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Protein

Transcription factor 12

Gene

TCF12

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

Functioni

Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3').

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processDifferentiation, Neurogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-375170 CDO in myogenesis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
SIGNORiQ99081

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor 12
Short name:
TCF-12
Alternative name(s):
Class B basic helix-loop-helix protein 20
Short name:
bHLHb20
DNA-binding protein HTF4
E-box-binding protein
Transcription factor HTF-4
Gene namesi
Name:TCF12
Synonyms:BHLHB20, HEB, HTF4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140262.17
HGNCiHGNC:11623 TCF12
MIMi600480 gene
neXtProtiNX_Q99081

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Craniosynostosis 3 (CRS3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.
See also OMIM:615314
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072271483L → R in CRS3. 1 PublicationCorresponds to variant dbSNP:rs36060670Ensembl.1
Natural variantiVAR_070096600L → P in CRS3. 1 Publication1
Natural variantiVAR_070097614Q → E in CRS3. 1 PublicationCorresponds to variant dbSNP:rs886037641Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi187P → A: Decreases interaction with RUNX1T1. 1 Publication1
Mutagenesisi191P → A: Decreases interaction with RUNX1T1. 1 Publication1
Mutagenesisi192S → A: Decreases interaction with RUNX1T1. 1 Publication1

Keywords - Diseasei

Craniosynostosis, Disease mutation

Organism-specific databases

DisGeNETi6938
MalaCardsiTCF12
MIMi615314 phenotype
OpenTargetsiENSG00000140262
Orphaneti209916 Extraskeletal myxoid chondrosarcoma
35099 Isolated brachycephaly
35098 Isolated plagiocephaly
PharmGKBiPA36381

Polymorphism and mutation databases

BioMutaiTCF12
DMDMi1708332

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001272281 – 682Transcription factor 12Add BLAST682

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47PhosphoserineCombined sources1
Modified residuei67PhosphoserineCombined sources1
Modified residuei79PhosphoserineCombined sources1
Modified residuei98PhosphoserineCombined sources1
Cross-linki110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei116PhosphoserineCombined sources1
Cross-linki181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei313PhosphothreonineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Cross-linki519Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei540PhosphoserineCombined sources1
Cross-linki550Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei557PhosphothreonineCombined sources1
Modified residuei558PhosphoserineCombined sources1
Modified residuei559PhosphoserineCombined sources1
Cross-linki609Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki653Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99081
MaxQBiQ99081
PaxDbiQ99081
PeptideAtlasiQ99081
PRIDEiQ99081
ProteomicsDBi78231
78232 [Q99081-2]
78233 [Q99081-3]

PTM databases

iPTMnetiQ99081
PhosphoSitePlusiQ99081

Expressioni

Tissue specificityi

Expressed in several tissues and cell types including skeletal muscle, thymus, and a B-cell line.

Gene expression databases

BgeeiENSG00000140262 Expressed in 236 organ(s), highest expression level in corpus callosum
CleanExiHS_TCF12
ExpressionAtlasiQ99081 baseline and differential
GenevisibleiQ99081 HS

Organism-specific databases

HPAiCAB004432
HPA065827

Interactioni

Subunit structurei

Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin, E12 and ITF2 proteins. Interacts with PTF1A. Interacts with NEUROD2 (By similarity). Interacts with RUNX1T1. Interacts with AML1-MTG8/ETO (via nervy homology region 2 in oligomerized form) (PubMed:23812588). Interacts with BHLHA9 (PubMed:25466284).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112798, 79 interactors
CORUMiQ99081
DIPiDIP-29403N
IntActiQ99081, 89 interactors
MINTiQ99081
STRINGi9606.ENSP00000331057

Structurei

Secondary structure

1682
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99081
SMRiQ99081
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99081

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini577 – 630bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni119 – 140Leucine-zipperAdd BLAST22
Regioni182 – 196Interaction with RUNX1T11 PublicationAdd BLAST15
Regioni632 – 655Class A specific domainAdd BLAST24

