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Protein

Glycine receptor subunit alpha-3

Gene

GLRA3

Organism
Homo sapiens (Human)
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:9677400, PubMed:26416729). 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 (By similarity). Contributes to the generation of inhibitory postsynaptic currents (By similarity). Contributes to increased pain perception in response to increased prostaglandin E2 levels (By similarity). Plays a role in cellular responses to ethanol (By similarity).By similarity2 Publications

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 conformation1 Publication

GO - Molecular functioni

  • extracellular-glycine-gated chloride channel activity Source: UniProtKB
  • glycine binding Source: InterPro
  • glycine-gated chloride ion channel activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

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-HSA-975298. Ligand-gated ion channel transport.

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-3
Gene namesi
Name:GLRA3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4328. GLRA3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini34 – 255222Extracellular1 PublicationAdd
BLAST
Transmembranei256 – 27722Helical; Name=11 PublicationAdd
BLAST
Topological domaini278 – 2825Cytoplasmic1 Publication
Transmembranei283 – 30321Helical; Name=21 PublicationAdd
BLAST
Topological domaini304 – 31411Extracellular1 PublicationAdd
BLAST
Transmembranei315 – 33521Helical; Name=31 PublicationAdd
BLAST
Topological domaini336 – 43095Cytoplasmic1 PublicationAdd
BLAST
Transmembranei431 – 45121Helical; Name=41 PublicationAdd
BLAST
Topological domaini452 – 46413Extracellular1 PublicationAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • dendrite Source: UniProtKB-SubCell
  • glycine-gated chloride channel complex Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
  • postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28729.

Chemistry

ChEMBLiCHEMBL1075092.
DrugBankiDB00145. Glycine.
DB00602. Ivermectin.
DB00431. Lindane.
GuidetoPHARMACOLOGYi425.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3333Sequence analysisAdd
BLAST
Chaini34 – 464431Glycine receptor subunit alpha-3PRO_0000000419Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi71 – 711N-linked (GlcNAc...)Sequence analysisCombined sources1 Publication
Disulfide bondi171 ↔ 185Combined sources1 Publication
Disulfide bondi231 ↔ 242Combined sources1 Publication
Modified residuei370 – 3701PhosphoserineBy similarity
Modified residuei379 – 3791PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by PKA; this causes down-regulation of channel activity.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO75311.
PeptideAtlasiO75311.
PRIDEiO75311.

PTM databases

iPTMnetiO75311.
PhosphoSiteiO75311.

Expressioni

Tissue specificityi

Widely distributed throughout the central nervous system.1 Publication

Gene expression databases

BgeeiO75311.
CleanExiHS_GLRA3.
GenevisibleiO75311. HS.

Organism-specific databases

HPAiHPA014805.

Interactioni

Subunit structurei

Homopentamer (in vitro) (PubMed:26416729). Heteropentamer composed of GLRA3 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi113705. 1 interaction.
DIPiDIP-61773N.
STRINGi9606.ENSP00000274093.

Chemistry

BindingDBiO75311.

Structurei

Secondary structure

1
464
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 519Combined sources
Turni53 – 553Combined sources
Beta strandi66 – 683Combined sources
Beta strandi70 – 8516Combined sources
Turni86 – 894Combined sources
Beta strandi90 – 10213Combined sources
Turni104 – 1063Combined sources
Beta strandi110 – 1189Combined sources
Helixi123 – 1253Combined sources
Beta strandi131 – 1333Combined sources
Beta strandi136 – 1405Combined sources
Beta strandi144 – 1463Combined sources
Beta strandi149 – 1546Combined sources
Beta strandi157 – 17014Combined sources
Turni176 – 1794Combined sources
Beta strandi186 – 1938Combined sources
Turni196 – 1983Combined sources
Beta strandi199 – 2035Combined sources
Beta strandi209 – 2113Combined sources
Beta strandi218 – 2225Combined sources
Beta strandi227 – 2304Combined sources
Beta strandi233 – 2353Combined sources
Beta strandi238 – 2403Combined sources
Beta strandi242 – 2465Combined sources
Beta strandi249 – 2513Combined sources
Helixi254 – 2596Combined sources
Helixi261 – 27313Combined sources
Helixi274 – 2763Combined sources
Helixi282 – 30423Combined sources
Helixi315 – 34026Combined sources
Helixi419 – 43214Combined sources
Turni433 – 4353Combined sources
Helixi436 – 45116Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CFBX-ray3.04A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
ProteinModelPortaliO75311.
SMRiO75311. Positions 47-345, 424-451.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni235 – 2406Strychnine-binding1 Publication

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 (PubMed:26416729). The cytoplasmic loop is an important determinant of channel inactivation kinetics.Curated1 Publication

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiO75311.
KOiK05195.
OMAiPKNSDEM.
OrthoDBiEOG712TVZ.
PhylomeDBiO75311.
TreeFamiTF315453.

