GLRA4_MOUSE
ID GLRA4_MOUSE Reviewed; 456 AA.
AC Q61603; A2AEA9; Q45V76; Q8VHF3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Glycine receptor subunit alpha-4;
DE Flags: Precursor;
GN Name=Glra4;
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], FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION.
RC STRAIN=C57BL/6J;
RX PubMed=10762330; DOI=10.1046/j.1460-9568.2000.00993.x;
RA Harvey R.J., Schmieden V., Von Holst A., Laube B., Rohrer H., Betz H.;
RT "Glycine receptors containing the alpha4 subunit in the embryonic
RT sympathetic nervous system, spinal cord and male genital ridge.";
RL Eur. J. Neurosci. 12:994-1001(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 24-360.
RC STRAIN=BALB/cJ;
RX PubMed=7507926; DOI=10.1016/s0021-9258(17)41987-9;
RA Matzenbach B., Maulet Y., Sefton L., Courtier B., Avner P., Guenet J.-L.,
RA Betz H.;
RT "Structural analysis of mouse glycine receptor alpha subunit genes.
RT Identification and chromosomal localization of a novel variant.";
RL J. Biol. Chem. 269:2607-2612(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 41-456.
RC STRAIN=B6C3/Fe; TISSUE=Spinal cord;
RA Groemer T.-W., Becker C.-M., Becker K.;
RT "Localization of different glycine receptor isoforms in murine spinal
RT cord.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17154252; DOI=10.1002/cne.21201;
RA Heinze L., Harvey R.J., Haverkamp S., Waessle H.;
RT "Diversity of glycine receptors in the mouse retina: localization of the
RT alpha4 subunit.";
RL J. Comp. Neurol. 500:693-707(2007).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22592841; DOI=10.1002/cne.23139;
RA Weltzien F., Puller C., O'Sullivan G.A., Paarmann I., Betz H.;
RT "Distribution of the glycine receptor beta-subunit in the mouse CNS as
RT revealed by a novel monoclonal antibody.";
RL J. Comp. Neurol. 520:3962-3981(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 (PubMed:10762330). Plays a role
CC in the down-regulation of neuronal excitability. Contributes to the
CC generation of inhibitory postsynaptic currents (Probable).
CC {ECO:0000269|PubMed:10762330, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by strychnine (PubMed:10762330).
CC {ECO:0000269|PubMed:10762330}.
CC -!- SUBUNIT: Homopentamer (in vitro). Heteropentamer composed of GLRA4 and
CC GLRB. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:17154252}; Multi-pass membrane protein
CC {ECO:0000305}. Synapse {ECO:0000269|PubMed:17154252,
CC ECO:0000269|PubMed:22592841}. Perikaryon {ECO:0000269|PubMed:17154252}.
CC Cell projection, dendrite {ECO:0000269|PubMed:17154252}. Cell membrane
CC {ECO:0000269|PubMed:10762330, ECO:0000269|PubMed:22592841,
CC ECO:0000305|PubMed:17154252}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in the retina inner plexiform layer,
CC especially at the border between layer three and four (at protein
CC level) (PubMed:17154252). {ECO:0000269|PubMed:17154252,
CC ECO:0000269|PubMed:22592841}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000269|PubMed:10762330}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glycine receptor (TC 1.A.9.3) subfamily. GLRA4 sub-subfamily.
CC {ECO:0000305}.
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DR EMBL; DQ109809; AAZ17380.1; -; mRNA.
DR EMBL; AL671887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X75850; CAA53468.1; -; Genomic_DNA.
DR EMBL; X75851; CAA53468.1; JOINED; Genomic_DNA.
DR EMBL; X75852; CAA53468.1; JOINED; Genomic_DNA.
DR EMBL; X75853; CAA53468.1; JOINED; Genomic_DNA.
DR EMBL; AF462147; AAL69899.1; -; mRNA.
DR CCDS; CCDS53195.1; -.
DR PIR; A49970; A49970.
DR RefSeq; NP_034427.2; NM_010297.2.
DR AlphaFoldDB; Q61603; -.
DR SMR; Q61603; -.
DR STRING; 10090.ENSMUSP00000018739; -.
DR BindingDB; Q61603; -.
DR ChEMBL; CHEMBL3500; -.
DR GlyGen; Q61603; 1 site.
DR iPTMnet; Q61603; -.
DR PhosphoSitePlus; Q61603; -.
DR PaxDb; Q61603; -.
DR PRIDE; Q61603; -.
DR ProteomicsDB; 267457; -.
DR DNASU; 14657; -.
DR Ensembl; ENSMUST00000018739; ENSMUSP00000018739; ENSMUSG00000018595.
DR GeneID; 14657; -.
DR KEGG; mmu:14657; -.
DR UCSC; uc009uiz.2; mouse.
DR CTD; 441509; -.
DR MGI; MGI:95750; Glra4.
DR VEuPathDB; HostDB:ENSMUSG00000018595; -.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000158789; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; Q61603; -.
DR OMA; IQTCAMQ; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; Q61603; -.
DR TreeFam; TF315453; -.
DR BioGRID-ORCS; 14657; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Glra4; mouse.
DR PRO; PR:Q61603; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q61603; protein.
DR Bgee; ENSMUSG00000018595; Expressed in animal zygote and 16 other tissues.
DR Genevisible; Q61603; 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:0030425; C:dendrite; IEA:UniProtKB-SubCell.
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: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: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:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0043200; P:response to amino acid; IDA:UniProtKB.
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; 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; 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; Postsynaptic cell membrane; Receptor; Reference proteome; Signal;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..456
FT /note="Glycine receptor subunit alpha-4"
FT /id="PRO_0000000422"
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..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TRANSMEM 424..444
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT TOPO_DOM 445..456
FT /note="Extracellular"
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 SITE 295
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 171..185
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT DISULFID 232..243
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT CONFLICT 119
FT /note="D -> N (in Ref. 4; AAL69899)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="D -> E (in Ref. 4; AAL69899)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 52514 MW; 4199CB8404E05BEA CRC64;
MTTLVPASLF LLLWTLPGKV LLSVALAKED VKSGLKGSQP MSPSDFLDKL MGRTSGYDAR
IRPNFKGPPV NVTCNIFINS FGSVTETTMD YRVNVFLRQQ WNDPRLAYRE YPDDSLDLDP
SMLDSIWKPD LFFANEKGAN FHEVTTDNKL LRIFKNGNVL YSIRLTLILS CPMDLKNFPM
DIQTCTMQLE SFGYTMNDLM FEWLEDAPAV QVAEGLTLPQ FILRDEKDLG YCTKHYNTGK
FTCIEVKFHL ERQMGYYLIQ MYIPSLLIVI LSWVSFWINM DAAPARVGLG ITTVLTMTTQ
SSGSRASLPK VSYVKAIDIW MAVCLLFVFA ALLEYAAVNF VSRQHKEFMR LRRRQRRQRM
EEDIIRESRF YFRGYGLGHC LQARDGGPME GSSIYSPQPP TPLLKEGETM RKLYVDRAKR
IDTISRAVFP FTFLVFNIFY WVVYKVLRSE DIHQAL
