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Protein

Heat shock protein HSP 90-alpha

Gene

Hsp90aa1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation.By similarity

Activity regulationi

In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (By similarity). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (By similarity). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (By similarity). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by Ganetespib (STA-9090) and SNX-2112 (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei51ATPBy similarity1
Binding sitei93ATPBy similarity1
Binding sitei112ATPBy similarity1
Binding sitei138ATP; via amide nitrogenBy similarity1
Binding sitei401ATPBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone
Biological processStress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1227986 Signaling by ERBB2
R-MMU-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-203615 eNOS activation
R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-MMU-3371511 HSF1 activation
R-MMU-3371568 Attenuation phase
R-MMU-3371571 HSF1-dependent transactivation
R-MMU-380259 Loss of Nlp from mitotic centrosomes
R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes
R-MMU-380320 Recruitment of NuMA to mitotic centrosomes
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-399954 Sema3A PAK dependent Axon repulsion
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-5218920 VEGFR2 mediated vascular permeability
R-MMU-5620912 Anchoring of the basal body to the plasma membrane
R-MMU-6798695 Neutrophil degranulation
R-MMU-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-MMU-8854518 AURKA Activation by TPX2
R-MMU-8863795 Downregulation of ERBB2 signaling
R-MMU-8939211 ESR-mediated signaling
R-MMU-9018519 Estrogen-dependent gene expression

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock protein HSP 90-alpha
Alternative name(s):
Heat shock 86 kDa
Short name:
HSP 86
Short name:
HSP86
Tumor-specific transplantation 86 kDa antigen
Short name:
TSTA
Gene namesi
Name:Hsp90aa1
Synonyms:Hsp86, Hsp86-1, Hspca
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:96250 Hsp90aa1

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

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4197

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00000629122 – 733Heat shock protein HSP 90-alphaAdd BLAST732

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphothreonine; by PRKDC1 Publication1
Modified residuei7Phosphothreonine; by PRKDC1 Publication1
Modified residuei58N6-acetyllysineCombined sources1
Modified residuei84N6-acetyllysineCombined sources1
Modified residuei231PhosphoserineCombined sources1
Modified residuei252PhosphoserineBy similarity1
Modified residuei263PhosphoserineCombined sources1
Modified residuei314PhosphotyrosineCombined sources1
Modified residuei444N6-acetyllysineBy similarity1
Modified residuei454PhosphoserineBy similarity1
Modified residuei459N6-acetyllysineBy similarity1
Modified residuei477PhosphoserineCombined sources1
Modified residuei490N6-acetyllysineBy similarity1
Modified residuei493PhosphotyrosineCombined sources1
Modified residuei586N6-acetyllysineBy similarity1
Modified residuei599S-nitrosocysteineBy similarity1
Modified residuei642PhosphoserineBy similarity1

Post-translational modificationi

ISGylated.1 Publication
S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.By similarity
Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiP07901
PaxDbiP07901
PeptideAtlasiP07901
PRIDEiP07901

2D gel databases

REPRODUCTION-2DPAGEiP07901

PTM databases

CarbonylDBiP07901
iPTMnetiP07901
PhosphoSitePlusiP07901
SwissPalmiP07901

Expressioni

Gene expression databases

BgeeiENSMUSG00000021270 Expressed in 52 organ(s), highest expression level in female gonad
ExpressionAtlasiP07901 baseline and differential
GenevisibleiP07901 MM

Interactioni

Subunit structurei

Homodimer (PubMed:8289821). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:9195923, PubMed:11278753, PubMed:11751894). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By similarity). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (By similarity). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (By similarity). Interacts with CHORDC1 and DNAJC7 (By similarity). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (By similarity). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (By similarity). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (By similarity). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (By similarity). May interact with NWD1 (By similarity). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (By similarity). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (By similarity). Interacts with HSP70, STIP1 and PTGES3 (By similarity). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (By similarity). Interacts with SGTA (via TPR repeats) (By similarity). Interacts with TTC1 (via TPR repeats) (By similarity). Interacts with HSF1 in an ATP-dependent manner (By similarity). Interacts with MET; the interaction suppresses MET kinase activity (By similarity). Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (By similarity). Interacts with HIF1A, KEAP1 and RHOBTB2 (By similarity). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (By similarity). Interacts with STUB1 and SMAD3 (By similarity). Interacts with HSP90AB1; interaction is constitutive (By similarity). Interacts with HECTD1 (via N-terminus) (PubMed:22431752).By similarity7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200455, 27 interactors
ComplexPortaliCPX-3289 HSP90A-CDC37 chaperone complex
CORUMiP07901
DIPiDIP-30975N
ELMiP07901
IntActiP07901, 36 interactors
MINTiP07901
STRINGi10090.ENSMUSP00000021698

