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Protein

Glycine receptor subunit alpha-2

Gene

GLRA2

Organism
Homo sapiens (Human)
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:2155780, PubMed:15302677, PubMed:16144831, PubMed:23895467, PubMed:25445488). Channel opening is also triggered by taurine and beta-alanine (PubMed:15302677). Plays a role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Plays a role in cellular responses to ethanol (PubMed:23895467).5 Publications

Enzyme regulationi

Inhibited by strychnine (PubMed:2155780, PubMed:15302677). Inhibited by picrotoxin (PubMed:15302677). Channel activity is potentiated by 10-100 µM Zn2+ (PubMed:15302677, PubMed:16144831, PubMed:23895467). Channel activity is marginally increased by 50 mM ethanol; it is strongly increased by a combination of 0.5 µM Zn2+ and 50 mM ethanol (PubMed:23895467). Channel activity is inhibited by 100-1000 µM Zn2+ (PubMed:15302677).4 Publications

Kineticsi

For isoform Alpha-2* homopentamers, a concentration of about 66 µM glycine results in half-maximal channel conductance. For isoform Alpha-2B homopentamers, a concentration of about 34 µM glycine results in half-maximal channel conductance.

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Metal bindingi226ZincBy similarity1
      Metal bindingi228ZincBy similarity1
      Metal bindingi249ZincBy similarity1
      Sitei295Important for obstruction of the ion pore in the closed conformationBy similarity1

      GO - Molecular functioni

      • extracellular-glycine-gated chloride channel activity Source: UniProtKB
      • glycine binding Source: UniProtKB
      • glycine-gated chloride ion channel activity Source: UniProtKB
      • metal ion binding Source: UniProtKB-KW

      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
      • ion transmembrane transport Source: UniProtKB
      • neuropeptide signaling pathway Source: UniProtKB
      • synaptic transmission, glycinergic Source: GO_Central
      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, Zinc

      Enzyme and pathway databases

      BioCyciZFISH:ENSG00000101958-MONOMER.
      ReactomeiR-HSA-975298. Ligand-gated ion channel transport.

      Protein family/group databases

      TCDBi1.A.9.3.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Glycine receptor subunit alpha-2
      Gene namesi
      Name:GLRA2
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      Proteomesi
      • UP000005640 Componenti: Chromosome X

      Organism-specific databases

      HGNCiHGNC:4327. GLRA2.

      Subcellular locationi

      Topology

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Topological domaini28 – 256ExtracellularBy similarityAdd BLAST229
      Transmembranei257 – 278Helical; Name=1By similarityAdd BLAST22
      Topological domaini279 – 283CytoplasmicBy similarity5
      Transmembranei284 – 304Helical; Name=2By similarityAdd BLAST21
      Topological domaini305 – 315ExtracellularBy similarityAdd BLAST11
      Transmembranei316 – 336Helical; Name=3By similarityAdd BLAST21
      Topological domaini337 – 420CytoplasmicBy similarityAdd BLAST84
      Transmembranei421 – 441Helical; Name=4By similarityAdd BLAST21
      Topological domaini442 – 452ExtracellularBy similarityAdd BLAST11

      GO - Cellular componenti

      Complete GO annotation...

      Keywords - Cellular componenti

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

      Pathology & Biotechi

      Organism-specific databases

      DisGeNETi2742.
      OpenTargetsiENSG00000101958.
      PharmGKBiPA28728.

      Chemistry databases

      ChEMBLiCHEMBL5871.
      DrugBankiDB00898. Ethanol.
      DB00145. Glycine.
      DB00431. Lindane.
      GuidetoPHARMACOLOGYi424.

      Polymorphism and mutation databases

      BioMutaiGLRA2.
      DMDMi121578.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Signal peptidei1 – 27Sequence analysisAdd BLAST27
      ChainiPRO_000000041628 – 452Glycine receptor subunit alpha-2Add BLAST425

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Glycosylationi72N-linked (GlcNAc...)Sequence analysis1
      Glycosylationi103N-linked (GlcNAc...)Sequence analysis1
      Disulfide bondi172 ↔ 186By similarity
      Disulfide bondi232 ↔ 243By similarity
      Modified residuei368PhosphoserineBy similarity1

      Keywords - PTMi

      Disulfide bond, Glycoprotein, Phosphoprotein

      Proteomic databases

      PaxDbiP23416.
      PRIDEiP23416.

      PTM databases

      iPTMnetiP23416.
      PhosphoSitePlusiP23416.

