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Protein

Glycine receptor subunit alpha-3

Gene

GLRA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

The alpha subunit binds strychnine.1 Publication

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

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport
LigandChloride, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission

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

EuPathDBiHostDB:ENSG00000145451.12
HGNCiHGNC:4328 GLRA3
MIMi600421 gene
neXtProtiNX_O75311

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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
DB00466 Picrotoxin
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...) asparagineSequence 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
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
Turni63 – 66Combined sources4
Beta strandi70 – 85Combined sources16
Turni86 – 89Combined sources4
Beta strandi90 – 102Combined sources13
Helixi104 – 106Combined sources3
Beta strandi114 – 118Combined sources5
Helixi120 – 125Combined sources6
Beta strandi131 – 133Combined sources3
Beta strandi136 – 141Combined sources6
Beta strandi144 – 146Combined sources3
Beta strandi149 – 154Combined sources6
Beta strandi157 – 170Combined sources14
Turni176 – 179Combined sources4
Beta strandi182 – 193Combined sources12
Turni196 – 198Combined sources3
Beta strandi199 – 203Combined sources5
Beta strandi208 – 211Combined sources4
Beta strandi218 – 222Combined sources5
Beta strandi227 – 230Combined sources4
Beta strandi233 – 235Combined sources3
Beta strandi238 – 240Combined sources3
Beta strandi242 – 251Combined sources10
Helixi254 – 259Combined sources6
Helixi261 – 273Combined sources13
Helixi274 – 276Combined sources3
Helixi282 – 302Combined sources21
Turni303 – 306Combined sources4
Helixi315 – 340Combined sources26
Helixi419 – 450Combined sources32

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[»]
5TINX-ray2.61A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
5TIOX-ray3.25A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
5VDHX-ray2.85A/B/C/D/E34-342[»]
A/B/C/D/E419-460[»]
5VDIX-ray3.10A/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
OMAiMPMSPSD
OrthoDBiEOG091G0805
PhylomeDBiO75311
TreeFamiTF315453

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR006028 GABAA/Glycine_rcpt
IPR008127 Glycine_rcpt_A
IPR008130 Glycine_rcpt_A3
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR00253 GABAARECEPTR
PR01673 GLYRALPHA
PR01676 GLYRALPHA3
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiGLRA3_HUMAN
AccessioniPrimary (citable) accession number: O75311
Secondary accession number(s): D3DP44, O75816, Q5D0E3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 17, 2006
Last modified: February 28, 2018
This is version 174 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health