
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 166..180
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT DISULFID 226..237
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT VAR_SEQ 354..361
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:1716350,
FT ECO:0000303|PubMed:3037383"
FT /id="VSP_000081"
FT CONFLICT 26
FT /note="A -> V (in Ref. 5; CAA68378)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 457 AA; 52617 MW; 0379C33A83C71FAA CRC64;
MYSFNTLRFY LWETIVFFSL AASKEADAAR SAPKPMSPSD FLDKLMGRTS GYDARIRPNF
KGPPVNVSCN IFINSFGSIA ETTMDYRVNI FLRQQWNDPR LAYNEYPDDS LDLDPSMLDS
IWKPDLFFAN EKGAHFHEIT TDNKLLRISR NGNVLYSIRI TLTLACPMDL KNFPMDVQTC
IMQLESFGYT MNDLIFEWQE QGAVQVADGL TLPQFILKEE KDLRYCTKHY NTGKFTCIEA
RFHLERQMGY YLIQMYIPSL LIVILSWISF WINMDAAPAR VGLGITTVLT MTTQSSGSRA
SLPKVSYVKA IDIWMAVCLL FVFSALLEYA AVNFVSRQHK ELLRFRRKRR HHKSPMLNLF
QDDEGGEGRF NFSAYGMGPA CLQAKDGISV KGANNNNTTN PAPAPSKSPE EMRKLFIQRA
KKIDKISRIG FPMAFLIFNM FYWIIYKIVR REDVHNK
