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Protein

Kallikrein-8

Gene

KLK8

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

Functioni

Serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. Also cleaves L1CAM in response to increased neural activity. Induces neurite outgrowth and fasciculation of cultured hippocampal neurons. Plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway, regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. Involved in skin desquamation and keratinocyte proliferation. Plays a role in the secondary phase of pathogenesis following spinal cord injury.1 Publication

Miscellaneous

Expressed at high levels in serum, ascites fluid and tumor cytosol of advanced stage ovarian cancer patients and may serve as a marker of ovarian cancer.

Catalytic activityi

Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys.1 Publication

Activity regulationi

Inhibited by a range of serine protease inhibitors including antipain, aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor.1 Publication

Kineticsi

  1. KM=0.07 mM for Pro-Phe-Arg-MCA1 Publication
  2. KM=0.07 mM for Z-Val-Val-Arg-MCA1 Publication
  3. KM=0.07 mM for Boc-Val-Pro-Arg-MCA1 Publication
  4. KM=0.10 mM for Boc-Leu-Lys-Arg-MCA1 Publication
  5. KM=0.10 mM for Boc-Val-Leu-Lys-MCA1 Publication
  6. KM=0.07 mM for Boc-Phe-Ser-Arg-MCA1 Publication
  1. Vmax=7.1 µmol/min/mg enzyme toward Pro-Phe-Arg-MCA1 Publication
  2. Vmax=5.4 µmol/min/mg enzyme toward Z-Val-Val-Arg-MCA1 Publication
  3. Vmax=3.9 µmol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA1 Publication
  4. Vmax=2.6 µmol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA1 Publication
  5. Vmax=1.9 µmol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA1 Publication
  6. Vmax=1.6 µmol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA1 Publication

pH dependencei

Optimum pH is 8.5. Active from pH 7-10.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei73Charge relay systemBy similarity1
Active sitei120Charge relay systemBy similarity1
Active sitei212Charge relay systemBy similarity1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.118 2681
ReactomeiR-HSA-6809371 Formation of the cornified envelope

Protein family/group databases

MEROPSiS01.244

Names & Taxonomyi

Protein namesi
Recommended name:
Kallikrein-8 (EC:3.4.21.118)
Short name:
hK8
Alternative name(s):
Neuropsin
Short name:
NP
Ovasin
Serine protease 19
Serine protease TADG-14
Tumor-associated differentially expressed gene 14 protein
Gene namesi
Name:KLK8
Synonyms:NRPN, PRSS19, TADG14
ORF Names:UNQ283/PRO322
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000129455.15
HGNCiHGNC:6369 KLK8
MIMi605644 gene
neXtProtiNX_O60259

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

Cytoplasm, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi11202
OpenTargetsiENSG00000129455
PharmGKBiPA30158

Chemistry databases

ChEMBLiCHEMBL4812

Polymorphism and mutation databases

BioMutaiKLK8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
PropeptideiPRO_000002794629 – 32By similarity4
ChainiPRO_000002794733 – 260Kallikrein-8Add BLAST228

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 173PROSITE-ProRule annotation
Disulfide bondi58 ↔ 74PROSITE-ProRule annotation
Glycosylationi110N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi145 ↔ 246PROSITE-ProRule annotation
Disulfide bondi152 ↔ 218PROSITE-ProRule annotation
Disulfide bondi184 ↔ 198PROSITE-ProRule annotation
Disulfide bondi208 ↔ 233PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiO60259
PeptideAtlasiO60259
PRIDEiO60259
ProteomicsDBi49286
49287 [O60259-2]
49288 [O60259-3]
49289 [O60259-4]

PTM databases

PhosphoSitePlusiO60259

Expressioni

Tissue specificityi

Isoform 1 is predominantly expressed in the pancreas. Isoform 2 is expressed in adult brain and hippocampus. Isoform 1 and isoform 2 are found in fetal brain and placenta. Detected in salivary gland, uterus, thymus, breast, testis and kidney but not in spleen, liver, lung or normal ovarian tissue. Displays an 11.5-fold increase in Alzheimer disease hippocampus compared to controls and is overexpressed in some ovarian carcinomas. Expressed at low levels in normal skin while high levels are found in psoriasis vulgaris, seborrheic keratosis, lichen planus and squamous cell carcinoma skin samples. Expressed in the keratinocytes.4 Publications

