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Protein

Glycine receptor subunit alphaZ1

Gene

glra1

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
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:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).By similarity2 Publications

Enzyme regulationi

Activated by glycine and taurine. Inhibited by strychnine (PubMed:10188956, PubMed:26344198). Allosterically activated by ivermectin (PubMed:26344198). Inhibited by picrotoxinin (PubMed:26344198). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (PubMed:26344198). Can also be activated by GABA and inhibited by bicuculline, but this requires heterologous expression in human cells (PubMed:10188956).2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi216 – 2161ZincBy similarity
Metal bindingi218 – 2181ZincBy similarity
Metal bindingi239 – 2391ZincBy similarity
Sitei285 – 2851Important for obstruction of the ion pore in the closed conformation1 Publication

GO - Molecular functioni

  • extracellular-glycine-gated chloride channel activity Source: ZFIN
  • glycine binding Source: ZFIN
  • transmitter-gated ion channel activity Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to ethanol Source: UniProtKB
  • cellular response to zinc ion Source: UniProtKB
  • central nervous system development Source: ZFIN
  • chloride transmembrane transport Source: GOC
  • ion transport Source: ZFIN
  • protein homooligomerization Source: ZFIN
  • regulation of neuron differentiation Source: ZFIN
  • response to amino acid Source: ZFIN
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

Enzyme and pathway databases

ReactomeiR-DRE-975298. Ligand-gated ion channel transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine receptor subunit alphaZ1
Gene namesi
Name:glra1
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 14

Organism-specific databases

ZFINiZDB-GENE-991117-1. glra1.

Subcellular locationi

  • Cell junctionsynapsepostsynaptic cell membrane By similarity; Multi-pass membrane protein By similarity
  • Cell junctionsynapse By similarity
  • Perikaryon By similarity
  • Cell projectiondendrite By similarity
  • Cell membrane 2 Publications; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 246222Extracellular1 PublicationAdd
BLAST
Transmembranei247 – 26822Helical; Name=11 PublicationAdd
BLAST
Topological domaini269 – 2735Cytoplasmic1 Publication
Transmembranei274 – 29421Helical; Name=21 PublicationAdd
BLAST
Topological domaini295 – 30511Extracellular1 PublicationAdd
BLAST
Transmembranei306 – 32621Helical; Name=31 PublicationAdd
BLAST
Topological domaini327 – 41286Cytoplasmic1 PublicationAdd
BLAST
Transmembranei413 – 43321Helical; Name=41 PublicationAdd
BLAST
Topological domaini434 – 44411Extracellular1 PublicationAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 444420Glycine receptor subunit alphaZ1PRO_0000000415Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi62 – 621N-linked (GlcNAc...)Sequence analysis1 Publication
Disulfide bondi162 ↔ 176By similarity
Disulfide bondi222 ↔ 2331 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO93430.
PRIDEiO93430.

Expressioni

Tissue specificityi

Expressed in brain.1 Publication

Gene expression databases

BgeeiO93430.

Interactioni

Subunit structurei

Homopentamer (in vitro) (PubMed:26344198). Heteropentamer composed of glra1 and glrb (By similarity). Both homopentamers and heteropentamers form functional ion channels (By similarity).By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-61772N.
STRINGi7955.ENSDARP00000066196.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3JADelectron microscopy3.90A/B/C/D/E34-434[»]
3JAEelectron microscopy3.90A/B/C/D/E34-434[»]
3JAFelectron microscopy3.80A/B/C/D/E34-434[»]
ProteinModelPortaliO93430.
SMRiO93430. Positions 273-333.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni226 – 2316Strychnine-binding1 Publication

Domaini

The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore.1 Publication

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiO93430.
KOiK05193.

Family and domain databases

Gene3Di2.70.170.10. 1 hit.
InterProiIPR006028. GABAA/Glycine_rcpt.
IPR008127. Glycine_rcpt_A.
IPR008128. Glycine_rcpt_A1.
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.
PR01674. GLYRALPHA1.
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.

