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Protein

Glycine receptor subunit alpha-1

Gene

Glra1

Organism
Mus musculus (Mouse)
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:16672662, PubMed:17114051, PubMed:24801766). Channel opening is also triggered by taurine and beta-alanine (By similarity). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (By similarity). Plays an important role in the down-regulation of neuronal excitability (PubMed:9145798). Contributes to the generation of inhibitory postsynaptic currents (PubMed:16672662, PubMed:17114051, PubMed:24801766). Channel activity is potentiated by ethanol. Potentiation of channel activity by intoxicating levels ot ethanol contribute to the sedative effects of ethanol (PubMed:24801766).By similarity4 Publications

Enzyme regulationi

Inhibited by strychnine. Inhibited by picrotoxin (PubMed:16672662). Channel activity is enhanced by 5 µM Zn2+ and inhibited by 100 µM Zn2+ (PubMed:17114051).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi220ZincBy similarity1
Metal bindingi222ZincBy similarity1
Metal bindingi243ZincBy similarity1
Sitei289Important for obstruction of the ion pore in the closed conformationBy similarity1

GO - Molecular functioni

GO - Biological processi

  • acrosome reaction Source: MGI
  • action potential Source: MGI
  • adult walking behavior Source: MGI
  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to ethanol Source: UniProtKB
  • cellular response to zinc ion Source: UniProtKB
  • chemical synaptic transmission Source: MGI
  • chloride transmembrane transport Source: MGI
  • chloride transport Source: UniProtKB
  • inhibitory postsynaptic potential Source: UniProtKB
  • ion transport Source: UniProtKB
  • muscle contraction Source: UniProtKB
  • negative regulation of transmission of nerve impulse Source: UniProtKB
  • neuromuscular process Source: MGI
  • neuromuscular process controlling posture Source: MGI
  • neuropeptide signaling pathway Source: UniProtKB
  • positive regulation of acrosome reaction Source: MGI
  • protein heterooligomerization Source: Ensembl
  • protein homooligomerization Source: Ensembl
  • regulation of membrane potential Source: MGI
  • regulation of respiratory gaseous exchange Source: MGI
  • regulation of respiratory gaseous exchange by neurological system process Source: MGI
  • response to alcohol Source: UniProtKB
  • response to amino acid Source: GO_Central
  • righting reflex Source: MGI
  • startle response Source: UniProtKB
  • synaptic transmission, glycinergic Source: UniProtKB
  • visual perception Source: MGI
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

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

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine receptor subunit alpha-1
Alternative name(s):
Glycine receptor 48 kDa subunit
Glycine receptor strychnine-binding subunit
Gene namesi
Name:Glra1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:95747. Glra1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 250ExtracellularBy similarityAdd BLAST222
Transmembranei251 – 272Helical; Name=1By similarityAdd BLAST22
Topological domaini273 – 277CytoplasmicBy similarity5
Transmembranei278 – 298Helical; Name=2By similarityAdd BLAST21
Topological domaini299 – 309ExtracellularBy similarityAdd BLAST11
Transmembranei310 – 330Helical; Name=3By similarityAdd BLAST21
Topological domaini331 – 425CytoplasmicBy similarityAdd BLAST95
Transmembranei426 – 446Helical; Name=4By similarityAdd BLAST21
Topological domaini447 – 457ExtracellularBy similarityAdd BLAST11

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • chloride channel complex Source: UniProtKB-KW
  • dendrite Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: Ensembl
  • external side of plasma membrane Source: MGI
  • inhibitory synapse Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: MGI
  • intracellular membrane-bounded organelle Source: UniProtKB
  • membrane Source: MGI
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perikaryon Source: UniProtKB-SubCell
  • postsynaptic membrane Source: MGI
  • synapse Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Defects in Glra1 are the cause of the spasmodic (spd) phenotype, a mouse mutant which resembles the human neurological disease, hyperekplexia (or startle disease (STHE)) (PubMed:7920629). Defects in Glra1 are the cause of the lethal oscillator (spd-ot) phenotype. Mutant mice display a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age (PubMed:7874121). Heterozygous mice show an increased acoustic startle response (PubMed:9145798). Neurons from homozygous oscillator mice have dramatically reduced amplitude and frequency of glycinergic inhibitory postsynaptic currents (PubMed:16672662). The oscillator phenotype is due to the complete absence of Glra1 protein (PubMed:9145798).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi108D → A: Eliminates potentiation of glycine-mediated currents by Zn(2+) and causes neuromotor defects similar to human startle disease. 1 Publication1
Mutagenesisi421 – 422KK → AA: Reduces the increase of channel activity in response to ethanol and improves tolerance of intoxicating levels of alcohol. 1 Publication2

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28By similarityAdd BLAST28
ChainiPRO_000000041329 – 457Glycine receptor subunit alpha-1Add BLAST429

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi66N-linked (GlcNAc...)Curated1
Disulfide bondi166 ↔ 180By similarity
Disulfide bondi226 ↔ 237By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ64018.
PRIDEiQ64018.

PTM databases

iPTMnetiQ64018.
PhosphoSitePlusiQ64018.

Expressioni

Tissue specificityi

Detected in spinal cord neurons (PubMed:9145798, PubMed:17114051, PubMed:24801766). Detected in brain stem neurons (PubMed:16672662, PubMed:24801766). Detected at lower levels in hippocampus and cerebellum (PubMed:24801766). Detected in the inner plexiform layer of the retina (at protein level) (PubMed:12975813).5 Publications

Gene expression databases

BgeeiENSMUSG00000000263.
CleanExiMM_GLRA1.
ExpressionAtlasiQ64018. baseline and differential.
GenevisibleiQ64018. MM.

