GLRA1_DANRE
ID GLRA1_DANRE Reviewed; 444 AA.
AC O93430;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Glycine receptor subunit alphaZ1;
DE Flags: Precursor;
GN Name=glra1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10188956; DOI=10.1016/s0306-4522(98)00430-8;
RA David-Watine B., Goblet C., de Saint Jan D., Fucile S., Devignot V.,
RA Bregestovski P., Korn H.;
RT "Cloning, expression and electrophysiological characterization of glycine
RT receptor alpha subunit from zebrafish.";
RL Neuroscience 90:303-317(1999).
RN [2] {ECO:0007744|PDB:3JAD, ECO:0007744|PDB:3JAE, ECO:0007744|PDB:3JAF}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 34-434 IN COMPLEXES
RP WITH GLYCINE; IVERMECTINE AND STRYCHNINE, FUNCTION, ACTIVITY REGULATION,
RP SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-62.
RX PubMed=26344198; DOI=10.1038/nature14853;
RA Du J., Lu W., Wu S., Cheng Y., Gouaux E.;
RT "Glycine receptor mechanism elucidated by electron cryo-microscopy.";
RL Nature 526:224-229(2015).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel
CC opening is triggered by extracellular glycine (PubMed:10188956,
CC PubMed:26344198). 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). {ECO:0000250|UniProtKB:P23415,
CC ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198}.
CC -!- ACTIVITY REGULATION: Activated by glycine and taurine. Inhibited by
CC strychnine (PubMed:10188956, PubMed:26344198). Allosterically activated
CC by ivermectin (PubMed:26344198). Inhibited by picrotoxinin
CC (PubMed:26344198). Strychnine binding locks the channel in a closed
CC conformation and prevents channel opening in response to extracellular
CC glycine (PubMed:26344198). Can also be activated by GABA and inhibited
CC by bicuculline, but this requires heterologous expression in human
CC cells (PubMed:10188956). {ECO:0000269|PubMed:10188956,
CC ECO:0000269|PubMed:26344198}.
CC -!- SUBUNIT: Homopentamer (in vitro) (PubMed:26344198). Heteropentamer
CC composed of glra1 and glrb (By similarity). Both homopentamers and
CC heteropentamers form functional ion channels (By similarity).
CC {ECO:0000250|UniProtKB:P23415, ECO:0000269|PubMed:26344198}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q64018}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q64018}. Synapse {ECO:0000250|UniProtKB:Q64018}.
CC Perikaryon {ECO:0000250|UniProtKB:Q64018}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q64018}. Cell membrane
CC {ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:26344198}.
CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:10188956}.
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:0000269|PubMed:26344198}.
CC -!- MISCELLANEOUS: Highly sensitive to activation by taurine despite the
CC presence of Val in position 135. In mammals, Val-135 causes a drastic
CC loss of taurine efficacy. {ECO:0000269|PubMed:10188956}.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198}.
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; AJ005812; CAA06711.1; -; mRNA.
DR RefSeq; NP_571477.1; NM_131402.1.
DR PDB; 3JAD; EM; 3.90 A; A/B/C/D/E=34-434.
DR PDB; 3JAE; EM; 3.90 A; A/B/C/D/E=34-434.
DR PDB; 3JAF; EM; 3.80 A; A/B/C/D/E=34-434.
DR PDB; 6PLO; EM; 3.30 A; A/B/C/D/E=1-444.
DR PDB; 6PLP; EM; 3.30 A; A/B/C/D/E=1-444.
DR PDB; 6PLQ; EM; 3.40 A; A/B/C/D/E=1-444.
DR PDB; 6PLR; EM; 3.20 A; A/B/C/D/E=1-444.
DR PDB; 6PLS; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PLT; EM; 3.20 A; A/B/C/D/E=1-444.
DR PDB; 6PLU; EM; 3.30 A; A/B/C/D/E=1-444.
DR PDB; 6PLV; EM; 3.30 A; A/B/C/D/E=1-444.
DR PDB; 6PLW; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PLX; EM; 2.90 A; A/B/C/D/E=1-444.
DR PDB; 6PLY; EM; 2.90 A; A/B/C/D/E=1-444.
DR PDB; 6PLZ; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PM0; EM; 3.10 A; A/B/C/D/E=1-444.
DR PDB; 6PM1; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PM2; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PM3; EM; 3.00 A; A/B/C/D/E=1-444.
DR PDB; 6PM4; EM; 4.00 A; A/B/C/D/E=1-444.
DR PDB; 6PM5; EM; 3.10 A; A/B/C/D/E=1-444.
DR PDB; 6PM6; EM; 2.90 A; A/B/C/D/E=1-444.
DR PDB; 6PXD; EM; 2.90 A; A/B/C/D/E=1-333, A/B/C/D/E=401-434.
DR PDB; 6UBS; EM; 3.33 A; A/B/C/D/E=1-444.
DR PDB; 6UBT; EM; 3.55 A; A/B/C/D/E=1-444.
DR PDB; 6UD3; EM; 3.50 A; A/B/C/D/E=1-444.
DR PDB; 6VM0; EM; 3.14 A; A/B/C/D/E=1-444.
DR PDB; 6VM2; EM; 3.34 A; A/B/C/D/E=1-444.
DR PDB; 6VM3; EM; 3.07 A; A/B/C/D/E=1-444.
DR PDBsum; 3JAD; -.
DR PDBsum; 3JAE; -.
