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Protein

Glycine receptor subunit alpha-3

Gene

Glra3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:15131310, PubMed:23834509, PubMed:23895467, PubMed:23613537). Channel characteristics depend on the subunit composition; heteropentameric channels display faster channel closure (PubMed:25445488). Plays an important role in the down-regulation of neuronal excitability (By similarity). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Contributes to increased pain perception in response to increased prostaglandin E2 levels (By similarity). Plays a role in cellular responses to ethanol (PubMed:23895467).By similarity4 Publications

Enzyme regulationi

Low levels of Zn2+ ions (1 µM) increase glycine sensitivity and decrease the glycine concentration required for half-maximal channel activity (PubMed:23895467). Channel activity is strongly enhanced by ethanol (PubMed:23895467). Inhibited by picrotoxin (PubMed:23834509). Inhibited by prostaglandin E2, probably via PKA-mediated phosphorylation at Ser-379 (PubMed:15131310).3 Publications

Kineticsi

A concentration of about 900 µM glycine results in half-maximal channel conductance in the absence of Zn2+. In the presence of 1 µM Zn2+, 400uM glycine results in half-maximal channel conductance.1 Publication

      Sites

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Metal bindingi225 – 2251ZincBy similarity
      Metal bindingi227 – 2271ZincBy similarity
      Metal bindingi248 – 2481ZincBy similarity
      Sitei294 – 2941Important for obstruction of the ion pore in the closed conformationBy similarity

      GO - Molecular functioni

      GO - Biological processi

      • cellular response to amino acid stimulus Source: UniProtKB
      • cellular response to ethanol Source: UniProtKB
      • cellular response to zinc ion Source: UniProtKB
      • chloride transmembrane transport Source: UniProtKB
      Complete GO annotation...

      Keywords - Molecular functioni

      Chloride channel, Ion channel, Ligand-gated ion channel, Receptor

      Keywords - Biological processi

      Ion transport, Transport

      Keywords - Ligandi

      Chloride, Metal-binding

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Glycine receptor subunit alpha-3
      Gene namesi
      Name:Glra3
      OrganismiRattus norvegicus (Rat)
      Taxonomic identifieri10116 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
      Proteomesi
      • UP000002494 Componenti: Unplaced

      Organism-specific databases

      RGDi621229. Glra3.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini34 – 255222ExtracellularBy similarityAdd
      BLAST
      Transmembranei256 – 27722Helical; Name=1By similarityAdd
      BLAST
      Topological domaini278 – 2825CytoplasmicBy similarity
      Transmembranei283 – 30321Helical; Name=2By similarityAdd
      BLAST
      Topological domaini304 – 31411ExtracellularBy similarityAdd
      BLAST
      Transmembranei315 – 33521Helical; Name=3By similarityAdd
      BLAST
      Topological domaini336 – 43095CytoplasmicBy similarityAdd
      BLAST
      Transmembranei431 – 45121Helical; Name=4By similarityAdd
      BLAST
      Topological domaini452 – 46413ExtracellularBy similarityAdd
      BLAST

      GO - Cellular componenti

      Complete GO annotation...

      Keywords - Cellular componenti

      Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

      Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi218 – 2181P → L: Strongly enhances glycine sensitivity so that the channel starts to be activated at 0.001 mM glycine. 1 Publication
      Mutagenesisi379 – 3791S → A: Loss of a predicted PKA phosphorylation site. Nearly abolishes down-regulation of inhibitory postsynaptic currents by prostaglandin E2. 1 Publication
      Mutagenesisi379 – 3791S → E: Phosphomimetic mutant that triggers a local conformation change. 1 Publication
      Mutagenesisi379 – 3791S → G: Loss of a predicted PKA phosphorylation site. Abolishes the conformation change observed after treatment with forskolin. 1 Publication