      Expressioni

      Gene expression databases

      BgeeiENSG00000101958.
      CleanExiHS_GLRA2.
      ExpressionAtlasiP23416. baseline and differential.
      GenevisibleiP23416. HS.

      Organism-specific databases

      HPAiCAB070422.

      Interactioni

      Subunit structurei

      Homopentamer (in vitro). Interacts with GLRB (PubMed:16144831). Heteropentamer composed of GLRA2 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (PubMed:15302677).1 Publication1 Publication

      Protein-protein interaction databases

      BioGridi109004. 27 interactors.
      IntActiP23416. 6 interactors.
      MINTiMINT-1412636.
      STRINGi9606.ENSP00000218075.

      Chemistry databases

      BindingDBiP23416.

      Structurei

      3D structure databases

      ProteinModelPortaliP23416.
      SMRiP23416.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Regioni236 – 241Strychnine-bindingBy similarity6

      Sequence similaritiesi

      Keywords - Domaini

      Signal, Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG3643. Eukaryota.
      ENOG410XPWH. LUCA.
      GeneTreeiENSGT00760000118821.
      HOGENOMiHOG000231336.
      HOVERGENiHBG051707.
      InParanoidiP23416.
      KOiK05194.
      OMAiFREAFCK.
      OrthoDBiEOG091G0805.
      PhylomeDBiP23416.
      TreeFamiTF315453.

      Family and domain databases

      Gene3Di2.70.170.10. 1 hit.
      InterProiIPR006028. GABAA/Glycine_rcpt.
      IPR008127. Glycine_rcpt_A.
      IPR008129. Glycine_rcpt_A2.
      IPR006202. Neur_chan_lig-bd.
      IPR006201. Neur_channel.
      IPR006029. Neurotrans-gated_channel_TM.
      IPR018000. Neurotransmitter_ion_chnl_CS.
      [Graphical view]
      PANTHERiPTHR18945. PTHR18945. 1 hit.
      PfamiPF02931. Neur_chan_LBD. 1 hit.
      PF02932. Neur_chan_memb. 1 hit.
      [Graphical view]
      PRINTSiPR00253. GABAARECEPTR.
      PR01673. GLYRALPHA.
      PR01675. GLYRALPHA2.
      PR00252. NRIONCHANNEL.
      SUPFAMiSSF63712. SSF63712. 1 hit.
      SSF90112. SSF90112. 1 hit.
      TIGRFAMsiTIGR00860. LIC. 1 hit.
      PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
      [Graphical view]

      Sequences (3)i

      Sequence statusi: Complete.

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

      This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

      Isoform Alpha-2* (identifier: P23416-1) [UniParc]FASTAAdd to basket

      This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

      « Hide

              10         20         30         40         50
      MNRQLVNILT ALFAFFLETN HFRTAFCKDH DSRSGKQPSQ TLSPSDFLDK
      60 70 80 90 100
      LMGRTSGYDA RIRPNFKGPP VNVTCNIFIN SFGSVTETTM DYRVNIFLRQ
      110 120 130 140 150
      QWNDSRLAYS EYPDDSLDLD PSMLDSIWKP DLFFANEKGA NFHDVTTDNK
      160 170 180 190 200
      LLRISKNGKV LYSIRLTLTL SCPMDLKNFP MDVQTCTMQL ESFGYTMNDL
      210 220 230 240 250
      IFEWLSDGPV QVAEGLTLPQ FILKEEKELG YCTKHYNTGK FTCIEVKFHL
      260 270 280 290 300
      ERQMGYYLIQ MYIPSLLIVI LSWVSFWINM DAAPARVALG ITTVLTMTTQ
      310 320 330 340 350
      SSGSRASLPK VSYVKAIDIW MAVCLLFVFA ALLEYAAVNF VSRQHKEFLR
      360 370 380 390 400
      LRRRQKRQNK EEDVTRESRF NFSGYGMGHC LQVKDGTAVK ATPANPLPQP
      410 420 430 440 450
      PKDGDAIKKK FVDRAKRIDT ISRAAFPLAF LIFNIFYWIT YKIIRHEDVH

      KK
      Length:452
      Mass (Da):52,002
      Last modified:November 1, 1991 - v1
      Checksum:i9EE74B3F49A555EA
      GO
      Isoform Alpha-2B (identifier: P23416-2) [UniParc]FASTAAdd to basket

      The sequence of this isoform differs from the canonical sequence as follows:
           85-86: VT → IA

      Show »
      Length:452
      Mass (Da):51,986
      Checksum:i949E968DD0D8C722
      GO
      Isoform 3 (identifier: P23416-3) [UniParc]FASTAAdd to basket

      The sequence of this isoform differs from the canonical sequence as follows:
           1-89: Missing.