Gene expression databases

BgeeiENSG00000129455 Expressed in 105 organ(s), highest expression level in lower esophagus mucosa
ExpressionAtlasiO60259 baseline and differential
GenevisibleiO60259 HS

Organism-specific databases

HPAiCAB019393
HPA035761

Interactioni

Subunit structurei

Interacts with SPINK9.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi116371, 17 interactors
IntActiO60259, 9 interactors

Chemistry databases

BindingDBiO60259

Structurei

Secondary structure

1260
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60259
SMRiO60259
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 257Peptidase S1PROSITE-ProRule annotationAdd BLAST225

Sequence similaritiesi

Belongs to the peptidase S1 family. Kallikrein subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

GeneTreeiENSGT00760000118862
HOVERGENiHBG013304
InParanoidiO60259
KOiK08650
OMAiTKLYAEN
OrthoDBiEOG091G0DF7
PhylomeDBiO60259
TreeFamiTF331065

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

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

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60259-1) [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
MGRPRPRAAK TWMFLLLLGG AWAGHSRAQE DKVLGGHECQ PHSQPWQAAL
60 70 80 90 100
FQGQQLLCGG VLVGGNWVLT AAHCKKPKYT VRLGDHSLQN KDGPEQEIPV
110 120 130 140 150
VQSIPHPCYN SSDVEDHNHD LMLLQLRDQA SLGSKVKPIS LADHCTQPGQ
160 170 180 190 200
KCTVSGWGTV TSPRENFPDT LNCAEVKIFP QKKCEDAYPG QITDGMVCAG
210 220 230 240 250
SSKGADTCQG DSGGPLVCDG ALQGITSWGS DPCGRSDKPG VYTNICRYLD
260
WIKKIIGSKG
Length:260
Mass (Da):28,048
Last modified:August 1, 1998 - v1
Checksum:iEF439E5B8C83E660
GO
Isoform 2 (identifier: O60259-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: A → AACGSLDLLTKLYAENLPCVHLNPQWPSQPSHCPRGWRSNPLPPAA

Note: Produced as a result of a human-specific mutation which is not found in other primates.
Show »
Length:305
Mass (Da):32,966
Checksum:i2972CED7B2706AF0
GO
Isoform 3 (identifier: O60259-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-164: Missing.

Show »
Length:119
Mass (Da):12,719
Checksum:i2FD8164DF1641FFF
GO
Isoform 4 (identifier: O60259-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     25-32: HSRAQEDK → RFWRPPGV
     33-260: Missing.

Show »
Length:32
Mass (Da):3,653
Checksum:i905DA8F5F9C8A664
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R231M0R231_HUMAN
Kallikrein-8
KLK8
97Annotation score:
A0A0A0MQY9A0A0A0MQY9_HUMAN
Kallikrein-8
KLK8
139Annotation score:
M0R390M0R390_HUMAN
Kallikrein-8
KLK8
54Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195G → V in AAH40887 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051855154V → I. Corresponds to variant dbSNP:rs16988799Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00540123A → AACGSLDLLTKLYAENLPCV HLNPQWPSQPSHCPRGWRSN PLPPAA in isoform 2. 1 Publication1
Alternative sequenceiVSP_03035024 – 164Missing in isoform 3. 1 PublicationAdd BLAST141
Alternative sequenceiVSP_03035125 – 32HSRAQEDK → RFWRPPGV in isoform 4. Curated8
Alternative sequenceiVSP_03035233 – 260Missing in isoform 4. CuratedAdd BLAST228

