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Protein

Potassium voltage-gated channel subfamily KQT member 3

Gene

KCNQ3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability.4 Publications

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • delayed rectifier potassium channel activity Source: GO_Central
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels
R-HSA-445095 Interaction between L1 and Ankyrins
SIGNORiO43525

Protein family/group databases

TCDBi1.A.1.15.3 the voltage-gated ion channel (vic) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily KQT member 3Curated
Alternative name(s):
KQT-like 3
Potassium channel subunit alpha KvLQT3
Voltage-gated potassium channel subunit Kv7.3
Gene namesi
Name:KCNQ3Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000184156.15
HGNCiHGNC:6297 KCNQ3
MIMi602232 gene
neXtProtiNX_O43525

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 domaini1 – 121CytoplasmicSequence analysisAdd BLAST121
Transmembranei122 – 142Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini143 – 152ExtracellularSequence analysis10
Transmembranei153 – 173Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini174 – 196CytoplasmicSequence analysisAdd BLAST23
Transmembranei197 – 217Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini218 – 225ExtracellularSequence analysis8
Transmembranei226 – 247Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST22
Topological domaini248 – 261CytoplasmicSequence analysisAdd BLAST14
Transmembranei262 – 282Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini283 – 303ExtracellularSequence analysisAdd BLAST21
Intramembranei304 – 324Pore-forming; Name=Segment H5Sequence analysisAdd BLAST21
Topological domaini325 – 330ExtracellularSequence analysis6
Transmembranei331 – 351Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini352 – 872CytoplasmicSequence analysisAdd BLAST521

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Seizures, benign familial neonatal 2 (BFNS2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset.
See also OMIM:121201
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026994305D → G in BFNS2; reduces the maximal heteromeric current by 40% with no alteration in voltage dependence of activation or deactivation kinetics. 1 PublicationCorresponds to variant dbSNP:rs118192248EnsemblClinVar.1
Natural variantiVAR_010935309W → R in BFNS2. 1 PublicationCorresponds to variant dbSNP:rs118192249EnsemblClinVar.1
Natural variantiVAR_001546310G → V in BFNS2; about 50% reduction of wild-type heteromeric current; ratio of 1:1; or 20%; ratio of 1:1:2. 3 PublicationsCorresponds to variant dbSNP:rs118192250EnsemblClinVar.1
Natural variantiVAR_078681340G → V in BFNS2; unknown pathological significance. 1 Publication1
Defects in KCNQ3 may be involved in epileptic disorders. These are characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi246T → A: No effect on current or expression. 1 Publication1
Mutagenesisi246T → D: Abolishes currents without reducing channel protein expression. 1 Publication1
Mutagenesisi318G → S: >50% Reduction of wt heteromeric current; ratio of 1:1 and 1:1:2. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi3786
MalaCardsiKCNQ3
MIMi121201 phenotype
OpenTargetsiENSG00000184156
Orphaneti306 Benign familial infantile epilepsy
1949 Benign familial neonatal epilepsy
307 Juvenile myoclonic epilepsy
PharmGKBiPA30075

Chemistry databases

ChEMBLiCHEMBL2684
DrugBankiDB00321 Amitriptyline
DB00586 Diclofenac
DB04953 Ezogabine
DB06089 ICA-105665
DB00939 Meclofenamic acid
GuidetoPHARMACOLOGYi562

Polymorphism and mutation databases

BioMutaiKCNQ3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540341 – 872Potassium voltage-gated channel subfamily KQT member 3Add BLAST872

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei81PhosphothreonineBy similarity1
Modified residuei246Phosphothreonine1 Publication1

Post-translational modificationi

KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation (Probable). Degradation induced by NEDD4L is inhibited by USP36 (PubMed:27445338).1 Publication1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO43525
PeptideAtlasiO43525
PRIDEiO43525
ProteomicsDBi49030

PTM databases

iPTMnetiO43525
PhosphoSitePlusiO43525

Expressioni

Tissue specificityi

Predominantly expressed in brain.

