ID GLRA1_BOVIN Reviewed; 457 AA. AC P57695; Q9GKE9; Q9GKF0; DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 08-DEC-2000, sequence version 1. DT 24-JUL-2024, entry version 168. 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; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS A AND B), DISEASE, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=11178872; DOI=10.1006/mcne.2000.0934; RA Pierce K.D., Handford C.A., Morris R., Vafa B., Dennis J.A., Healy P.J., RA Schofield P.R.; RT "A nonsense mutation in the alpha1 subunit of the inhibitory glycine RT receptor associated with bovine myoclonus."; RL Mol. Cell. Neurosci. 17:354-363(2001). 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. Channel characteristics depend CC on the subunit composition; heteropentameric channels are activated by CC lower glycine levels and display faster desensitization (By CC similarity). Plays an important role in the down-regulation of neuronal CC excitability (PubMed:11178872). Contributes to the generation of CC inhibitory postsynaptic currents. Channel activity is potentiated by CC ethanol (By similarity). Potentiation of channel activity by CC intoxicating levels of ethanol contribute to the sedative effects of CC ethanol (By similarity). {ECO:0000250|UniProtKB:P23415, CC ECO:0000250|UniProtKB:Q64018, ECO:0000269|PubMed:11178872}. CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823, CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:P23415}; 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. Interacts with GLRB (By CC similarity). {ECO:0000250|UniProtKB:P23415}. 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:0000269|PubMed:11178872}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:Q64018}. Cell membrane CC {ECO:0000269|PubMed:11178872}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P23415, ECO:0000250|UniProtKB:Q64018}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=P57695-1; Sequence=Displayed; CC Name=b; CC IsoId=P57695-2; Sequence=VSP_021141; CC -!- TISSUE SPECIFICITY: Detected on spinal cord neurons (at protein level). CC Detected in spinal cord. {ECO:0000269|PubMed:11178872}. 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 -!- DISEASE: Note=Defects in GLRA1 are the cause of inherited congenital CC myoclonus of Poll Hereford calves. It is an autosomal recessive disease CC characterized by hyperesthesia and myoclonic jerks of the skeletal CC musculature that occur both spontaneously and in response to sensory CC stimuli. {ECO:0000269|PubMed:11178872}. CC -!- MISCELLANEOUS: The alpha subunit binds strychnine. CC {ECO:0000305|PubMed:11178872}. 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}. 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; AF268375; AAG14346.1; -; mRNA. DR EMBL; AF268366; AAG41140.1; -; Genomic_DNA. DR EMBL; AF268358; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268360; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268361; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268359; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268362; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268364; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268365; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268363; AAG41140.1; JOINED; Genomic_DNA. DR EMBL; AF268366; AAG41141.1; -; Genomic_DNA. DR EMBL; AF268358; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268360; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268361; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268359; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268362; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268364; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268365; AAG41141.1; JOINED; Genomic_DNA. DR EMBL; AF268363; AAG41141.1; JOINED; Genomic_DNA. DR RefSeq; NP_776746.1; NM_174321.2. [P57695-1] DR AlphaFoldDB; P57695; -. DR BMRB; P57695; -. DR SMR; P57695; -. DR STRING; 9913.ENSBTAP00000019143; -. DR GlyCosmos; P57695; 1 site, No reported glycans. DR PaxDb; 9913-ENSBTAP00000019143; -. DR Ensembl; ENSBTAT00000019143.4; ENSBTAP00000019143.3; ENSBTAG00000014395.5. [P57695-1] DR GeneID; 281783; -. DR KEGG; bta:281783; -. DR CTD; 2741; -. DR VEuPathDB; HostDB:ENSBTAG00000014395; -. DR eggNOG; KOG3644; Eukaryota. DR GeneTree; ENSGT00940000159047; -. DR HOGENOM; CLU_010920_1_4_1; -. DR InParanoid; P57695; -. DR OMA; LVFWLEP; -. DR OrthoDB; 4265336at2759; -. DR TreeFam; TF315453; -. DR Reactome; R-BTA-112314; Neurotransmitter receptors and postsynaptic signal transmission. DR Proteomes; UP000009136; Chromosome 7. DR Bgee; ENSBTAG00000014395; Expressed in oocyte and 10 other cell types or tissues. DR ExpressionAtlas; P57695; baseline. DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB. 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:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:1902495; C:transmembrane transporter complex; IBA:GO_Central. DR GO; GO:0016934; F:extracellularly glycine-gated chloride channel activity; ISS:UniProtKB. DR GO; GO:0016594; F:glycine binding; ISS:UniProtKB. DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central. DR GO; GO:0030977; F:taurine binding; ISS:UniProtKB. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro. DR GO; GO:0022824; F:transmitter-gated monoatomic ion channel activity; IEA:InterPro. 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:1902476; P:chloride transmembrane transport; IBA:GO_Central. DR GO; GO:0006821; P:chloride transport; ISS:UniProtKB. DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISS:UniProtKB. DR GO; GO:0006811; P:monoatomic 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:0007218; P:neuropeptide signaling pathway; ISS:UniProtKB. DR GO; GO:0097305; P:response to alcohol; ISS:UniProtKB. DR GO; GO:0001964; P:startle response; ISS:UniProtKB. DR GO; GO:0060012; P:synaptic transmission, glycinergic; ISS:UniProtKB. DR CDD; cd19009; LGIC_ECD_GlyR_alpha; 1. DR CDD; cd19060; LGIC_TM_GlyR_alpha; 1. DR Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1. DR Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 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 NCBIfam; TIGR00860; LIC; 1. DR PANTHER; PTHR18945:SF213; GLYCINE RECEPTOR SUBUNIT ALPHA-1; 1. DR PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 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; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1. DR SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 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; 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..28 FT /evidence="ECO:0000250|UniProtKB:P07727" FT CHAIN 29..457 FT /note="Glycine receptor subunit alpha-1" FT /id="PRO_0000000411" 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 REGION 391..410 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" 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 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:0000255" 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:11178872" FT /id="VSP_021141" SQ SEQUENCE 457 AA; 52614 MW; 0C60A814C8ADFDDE CRC64; MYSFNTLRLY LWETIVFFSL AASKEAEAAR SASKPMSPSD 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 QEDEAGEGRF NFSAYGMGPA CLQAKDGISV KGANNSNTTN PPPAPSKSPE EMRKLFIQRA KKIDKISRIG FPMAFLIFNM FYWIIYKIVR REDVHNQ //