Chemistry databases

BindingDBiP07901

Structurei

Secondary structure

1733
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP07901
SMRiP07901
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni285 – 733Interaction with FLCN and FNIP1By similarityAdd BLAST449
Regioni285 – 621Interaction with FNIP2 and TSC1By similarityAdd BLAST337
Regioni683 – 733Required for homodimerizationBy similarityAdd BLAST51
Regioni729 – 733Essential for interaction with SMYD3, TSC1 and STIP1/HOPBy similarity5
Regioni730 – 733Essential for interaction with SGTA and TTC1By similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi724 – 733TPR repeat-bindingBy similarity10

Domaini

The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.By similarity

Sequence similaritiesi

Belongs to the heat shock protein 90 family.Curated

Phylogenomic databases

eggNOGiKOG0019 Eukaryota
KOG0020 Eukaryota
COG0326 LUCA
GeneTreeiENSGT00920000149016
HOGENOMiHOG000031988
HOVERGENiHBG007374
InParanoidiP07901
KOiK04079
OMAiVKRHSEF
OrthoDBiEOG091G0270
PhylomeDBiP07901
TreeFamiTF300686

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di1.20.120.790, 1 hit
3.30.565.10, 1 hit
HAMAPiMF_00505 HSP90, 1 hit
InterProiView protein in InterPro
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR019805 Heat_shock_protein_90_CS
IPR037196 HSP90_C
IPR001404 Hsp90_fam
IPR020575 Hsp90_N
IPR020568 Ribosomal_S5_D2-typ_fold
PANTHERiPTHR11528 PTHR11528, 1 hit
PfamiView protein in Pfam
PF02518 HATPase_c, 1 hit
PF00183 HSP90, 1 hit
PIRSFiPIRSF002583 Hsp90, 1 hit
PRINTSiPR00775 HEATSHOCK90
SMARTiView protein in SMART
SM00387 HATPase_c, 1 hit
SUPFAMiSSF110942 SSF110942, 1 hit
SSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
PROSITEiView protein in PROSITE
PS00298 HSP90, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P07901-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS
60 70 80 90 100
NSSDALDKIR YESLTDPSKL DSGKELHINL IPSKQDRTLT IVDTGIGMTK
110 120 130 140 150
ADLINNLGTI AKSGTKAFME ALQAGADISM IGQFGVGFYS AYLVAEKVTV
160 170 180 190 200
ITKHNDDEQY AWESSAGGSF TVRTDTGEPM GRGTKVILHL KEDQTEYLEE
210 220 230 240 250
RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKEE KEEEKEKEEK
260 270 280 290 300
ESDDKPEIED VGSDEEEEEK KDGDKKKKKK IKEKYIDQEE LNKTKPIWTR
310 320 330 340 350
NPDDITNEEY GEFYKSLTND WEEHLAVKHF SVEGQLEFRA LLFVPRRAPF
360 370 380 390 400
DLFENRKKKN NIKLYVRRVF IMDNCEELIP EYLNFIRGVV DSEDLPLNIS
410 420 430 440 450
REMLQQSKIL KVIRKNLVKK CLELFTELAE DKENYKKFYE QFSKNIKLGI
460 470 480 490 500
HEDSQNRKKL SELLRYYTSA SGDEMVSLKD YCTRMKENQK HIYFITGETK
510 520 530 540 550
DQVANSAFVE RLRKHGLEVI YMIEPIDEYC VQQLKEFEGK TLVSVTKEGL
560 570 580 590 600
ELPEDEEEKK KQEEKKTKFE NLCKIMKDIL EKKVEKVVVS NRLVTSPCCI
610 620 630 640 650
VTSTYGWTAN MERIMKAQAL RDNSTMGYMA AKKHLEINPD HSIIETLRQK
660 670 680 690 700
AEADKNDKSV KDLVILLYET ALLSSGFSLE DPQTHANRIY RMIKLGLGID
710 720 730
EDDPTVDDTS AAVTEEMPPL EGDDDTSRME EVD
Length:733
Mass (Da):84,788
Last modified:January 23, 2007 - v4
Checksum:iD92B8FD38A463B4E
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7ZC50B7ZC50_MOUSE
Heat shock protein HSP 90-alpha
Hsp90aa1
201Annotation score:
B7ZC49B7ZC49_MOUSE
Heat shock protein HSP 90-alpha
Hsp90aa1
103Annotation score:
A2A6A2A2A6A2_MOUSE
Heat shock protein HSP 90-alpha
Hsp90aa1
98Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7T → A in AAA37868 (PubMed:2469626).Curated1
Sequence conflicti242 – 245Missing in AAA37868 (PubMed:2469626).Curated4
Sequence conflicti356R → K in AAA37868 (PubMed:2469626).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04633 mRNA Translation: AAA53068.1
M57673 Genomic DNA Translation: AAA37867.1
BC046614 mRNA Translation: AAH46614.1
M36830 mRNA Translation: AAA37868.1
X16857 mRNA Translation: CAA34748.1
CCDSiCCDS26172.1
PIRiB32848 HHMS86
RefSeqiNP_034610.1, NM_010480.5
UniGeneiMm.1843
Mm.315997
Mm.341186
Mm.440626
Mm.486334