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 279aaTAD9

Domaini

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.1 Publication

Phylogenomic databases

eggNOGiKOG3910 Eukaryota
ENOG410XYUA LUCA
GeneTreeiENSGT00510000046438
HOGENOMiHOG000234180
HOVERGENiHBG003854
InParanoidiQ99081
KOiK15603
OMAiYYSFSAT
PhylomeDBiQ99081
TreeFamiTF321672

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q99081-1) [UniParc]FASTAAdd to basket
Also known as: a

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
MNPQQQRMAA IGTDKELSDL LDFSAMFSPP VNSGKTRPTT LGSSQFSGSG
60 70 80 90 100
IDERGGTTSW GTSGQPSPSY DSSRGFTDSP HYSDHLNDSR LGAHEGLSPT
110 120 130 140 150
PFMNSNLMGK TSERGSFSLY SRDTGLPGCQ SSLLRQDLGL GSPAQLSSSG
160 170 180 190 200
KPGTAYYSFS ATSSRRRPLH DSAALDPLQA KKVRKVPPGL PSSVYAPSPN
210 220 230 240 250
SDDFNRESPS YPSPKPPTSM FASTFFMQDG THNSSDLWSS SNGMSQPGFG
260 270 280 290 300
GILGTSTSHM SQSSSYGNLH SHDRLSYPPH SVSPTDINTS LPPMSSFHRG
310 320 330 340 350
STSSSPYVAA SHTPPINGSD SILGTRGNAA GSSQTGDALG KALASIYSPD
360 370 380 390 400
HTSSSFPSNP STPVGSPSPL TGTSQWPRPG GQAPSSPSYE NSLHSLQSRM
410 420 430 440 450
EDRLDRLDDA IHVLRNHAVG PSTSLPAGHS DIHSLLGPSH NAPIGSLNSN
460 470 480 490 500
YGGSSLVASS RSASMVGTHR EDSVSLNGNH SVLSSTVTTS STDLNHKTQE
510 520 530 540 550
NYRGGLQSQS GTVVTTEIKT ENKEKDENLH EPPSSDDMKS DDESSQKDIK
560 570 580 590 600
VSSRGRTSST NEDEDLNPEQ KIEREKERRM ANNARERLRV RDINEAFKEL
610 620 630 640 650
GRMCQLHLKS EKPQTKLLIL HQAVAVILSL EQQVRERNLN PKAACLKRRE
660 670 680
EEKVSAVSAE PPTTLPGTHP GLSETTNPMG HM
Length:682
Mass (Da):72,965
Last modified:October 1, 1996 - v1
Checksum:i9736113D9361D3F5
GO
Isoform 2 (identifier: Q99081-2) [UniParc]FASTAAdd to basket
Also known as: b

The sequence of this isoform differs from the canonical sequence as follows:
     1-170: Missing.
     171-193: DSAALDPLQAKKVRKVPPGLPSS → MYCAYPVPGMGSNSLMYYYNGKT

Show »
Length:512
Mass (Da):55,142
Checksum:i98AF7F83F8A2AEF4
GO
Isoform 3 (identifier: Q99081-3) [UniParc]FASTAAdd to basket
Also known as: c

The sequence of this isoform differs from the canonical sequence as follows:
     396-396: L → LKNRVEQQLHEHLQDAMSFLKDVCE

Show »
Length:706
Mass (Da):75,845
Checksum:i75B7B4173C9B660D
GO
Isoform 4 (identifier: Q99081-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MNPQQQRMAA...PVNSGKTRPT → MGKRYMHHPQ...VCSLALSLCK
     40-275: Missing.

