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Protein

Glycine receptor subunit alpha-3

Gene

Glra3

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:15131310, PubMed:20978350). Channel characteristics depend on the subunit composition; heteropentameric channels display faster channel closure (By similarity). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (PubMed:15131310). Contributes to increased pain perception in response to increased prostaglandin E2 levels (PubMed:15131310). Plays a role in the regulation of breathing rhytm, especially of the duration of the postinspiratory phase (PubMed:20978350). Plays a role in cellular responses to ethanol (By similarity).By similarity2 Publications

Enzyme regulationi

Inhibited by prostaglandin E2, probably via PKA-mediated phosphorylation at Ser-379 (PubMed:15131310).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

  • chloride transmembrane transport Source: UniProtKB
  • gamma-aminobutyric acid receptor clustering Source: MGI
  • neuropeptide signaling pathway Source: GO_Central
  • neurotransmitter-gated ion channel clustering Source: MGI
  • protein homooligomerization Source: MGI
  • receptor clustering Source: MGI
  • response to amino acid Source: GO_Central
  • 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

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine receptor subunit alpha-3
Gene namesi
Name:Glra3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:95749. 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

Disruption phenotypei

Mutant mice are born at the expected Mendelian rate, appear normal and are fertile. They do not display notable alterations in motor coordination and startle response, or other neuromotor defects. Glycinergic postsynaptic inhibitory currents in spinal cord appear unchanged, but are not inhibited by prostaglandin E2, contrary to what is observed with wild-type. Basal nociception is unchanged, but contrary to wild-type, mutant mice do not display increased sensitivity to pain after prostaglandin E2 injection. Likewise, they show a more rapid decrease of the increased pain sensitivity caused by agents that cause local inflammation, such as subcutaneous zymosan injection (PubMed:15131310). Mutant mice display altered phrenic nerve activity, resulting in an irregular breathing rhytm that affects especially the duration of the postinspiratory phase. Contrary to wild-type, their respiratory rhytm is not accelerated by serotonin (PubMed:20978350).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3333Sequence analysisAdd
BLAST
Chaini34 – 464431Glycine receptor subunit alpha-3PRO_0000000420Add
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 – 3701PhosphoserineCombined sources
Modified residuei379 – 3791Phosphoserine; by PKA1 Publication

Post-translational modificationi

Phosphorylated by PKA; this causes down-regulation of channel activity. Dephosphorylated in response to activation of HTR1A signaling; this increases channel activity (PubMed:20978350).By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ91XP5.
PRIDEiQ91XP5.

PTM databases

iPTMnetiQ91XP5.
PhosphoSiteiQ91XP5.

Expressioni

Tissue specificityi

Detected in brainstem, also in neurons that control rhytmic breathing (PubMed:20978350). Detected in superficial laminae of the dorsal horn of the thoracic spinal cord (PubMed:15131310). Detected in dentate gyrus in hippocampus, especially in stratum granulare (PubMed:19723286). Detected in the inner plexiform layer in the retina (at protein level) (PubMed:12975813). Detected in midbrain, thalamus, brain cortex, hippocampus, and at lower levels in cerebellum (PubMed:19723286).4 Publications

Gene expression databases

BgeeiQ91XP5.
CleanExiMM_GLRA3.

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000000275.

Structurei

3D structure databases

ProteinModelPortaliQ91XP5.
SMRiQ91XP5. Positions 47-345, 424-451.
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

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiQ91XP5.
KOiK05195.
PhylomeDBiQ91XP5.

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.

Q91XP5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHVRHFRTL VSGFYFWEAA 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 FSFTAYGMGP CLQAKDGVVP
410 420 430 440 450
KGPNHAVQVM PKSPDEMRKV FIDRAKKIDT ISRACFPLAF LIFNIFYWVI
460
YKILRHEDIH QQQD
Length:464
Mass (Da):53,709
Last modified:May 24, 2005 - v2
Checksum:i0963FD4A3727AA1D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti110 – 1101Missing in AAK51962 (Ref. 1) Curated
Sequence conflicti293 – 2931V → D in AAK51962 (Ref. 1) Curated
Sequence conflicti461 – 4611Q → H in AAK51962 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF362764 mRNA. Translation: AAK51962.1.
AY230204 mRNA. Translation: AAP22967.1.
RefSeqiNP_536686.2. NM_080438.2.
UniGeneiMm.307061.

Genome annotation databases

GeneIDi110304.
KEGGimmu:110304.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF362764 mRNA. Translation: AAK51962.1.
AY230204 mRNA. Translation: AAP22967.1.
RefSeqiNP_536686.2. NM_080438.2.
UniGeneiMm.307061.

3D structure databases

ProteinModelPortaliQ91XP5.
SMRiQ91XP5. Positions 47-345, 424-451.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000000275.

PTM databases

iPTMnetiQ91XP5.
PhosphoSiteiQ91XP5.

Proteomic databases

PaxDbiQ91XP5.
PRIDEiQ91XP5.

Protocols and materials databases

DNASUi110304.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi110304.
KEGGimmu:110304.

Organism-specific databases

CTDi8001.
MGIiMGI:95749. Glra3.

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiQ91XP5.
KOiK05195.
PhylomeDBiQ91XP5.

Miscellaneous databases

PROiQ91XP5.
SOURCEiSearch...

Gene expression databases

BgeeiQ91XP5.
CleanExiMM_GLRA3.

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

« Hide 'large scale' publications
  1. "Different glycine receptor isoforms are expressed in murine cerebellum."
    Noegel S., Becker C., Becker K.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Spinal cord.
  2. "Diversity of glycine receptors in the mouse retina: localization of the alpha3 subunit."
    Haverkamp S., Mueller U., Harvey K., Harvey R.J., Betz H., Waessle H.
    J. Comp. Neurol. 465:524-539(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: C57BL/6J.
  3. Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, ENZYME REGULATION.
  4. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  6. "Serotonin receptor 1A-modulated phosphorylation of glycine receptor alpha3 controls breathing in mice."
    Manzke T., Niebert M., Koch U.R., Caley A., Vogelgesang S., Huelsmann S., Ponimaskin E., Mueller U., Smart T.G., Harvey R.J., Richter D.W.
    J. Clin. Invest. 120:4118-4128(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-379, TISSUE SPECIFICITY.

Entry informationi

Entry nameiGLRA3_MOUSE
AccessioniPrimary (citable) accession number: Q91XP5
Secondary accession number(s): Q7TSQ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: May 24, 2005
Last modified: July 6, 2016
This is version 124 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.By similarity

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.