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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)DescriptionActionsGraphical viewLength
Metal bindingi225ZincBy similarity1
Metal bindingi227ZincBy similarity1
Metal bindingi248ZincBy similarity1
Sitei294Important for obstruction of the ion pore in the closed conformation1 Publication1

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

BioCyciZFISH:ENSG00000145451-MONOMER.
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)DescriptionActionsGraphical viewLength
Topological domaini34 – 255Extracellular1 PublicationAdd BLAST222
Transmembranei256 – 277Helical; Name=11 PublicationAdd BLAST22
Topological domaini278 – 282Cytoplasmic1 Publication5
Transmembranei283 – 303Helical; Name=21 PublicationAdd BLAST21
Topological domaini304 – 314Extracellular1 PublicationAdd BLAST11
Transmembranei315 – 335Helical; Name=31 PublicationAdd BLAST21
Topological domaini336 – 430Cytoplasmic1 PublicationAdd BLAST95
Transmembranei431 – 451Helical; Name=41 PublicationAdd BLAST21
Topological domaini452 – 464Extracellular1 PublicationAdd BLAST13

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

DisGeNETi8001.
OpenTargetsiENSG00000145451.
PharmGKBiPA28729.

Chemistry databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000000041934 – 464Glycine receptor subunit alpha-3Add BLAST431

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...)Sequence analysisCombined sources1 Publication1
Disulfide bondi171 ↔ 185Combined sources1 Publication
Disulfide bondi231 ↔ 242Combined sources1 Publication
Modified residuei370PhosphoserineBy similarity1
Modified residuei379PhosphoserineBy similarity1

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.
PhosphoSitePlusiO75311.

Expressioni

Tissue specificityi

Widely distributed throughout the central nervous system.1 Publication

Gene expression databases

BgeeiENSG00000145451.
CleanExiHS_GLRA3.
GenevisibleiO75311. HS.

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 interactor.
DIPiDIP-61773N.
STRINGi9606.ENSP00000274093.

Chemistry databases

BindingDBiO75311.

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 51Combined sources9
Turni53 – 55Combined sources3
Beta strandi66 – 68Combined sources3
Beta strandi70 – 85Combined sources16
Turni86 – 89Combined sources4
Beta strandi90 – 102Combined sources13
Turni104 – 106Combined sources3
Beta strandi110 – 118Combined sources9
Helixi123 – 125Combined sources3
Beta strandi131 – 133Combined sources3
Beta strandi136 – 140Combined sources5
Beta strandi144 – 146Combined sources3
Beta strandi149 – 154Combined sources6
Beta strandi157 – 170Combined sources14
Turni176 – 179Combined sources4
Beta strandi186 – 193Combined sources8
Turni196 – 198Combined sources3
Beta strandi199 – 203Combined sources5
Beta strandi209 – 211Combined sources3
Beta strandi218 – 222Combined sources5
Beta strandi227 – 230Combined sources4
Beta strandi233 – 235Combined sources3
Beta strandi238 – 240Combined sources3
Beta strandi242 – 246Combined sources5
Beta strandi249 – 251Combined sources3
Helixi254 – 259Combined sources6
Helixi261 – 273Combined sources13
Helixi274 – 276Combined sources3
Helixi282 – 304Combined sources23
Helixi315 – 340Combined sources26
Helixi419 – 432Combined sources14
Turni433 – 435Combined sources3
Helixi436 – 451Combined sources16

3D structure databases

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

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni235 – 240Strychnine-binding1 Publication6

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.
OrthoDBiEOG091G0805.
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)DescriptionActionsGraphical viewLength
Sequence conflicti460H → HH in AAC39919 (PubMed:9677400).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000084358 – 372Missing in isoform Alpha-3K. 1 PublicationAdd BLAST15

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CFBX-ray3.04A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
ProteinModelPortaliO75311.
SMRiO75311.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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.
PhosphoSitePlusiO75311.

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.
DisGeNETi8001.
GeneCardsiGLRA3.
HGNCiHGNC:4328. GLRA3.
MIMi600421. gene.
neXtProtiNX_O75311.
OpenTargetsiENSG00000145451.
PharmGKBiPA28729.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3643. Eukaryota.
ENOG410XPWH. LUCA.
GeneTreeiENSGT00760000118821.
HOGENOMiHOG000231336.
HOVERGENiHBG051707.
InParanoidiO75311.
KOiK05195.
OMAiPKNSDEM.
OrthoDBiEOG091G0805.
PhylomeDBiO75311.
TreeFamiTF315453.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000145451-MONOMER.
ReactomeiR-HSA-975298. Ligand-gated ion channel transport.

Miscellaneous databases

GeneWikiiGLRA3.
GenomeRNAii8001.
PROiO75311.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145451.
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...

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: November 2, 2016
This is version 161 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.