DR PDBsum; 3JAF; -.
DR PDBsum; 6PLO; -.
DR PDBsum; 6PLP; -.
DR PDBsum; 6PLQ; -.
DR PDBsum; 6PLR; -.
DR PDBsum; 6PLS; -.
DR PDBsum; 6PLT; -.
DR PDBsum; 6PLU; -.
DR PDBsum; 6PLV; -.
DR PDBsum; 6PLW; -.
DR PDBsum; 6PLX; -.
DR PDBsum; 6PLY; -.
DR PDBsum; 6PLZ; -.
DR PDBsum; 6PM0; -.
DR PDBsum; 6PM1; -.
DR PDBsum; 6PM2; -.
DR PDBsum; 6PM3; -.
DR PDBsum; 6PM4; -.
DR PDBsum; 6PM5; -.
DR PDBsum; 6PM6; -.
DR PDBsum; 6PXD; -.
DR PDBsum; 6UBS; -.
DR PDBsum; 6UBT; -.
DR PDBsum; 6UD3; -.
DR PDBsum; 6VM0; -.
DR PDBsum; 6VM2; -.
DR PDBsum; 6VM3; -.
DR AlphaFoldDB; O93430; -.
DR BMRB; O93430; -.
DR SMR; O93430; -.
DR DIP; DIP-61772N; -.
DR STRING; 7955.ENSDARP00000066196; -.
DR iPTMnet; O93430; -.
DR PaxDb; O93430; -.
DR Ensembl; ENSDART00000005499; ENSDARP00000003268; ENSDARG00000012019.
DR GeneID; 30676; -.
DR KEGG; dre:30676; -.
DR CTD; 2741; -.
DR ZFIN; ZDB-GENE-991117-1; glra1.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000159047; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; O93430; -.
DR OMA; RHMKEDP; -.
DR PhylomeDB; O93430; -.
DR Reactome; R-DRE-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR PRO; PR:O93430; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000012019; Expressed in brain and 9 other tissues.
DR ExpressionAtlas; O93430; baseline.
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:0016021; C:integral component of membrane; IDA:ZFIN.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
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; IDA:ZFIN.
DR GO; GO:0016933; F:extracellularly glycine-gated ion channel activity; IDA:ZFIN.
DR GO; GO:0016594; F:glycine binding; IDA:ZFIN.
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:0008270; F:zinc ion binding; ISS:UniProtKB.
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:0007417; P:central nervous system development; IMP:ZFIN.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; IDA:ZFIN.
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:0045664; P:regulation of neuron differentiation; IMP:ZFIN.
DR GO; GO:0043200; P:response to amino acid; IDA:ZFIN.
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; 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 3D-structure; Cell membrane; Cell projection; Chloride; Chloride channel;
KW 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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..444
FT /note="Glycine receptor subunit alphaZ1"
FT /id="PRO_0000000415"
FT TOPO_DOM 25..246
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TRANSMEM 247..268
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TOPO_DOM 269..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TRANSMEM 274..294
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TOPO_DOM 295..305
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TRANSMEM 306..326
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TOPO_DOM 327..412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TRANSMEM 413..433
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:26344198"
FT TOPO_DOM 434..444
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26344198"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT BINDING 226..231
FT /ligand="strychnine"
FT /ligand_id="ChEBI:CHEBI:90700"
FT /evidence="ECO:0000269|PubMed:26344198"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT SITE 285
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000269|PubMed:26344198"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26344198"
FT DISULFID 162..176
FT /evidence="ECO:0000250|UniProtKB:P23415"
FT DISULFID 222..233
FT /evidence="ECO:0000269|PubMed:26344198"
FT HELIX 34..42
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:6PXD"
FT STRAND 61..76
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 77..80
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 81..93
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:6PLW"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 140..161
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:6PXD"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 173..185
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 233..242
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:6PLP"
FT HELIX 254..261
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 262..267
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:6PM6"
FT HELIX 273..292
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:6PLX"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:6VM0"
FT HELIX 308..332
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 398..409
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 410..413
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:6PLX"
FT HELIX 422..432
FT /evidence="ECO:0007829|PDB:6PLX"
FT TURN 433..435
FT /evidence="ECO:0007829|PDB:6PLX"
SQ SEQUENCE 444 AA; 50766 MW; 77F6FC8C14E80581 CRC64;
MFALGIYLWE TIVFFSLAAS QQAAARKAAS PMPPSEFLDK LMGKVSGYDA RIRPNFKGPP
VNVTCNIFIN SFGSIAETTM DYRVNIFLRQ QWNDPRLAYS EYPDDSLDLD PSMLDSIWKP
DLFFANEKGA NFHEVTTDNK LLRISKNGNV LYSIRITLVL ACPMDLKNFP MDVQTCIMQL
ESFGYTMNDL IFEWDEKGAV QVADGLTLPQ FILKEEKDLR YCTKHYNTGK FTCIEARFHL
ERQMGYYLIQ MYIPSLLIVI LSWVSFWINM DAAPARVGLG ITTVLTMTTQ SSGSRASLPK
VSYVKAIDIW MAVCLLFVFS ALLEYAAVNF IARQHKELLR FQRRRRHLKE DEAGDGRFSF
AAYGMGPACL QAKDGMAIKG NNNNAPTSTN PPEKTVEEMR KLFISRAKRI DTVSRVAFPL
VFLIFNIFYW ITYKIIRSED IHKQ
