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Protein

Glycine receptor subunit alpha-2

Gene

Glra2

Organism
Rattus norvegicus (Rat)
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. Channel opening is also triggered by taurine and beta-alanine (PubMed:2176511). Plays a role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Plays a role in cellular responses to ethanol.By similarity1 Publication

Enzyme regulationi

Inhibited by strychnine.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei194 – 1941Important for glycine and strychnine binding1 Publication
Metal bindingi226 – 2261ZincBy similarity
Metal bindingi228 – 2281ZincBy similarity
Metal bindingi249 – 2491ZincBy similarity
Sitei295 – 2951Important for obstruction of the ion pore in the closed conformationBy similarity

GO - Molecular functioni

GO - Biological processi

  • chloride transmembrane transport Source: GOC
  • spinal cord development Source: RGD
  • synapse assembly Source: RGD
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-2
Alternative name(s):
Glycine receptor strychnine-binding subunit
Gene namesi
Name:Glra2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2705. Glra2.

Subcellular locationi

  • Cell junctionsynapsepostsynaptic cell membrane By similarity; Multi-pass membrane protein By similarity
  • Cell junctionsynapse By similarity
  • Cell membrane 1 Publication; Multi-pass membrane protein By similarity
  • Cell projection By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 256229ExtracellularBy similarityAdd
BLAST
Transmembranei257 – 27822Helical; Name=1By similarityAdd
BLAST
Topological domaini279 – 2835CytoplasmicBy similarity
Transmembranei284 – 30421Helical; Name=2By similarityAdd
BLAST
Topological domaini305 – 31511ExtracellularBy similarityAdd
BLAST
Transmembranei316 – 33621Helical; Name=3By similarityAdd
BLAST
Topological domaini337 – 42084CytoplasmicBy similarityAdd
BLAST
Transmembranei421 – 44121Helical; Name=4By similarityAdd
BLAST
Topological domaini442 – 45211ExtracellularBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3392921.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 452425Glycine receptor subunit alpha-2PRO_0000000418Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi72 – 721N-linked (GlcNAc...)Sequence analysis
Glycosylationi103 – 1031N-linked (GlcNAc...)Sequence analysis
Disulfide bondi172 ↔ 186By similarity
Disulfide bondi232 ↔ 243By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP22771.

Expressioni

Developmental stagei

The alpha-2* subunit isoform is present in neonatal rats, but not in older animals (PubMed:2176511, PubMed:1707830). Isoform Alpha-2* and isoform Alpha-2B are detected in embryonic and neonatal brain. At later postnatal stages, isoform Alpha-2* levels greatly decrease while isoform Alpha-2B is barely detectable (PubMed:1645300).2 Publications

Interactioni

Subunit structurei

Homopentamer (in vitro). Interacts with GLRB. Heteropentamer composed of GLRA2 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000004443.

Chemistry

BindingDBiP22771.

Structurei

3D structure databases

ProteinModelPortaliP22771.
SMRiP22771. Positions 284-343.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni236 – 2416Strychnine-bindingBy similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiP22771.
KOiK05194.
OrthoDBiEOG712TVZ.
PhylomeDBiP22771.
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 (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 Alpha-2* (identifier: P22771-1) [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 ALFAFFLGTN HFREAFCKDH DSRSGKHPSQ 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 ESFEYTMNDL
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
PKDADAIKKK FVDRAKRIDT ISRAAFPLAF LIFNIFYWIT YKIIRHEDVH

KK
Length:452
Mass (Da):52,053
Last modified:August 1, 1991 - v1
Checksum:iA9EBC6D1552A3A1C
GO
Isoform Alpha-2B (identifier: P22771-2) [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):52,037
Checksum:iA3921B63CC57A8D4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti194 – 1941E → G Increased sensitivity to strychnine. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei85 – 862VT → IA in isoform Alpha-2B. CuratedVSP_000083

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57281 mRNA. Translation: CAA40549.1.
X61159 mRNA. Translation: CAA43471.1.
AJ310837 mRNA. Translation: CAC35981.1.
PIRiS14816.
S18836.
RefSeqiNP_036700.1. NM_012568.3.
XP_003752087.1. XM_003752039.3.
UniGeneiRn.10379.

Genome annotation databases

GeneIDi24397.
KEGGirno:24397.
UCSCiRGD:2705. rat. [P22771-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57281 mRNA. Translation: CAA40549.1.
X61159 mRNA. Translation: CAA43471.1.
AJ310837 mRNA. Translation: CAC35981.1.
PIRiS14816.
S18836.
RefSeqiNP_036700.1. NM_012568.3.
XP_003752087.1. XM_003752039.3.
UniGeneiRn.10379.

3D structure databases

ProteinModelPortaliP22771.
SMRiP22771. Positions 284-343.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000004443.

Chemistry

BindingDBiP22771.
ChEMBLiCHEMBL3392921.

Proteomic databases

PaxDbiP22771.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24397.
KEGGirno:24397.
UCSCiRGD:2705. rat. [P22771-1]

Organism-specific databases

CTDi2742.
RGDi2705. Glra2.

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiP22771.
KOiK05194.
OrthoDBiEOG712TVZ.
PhylomeDBiP22771.
TreeFamiTF315453.

Miscellaneous databases

NextBioi603187.
PROiP22771.

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...

Publicationsi

  1. "A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit."
    Kuhse J., Schmieden V., Betz H.
    Neuron 5:867-873(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, DEVELOPMENTAL STAGE, VARIANT GLY-194, CHARACTERIZATION OF VARIANT GLY-194.
    Tissue: Brain.
  2. "Cloning of a glycine receptor subtype expressed in rat brain and spinal cord during a specific period of neuronal development."
    Akagi H., Hirai K., Hishinuma F.
    FEBS Lett. 281:160-166(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*), DEVELOPMENTAL STAGE.
    Strain: Wistar.
    Tissue: Spinal cord.
  3. "Alternative splicing generates two isoforms of the alpha 2 subunit of the inhibitory glycine receptor."
    Kuhse J., Kuryatov A., Maulet Y., Malosio M.L., Schmieden V., Betz H.
    FEBS Lett. 283:73-77(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-2* AND ALPHA-2B), DEVELOPMENTAL STAGE.
    Tissue: Brain.
  4. "Concentration dependence of single channel currents through rat recombinant alpha 1 glycine receptors."
    Beato M., Groot Kormelink P.J., Colquhoun D., Sivilotti L.G.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2*).
    Strain: Sprague-Dawley.
    Tissue: Brain.

Entry informationi

Entry nameiGLRA2_RAT
AccessioniPrimary (citable) accession number: P22771
Secondary accession number(s): Q91W28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: May 11, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The alpha subunit binds strychnine.1 Publication
Identical to the human subunit alpha-2, except for 5 substitutions at positions 18, 24, 37, 194 and 404. Substitution at position 194 (G -> E) accounts for the lower strychnine sensitivity observed in neonatal rats.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.