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009849 mRNA Translation: BAA28673.1
AB012761 Genomic DNA Translation: BAA28676.1
AF055982 mRNA Translation: AAD56050.1
AB008390 mRNA Translation: BAA82665.1
AB008927 mRNA Translation: BAA82666.1
AB010780 Genomic DNA Translation: BAA88684.1
AF243527 Genomic DNA Translation: AAG33361.1
AF251125 Genomic DNA Translation: AAF79144.1
AF251125 Genomic DNA Translation: AAF79145.1
AF095742 mRNA Translation: AAD25979.1
AF095743 Genomic DNA Translation: AAD29574.1
DQ267420 mRNA Translation: ABB83339.1
AY359036 mRNA Translation: AAQ89395.1
AC011473 Genomic DNA Translation: AAG23254.1
AC011483 Genomic DNA No translation available.
CH471135 Genomic DNA Translation: EAW71962.1
BC040887 mRNA Translation: AAH40887.1
AY563055 Genomic DNA Translation: AAT76913.1
AY563055 Genomic DNA Translation: AAT76914.1
AY563056 Genomic DNA Translation: AAT76915.1
AY563056 Genomic DNA Translation: AAT76916.1
AY563057 Genomic DNA Translation: AAT76917.1
AY563057 Genomic DNA Translation: AAT76918.1
AY563058 Genomic DNA Translation: AAT76919.1
AY563058 Genomic DNA Translation: AAT76920.1
AY563059 Genomic DNA Translation: AAT76921.1
AY563059 Genomic DNA Translation: AAT76922.1
AY563060 Genomic DNA Translation: AAT76923.1
AY563060 Genomic DNA Translation: AAT76924.1
AY563061 Genomic DNA Translation: AAT76925.1
AY563061 Genomic DNA Translation: AAT76926.1
AY563062 Genomic DNA Translation: AAT76927.1
AY563062 Genomic DNA Translation: AAT76928.1
AY563063 Genomic DNA Translation: AAT76929.1
AY563063 Genomic DNA Translation: AAT76930.1
AY563064 Genomic DNA Translation: AAT76931.1
AY563064 Genomic DNA Translation: AAT76932.1
AY563065 Genomic DNA Translation: AAT76933.1
AY563065 Genomic DNA Translation: AAT76934.1
AY563066 Genomic DNA Translation: AAT76935.1
AY563066 Genomic DNA Translation: AAT76936.1
AY563067 Genomic DNA Translation: AAT76937.1
AY563067 Genomic DNA Translation: AAT76938.1
CCDSiCCDS12813.1 [O60259-1]
CCDS12814.1 [O60259-3]
CCDS12815.1 [O60259-4]
CCDS42600.1 [O60259-2]
RefSeqiNP_001268360.1, NM_001281431.1
NP_009127.1, NM_007196.3 [O60259-1]
NP_653088.1, NM_144505.2 [O60259-2]
NP_653089.1, NM_144506.2 [O60259-3]
NP_653090.1, NM_144507.2 [O60259-4]
UniGeneiHs.104570

Genome annotation databases

EnsembliENST00000320838; ENSP00000325072; ENSG00000129455 [O60259-4]
ENST00000347619; ENSP00000341555; ENSG00000129455 [O60259-3]
ENST00000391806; ENSP00000375682; ENSG00000129455 [O60259-2]
ENST00000593490; ENSP00000469278; ENSG00000129455 [O60259-4]
ENST00000600767; ENSP00000472016; ENSG00000129455 [O60259-1]
GeneIDi11202
KEGGihsa:11202
UCSCiuc002puq.2 human [O60259-1]