Genome annotation databases

EnsembliENSMUST00000021698; ENSMUSP00000021698; ENSMUSG00000021270
ENSMUST00000094361; ENSMUSP00000091921; ENSMUSG00000021270
GeneIDi15519
KEGGimmu:15519
UCSCiuc007pbq.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04633 mRNA Translation: AAA53068.1
M57673 Genomic DNA Translation: AAA37867.1
BC046614 mRNA Translation: AAH46614.1
M36830 mRNA Translation: AAA37868.1
X16857 mRNA Translation: CAA34748.1
CCDSiCCDS26172.1
PIRiB32848 HHMS86
RefSeqiNP_034610.1, NM_010480.5
UniGeneiMm.1843
Mm.315997
Mm.341186
Mm.440626
Mm.486334

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5H22X-ray1.50A10-224[»]
ProteinModelPortaliP07901
SMRiP07901
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200455, 27 interactors
ComplexPortaliCPX-3289 HSP90A-CDC37 chaperone complex
CORUMiP07901
DIPiDIP-30975N
ELMiP07901
IntActiP07901, 36 interactors
MINTiP07901
STRINGi10090.ENSMUSP00000021698

Chemistry databases

BindingDBiP07901
ChEMBLiCHEMBL4197

PTM databases

CarbonylDBiP07901
iPTMnetiP07901
PhosphoSitePlusiP07901
SwissPalmiP07901

2D gel databases

REPRODUCTION-2DPAGEiP07901

Proteomic databases

EPDiP07901
PaxDbiP07901
PeptideAtlasiP07901
PRIDEiP07901

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021698; ENSMUSP00000021698; ENSMUSG00000021270
ENSMUST00000094361; ENSMUSP00000091921; ENSMUSG00000021270
GeneIDi15519
KEGGimmu:15519
UCSCiuc007pbq.2 mouse

Organism-specific databases

CTDi3320
MGIiMGI:96250 Hsp90aa1

Phylogenomic databases

eggNOGiKOG0019 Eukaryota
KOG0020 Eukaryota
COG0326 LUCA
GeneTreeiENSGT00920000149016
HOGENOMiHOG000031988
HOVERGENiHBG007374
InParanoidiP07901
KOiK04079
OMAiVKRHSEF
OrthoDBiEOG091G0270
PhylomeDBiP07901
TreeFamiTF300686

Enzyme and pathway databases

ReactomeiR-MMU-1227986 Signaling by ERBB2
R-MMU-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-203615 eNOS activation
R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-MMU-3371511 HSF1 activation
R-MMU-3371568 Attenuation phase
R-MMU-3371571 HSF1-dependent transactivation
R-MMU-380259 Loss of Nlp from mitotic centrosomes
R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes
R-MMU-380320 Recruitment of NuMA to mitotic centrosomes
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-399954 Sema3A PAK dependent Axon repulsion
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-5218920 VEGFR2 mediated vascular permeability
R-MMU-5620912 Anchoring of the basal body to the plasma membrane
R-MMU-6798695 Neutrophil degranulation
R-MMU-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-MMU-8854518 AURKA Activation by TPX2
R-MMU-8863795 Downregulation of ERBB2 signaling
R-MMU-8939211 ESR-mediated signaling
R-MMU-9018519 Estrogen-dependent gene expression

Miscellaneous databases

PROiPR:P07901
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021270 Expressed in 52 organ(s), highest expression level in female gonad
ExpressionAtlasiP07901 baseline and differential
GenevisibleiP07901 MM

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di1.20.120.790, 1 hit
3.30.565.10, 1 hit
HAMAPiMF_00505 HSP90, 1 hit
InterProiView protein in InterPro
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR019805 Heat_shock_protein_90_CS
IPR037196 HSP90_C
IPR001404 Hsp90_fam
IPR020575 Hsp90_N
IPR020568 Ribosomal_S5_D2-typ_fold
PANTHERiPTHR11528 PTHR11528, 1 hit
PfamiView protein in Pfam
PF02518 HATPase_c, 1 hit
PF00183 HSP90, 1 hit
PIRSFiPIRSF002583 Hsp90, 1 hit
PRINTSiPR00775 HEATSHOCK90
SMARTiView protein in SMART
SM00387 HATPase_c, 1 hit
SUPFAMiSSF110942 SSF110942, 1 hit
SSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
PROSITEiView protein in PROSITE
PS00298 HSP90, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHS90A_MOUSE
AccessioniPrimary (citable) accession number: P07901
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 207 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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