      Chemistry

      ChEMBLiCHEMBL3392921.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Signal peptidei1 – 3333Sequence analysisAdd
      BLAST
      Chaini34 – 464431Glycine receptor subunit alpha-3PRO_0000000421Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Glycosylationi71 – 711N-linked (GlcNAc...)Sequence analysis
      Disulfide bondi171 ↔ 185By similarity
      Disulfide bondi231 ↔ 242By similarity
      Modified residuei370 – 3701PhosphoserineBy similarity
      Modified residuei379 – 3791Phosphoserine; by PKA2 Publications

      Post-translational modificationi

      Phosphorylated by PKA; this causes down-regulation of channel activity (Probable).2 Publications

      Keywords - PTMi

      Disulfide bond, Glycoprotein, Phosphoprotein

      Proteomic databases

      PRIDEiP24524.

      PTM databases

      iPTMnetiP24524.

      Interactioni

      Subunit structurei

      Homopentamer (in vitro) (By similarity). Heteropentamer composed of GLRA3 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (PubMed:25445488).By similarity1 Publication

      Structurei

      3D structure databases

      ProteinModelPortaliP24524.
      SMRiP24524. Positions 283-342.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni235 – 2406Strychnine-bindingBy similarity

      Domaini

      The N-terminal domain carries structural determinants essential for agonist and antagonist binding. The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. The cytoplasmic loop is an important determinant of channel inactivation kinetics.By similarity

      Sequence similaritiesi

      Keywords - Domaini

      Signal, Transmembrane, Transmembrane helix

      Phylogenomic databases

      HOVERGENiHBG051707.
      InParanoidiP24524.

      Family and domain databases

      Gene3Di2.70.170.10. 1 hit.
      InterProiIPR006028. GABAA/Glycine_rcpt.
      IPR008127. Glycine_rcpt_A.
      IPR008130. Glycine_rcpt_A3.
      IPR006202. Neur_chan_lig-bd.
      IPR006201. Neur_channel.
      IPR006029. Neurotrans-gated_channel_TM.
      IPR018000. Neurotransmitter_ion_chnl_CS.
      [Graphical view]
      PANTHERiPTHR18945. PTHR18945. 2 hits.
      PfamiPF02931. Neur_chan_LBD. 1 hit.
      PF02932. Neur_chan_memb. 1 hit.
      [Graphical view]
      PRINTSiPR00253. GABAARECEPTR.
      PR01673. GLYRALPHA.
      PR01676. GLYRALPHA3.
      PR00252. NRIONCHANNEL.
      SUPFAMiSSF63712. SSF63712. 1 hit.
      SSF90112. SSF90112. 1 hit.
      TIGRFAMsiTIGR00860. LIC. 1 hit.
      PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
      [Graphical view]

      Sequencei

      Sequence statusi: Complete.

      Sequence processingi: The displayed sequence is further processed into a mature form.

      P24524-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MAHVRHFRTL LSGFYFWEAA LLLSLVATKE TNSARSRSAP MSPSDFLDKL
      60 70 80 90 100
      MGRTSGYDAR IRPNFKGPPV NVTCNIFINS FGSIAETTMD YRVNIFLRQK
      110 120 130 140 150
      WNDPRLAYSE YPDDSLDLDP SMLDSIWKPD LFFANEKGAN FHEVTTDNKL
      160 170 180 190 200
      LRIFKNGNVL YSIRLTLTLS CPMDLKNFPM DVQTCIMQLE SFGYTMNDLI
      210 220 230 240 250
      FEWQDEAPVQ VAEGLTLPQF LLKEEKDLRY CTKHYNTGKF TCIEVRFHLE
      260 270 280 290 300
      RQMGYYLIQM YIPSLLIVIL SWVSFWINMD AAPARVALGI TTVLTMTTQS
      310 320 330 340 350
      SGSRASLPKV SYVKAIDIWM AVCLLFVFSA LLEYAAVNFV SRQHKELLRF
      360 370 380 390 400
      RRKRKNKTEA FALEKFYRFS DTDDEVRESR LSFTAYGMGP CLQAKDGVVP
      410 420 430 440 450
      KGPNHAVQVM PKSADEMRKV FIDRAKKIDT ISRACFPLAF LIFNIFYWVI
      460
      YKILRHEDIH HQQD
      Length:464
      Mass (Da):53,672
      Last modified:March 1, 1992 - v1
      Checksum:i5A429F4C6F16E40D
      GO

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      M55250 mRNA. Translation: AAA63492.1.
      PIRiA23682.
      UniGeneiRn.10038.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      M55250 mRNA. Translation: AAA63492.1.
      PIRiA23682.
      UniGeneiRn.10038.