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]
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]

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-3L (identifier: O75311-1) [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
MAHVRHFRTL VSGFYFWEAA LLLSLVATKE TDSARSRSAP 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 DMDDEVRESR FSFTAYGMGP CLQAKDGMTP
410 420 430 440 450
KGPNHPVQVM PKSPDEMRKV FIDRAKKIDT ISRACFPLAF LIFNIFYWVI
460
YKILRHEDIH QQQD
Length:464
Mass (Da):53,800
Last modified:October 17, 2006 - v2
Checksum:i8E17A30B3C6E648D
GO
Isoform Alpha-3K (identifier: O75311-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-372: Missing.

Show »
Length:449
Mass (Da):51,963
Checksum:i342BB384CCA4D33E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti460 – 4601H → HH in AAC39919 (PubMed:9677400).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei358 – 37215Missing in isoform Alpha-3K. 1 PublicationVSP_000084Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017724
, AF017715, AF017716, AF017717, AF017718, AF017719, AF017720, AF017721, AF017722, AF017723 Genomic DNA. Translation: AAC39919.1.
U93917 mRNA. Translation: AAC39917.1.
CH471056 Genomic DNA. Translation: EAX04730.1.
CH471056 Genomic DNA. Translation: EAX04732.1.
BC036086 mRNA. Translation: AAH36086.1.
CCDSiCCDS3822.1. [O75311-1]
CCDS43283.1. [O75311-2]
RefSeqiNP_001036008.1. NM_001042543.2. [O75311-2]
NP_006520.2. NM_006529.3. [O75311-1]
UniGeneiHs.413099.

Genome annotation databases

EnsembliENST00000274093; ENSP00000274093; ENSG00000145451. [O75311-1]
ENST00000340217; ENSP00000345284; ENSG00000145451. [O75311-2]
GeneIDi8001.
KEGGihsa:8001.
UCSCiuc003ity.3. human. [O75311-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017724
, AF017715, AF017716, AF017717, AF017718, AF017719, AF017720, AF017721, AF017722, AF017723 Genomic DNA. Translation: AAC39919.1.
U93917 mRNA. Translation: AAC39917.1.
CH471056 Genomic DNA. Translation: EAX04730.1.
CH471056 Genomic DNA. Translation: EAX04732.1.
BC036086 mRNA. Translation: AAH36086.1.
CCDSiCCDS3822.1. [O75311-1]
CCDS43283.1. [O75311-2]
RefSeqiNP_001036008.1. NM_001042543.2. [O75311-2]
NP_006520.2. NM_006529.3. [O75311-1]
UniGeneiHs.413099.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CFBX-ray3.04A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
ProteinModelPortaliO75311.
SMRiO75311. Positions 47-345, 424-451.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113705. 1 interaction.
DIPiDIP-61773N.
STRINGi9606.ENSP00000274093.

Chemistry

BindingDBiO75311.
ChEMBLiCHEMBL1075092.
DrugBankiDB00145. Glycine.
DB00602. Ivermectin.
DB00431. Lindane.
GuidetoPHARMACOLOGYi425.

Protein family/group databases

TCDBi1.A.9.3.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

iPTMnetiO75311.
PhosphoSiteiO75311.

Proteomic databases

PaxDbiO75311.
PeptideAtlasiO75311.
PRIDEiO75311.

Protocols and materials databases

DNASUi8001.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274093; ENSP00000274093; ENSG00000145451. [O75311-1]
ENST00000340217; ENSP00000345284; ENSG00000145451. [O75311-2]
GeneIDi8001.
KEGGihsa:8001.
UCSCiuc003ity.3. human. [O75311-1]

Organism-specific databases

CTDi8001.
GeneCardsiGLRA3.
HGNCiHGNC:4328. GLRA3.
HPAiHPA014805.
MIMi600421. gene.
neXtProtiNX_O75311.
PharmGKBiPA28729.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiO75311.
KOiK05195.
OMAiPKNSDEM.
OrthoDBiEOG712TVZ.
PhylomeDBiO75311.
TreeFamiTF315453.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiGLRA3.
GenomeRNAii8001.
PROiO75311.
SOURCEiSearch...

Gene expression databases

BgeeiO75311.
CleanExiHS_GLRA3.
GenevisibleiO75311. HS.

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]
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. "The human glycine receptor subunit alpha3. GLRA3 gene structure, chromosomal localization, and functional characterization of alternative transcripts."
    Nikolic Z., Laube B., Weber R.G., Lichter P., Kioschis P., Poustka A., Muelhardt C., Becker C.-M.
    J. Biol. Chem. 273:19708-19714(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA-3K AND ALPHA-3L), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Fetal brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-3L).
    Tissue: Brain.
  4. "Crystal structure of human glycine receptor-alpha3 bound to antagonist strychnine."
    Huang X., Chen H., Michelsen K., Schneider S., Shaffer P.L.
    Nature 526:277-280(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.04 ANGSTROMS) OF 34-342 AND 419-460 IN COMPLEX WITH STRYCHNINE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BONDS, GLYCOSYLATION AT ASN-71, DOMAIN.

Entry informationi

Entry nameiGLRA3_HUMAN
AccessioniPrimary (citable) accession number: O75311
Secondary accession number(s): D3DP44, O75816, Q5D0E3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 17, 2006
Last modified: July 6, 2016
This is version 158 of the entry and version 2 of the sequence. [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

Miscellaneous

The alpha subunit binds strychnine.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.