Note: No experimental confirmation available.
Show »
Length:446
Mass (Da):48,157
Checksum:i1165CAD3B87F74DD
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DGI9B4DGI9_HUMAN
cDNA FLJ52589, highly similar to Tr...
TCF12
666Annotation score:
H0YNQ5H0YNQ5_HUMAN
Transcription factor 12
TCF12
157Annotation score:
F5GY10F5GY10_HUMAN
Transcription factor 12
TCF12
536Annotation score:
B4DZP2B4DZP2_HUMAN
cDNA FLJ51686, highly similar to Tr...
TCF12
316Annotation score:
H0YNP8H0YNP8_HUMAN
Transcription factor 12
TCF12
339Annotation score:
H0YML2H0YML2_HUMAN
Transcription factor 12
TCF12
58Annotation score:
H3BNF4H3BNF4_HUMAN
Transcription factor 12
TCF12
48Annotation score:
H3BRK2H3BRK2_HUMAN
Transcription factor 12
TCF12
44Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti523K → E in CAD89914 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049543300G → S. Corresponds to variant dbSNP:rs12442879EnsemblClinVar.1
Natural variantiVAR_072271483L → R in CRS3. 1 PublicationCorresponds to variant dbSNP:rs36060670Ensembl.1
Natural variantiVAR_070096600L → P in CRS3. 1 Publication1
Natural variantiVAR_070097614Q → E in CRS3. 1 PublicationCorresponds to variant dbSNP:rs886037641Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0391091 – 170Missing in isoform 2. 1 PublicationAdd BLAST170
Alternative sequenceiVSP_0574191 – 39MNPQQ…KTRPT → MGKRYMHHPQIQMISTVNLL VIHLLSHQPVCSLALSLCK in isoform 4. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_05742040 – 275Missing in isoform 4. 1 PublicationAdd BLAST236
Alternative sequenceiVSP_039110171 – 193DSAAL…GLPSS → MYCAYPVPGMGSNSLMYYYN GKT in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_040024396L → LKNRVEQQLHEHLQDAMSFL KDVCE in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83233 mRNA Translation: AAB62389.1
M80627 mRNA Translation: AAA58632.1
AL831981 mRNA Translation: CAD89914.1
AK304007 mRNA Translation: BAG64923.1
BX537967 mRNA Translation: CAD97931.1
AC010999 Genomic DNA No translation available.
AC016525 Genomic DNA No translation available.
AC090511 Genomic DNA No translation available.
AC090532 Genomic DNA No translation available.
KF456057 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77512.1
BC050556 mRNA Translation: AAH50556.1
M65209 mRNA Translation: AAC37571.1
BK001049 mRNA Translation: DAA01129.1
CCDSiCCDS10159.1 [Q99081-1]
CCDS10160.1 [Q99081-3]
CCDS42042.1 [Q99081-2]
CCDS76761.1 [Q99081-4]
PIRiA42121
RefSeqiNP_001293149.1, NM_001306220.2 [Q99081-4]
NP_001309080.1, NM_001322151.1 [Q99081-3]
NP_001309086.1, NM_001322157.1 [Q99081-1]
NP_001309088.1, NM_001322159.1 [Q99081-3]
NP_001309091.1, NM_001322162.1 [Q99081-3]
NP_001309094.1, NM_001322165.1 [Q99081-1]
NP_003196.1, NM_003205.3 [Q99081-1]
NP_996919.1, NM_207036.1 [Q99081-3]
NP_996920.1, NM_207037.1 [Q99081-3]
NP_996921.1, NM_207038.1 [Q99081-1]
NP_996923.1, NM_207040.1 [Q99081-2]
UniGeneiHs.511504

Genome annotation databases

EnsembliENST00000267811; ENSP00000267811; ENSG00000140262 [Q99081-1]
ENST00000333725; ENSP00000331057; ENSG00000140262 [Q99081-3]
ENST00000343827; ENSP00000342459; ENSG00000140262 [Q99081-2]
ENST00000438423; ENSP00000388940; ENSG00000140262 [Q99081-3]
ENST00000537840; ENSP00000444696; ENSG00000140262 [Q99081-4]
ENST00000557843; ENSP00000453737; ENSG00000140262 [Q99081-1]
GeneIDi6938
KEGGihsa:6938
UCSCiuc002aea.4 human [Q99081-1]
uc010ugo.3 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83233 mRNA Translation: AAB62389.1
M80627 mRNA Translation: AAA58632.1
AL831981 mRNA Translation: CAD89914.1
AK304007 mRNA Translation: BAG64923.1
BX537967 mRNA Translation: CAD97931.1
AC010999 Genomic DNA No translation available.
AC016525 Genomic DNA No translation available.
AC090511 Genomic DNA No translation available.
AC090532 Genomic DNA No translation available.
KF456057 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77512.1
BC050556 mRNA Translation: AAH50556.1
M65209 mRNA Translation: AAC37571.1
BK001049 mRNA Translation: DAA01129.1
CCDSiCCDS10159.1 [Q99081-1]
CCDS10160.1 [Q99081-3]
CCDS42042.1 [Q99081-2]
CCDS76761.1 [Q99081-4]
PIRiA42121
RefSeqiNP_001293149.1, NM_001306220.2 [Q99081-4]
NP_001309080.1, NM_001322151.1 [Q99081-3]
NP_001309086.1, NM_001322157.1 [Q99081-1]
NP_001309088.1, NM_001322159.1 [Q99081-3]
NP_001309091.1, NM_001322162.1 [Q99081-3]
NP_001309094.1, NM_001322165.1 [Q99081-1]
NP_003196.1, NM_003205.3 [Q99081-1]
NP_996919.1, NM_207036.1 [Q99081-3]
NP_996920.1, NM_207037.1 [Q99081-3]
NP_996921.1, NM_207038.1 [Q99081-1]
NP_996923.1, NM_207040.1 [Q99081-2]
UniGeneiHs.511504