O93430-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFALGIYLWE TIVFFSLAAS QQAAARKAAS PMPPSEFLDK LMGKVSGYDA
60 70 80 90 100
RIRPNFKGPP VNVTCNIFIN SFGSIAETTM DYRVNIFLRQ QWNDPRLAYS
110 120 130 140 150
EYPDDSLDLD PSMLDSIWKP DLFFANEKGA NFHEVTTDNK LLRISKNGNV
160 170 180 190 200
LYSIRITLVL ACPMDLKNFP MDVQTCIMQL ESFGYTMNDL IFEWDEKGAV
210 220 230 240 250
QVADGLTLPQ FILKEEKDLR YCTKHYNTGK FTCIEARFHL ERQMGYYLIQ
260 270 280 290 300
MYIPSLLIVI LSWVSFWINM DAAPARVGLG ITTVLTMTTQ SSGSRASLPK
310 320 330 340 350
VSYVKAIDIW MAVCLLFVFS ALLEYAAVNF IARQHKELLR FQRRRRHLKE
360 370 380 390 400
DEAGDGRFSF AAYGMGPACL QAKDGMAIKG NNNNAPTSTN PPEKTVEEMR
410 420 430 440
KLFISRAKRI DTVSRVAFPL VFLIFNIFYW ITYKIIRSED IHKQ
Length:444
Mass (Da):50,766
Last modified:November 1, 1998 - v1
Checksum:i77F6FC8C14E80581
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005812 mRNA. Translation: CAA06711.1.
RefSeqiNP_571477.1. NM_131402.1.
UniGeneiDr.75842.

Genome annotation databases

EnsembliENSDART00000005499; ENSDARP00000003268; ENSDARG00000012019.
GeneIDi30676.
KEGGidre:30676.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005812 mRNA. Translation: CAA06711.1.
RefSeqiNP_571477.1. NM_131402.1.
UniGeneiDr.75842.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3JADelectron microscopy3.90A/B/C/D/E34-434[»]
3JAEelectron microscopy3.90A/B/C/D/E34-434[»]
3JAFelectron microscopy3.80A/B/C/D/E34-434[»]
ProteinModelPortaliO93430.
SMRiO93430. Positions 273-333.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61772N.
STRINGi7955.ENSDARP00000066196.

Proteomic databases

PaxDbiO93430.
PRIDEiO93430.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSDART00000005499; ENSDARP00000003268; ENSDARG00000012019.
GeneIDi30676.
KEGGidre:30676.

Organism-specific databases

CTDi2741.
ZFINiZDB-GENE-991117-1. glra1.

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiO93430.
KOiK05193.

Enzyme and pathway databases

ReactomeiR-DRE-975298. Ligand-gated ion channel transport.

Miscellaneous databases

NextBioi20807029.
PROiO93430.

Gene expression databases

BgeeiO93430.

Family and domain databases

Gene3Di2.70.170.10. 1 hit.
InterProiIPR006028. GABAA/Glycine_rcpt.
IPR008127. Glycine_rcpt_A.
IPR008128. Glycine_rcpt_A1.
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.
PR01674. GLYRALPHA1.
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. "Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish."
    David-Watine B., Goblet C., de Saint Jan D., Fucile S., Devignot V., Bregestovski P., Korn H.
    Neuroscience 90:303-317(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Glycine receptor mechanism elucidated by electron cryo-microscopy."
    Du J., Lu W., Wu S., Cheng Y., Gouaux E.
    Nature 526:224-229(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 34-434 IN COMPLEXES WITH GLYCINE; IVERMECTINE AND STRYCHNINE, FUNCTION, ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-62.

Entry informationi

Entry nameiGLRA1_DANRE
AccessioniPrimary (citable) accession number: O93430
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1998
Last modified: May 11, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Highly sensitive to activation by taurine despite the presence of Val in position 135. In mammals, Val-135 causes a drastic loss of taurine efficacy.1 Publication
The alpha subunit binds strychnine.2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.