GLRA3_RAT
ID GLRA3_RAT Reviewed; 464 AA.
AC P24524;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Glycine receptor subunit alpha-3;
DE Flags: Precursor;
GN Name=Glra3;
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].
RC TISSUE=Brain;
RX PubMed=2176214; DOI=10.1016/s0021-9258(18)45707-9;
RA Kuhse J., Schmieden V., Betz H.;
RT "Identification and functional expression of a novel ligand binding subunit
RT of the inhibitory glycine receptor.";
RL J. Biol. Chem. 265:22317-22320(1990).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-379, AND MUTAGENESIS
RP OF SER-379.
RX PubMed=15131310; DOI=10.1126/science.1094925;
RA Harvey R.J., Depner U.B., Waessle H., Ahmadi S., Heindl C., Reinold H.,
RA Smart T.G., Harvey K., Schuetz B., Abo-Salem O.M., Zimmer A., Poisbeau P.,
RA Welzl H., Wolfer D.P., Betz H., Zeilhofer H.U., Mueller U.;
RT "GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory
RT pain sensitization.";
RL Science 304:884-887(2004).
RN [3]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19723286; DOI=10.1111/j.1460-9568.2009.06903.x;
RA Eichler S.A., Foerstera B., Smolinsky B., Juettner R., Lehmann T.N.,
RA Faehling M., Schwarz G., Legendre P., Meier J.C.;
RT "Splice-specific roles of glycine receptor alpha3 in the hippocampus.";
RL Eur. J. Neurosci. 30:1077-1091(2009).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, PHOSPHORYLATION AT
RP SER-379, AND MUTAGENESIS OF SER-379.
RX PubMed=23834509; DOI=10.1021/cn400097j;
RA Han L., Talwar S., Wang Q., Shan Q., Lynch J.W.;
RT "Phosphorylation of alpha3 glycine receptors induces a conformational
RT change in the glycine-binding site.";
RL ACS Chem. Neurosci. 4:1361-1370(2013).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF PRO-218.
RX PubMed=23895467; DOI=10.1111/acer.12192;
RA McCracken L.M., Trudell J.R., McCracken M.L., Harris R.A.;
RT "Zinc-dependent modulation of alpha2- and alpha3-glycine receptor subunits
RT by ethanol.";
RL Alcohol. Clin. Exp. Res. 37:2002-2010(2013).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23613537; DOI=10.1113/jphysiol.2013.252189;
RA Marabelli A., Moroni M., Lape R., Sivilotti L.G.;
RT "The kinetic properties of the alpha3 rat glycine receptor make it suitable
RT for mediating fast synaptic inhibition.";
RL J. Physiol. (Lond.) 591:3289-3308(2013).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=25445488; DOI=10.1016/j.neuropharm.2014.10.026;
RA Zhang Y., Dixon C.L., Keramidas A., Lynch J.W.;
RT "Functional reconstitution of glycinergic synapses incorporating defined
RT glycine receptor subunit combinations.";
RL Neuropharmacology 89:391-397(2015).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel
CC opening is triggered by extracellular glycine (PubMed:15131310,
CC PubMed:23834509, PubMed:23895467, PubMed:23613537). Channel
CC characteristics depend on the subunit composition; heteropentameric
CC channels display faster channel closure (PubMed:25445488). Plays an
CC important role in the down-regulation of neuronal excitability (By
CC similarity). Contributes to the generation of inhibitory postsynaptic
CC currents (PubMed:25445488). Contributes to increased pain perception in
CC response to increased prostaglandin E2 levels (By similarity). Plays a
CC role in cellular responses to ethanol (PubMed:23895467).
CC {ECO:0000250|UniProtKB:Q91XP5, ECO:0000269|PubMed:15131310,
CC ECO:0000269|PubMed:23834509, ECO:0000269|PubMed:23895467,
CC ECO:0000269|PubMed:25445488}.
CC -!- ACTIVITY REGULATION: Low levels of Zn(2+) ions (1 uM) increase glycine
CC sensitivity and decrease the glycine concentration required for half-
CC maximal channel activity (PubMed:23895467). Channel activity is
CC strongly enhanced by ethanol (PubMed:23895467). Inhibited by picrotoxin
CC (PubMed:23834509). Inhibited by prostaglandin E2, probably via PKA-
CC mediated phosphorylation at Ser-379 (PubMed:15131310).
CC {ECO:0000269|PubMed:15131310, ECO:0000269|PubMed:23834509,
CC ECO:0000269|PubMed:23895467}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=A concentration of about 900 uM glycine results in half-maximal
CC channel conductance in the absence of Zn(2+). In the presence of 1 uM
CC Zn(2+), 400uM glycine results in half-maximal channel conductance.
CC {ECO:0000269|PubMed:23895467};
CC -!- SUBUNIT: Homopentamer (in vitro) (By similarity). Heteropentamer
CC composed of GLRA3 and GLRB. Both homopentamers and heteropentamers form
CC functional ion channels, but their characteristics are subtly different
CC (PubMed:25445488). {ECO:0000250, ECO:0000269|PubMed:25445488}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:19723286}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O75311}. Perikaryon
CC {ECO:0000269|PubMed:19723286}. Cell projection, dendrite
CC {ECO:0000269|PubMed:19723286}. Synapse {ECO:0000269|PubMed:19723286}.