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KNHNMR-B11-28[»]
4JOLX-ray2.91E/F/G/H177-200[»]
ProteinModelPortaliQ99081
SMRiQ99081
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112798, 79 interactors
CORUMiQ99081
DIPiDIP-29403N
IntActiQ99081, 89 interactors
MINTiQ99081
STRINGi9606.ENSP00000331057

PTM databases

iPTMnetiQ99081
PhosphoSitePlusiQ99081

Polymorphism and mutation databases

BioMutaiTCF12
DMDMi1708332

Proteomic databases

EPDiQ99081
MaxQBiQ99081
PaxDbiQ99081
PeptideAtlasiQ99081
PRIDEiQ99081
ProteomicsDBi78231
78232 [Q99081-2]
78233 [Q99081-3]

Protocols and materials databases

DNASUi6938
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267811; ENSP00000267811; ENSG00000140262 [Q99081-1]
ENST00000333725; ENSP00000331057; ENSG00000140262 [Q99081-3]
ENST00000343827; ENSP00000342459; ENSG00000140262 [Q99081-2]
ENST00000438423; ENSP00000388940; ENSG00000140262 [Q99081-3]
ENST00000537840; ENSP00000444696; ENSG00000140262 [Q99081-4]
ENST00000557843; ENSP00000453737; ENSG00000140262 [Q99081-1]
GeneIDi6938
KEGGihsa:6938
UCSCiuc002aea.4 human [Q99081-1]
uc010ugo.3 human

Organism-specific databases

CTDi6938
DisGeNETi6938
EuPathDBiHostDB:ENSG00000140262.17
GeneCardsiTCF12
HGNCiHGNC:11623 TCF12
HPAiCAB004432
HPA065827
MalaCardsiTCF12
MIMi600480 gene
615314 phenotype
neXtProtiNX_Q99081
OpenTargetsiENSG00000140262
Orphaneti209916 Extraskeletal myxoid chondrosarcoma
35099 Isolated brachycephaly
35098 Isolated plagiocephaly
PharmGKBiPA36381
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3910 Eukaryota
ENOG410XYUA LUCA
GeneTreeiENSGT00510000046438
HOGENOMiHOG000234180
HOVERGENiHBG003854
InParanoidiQ99081
KOiK15603
OMAiYYSFSAT
PhylomeDBiQ99081
TreeFamiTF321672

Enzyme and pathway databases

ReactomeiR-HSA-375170 CDO in myogenesis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
SIGNORiQ99081

Miscellaneous databases

ChiTaRSiTCF12 human
EvolutionaryTraceiQ99081
GeneWikiiTCF12
GenomeRNAii6938
PROiPR:Q99081
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140262 Expressed in 236 organ(s), highest expression level in corpus callosum
CleanExiHS_TCF12
ExpressionAtlasiQ99081 baseline and differential
GenevisibleiQ99081 HS

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHTF4_HUMAN
AccessioniPrimary (citable) accession number: Q99081
Secondary accession number(s): B4E1W1
, Q7Z3D9, Q86TC1, Q86VM2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 174 of the entry and version 1 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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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