ID GLRA3_HUMAN Reviewed; 464 AA. AC O75311; D3DP44; O75816; Q5D0E3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 13-FEB-2019, entry version 181. DE RecName: Full=Glycine receptor subunit alpha-3; DE Flags: Precursor; GN Name=GLRA3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA-3K AND RP ALPHA-3L), FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=9677400; DOI=10.1074/jbc.273.31.19708; RA Nikolic Z., Laube B., Weber R.G., Lichter P., Kioschis P., Poustka A., RA Muelhardt C., Becker C.-M.; RT "The human glycine receptor subunit alpha3. GLRA3 gene structure, RT chromosomal localization, and functional characterization of RT alternative transcripts."; RL J. Biol. Chem. 273:19708-19714(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-3L). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] {ECO:0000244|PDB:5CFB} RP X-RAY CRYSTALLOGRAPHY (3.04 ANGSTROMS) OF 34-342 AND 419-460 IN RP COMPLEX WITH STRYCHNINE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, RP TOPOLOGY, DISULFIDE BONDS, GLYCOSYLATION AT ASN-71, AND DOMAIN. RX PubMed=26416729; DOI=10.1038/nature14972; RA Huang X., Chen H., Michelsen K., Schneider S., Shaffer P.L.; RT "Crystal structure of human glycine receptor-alpha3 bound to RT antagonist strychnine."; RL Nature 526:277-280(2015). CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels. CC Channel opening is triggered by extracellular glycine CC (PubMed:9677400, PubMed:26416729). Channel characteristics depend CC on the subunit composition; heteropentameric channels display CC faster channel closure (By similarity). Plays an important role in CC the down-regulation of neuronal excitability (By similarity). CC Contributes to the generation of inhibitory postsynaptic currents CC (By similarity). Contributes to increased pain perception in CC response to increased prostaglandin E2 levels (By similarity). CC Plays a role in cellular responses to ethanol (By similarity). CC {ECO:0000250|UniProtKB:P24524, ECO:0000250|UniProtKB:Q91XP5, CC ECO:0000269|PubMed:26416729, ECO:0000269|PubMed:9677400}. CC -!- SUBUNIT: Homopentamer (in vitro) (PubMed:26416729). Heteropentamer CC composed of GLRA3 and GLRB. Both homopentamers and heteropentamers CC form functional ion channels, but their characteristics are subtly CC different (By similarity). {ECO:0000250|UniProtKB:P24524, CC ECO:0000269|PubMed:26416729}. CC -!- SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell CC membrane {ECO:0000250|UniProtKB:P24524}; Multi-pass membrane CC protein {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:P24524}. CC Cell projection, dendrite {ECO:0000250|UniProtKB:P24524}. Cell CC junction, synapse {ECO:0000250|UniProtKB:P24524}. Cell membrane CC {ECO:0000269|PubMed:26416729, ECO:0000269|PubMed:9677400}; Multi- CC pass membrane protein {ECO:0000269|PubMed:26416729}. CC Note=Partially colocalizes with GPHN that is known to mediate CC receptor clustering at postsynaptic membranes. CC {ECO:0000250|UniProtKB:P24524}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Alpha-3L; CC IsoId=O75311-1; Sequence=Displayed; CC Name=Alpha-3K; CC IsoId=O75311-2; Sequence=VSP_000084; CC -!- TISSUE SPECIFICITY: Widely distributed throughout the central CC nervous system. {ECO:0000269|PubMed:9677400}. CC -!- DOMAIN: The N-terminal domain carries structural determinants CC essential for agonist and antagonist binding. The channel pore is CC formed by pentameric assembly of the second transmembrane domain CC from all five subunits (PubMed:26416729). The cytoplasmic loop is CC an important determinant of channel inactivation kinetics. CC {ECO:0000269|PubMed:26416729, ECO:0000305}. CC -!- PTM: Phosphorylated by PKA; this causes down-regulation of channel CC activity. {ECO:0000250|UniProtKB:P24524}. CC -!