Interactioni

Subunit structurei

Homopentamer (in vitro). Interacts with GLRB to form heteropentameric channels; this is probably the predominant form in vivo. Heteropentamer composed of two GLRA1 and three GLRB. Heteropentamer composed of three GLRA1 and two GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099777.

Structurei

3D structure databases

ProteinModelPortaliQ64018.
SMRiQ64018.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni230 – 235Strychnine-bindingBy similarity6

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.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiQ64018.
KOiK05193.
OMAiFNFAYGM.
OrthoDBiEOG091G0805.
PhylomeDBiQ64018.
TreeFamiTF315453.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform a (identifier: Q64018-1) [UniParc]FASTAAdd to basket
Also known as: Long

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
MYSFNTLRFY LWETIVFFSL AASKEAEAAR SAPKPMSPSD FLDKLMGRTS
60 70 80 90 100
GYDARIRPNF KGPPVNVSCN IFINSFGSIA ETTMDYRVNI FLRQQWNDPR
110 120 130 140 150
LAYNEYPDDS LDLDPSMLDS IWKPDLFFAN EKGAHFHEIT TDNKLLRISR
160 170 180 190 200
NGNVLYSIRI TLTLACPMDL KNFPMDVQTC IMQLESFGYT MNDLIFEWQE
210 220 230 240 250
QGAVQVADGL TLPQFILKEE KDLRYCTKHY NTGKFTCIEA RFHLERQMGY
260 270 280 290 300
YLIQMYIPSL LIVILSWISF WINMDAAPAR VGLGITTVLT MTTQSSGSRA
310 320 330 340 350
SLPKVSYVKA IDIWMAVCLL FVFSALLEYA AVNFVSRQHK ELLRFRRKRR
360 370 380 390 400
HHKSPMLNLF QDDEGGEGRF NFSAYGMGPA CLQAKDGISV KGANNNNTTN
410 420 430 440 450
PPPAPSKSPE EMRKLFIQRA KKIDKISRIG FPMAFLIFNM FYWIIYKIVR

REDVHNK
Length:457
Mass (Da):52,657
Last modified:December 8, 2000 - v2
Checksum:i29268DC4991A6E20
GO
Isoform b (identifier: Q64018-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     354-361: Missing.

Show »
Length:449
Mass (Da):51,726
Checksum:i4EDDAEB87874A153
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti84M → I in CAB52398 (PubMed:7507926).Curated1
Sequence conflicti84M → I in CAB52399 (PubMed:7507926).Curated1
Sequence conflicti426 – 429ISRI → NISH in CAB52398 (PubMed:7507926).Curated4
Sequence conflicti426 – 429ISRI → NISH in CAB52399 (PubMed:7507926).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti80A → S in spd. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000080354 – 361Missing in isoform b. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73717 mRNA. Translation: AAB32157.2.
S73718 mRNA. Translation: AAB32158.2.
X75832
, X75833, X75834, X75835, X75836, X75837, X75838, X75839, X75840 Genomic DNA. Translation: CAB52398.1.
X75832
, X75833, X75834, X75835, X75836, X75837, X75838, X75839, X75840 Genomic DNA. Translation: CAB52399.1.
AL596207 Genomic DNA. Translation: CAI35359.1.
CCDSiCCDS24715.1. [Q64018-2]
CCDS70190.1. [Q64018-1]
PIRiC49970.
RefSeqiNP_001277750.1. NM_001290821.1. [Q64018-1]
UniGeneiMm.89320.

Genome annotation databases

EnsembliENSMUST00000075603; ENSMUSP00000075032; ENSMUSG00000000263. [Q64018-1]
ENSMUST00000102716; ENSMUSP00000099777; ENSMUSG00000000263. [Q64018-2]
GeneIDi14654.
KEGGimmu:14654.
UCSCiuc007izo.2. mouse. [Q64018-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73717 mRNA. Translation: AAB32157.2.
S73718 mRNA. Translation: AAB32158.2.
X75832
, X75833, X75834, X75835, X75836, X75837, X75838, X75839, X75840 Genomic DNA. Translation: CAB52398.1.
X75832
, X75833, X75834, X75835, X75836, X75837, X75838, X75839, X75840 Genomic DNA. Translation: CAB52399.1.
AL596207 Genomic DNA. Translation: CAI35359.1.
CCDSiCCDS24715.1. [Q64018-2]
CCDS70190.1. [Q64018-1]
PIRiC49970.
RefSeqiNP_001277750.1. NM_001290821.1. [Q64018-1]
UniGeneiMm.89320.

3D structure databases

ProteinModelPortaliQ64018.
SMRiQ64018.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099777.

PTM databases

iPTMnetiQ64018.
PhosphoSitePlusiQ64018.

Proteomic databases

PaxDbiQ64018.
PRIDEiQ64018.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075603; ENSMUSP00000075032; ENSMUSG00000000263. [Q64018-1]
ENSMUST00000102716; ENSMUSP00000099777; ENSMUSG00000000263. [Q64018-2]
GeneIDi14654.
KEGGimmu:14654.
UCSCiuc007izo.2. mouse. [Q64018-1]

Organism-specific databases

CTDi2741.
MGIiMGI:95747. Glra1.

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiQ64018.
KOiK05193.
OMAiFNFAYGM.
OrthoDBiEOG091G0805.
PhylomeDBiQ64018.
TreeFamiTF315453.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ64018.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000263.
CleanExiMM_GLRA1.
ExpressionAtlasiQ64018. baseline and differential.
GenevisibleiQ64018. MM.

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...

Entry informationi

Entry nameiGLRA1_MOUSE
AccessioniPrimary (citable) accession number: Q64018
Secondary accession number(s): Q5NCT8
, Q64019, Q9R0Y6, Q9R0Y7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 8, 2000
Last modified: November 2, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The alpha subunit binds strychnine.3 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  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.