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Protein

Glycine receptor subunit alpha-2

Gene

GLRA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

The alpha subunit binds strychnine.1 Publication

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

      • extracellularly 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
      • transmembrane signaling receptor activity Source: InterPro

      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

      Keywordsi

      Molecular functionChloride channel, Ion channel, Ligand-gated ion channel, Receptor
      Biological processIon transport, Transport
      LigandChloride, Metal-binding, Zinc

      Enzyme and pathway databases

      ReactomeiR-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission

      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

      EuPathDBiHostDB:ENSG00000101958.13
      HGNCiHGNC:4327 GLRA2
      MIMi305990 gene
      neXtProtiNX_P23416

      Subcellular locationi

      Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

      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

      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
      DB00466 Picrotoxin
      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...) asparagineSequence analysis1
      Glycosylationi103N-linked (GlcNAc...) asparagineSequence analysis1
      Disulfide bondi172 ↔ 186By similarity
      Disulfide bondi232 ↔ 243By similarity

      Keywords - PTMi

      Disulfide bond, Glycoprotein

      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
      STRINGi9606.ENSP00000218075

      Chemistry databases

      BindingDBiP23416

      Structurei

      3D structure databases

      ProteinModelPortaliP23416
      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
      OMAiFRTTFCK
      OrthoDBiEOG091G0805
      PhylomeDBiP23416
      TreeFamiTF315453

      Family and domain databases

      Gene3Di2.70.170.10, 1 hit
      InterProiView protein in InterPro
      IPR006028 GABAA/Glycine_rcpt
      IPR008127 Glycine_rcpt_A
      IPR008129 Glycine_rcpt_A2
      IPR006202 Neur_chan_lig-bd
      IPR036734 Neur_chan_lig-bd_sf
      IPR006201 Neur_channel
      IPR036719 Neuro-gated_channel_TM_sf
      IPR006029 Neurotrans-gated_channel_TM
      IPR018000 Neurotransmitter_ion_chnl_CS
      PANTHERiPTHR18945 PTHR18945, 1 hit
      PTHR18945:SF28 PTHR18945:SF28, 1 hit
      PfamiView protein in Pfam
      PF02931 Neur_chan_LBD, 1 hit
      PF02932 Neur_chan_memb, 1 hit
      PRINTSiPR00253 GABAARECEPTR
      PR01673 GLYRALPHA
      PR01675 GLYRALPHA2
      PR00252 NRIONCHANNEL
      SUPFAMiSSF63712 SSF63712, 1 hit
      SSF90112 SSF90112, 1 hit
      TIGRFAMsiTIGR00860 LIC, 1 hit
      PROSITEiView protein in PROSITE
      PS00236 NEUROTR_ION_CHANNEL, 1 hit

      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

      Similar proteinsi

      Entry informationi

      Entry nameiGLRA2_HUMAN
      AccessioniPrimary (citable) accession number: P23416
      Secondary accession number(s): A8K0J6
      , B2R6I8, B7Z4F5, J3KQ59, Q53YX7, Q6ICQ0, Q99862
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
      Last sequence update: November 1, 1991
      Last modified: May 23, 2018
      This is version 181 of the entry and version 1 of the sequence. See 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

      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

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