- MISCELLANEOUS: The alpha subunit binds strychnine. CC {ECO:0000269|PubMed:26416729}. CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) CC family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA3 sub- CC subfamily. {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; AF017724; AAC39919.1; -; Genomic_DNA. DR EMBL; AF017715; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017716; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017717; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017718; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017719; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017720; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017721; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017722; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; AF017723; AAC39919.1; JOINED; Genomic_DNA. DR EMBL; U93917; AAC39917.1; -; mRNA. DR EMBL; CH471056; EAX04730.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04732.1; -; Genomic_DNA. DR EMBL; BC036086; AAH36086.1; -; mRNA. DR CCDS; CCDS3822.1; -. [O75311-1] DR CCDS; CCDS43283.1; -. [O75311-2] DR RefSeq; NP_001036008.1; NM_001042543.2. [O75311-2] DR RefSeq; NP_006520.2; NM_006529.3. [O75311-1] DR UniGene; Hs.413099; -. DR PDB; 5CFB; X-ray; 3.04 A; A/B/C/D/E=34-342, A/B/C/D/E=419-460. DR PDB; 5TIN; X-ray; 2.61 A; A/B/C/D/E=34-342, A/B/C/D/E=419-460. DR PDB; 5TIO; X-ray; 3.25 A; A/B/C/D/E=34-342, A/B/C/D/E=419-460. DR PDB; 5VDH; X-ray; 2.85 A; A/B/C/D/E=34-342, A/B/C/D/E=419-460. DR PDB; 5VDI; X-ray; 3.10 A; A/B/C/D/E=34-342, A/B/C/D/E=419-460. DR PDBsum; 5CFB; -. DR PDBsum; 5TIN; -. DR PDBsum; 5TIO; -. DR PDBsum; 5VDH; -. DR PDBsum; 5VDI; -. DR ProteinModelPortal; O75311; -. DR SMR; O75311; -. DR BioGrid; 113705; 1. DR DIP; DIP-61773N; -. DR IntAct; O75311; 1. DR STRING; 9606.ENSP00000274093; -. DR BindingDB; O75311; -. DR ChEMBL; CHEMBL1075092; -. DR DrugBank; DB00145; Glycine. DR DrugBank; DB00602; Ivermectin. DR DrugBank; DB00431; Lindane. DR DrugBank; DB00466; Picrotoxin. DR GuidetoPHARMACOLOGY; 425; -. DR TCDB; 1.A.9.3.1; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family. DR iPTMnet; O75311; -. DR PhosphoSitePlus; O75311; -. DR BioMuta; GLRA3; -. DR jPOST; O75311; -. DR PaxDb; O75311; -. DR PRIDE; O75311; -. DR ProteomicsDB; 49887; -. DR ProteomicsDB; 49888; -. [O75311-2] DR DNASU; 8001; -. DR Ensembl; ENST00000274093; ENSP00000274093; ENSG00000145451. [O75311-1] DR Ensembl; ENST00000340217; ENSP00000345284; ENSG00000145451. [O75311-2] DR GeneID; 8001; -. DR KEGG; hsa:8001; -. DR UCSC; uc003ity.3; human. [O75311-1] DR CTD; 8001; -. DR DisGeNET; 8001; -. DR EuPathDB; HostDB:ENSG00000145451.12; -. DR GeneCards; GLRA3; -. DR HGNC; HGNC:4328; GLRA3. DR MIM; 600421; gene. DR neXtProt; NX_O75311; -. DR OpenTargets; ENSG00000145451; -. DR PharmGKB; PA28729; -. DR eggNOG; KOG3643; Eukaryota. DR eggNOG; ENOG410XPWH; LUCA. DR GeneTree; ENSGT00940000158368; -. DR HOGENOM; HOG000231336; -. DR HOVERGEN; HBG051707; -. DR InParanoid; O75311; -. DR KO; K05195; -. DR OMA; MPMSPSD; -. DR OrthoDB; 614790at2759; -. DR PhylomeDB; O75311; -. DR TreeFam; TF315453; -. DR Reactome; R-HSA-112314; Neurotransmitter receptors and postsynaptic signal transmission. DR ChiTaRS; GLRA3; human. DR GeneWiki; GLRA3; -. DR GenomeRNAi; 8001; -. DR PRO; PR:O75311; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000145451; Expressed in 56 organ(s), highest expression level in corpus callosum. DR Genevisible; O75311; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0016935; C:glycine-gated chloride channel complex; IDA:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; 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; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro. 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; IDA:UniProtKB. DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central. 