      Note: No experimental confirmation available.
      Show »
      Length:363
      Mass (Da):42,002
      Checksum:i0990033F04610697
      GO

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti389V → A in BAH12541 (PubMed:14702039).Curated1

      Alternative sequence

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Alternative sequenceiVSP_0454651 – 89Missing in isoform 3. 1 PublicationAdd BLAST89
      Alternative sequenceiVSP_00008285 – 86VT → IA in isoform Alpha-2B. 3 Publications2

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X52008 mRNA. Translation: CAA36257.1.
      AF053495
      , AF053487, AF053488, AF053489, AF053490, AF053491, AF053492, AF053493, AF053494 Genomic DNA. Translation: AAC35290.1.
      AY437083 mRNA. Translation: AAR87842.1.
      AY437084 mRNA. Translation: AAR87843.1.
      CR450343 mRNA. Translation: CAG29339.1.
      AK289561 mRNA. Translation: BAF82250.1.
      AK297304 mRNA. Translation: BAH12541.1.
      AK312591 mRNA. Translation: BAG35485.1.
      AC003658 Genomic DNA. No translation available.
      AC003683 Genomic DNA. No translation available.
      CH471074 Genomic DNA. Translation: EAW98859.1.
      CH471074 Genomic DNA. Translation: EAW98860.1.
      BC032864 mRNA. Translation: AAH32864.1.
      U77731
      , U77724, U77725, U77726, U77727, U77728, U77729, U77730 Genomic DNA. Translation: AAB38272.1.
      U77731
      , U77724, U77725, U77726, U77727, U77728, U77729, U77730 Genomic DNA. Translation: AAB38273.1.
      CCDSiCCDS14160.1. [P23416-1]
      CCDS48085.1. [P23416-2]
      CCDS55371.1. [P23416-3]
      PIRiS12381.
      RefSeqiNP_001112357.1. NM_001118885.1. [P23416-1]
      NP_001112358.1. NM_001118886.1. [P23416-2]
      NP_001165413.1. NM_001171942.1. [P23416-3]
      NP_002054.1. NM_002063.3. [P23416-1]
      XP_016884916.1. XM_017029427.1. [P23416-2]
      XP_016884917.1. XM_017029428.1. [P23416-3]
      XP_016884918.1. XM_017029429.1. [P23416-3]
      UniGeneiHs.2700.

      Genome annotation databases

      EnsembliENST00000218075; ENSP00000218075; ENSG00000101958. [P23416-1]
      ENST00000355020; ENSP00000347123; ENSG00000101958. [P23416-2]
      ENST00000443437; ENSP00000387756; ENSG00000101958. [P23416-3]
      GeneIDi2742.
      KEGGihsa:2742.
      UCSCiuc004cwe.5. human. [P23416-1]

      Keywords - Coding sequence diversityi

      Alternative splicing

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X52008 mRNA. Translation: CAA36257.1.
      AF053495
      , AF053487, AF053488, AF053489, AF053490, AF053491, AF053492, AF053493, AF053494 Genomic DNA. Translation: AAC35290.1.
      AY437083 mRNA. Translation: AAR87842.1.
      AY437084 mRNA. Translation: AAR87843.1.
      CR450343 mRNA. Translation: CAG29339.1.
      AK289561 mRNA. Translation: BAF82250.1.
      AK297304 mRNA. Translation: BAH12541.1.
      AK312591 mRNA. Translation: BAG35485.1.
      AC003658 Genomic DNA. No translation available.
      AC003683 Genomic DNA. No translation available.
      CH471074 Genomic DNA. Translation: EAW98859.1.
      CH471074 Genomic DNA. Translation: EAW98860.1.
      BC032864 mRNA. Translation: AAH32864.1.
      U77731
      , U77724, U77725, U77726, U77727, U77728, U77729, U77730 Genomic DNA. Translation: AAB38272.1.
      U77731
      , U77724, U77725, U77726, U77727, U77728, U77729, U77730 Genomic DNA. Translation: AAB38273.1.
      CCDSiCCDS14160.1. [P23416-1]
      CCDS48085.1. [P23416-2]
      CCDS55371.1. [P23416-3]
      PIRiS12381.
      RefSeqiNP_001112357.1. NM_001118885.1. [P23416-1]
      NP_001112358.1. NM_001118886.1. [P23416-2]
      NP_001165413.1. NM_001171942.1. [P23416-3]
      NP_002054.1. NM_002063.3. [P23416-1]
      XP_016884916.1. XM_017029427.1. [P23416-2]
      XP_016884917.1. XM_017029428.1. [P23416-3]
      XP_016884918.1. XM_017029429.1. [P23416-3]
      UniGeneiHs.2700.