Gene expression databases

BgeeiENSG00000184156 Expressed in 129 organ(s), highest expression level in caudate nucleus
CleanExiHS_KCNQ3
ExpressionAtlasiO43525 baseline and differential
GenevisibleiO43525 HS

Interactioni

Subunit structurei

Heterotetramer with KCNQ2; form the heterotetrameric M potassium channel (PubMed:27564677). Interacts with calmodulin; the interaction is calcium-independent, constitutive and participates to the proper assembly of a functional heterotetrameric M channel (PubMed:27564677). Heteromultimer with KCNQ5 (PubMed:11159685). May associate with KCNE2 (PubMed:11034315). Interacts with IQCJ-SCHIP1 (By similarity).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109987, 2 interactors
CORUMiO43525
STRINGi9606.ENSP00000373648

Chemistry databases

BindingDBiO43525

Structurei

Secondary structure

1872
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43525
SMRiO43525
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni356 – 537Mediates interaction with calmodulin1 PublicationAdd BLAST182

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi316 – 321Selectivity filterBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi13 – 24Poly-GlyAdd BLAST12

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1419 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00550000074513
HOGENOMiHOG000220839
HOVERGENiHBG059014
InParanoidiO43525
KOiK04928
OMAiHVTEYYP
OrthoDBiEOG091G02ZT
PhylomeDBiO43525
TreeFamiTF315186

Family and domain databases

InterProiView protein in InterPro
IPR020969 Ankyrin-G_BS
IPR005821 Ion_trans_dom
IPR003937 K_chnl_volt-dep_KCNQ
IPR003948 K_chnl_volt-dep_KCNQ3
IPR013821 K_chnl_volt-dep_KCNQ_C
IPR028325 VG_K_chnl
PANTHERiPTHR11537 PTHR11537, 1 hit
PTHR11537:SF5 PTHR11537:SF5, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
PF03520 KCNQ_channel, 1 hit
PF11956 KCNQC3-Ank-G_bd, 1 hit
PRINTSiPR00169 KCHANNEL
PR01462 KCNQ3CHANNEL
PR01459 KCNQCHANNEL

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O43525-1) [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
MGLKARRAAG AAGGGGDGGG GGGGAANPAG GDAAAAGDEE RKVGLAPGDV
60 70 80 90 100
EQVTLALGAG ADKDGTLLLE GGGRDEGQRR TPQGIGLLAK TPLSRPVKRN
110 120 130 140 150
NAKYRRIQTL IYDALERPRG WALLYHALVF LIVLGCLILA VLTTFKEYET
160 170 180 190 200
VSGDWLLLLE TFAIFIFGAE FALRIWAAGC CCRYKGWRGR LKFARKPLCM
210 220 230 240 250
LDIFVLIASV PVVAVGNQGN VLATSLRSLR FLQILRMLRM DRRGGTWKLL
260 270 280 290 300
GSAICAHSKE LITAWYIGFL TLILSSFLVY LVEKDVPEVD AQGEEMKEEF
310 320 330 340 350
ETYADALWWG LITLATIGYG DKTPKTWEGR LIAATFSLIG VSFFALPAGI
360 370 380 390 400
LGSGLALKVQ EQHRQKHFEK RRKPAAELIQ AAWRYYATNP NRIDLVATWR
410 420 430 440 450
FYESVVSFPF FRKEQLEAAS SQKLGLLDRV RLSNPRGSNT KGKLFTPLNV
460 470 480 490 500
DAIEESPSKE PKPVGLNNKE RFRTAFRMKA YAFWQSSEDA GTGDPMAEDR
510 520 530 540 550
GYGNDFPIED MIPTLKAAIR AVRILQFRLY KKKFKETLRP YDVKDVIEQY
560 570 580 590 600
SAGHLDMLSR IKYLQTRIDM IFTPGPPSTP KHKKSQKGSA FTFPSQQSPR
610 620 630 640 650
NEPYVARPST SEIEDQSMMG KFVKVERQVQ DMGKKLDFLV DMHMQHMERL
660 670 680 690 700
QVQVTEYYPT KGTSSPAEAE KKEDNRYSDL KTIICNYSET GPPEPPYSFH
710 720 730 740 750
QVTIDKVSPY GFFAHDPVNL PRGGPSSGKV QATPPSSATT YVERPTVLPI
760 770 780 790 800
LTLLDSRVSC HSQADLQGPY SDRISPRQRR SITRDSDTPL SLMSVNHEEL
810 820 830 840 850
ERSPSGFSIS QDRDDYVFGP NGGSSWMREK RYLAEGETDT DTDPFTPSGS
860 870
MPLSSTGDGI SDSVWTPSNK PI
Length:872
Mass (Da):96,742
Last modified:July 15, 1999 - v2
Checksum:iBB79C69EE8591A84
GO
Isoform 2 (identifier: O43525-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MGLKARRAA → MKPAEHATM
     10-129: Missing.