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
AB009849 mRNA Translation: BAA28673.1
AB012761 Genomic DNA Translation: BAA28676.1
AF055982 mRNA Translation: AAD56050.1
AB008390 mRNA Translation: BAA82665.1
AB008927 mRNA Translation: BAA82666.1
AB010780 Genomic DNA Translation: BAA88684.1
AF243527 Genomic DNA Translation: AAG33361.1
AF251125 Genomic DNA Translation: AAF79144.1
AF251125 Genomic DNA Translation: AAF79145.1
AF095742 mRNA Translation: AAD25979.1
AF095743 Genomic DNA Translation: AAD29574.1
DQ267420 mRNA Translation: ABB83339.1
AY359036 mRNA Translation: AAQ89395.1
AC011473 Genomic DNA Translation: AAG23254.1
AC011483 Genomic DNA No translation available.
CH471135 Genomic DNA Translation: EAW71962.1
BC040887 mRNA Translation: AAH40887.1
AY563055 Genomic DNA Translation: AAT76913.1
AY563055 Genomic DNA Translation: AAT76914.1
AY563056 Genomic DNA Translation: AAT76915.1
AY563056 Genomic DNA Translation: AAT76916.1
AY563057 Genomic DNA Translation: AAT76917.1
AY563057 Genomic DNA Translation: AAT76918.1
AY563058 Genomic DNA Translation: AAT76919.1
AY563058 Genomic DNA Translation: AAT76920.1
AY563059 Genomic DNA Translation: AAT76921.1
AY563059 Genomic DNA Translation: AAT76922.1
AY563060 Genomic DNA Translation: AAT76923.1
AY563060 Genomic DNA Translation: AAT76924.1
AY563061 Genomic DNA Translation: AAT76925.1
AY563061 Genomic DNA Translation: AAT76926.1
AY563062 Genomic DNA Translation: AAT76927.1
AY563062 Genomic DNA Translation: AAT76928.1
AY563063 Genomic DNA Translation: AAT76929.1
AY563063 Genomic DNA Translation: AAT76930.1
AY563064 Genomic DNA Translation: AAT76931.1
AY563064 Genomic DNA Translation: AAT76932.1
AY563065 Genomic DNA Translation: AAT76933.1
AY563065 Genomic DNA Translation: AAT76934.1
AY563066 Genomic DNA Translation: AAT76935.1
AY563066 Genomic DNA Translation: AAT76936.1
AY563067 Genomic DNA Translation: AAT76937.1
AY563067 Genomic DNA Translation: AAT76938.1
CCDSiCCDS12813.1 [O60259-1]
CCDS12814.1 [O60259-3]
CCDS12815.1 [O60259-4]
CCDS42600.1 [O60259-2]
RefSeqiNP_001268360.1, NM_001281431.1
NP_009127.1, NM_007196.3 [O60259-1]
NP_653088.1, NM_144505.2 [O60259-2]
NP_653089.1, NM_144506.2 [O60259-3]
NP_653090.1, NM_144507.2 [O60259-4]
UniGeneiHs.104570

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5MS3X-ray2.30A33-260[»]
5MS4X-ray2.10A/B/C/D33-260[»]
ProteinModelPortaliO60259
SMRiO60259
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116371, 17 interactors
IntActiO60259, 9 interactors

Chemistry databases

BindingDBiO60259
ChEMBLiCHEMBL4812

Protein family/group databases

MEROPSiS01.244

PTM databases

PhosphoSitePlusiO60259

Polymorphism and mutation databases

BioMutaiKLK8

Proteomic databases

EPDiO60259
PeptideAtlasiO60259
PRIDEiO60259
ProteomicsDBi49286
49287 [O60259-2]
49288 [O60259-3]
49289 [O60259-4]

Protocols and materials databases

DNASUi11202
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320838; ENSP00000325072; ENSG00000129455 [O60259-4]
ENST00000347619; ENSP00000341555; ENSG00000129455 [O60259-3]
ENST00000391806; ENSP00000375682; ENSG00000129455 [O60259-2]
ENST00000593490; ENSP00000469278; ENSG00000129455 [O60259-4]
ENST00000600767; ENSP00000472016; ENSG00000129455 [O60259-1]
GeneIDi11202
KEGGihsa:11202
UCSCiuc002puq.2 human [O60259-1]

Organism-specific databases

CTDi11202
DisGeNETi11202
EuPathDBiHostDB:ENSG00000129455.15
GeneCardsiKLK8
HGNCiHGNC:6369 KLK8
HPAiCAB019393
HPA035761
MIMi605644 gene
neXtProtiNX_O60259
OpenTargetsiENSG00000129455
PharmGKBiPA30158
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000118862
HOVERGENiHBG013304
InParanoidiO60259
KOiK08650
OMAiTKLYAEN
OrthoDBiEOG091G0DF7
PhylomeDBiO60259
TreeFamiTF331065

Enzyme and pathway databases

BRENDAi3.4.21.118 2681
ReactomeiR-HSA-6809371 Formation of the cornified envelope

Miscellaneous databases

GeneWikiiKLK8
GenomeRNAii11202
PROiPR:O60259
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129455 Expressed in 105 organ(s), highest expression level in lower esophagus mucosa
ExpressionAtlasiO60259 baseline and differential
GenevisibleiO60259 HS

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKLK8_HUMAN
AccessioniPrimary (citable) accession number: O60259
Secondary accession number(s): Q5V9X1
, Q5V9X2, Q8IW69, Q9HCB3, Q9NR68, Q9NR69, Q9UIL9, Q9UQ47
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: November 7, 2018
This is version 166 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. 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. Peptidase families
    Classification of peptidase families and list of entries
  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
  6. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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