      3D structure databases

      ProteinModelPortaliP23416.
      SMRiP23416.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi109004. 27 interactors.
      IntActiP23416. 6 interactors.
      MINTiMINT-1412636.
      STRINGi9606.ENSP00000218075.

      Chemistry databases

      BindingDBiP23416.
      ChEMBLiCHEMBL5871.
      DrugBankiDB00898. Ethanol.
      DB00145. Glycine.
      DB00431. Lindane.
      GuidetoPHARMACOLOGYi424.

      Protein family/group databases

      TCDBi1.A.9.3.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

      PTM databases

      iPTMnetiP23416.
      PhosphoSitePlusiP23416.

      Polymorphism and mutation databases

      BioMutaiGLRA2.
      DMDMi121578.

      Proteomic databases

      PaxDbiP23416.
      PRIDEiP23416.

      Protocols and materials databases

      DNASUi2742.
      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENST00000218075; ENSP00000218075; ENSG00000101958. [P23416-1]
      ENST00000355020; ENSP00000347123; ENSG00000101958. [P23416-2]
      ENST00000443437; ENSP00000387756; ENSG00000101958. [P23416-3]
      GeneIDi2742.
      KEGGihsa:2742.
      UCSCiuc004cwe.5. human. [P23416-1]

      Organism-specific databases

      CTDi2742.
      DisGeNETi2742.
      GeneCardsiGLRA2.
      H-InvDBHIX0016955.
      HGNCiHGNC:4327. GLRA2.
      HPAiCAB070422.
      MIMi305990. gene.
      neXtProtiNX_P23416.
      OpenTargetsiENSG00000101958.
      PharmGKBiPA28728.
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiKOG3643. Eukaryota.
      ENOG410XPWH. LUCA.
      GeneTreeiENSGT00760000118821.
      HOGENOMiHOG000231336.
      HOVERGENiHBG051707.
      InParanoidiP23416.
      KOiK05194.
      OMAiFREAFCK.
      OrthoDBiEOG091G0805.
      PhylomeDBiP23416.
      TreeFamiTF315453.

      Enzyme and pathway databases

      BioCyciZFISH:ENSG00000101958-MONOMER.
      ReactomeiR-HSA-975298. Ligand-gated ion channel transport.

      Miscellaneous databases

      ChiTaRSiGLRA2. human.
      GeneWikiiGLRA2.
      GenomeRNAii2742.
      PROiP23416.
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSG00000101958.
      CleanExiHS_GLRA2.
      ExpressionAtlasiP23416. baseline and differential.
      GenevisibleiP23416. HS.

      Family and domain databases

      Gene3Di2.70.170.10. 1 hit.
      InterProiIPR006028. GABAA/Glycine_rcpt.
      IPR008127. Glycine_rcpt_A.
      IPR008129. Glycine_rcpt_A2.
      IPR006202. Neur_chan_lig-bd.
      IPR006201. Neur_channel.
      IPR006029. Neurotrans-gated_channel_TM.
      IPR018000. Neurotransmitter_ion_chnl_CS.
      [Graphical view]
      PANTHERiPTHR18945. PTHR18945. 1 hit.
      PfamiPF02931. Neur_chan_LBD. 1 hit.
      PF02932. Neur_chan_memb. 1 hit.
      [Graphical view]
      PRINTSiPR00253. GABAARECEPTR.
      PR01673. GLYRALPHA.
      PR01675. GLYRALPHA2.
      PR00252. NRIONCHANNEL.
      SUPFAMiSSF63712. SSF63712. 1 hit.
      SSF90112. SSF90112. 1 hit.
      TIGRFAMsiTIGR00860. LIC. 1 hit.
      PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
      [Graphical view]
      ProtoNetiSearch...

      Entry informationi

      Entry nameiGLRA2_HUMAN
      AccessioniPrimary (citable) accession number: P23416
      Secondary accession number(s): A8K0J6
      , B2R6I8, B7Z4F5, J3KQ59, Q53YX7, Q6ICQ0, Q99862
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: November 1, 1991
      Last sequence update: November 1, 1991
      Last modified: November 2, 2016
      This is version 169 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program
      DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

      Miscellaneousi

      Miscellaneous

      The alpha subunit binds strychnine.1 Publication

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. Human chromosome X
        Human chromosome X: entries, gene names and cross-references to MIM
      2. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      3. 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.