      3D structure databases

      ProteinModelPortaliP24524.
      SMRiP24524. Positions 283-342.
      ModBaseiSearch...
      MobiDBiSearch...

      Chemistry

      ChEMBLiCHEMBL3392921.

      PTM databases

      iPTMnetiP24524.

      Proteomic databases

      PRIDEiP24524.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Organism-specific databases

      RGDi621229. Glra3.

      Phylogenomic databases

      HOVERGENiHBG051707.
      InParanoidiP24524.

      Miscellaneous databases

      PROiP24524.

      Family and domain databases

      Gene3Di2.70.170.10. 1 hit.
      InterProiIPR006028. GABAA/Glycine_rcpt.
      IPR008127. Glycine_rcpt_A.
      IPR008130. Glycine_rcpt_A3.
      IPR006202. Neur_chan_lig-bd.
      IPR006201. Neur_channel.
      IPR006029. Neurotrans-gated_channel_TM.
      IPR018000. Neurotransmitter_ion_chnl_CS.
      [Graphical view]
      PANTHERiPTHR18945. PTHR18945. 2 hits.
      PfamiPF02931. Neur_chan_LBD. 1 hit.
      PF02932. Neur_chan_memb. 1 hit.
      [Graphical view]
      PRINTSiPR00253. GABAARECEPTR.
      PR01673. GLYRALPHA.
      PR01676. GLYRALPHA3.
      PR00252. NRIONCHANNEL.
      SUPFAMiSSF63712. SSF63712. 1 hit.
      SSF90112. SSF90112. 1 hit.
      TIGRFAMsiTIGR00860. LIC. 1 hit.
      PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
      [Graphical view]
      ProtoNetiSearch...

      Publicationsi

      1. "Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor."
        Kuhse J., Schmieden V., Betz H.
        J. Biol. Chem. 265:22317-22320(1990) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA].
        Tissue: Brain.
      2. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-379, MUTAGENESIS OF SER-379.
      3. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      4. "Phosphorylation of alpha3 glycine receptors induces a conformational change in the glycine-binding site."
        Han L., Talwar S., Wang Q., Shan Q., Lynch J.W.
        ACS Chem. Neurosci. 4:1361-1370(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, PHOSPHORYLATION AT SER-379, MUTAGENESIS OF SER-379.
      5. "Zinc-dependent modulation of alpha2- and alpha3-glycine receptor subunits by ethanol."
        McCracken L.M., Trudell J.R., McCracken M.L., Harris R.A.
        Alcohol. Clin. Exp. Res. 37:2002-2010(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF PRO-218.
      6. "The kinetic properties of the alpha3 rat glycine receptor make it suitable for mediating fast synaptic inhibition."
        Marabelli A., Moroni M., Lape R., Sivilotti L.G.
        J. Physiol. (Lond.) 591:3289-3308(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION.
      7. "Functional reconstitution of glycinergic synapses incorporating defined glycine receptor subunit combinations."
        Zhang Y., Dixon C.L., Keramidas A., Lynch J.W.
        Neuropharmacology 89:391-397(2015) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.

      Entry informationi

      Entry nameiGLRA3_RAT
      AccessioniPrimary (citable) accession number: P24524
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: March 1, 1992
      Last sequence update: March 1, 1992
      Last modified: June 8, 2016
      This is version 121 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Miscellaneous

      The alpha subunit binds strychnine.By similarity

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. SIMILARITY comments
        Index of protein domains and families

      Similar proteinsi

      Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
      100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
      90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
      50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.