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; 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; 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 3D-structure; Alternative splicing; Cell junction; Cell membrane; KW Cell projection; Chloride; Chloride channel; Complete proteome; KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; KW Ligand-gated ion channel; Membrane; Metal-binding; Phosphoprotein; KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; KW Synapse; Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1 33 {ECO:0000255}. FT CHAIN 34 464 Glycine receptor subunit alpha-3. FT /FTId=PRO_0000000419. FT TOPO_DOM 34 255 Extracellular. FT {ECO:0000269|PubMed:26416729}. FT TRANSMEM 256 277 Helical; Name=1. FT {ECO:0000269|PubMed:26416729}. FT TOPO_DOM 278 282 Cytoplasmic. FT {ECO:0000269|PubMed:26416729}. FT TRANSMEM 283 303 Helical; Name=2. FT {ECO:0000269|PubMed:26416729}. FT TOPO_DOM 304 314 Extracellular. FT {ECO:0000269|PubMed:26416729}. FT TRANSMEM 315 335 Helical; Name=3. FT {ECO:0000269|PubMed:26416729}. FT TOPO_DOM 336 430 Cytoplasmic. FT {ECO:0000269|PubMed:26416729}. FT TRANSMEM 431 451 Helical; Name=4. FT {ECO:0000269|PubMed:26416729}. FT TOPO_DOM 452 464 Extracellular. FT {ECO:0000269|PubMed:26416729}. FT REGION 235 240 Strychnine-binding. FT {ECO:0000269|PubMed:26416729}. FT METAL 225 225 Zinc. {ECO:0000250|UniProtKB:P23415}. FT METAL 227 227 Zinc. {ECO:0000250|UniProtKB:P23415}. FT METAL 248 248 Zinc. {ECO:0000250|UniProtKB:P23415}. FT SITE 294 294 Important for obstruction of the ion pore FT in the closed conformation. FT {ECO:0000269|PubMed:26416729}. FT MOD_RES 370 370 Phosphoserine. FT {ECO:0000250|UniProtKB:Q91XP5}. FT MOD_RES 379 379 Phosphoserine. FT {ECO:0000250|UniProtKB:Q91XP5}. FT CARBOHYD 71 71 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:5CFB, ECO:0000255, FT ECO:0000269|PubMed:26416729}. FT DISULFID 171 185 {ECO:0000244|PDB:5CFB, FT ECO:0000269|PubMed:26416729}. FT DISULFID 231 242 {ECO:0000244|PDB:5CFB, FT ECO:0000269|PubMed:26416729}. FT VAR_SEQ 358 372 Missing (in isoform Alpha-3K). FT {ECO:0000303|PubMed:9677400}. FT /FTId=VSP_000084. FT CONFLICT 460 460 H -> HH (in Ref. 1; AAC39919). FT {ECO:0000305}. FT HELIX 43 51 {ECO:0000244|PDB:5TIN}. FT TURN 53 55 {ECO:0000244|PDB:5TIN}. FT TURN 63 66 {ECO:0000244|PDB:5TIN}. FT STRAND 70 85 {ECO:0000244|PDB:5TIN}. FT TURN 86 89 {ECO:0000244|PDB:5TIN}. FT STRAND 90 102 {ECO:0000244|PDB:5TIN}. FT HELIX 104 106 {ECO:0000244|PDB:5TIN}. FT STRAND 114 118 {ECO:0000244|PDB:5TIN}. FT HELIX 120 125 {ECO:0000244|PDB:5TIN}. FT STRAND 131 133 {ECO:0000244|PDB:5TIN}. FT STRAND 136 141 {ECO:0000244|PDB:5TIN}. FT STRAND 144 146 {ECO:0000244|PDB:5TIN}. FT STRAND 149 154 {ECO:0000244|PDB:5TIN}. FT STRAND 157 170 {ECO:0000244|PDB:5TIN}. FT TURN 176 179 {ECO:0000244|PDB:5TIN}. FT STRAND 182 193 {ECO:0000244|PDB:5TIN}. FT TURN 196 198 {ECO:0000244|PDB:5TIN}. FT STRAND 199 203 {ECO:0000244|PDB:5TIN}. FT STRAND 208 211 {ECO:0000244|PDB:5TIN}. FT STRAND 218 222 {ECO:0000244|PDB:5TIN}. FT STRAND 227 230 {ECO:0000244|PDB:5TIN}. FT STRAND 233 235 {ECO:0000244|PDB:5TIN}. FT STRAND 238 240 {ECO:0000244|PDB:5TIN}. FT STRAND 242 251 {ECO:0000244|PDB:5TIN}. FT HELIX 254 259 {ECO:0000244|PDB:5TIN}. FT HELIX 261 273 {ECO:0000244|PDB:5TIN}. FT HELIX 274 276 {ECO:0000244|PDB:5TIN}. FT HELIX 282 302 {ECO:0000244|PDB:5TIN}. FT TURN 303 306 {ECO:0000244|PDB:5TIN}. FT HELIX 315 340 {ECO:0000244|PDB:5TIN}. FT HELIX 419 450 {ECO:0000244|PDB:5TIN}. SQ SEQUENCE 464 AA; 53800 MW; 8E17A30B3C6E648D CRC64; MAHVRHFRTL VSGFYFWEAA LLLSLVATKE TDSARSRSAP 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 DMDDEVRESR FSFTAYGMGP CLQAKDGMTP KGPNHPVQVM PKSPDEMRKV FIDRAKKIDT ISRACFPLAF LIFNIFYWVI YKILRHEDIH QQQD //