CC Cell membrane {ECO:0000269|PubMed:15131310,
CC ECO:0000269|PubMed:19723286, ECO:0000269|PubMed:23613537,
CC ECO:0000269|PubMed:23834509, ECO:0000269|PubMed:23895467,
CC ECO:0000269|PubMed:25445488}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O75311}. Note=Partially colocalizes with GPHN
CC that is known to mediate receptor clustering at postsynaptic membranes.
CC {ECO:0000269|PubMed:19723286}.
CC -!- DOMAIN: The N-terminal domain carries structural determinants essential
CC for agonist and antagonist binding. The channel pore is formed by
CC pentameric assembly of the second transmembrane domain from all five
CC subunits. The cytoplasmic loop is an important determinant of channel
CC inactivation kinetics. {ECO:0000250|UniProtKB:O75311}.
CC -!- PTM: Phosphorylated by PKA; this causes down-regulation of channel
CC activity (Probable). {ECO:0000305|PubMed:15131310,
CC ECO:0000305|PubMed:23834509}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000250|UniProtKB:O75311}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glycine receptor (TC 1.A.9.3) subfamily. GLRA3 sub-subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M55250; AAA63492.1; -; mRNA.
DR PIR; A23682; A23682.
DR AlphaFoldDB; P24524; -.
DR SMR; P24524; -.
DR STRING; 10116.ENSRNOP00000067536; -.
DR ChEMBL; CHEMBL3392921; -.
DR GlyGen; P24524; 1 site.
DR iPTMnet; P24524; -.
DR PhosphoSitePlus; P24524; -.
DR PaxDb; P24524; -.
DR PRIDE; P24524; -.
DR ABCD; P24524; 1 sequenced antibody.
DR RGD; 621229; Glra3.
DR eggNOG; KOG3644; Eukaryota.
DR InParanoid; P24524; -.
DR Reactome; R-RNO-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR PRO; PR:P24524; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0016935; C:glycine-gated chloride channel complex; ISS:UniProtKB.
DR GO; GO:0098690; C:glycinergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; 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; IDA:UniProtKB.
DR GO; GO:0016594; F:glycine binding; IEA:InterPro.
DR GO; GO:0022852; F:glycine-gated chloride ion channel activity; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
DR GO; GO:0071361; P:cellular response to ethanol; IDA:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0051260; P:protein homooligomerization; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
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; IPR008130; Glycine_rcpt_A3.
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; PR01676; GLYRALPHA3.
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; Phosphoprotein; Postsynaptic cell membrane;
KW Receptor; Reference proteome; Signal; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..464
FT /note="Glycine receptor subunit alpha-3"
FT /id="PRO_0000000421"
FT TOPO_DOM 34..255
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TRANSMEM 256..277
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TOPO_DOM 278..282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TRANSMEM 283..303
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TOPO_DOM 304..314
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TRANSMEM 315..335
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TOPO_DOM 336..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TRANSMEM 431..451
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT TOPO_DOM 452..464
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 235..240
FT /ligand="strychnine"
FT /ligand_id="ChEBI:CHEBI:90700"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT SITE 294
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91XP5"
FT MOD_RES 379
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000305|PubMed:15131310,
FT ECO:0000305|PubMed:23834509"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 171..185
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT DISULFID 231..242
FT /evidence="ECO:0000250|UniProtKB:O75311"
FT MUTAGEN 218
FT /note="P->L: Strongly enhances glycine sensitivity so that
FT the channel starts to be activated at 0.001 mM glycine."
FT /evidence="ECO:0000269|PubMed:23895467"
FT MUTAGEN 379
FT /note="S->A: Loss of a predicted PKA phosphorylation site.
FT Nearly abolishes down-regulation of inhibitory postsynaptic
FT currents by prostaglandin E2."
FT /evidence="ECO:0000269|PubMed:15131310"
FT MUTAGEN 379
FT /note="S->E: Phosphomimetic mutant that triggers a local
FT conformation change."
FT /evidence="ECO:0000269|PubMed:23834509"
FT MUTAGEN 379
FT /note="S->G: Loss of a predicted PKA phosphorylation site.
FT Abolishes the conformation change observed after treatment
FT with forskolin."
FT /evidence="ECO:0000269|PubMed:23834509"
SQ SEQUENCE 464 AA; 53672 MW; 5A429F4C6F16E40D CRC64;
MAHVRHFRTL LSGFYFWEAA LLLSLVATKE TNSARSRSAP MSPSDFLDKL MGRTSGYDAR
IRPNFKGPPV NVTCNIFINS FGSIAETTMD YRVNIFLRQK WNDPRLAYSE YPDDSLDLDP
SMLDSIWKPD LFFANEKGAN FHEVTTDNKL LRIFKNGNVL YSIRLTLTLS CPMDLKNFPM
DVQTCIMQLE SFGYTMNDLI FEWQDEAPVQ VAEGLTLPQF LLKEEKDLRY CTKHYNTGKF
TCIEVRFHLE RQMGYYLIQM YIPSLLIVIL SWVSFWINMD AAPARVALGI TTVLTMTTQS
SGSRASLPKV SYVKAIDIWM AVCLLFVFSA LLEYAAVNFV SRQHKELLRF RRKRKNKTEA
FALEKFYRFS DTDDEVRESR LSFTAYGMGP CLQAKDGVVP KGPNHAVQVM PKSADEMRKV
FIDRAKKIDT ISRACFPLAF LIFNIFYWVI YKILRHEDIH HQQD