Note: No experimental confirmation available.
Show »
Length:752
Mass (Da):84,804
Checksum:iBC8C18D5BE17F0DB
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZB4A0A087WZB4_HUMAN
Potassium voltage-gated channel sub...
KCNQ3
751Annotation score:
E7ET42E7ET42_HUMAN
Potassium voltage-gated channel sub...
KCNQ3
860Annotation score:
A0A1W2PQ71A0A1W2PQ71_HUMAN
Potassium voltage-gated channel sub...
KCNQ3
716Annotation score:
A0A1W2PNZ2A0A1W2PNZ2_HUMAN
Potassium voltage-gated channel sub...
KCNQ3
319Annotation score:
A0A1W2PRN8A0A1W2PRN8_HUMAN
Potassium voltage-gated channel sub...
KCNQ3
89Annotation score:

Sequence cautioni

The sequence AAI28577 differs from that shown. Aberrant splicing.Curated
The sequence AAI28577 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62D → N in AAI28577 (PubMed:15489334).Curated1
Sequence conflicti233Q → L in BAG58996 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026994305D → G in BFNS2; reduces the maximal heteromeric current by 40% with no alteration in voltage dependence of activation or deactivation kinetics. 1 PublicationCorresponds to variant dbSNP:rs118192248EnsemblClinVar.1
Natural variantiVAR_010935309W → R in BFNS2. 1 PublicationCorresponds to variant dbSNP:rs118192249EnsemblClinVar.1
Natural variantiVAR_001546310G → V in BFNS2; about 50% reduction of wild-type heteromeric current; ratio of 1:1; or 20%; ratio of 1:1:2. 3 PublicationsCorresponds to variant dbSNP:rs118192250EnsemblClinVar.1
Natural variantiVAR_078681340G → V in BFNS2; unknown pathological significance. 1 Publication1
Natural variantiVAR_053859414E → G. Corresponds to variant dbSNP:rs2303995EnsemblClinVar.1
Natural variantiVAR_026995468N → S Has no statistically significant effect on the current or biophysical properties of the heteromeric channel. 1 PublicationCorresponds to variant dbSNP:rs118192252Ensembl.1
Natural variantiVAR_072741574P → S Rare variant; found in a patient with rolandic epilepsy and additional features such as mild developmental delay and abnormal behavior; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs74582884EnsemblClinVar.1
Natural variantiVAR_078682780R → C Found in patients with benign familial infantile seizures; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138852641EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449061 – 9MGLKARRAA → MKPAEHATM in isoform 2. 1 Publication9
Alternative sequenceiVSP_04490710 – 129Missing in isoform 2. 1 PublicationAdd BLAST120

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF071491
, AF071478, AF071479, AF071480, AF071481, AF071482, AF071483, AF071484, AF071485, AF071486, AF071487, AF071488, AF071489, AF071490 Genomic DNA Translation: AAC96101.1
AK296293 mRNA Translation: BAG58996.1
AC018540 Genomic DNA No translation available.
AC123776 Genomic DNA No translation available.
AC131042 Genomic DNA No translation available.
AC136373 Genomic DNA No translation available.
BC128576 mRNA Translation: AAI28577.1 Sequence problems.
AF033347 mRNA Translation: AAB97314.1
CCDSiCCDS34943.1 [O43525-1]
CCDS56554.1 [O43525-2]
RefSeqiNP_001191753.1, NM_001204824.1 [O43525-2]
NP_004510.1, NM_004519.3 [O43525-1]
UniGeneiHs.374023

