GLRA3_MOUSE
ID GLRA3_MOUSE Reviewed; 464 AA.
AC Q91XP5; Q7TSQ2;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Glycine receptor subunit alpha-3;
DE Flags: Precursor;
GN Name=Glra3;
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 [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
RA Noegel S., Becker C., Becker K.;
RT "Different glycine receptor isoforms are expressed in murine cerebellum.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=12975813; DOI=10.1002/cne.10852;
RA Haverkamp S., Mueller U., Harvey K., Harvey R.J., Betz H., Waessle H.;
RT "Diversity of glycine receptors in the mouse retina: localization of the
RT alpha3 subunit.";
RL J. Comp. Neurol. 465:524-539(2003).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND ACTIVITY
RP REGULATION.
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 [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-379, AND TISSUE
RP SPECIFICITY.
RX PubMed=20978350; DOI=10.1172/jci43029;
RA Manzke T., Niebert M., Koch U.R., Caley A., Vogelgesang S., Huelsmann S.,
RA Ponimaskin E., Mueller U., Smart T.G., Harvey R.J., Richter D.W.;
RT "Serotonin receptor 1A-modulated phosphorylation of glycine receptor alpha3
RT controls breathing in mice.";
RL J. Clin. Invest. 120:4118-4128(2010).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel
CC opening is triggered by extracellular glycine (PubMed:15131310,
CC PubMed:20978350). Channel characteristics depend on the subunit
CC composition; heteropentameric channels display faster channel closure
CC (By similarity). Plays an important role in the down-regulation of
CC neuronal excitability. Contributes to the generation of inhibitory
CC postsynaptic currents (PubMed:15131310). Contributes to increased pain
CC perception in response to increased prostaglandin E2 levels
CC (PubMed:15131310). Plays a role in the regulation of breathing rhythm,
CC especially of the duration of the postinspiratory phase
CC (PubMed:20978350). Plays a role in cellular responses to ethanol (By
CC similarity). {ECO:0000250|UniProtKB:P24524,
CC ECO:0000269|PubMed:15131310, ECO:0000269|PubMed:20978350}.
CC -!- ACTIVITY REGULATION: Inhibited by prostaglandin E2, probably via PKA-
CC mediated phosphorylation at Ser-379 (PubMed:15131310).
CC {ECO:0000269|PubMed:15131310}.
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 (By similarity). {ECO:0000250|UniProtKB:O75311,
CC ECO:0000250|UniProtKB:P24524}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:12975813, ECO:0000305|PubMed:15131310,
CC ECO:0000305|PubMed:19723286}; Multi-pass membrane protein
CC {ECO:0000305}. Synapse {ECO:0000269|PubMed:12975813,
CC ECO:0000269|PubMed:15131310, ECO:0000269|PubMed:19723286}. Perikaryon
CC {ECO:0000269|PubMed:19723286}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P24524}. Cell membrane
CC {ECO:0000269|PubMed:20978350}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Partially colocalizes with GPHN that is known to
CC mediate receptor clustering at postsynaptic membranes.
CC {ECO:0000269|PubMed:15131310}.
CC -!- TISSUE SPECIFICITY: Detected in brainstem, also in neurons that control
CC rhythmic breathing (PubMed:20978350). Detected in superficial laminae
CC of the dorsal horn of the thoracic spinal cord (PubMed:15131310).
CC Detected in dentate gyrus in hippocampus, especially in stratum
CC granulare (PubMed:19723286). Detected in the inner plexiform layer in
CC the retina (at protein level) (PubMed:12975813). Detected in midbrain,
CC thalamus, brain cortex, hippocampus, and at lower levels in cerebellum
CC (PubMed:19723286). {ECO:0000269|PubMed:12975813,
CC ECO:0000269|PubMed:15131310, ECO:0000269|PubMed:19723286,
CC ECO:0000269|PubMed:20978350}.
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. Dephosphorylated in response to activation of HTR1A
CC signaling; this increases channel activity (PubMed:20978350).
CC {ECO:0000250|UniProtKB:P24524, ECO:0000269|PubMed:20978350}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, appear normal and are fertile. They do not display notable
CC alterations in motor coordination and startle response, or other
CC neuromotor defects. Glycinergic postsynaptic inhibitory currents in
CC spinal cord appear unchanged, but are not inhibited by prostaglandin
CC E2, contrary to what is observed with wild-type. Basal nociception is
CC unchanged, but contrary to wild-type, mutant mice do not display
CC increased sensitivity to pain after prostaglandin E2 injection.
CC Likewise, they show a more rapid decrease of the increased pain
CC sensitivity caused by agents that cause local inflammation, such as
CC subcutaneous zymosan injection (PubMed:15131310). Mutant mice display
CC altered phrenic nerve activity, resulting in an irregular breathing
CC rhythm that affects especially the duration of the postinspiratory
CC phase. Contrary to wild-type, their respiratory rhythm is not
CC accelerated by serotonin (PubMed:20978350).
CC {ECO:0000269|PubMed:15131310, ECO:0000269|PubMed:20978350}.
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}.
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DR EMBL; AF362764; AAK51962.1; -; mRNA.
DR EMBL; AY230204; AAP22967.1; -; mRNA.
DR CCDS; CCDS40340.1; -.
DR RefSeq; NP_536686.2; NM_080438.2.
DR AlphaFoldDB; Q91XP5; -.
DR SMR; Q91XP5; -.
DR STRING; 10090.ENSMUSP00000000275; -.
DR BindingDB; Q91XP5; -.
DR ChEMBL; CHEMBL4295912; -.
DR GlyGen; Q91XP5; 1 site.
DR iPTMnet; Q91XP5; -.
DR PhosphoSitePlus; Q91XP5; -.
DR PaxDb; Q91XP5; -.
DR PRIDE; Q91XP5; -.
DR ProteomicsDB; 271394; -.
DR ABCD; Q91XP5; 1 sequenced antibody.
DR Antibodypedia; 28583; 101 antibodies from 23 providers.
DR DNASU; 110304; -.
DR Ensembl; ENSMUST00000000275; ENSMUSP00000000275; ENSMUSG00000038257.
DR GeneID; 110304; -.
DR KEGG; mmu:110304; -.
DR CTD; 8001; -.
DR MGI; MGI:95749; Glra3.
DR VEuPathDB; HostDB:ENSMUSG00000038257; -.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000158368; -.
DR InParanoid; Q91XP5; -.
DR OMA; VMPKNPD; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; Q91XP5; -.
DR Reactome; R-MMU-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR BioGRID-ORCS; 110304; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Glra3; mouse.
DR PRO; PR:Q91XP5; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q91XP5; protein.
DR Bgee; ENSMUSG00000038257; Expressed in substantia nigra and 55 other tissues.
DR ExpressionAtlas; Q91XP5; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:MGI.
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; ISO:MGI.
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; 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; ISS: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:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
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_0000000420"
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:0007744|PubMed:21183079"
FT MOD_RES 379
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:20978350"
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 CONFLICT 110
FT /note="Missing (in Ref. 1; AAK51962)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="V -> D (in Ref. 1; AAK51962)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="Q -> H (in Ref. 1; AAK51962)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 53709 MW; 0963FD4A3727AA1D CRC64;
MAHVRHFRTL VSGFYFWEAA 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 FSFTAYGMGP CLQAKDGVVP KGPNHAVQVM PKSPDEMRKV
FIDRAKKIDT ISRACFPLAF LIFNIFYWVI YKILRHEDIH QQQD