Genome annotation databases

EnsembliENST00000388996; ENSP00000373648; ENSG00000184156 [O43525-1]
ENST00000521134; ENSP00000429799; ENSG00000184156 [O43525-2]
GeneIDi3786
KEGGihsa:3786
UCSCiuc003yti.4 human [O43525-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF071491
, AF071478, AF071479, AF071480, AF071481, AF071482, AF071483, AF071484, AF071485, AF071486, AF071487, AF071488, AF071489, AF071490 Genomic DNA Translation: AAC96101.1
AK296293 mRNA Translation: BAG58996.1
AC018540 Genomic DNA No translation available.
AC123776 Genomic DNA No translation available.
AC131042 Genomic DNA No translation available.
AC136373 Genomic DNA No translation available.
BC128576 mRNA Translation: AAI28577.1 Sequence problems.
AF033347 mRNA Translation: AAB97314.1
CCDSiCCDS34943.1 [O43525-1]
CCDS56554.1 [O43525-2]
RefSeqiNP_001191753.1, NM_001204824.1 [O43525-2]
NP_004510.1, NM_004519.3 [O43525-1]
UniGeneiHs.374023

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J03X-ray2.00A354-409[»]
ProteinModelPortaliO43525
SMRiO43525
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109987, 2 interactors
CORUMiO43525
STRINGi9606.ENSP00000373648

Chemistry databases

BindingDBiO43525
ChEMBLiCHEMBL2684
DrugBankiDB00321 Amitriptyline
DB00586 Diclofenac
DB04953 Ezogabine
DB06089 ICA-105665
DB00939 Meclofenamic acid
GuidetoPHARMACOLOGYi562

Protein family/group databases

TCDBi1.A.1.15.3 the voltage-gated ion channel (vic) superfamily

PTM databases

iPTMnetiO43525
PhosphoSitePlusiO43525

Polymorphism and mutation databases

BioMutaiKCNQ3

Proteomic databases

PaxDbiO43525
PeptideAtlasiO43525
PRIDEiO43525
ProteomicsDBi49030

Protocols and materials databases

DNASUi3786
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000388996; ENSP00000373648; ENSG00000184156 [O43525-1]
ENST00000521134; ENSP00000429799; ENSG00000184156 [O43525-2]
GeneIDi3786
KEGGihsa:3786
UCSCiuc003yti.4 human [O43525-1]

Organism-specific databases

CTDi3786
DisGeNETi3786
EuPathDBiHostDB:ENSG00000184156.15
GeneCardsiKCNQ3
HGNCiHGNC:6297 KCNQ3
MalaCardsiKCNQ3
MIMi121201 phenotype
602232 gene
neXtProtiNX_O43525
OpenTargetsiENSG00000184156
Orphaneti306 Benign familial infantile epilepsy
1949 Benign familial neonatal epilepsy
307 Juvenile myoclonic epilepsy
PharmGKBiPA30075
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1419 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00550000074513
HOGENOMiHOG000220839
HOVERGENiHBG059014
InParanoidiO43525
KOiK04928
OMAiHVTEYYP
OrthoDBiEOG091G02ZT
PhylomeDBiO43525
TreeFamiTF315186

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels
R-HSA-445095 Interaction between L1 and Ankyrins
SIGNORiO43525

Miscellaneous databases

ChiTaRSiKCNQ3 human
GeneWikiiKvLQT3
GenomeRNAii3786
PROiPR:O43525
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184156 Expressed in 129 organ(s), highest expression level in caudate nucleus
CleanExiHS_KCNQ3
ExpressionAtlasiO43525 baseline and differential
GenevisibleiO43525 HS

Family and domain databases

InterProiView protein in InterPro
IPR020969 Ankyrin-G_BS
IPR005821 Ion_trans_dom
IPR003937 K_chnl_volt-dep_KCNQ
IPR003948 K_chnl_volt-dep_KCNQ3
IPR013821 K_chnl_volt-dep_KCNQ_C
IPR028325 VG_K_chnl
PANTHERiPTHR11537 PTHR11537, 1 hit
PTHR11537:SF5 PTHR11537:SF5, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
PF03520 KCNQ_channel, 1 hit
PF11956 KCNQC3-Ank-G_bd, 1 hit
PRINTSiPR00169 KCHANNEL
PR01462 KCNQ3CHANNEL
PR01459 KCNQCHANNEL
ProtoNetiSearch...

Entry informationi

Entry nameiKCNQ3_HUMAN
AccessioniPrimary (citable) accession number: O43525
Secondary accession number(s): A2VCT8, B4DJY4, E7EQ89
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: November 7, 2018
This is version 179 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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