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Protein

Focal adhesion kinase 1

Gene

Ptk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 2 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Activity regulationi

Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is required for maximal kinase activity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei454ATPPROSITE-ProRule annotation1
Active sitei546Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi428 – 434ATPPROSITE-ProRule annotation7
Nucleotide bindingi500 – 502ATPPROSITE-ProRule annotation3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Transferase, Tyrosine-protein kinase
Biological processAngiogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 5301
ReactomeiR-RNO-111465 Apoptotic cleavage of cellular proteins
R-RNO-2029482 Regulation of actin dynamics for phagocytic cup formation
R-RNO-354192 Integrin alphaIIb beta3 signaling
R-RNO-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-RNO-372708 p130Cas linkage to MAPK signaling for integrins
R-RNO-375165 NCAM signaling for neurite out-growth
R-RNO-3928662 EPHB-mediated forward signaling
R-RNO-418885 DCC mediated attractive signaling
R-RNO-4420097 VEGFA-VEGFR2 Pathway
R-RNO-5663213 RHO GTPases Activate WASPs and WAVEs
R-RNO-5673001 RAF/MAP kinase cascade
R-RNO-8874081 MET activates PTK2 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Focal adhesion kinase 1 (EC:2.7.10.2)
Short name:
FADK 1
Alternative name(s):
Focal adhesion kinase-related nonkinase
Short name:
FRNK
Protein-tyrosine kinase 2
p125FAK
pp125FAK
Gene namesi
Name:Ptk2
Synonyms:Fak, Fak1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi3443 Ptk2

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 junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi152K → R: Abolishes sumoylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5773

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000880792 – 1055Focal adhesion kinase 1Add BLAST1054

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei5PhosphotyrosineBy similarity1
Modified residuei13PhosphothreonineBy similarity1
Modified residuei29PhosphoserineBy similarity1
Modified residuei54PhosphoserineBy similarity1
Cross-linki152Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei397Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei407PhosphotyrosineBy similarity1
Modified residuei570PhosphotyrosineBy similarity1
Modified residuei576PhosphotyrosineCombined sources1
Modified residuei577Phosphotyrosine; by RET and SRCBy similarity1
Modified residuei580PhosphoserineBy similarity1
Modified residuei722Phosphoserine1 Publication1
Modified residuei732Phosphoserine; by CDK5By similarity1
Modified residuei843PhosphoserineBy similarity1
Modified residuei861PhosphotyrosineBy similarity1
Modified residuei913PhosphoserineCombined sources1 Publication1
Modified residuei917PhosphothreonineBy similarity1
Modified residuei928PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-928, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-928 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21 (By similarity).By similarity
Sumoylated; this enhances autophosphorylation.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO35346
PeptideAtlasiO35346
PRIDEiO35346

PTM databases

iPTMnetiO35346
PhosphoSitePlusiO35346

Expressioni

Gene expression databases

BgeeiENSRNOG00000007916 Expressed in 10 organ(s), highest expression level in lung
ExpressionAtlasiO35346 baseline and differential
GenevisibleiO35346 RN

Interactioni

Subunit structurei

Interacts with GIT1. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with PIK3R1 or PIK3R2. Interacts with FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent). Interacts with P53/TP53. Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3, CASS4 and NEDD9. Interacts with TGFB1I1. Interacts with SRC, GRB2 and GRB7. Interacts with ARHGEF28. Interacts with SHB. Interacts with PXN and TLN1. Interacts with SORBS1. Interacts with STAT1. Interacts with WASL. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with ARHGEF7. Interacts with MDM2 (By similarity). Interacts with PIAS1. Interacts with DCC. Interacts with LPXN (via LD motif 3) (By similarity). Interacts with MISP (By similarity). Interacts with EMP2; regulates PTK2 activation and localization (By similarity).By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247643, 5 interactors
CORUMiO35346
DIPiDIP-41330N
IntActiO35346, 6 interactors
MINTiO35346
STRINGi10116.ENSRNOP00000011219

Structurei

3D structure databases

ProteinModelPortaliO35346
SMRiO35346
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 355FERMPROSITE-ProRule annotationAdd BLAST321
Domaini422 – 680Protein kinasePROSITE-ProRule annotationAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni707 – 1055Interaction with TGFB1I1By similarityAdd BLAST349
Regioni915 – 1055Interaction with ARHGEF28By similarityAdd BLAST141

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi712 – 733Pro-richAdd BLAST22
Compositional biasi863 – 916Pro-richAdd BLAST54

Domaini

The first Pro-rich domain interacts with the SH3 domain of CAS family members, such as BCAR1 and NEDD9.By similarity
The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4257 Eukaryota
ENOG410ZH9Y LUCA
GeneTreeiENSGT00760000118799
HOGENOMiHOG000069938
HOVERGENiHBG004018
InParanoidiO35346
KOiK05725
PhylomeDBiO35346

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
Gene3Di1.20.80.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR014352 FERM/acyl-CoA-bd_prot_sf
IPR035963 FERM_2
IPR019748 FERM_central
IPR000299 FERM_domain
IPR036137 Focal_adhe_kin_target_dom_sf
IPR005189 Focal_adhesion_kin_target_dom
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR029071 Ubiquitin-like_domsf
PfamiView protein in Pfam
PF00373 FERM_M, 1 hit
PF03623 Focal_AT, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
ProDomiView protein in ProDom or Entries sharing at least one domain
PD006413 Focal_adhesion_target_reg, 1 hit
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47031 SSF47031, 1 hit
SSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
SSF68993 SSF68993, 1 hit
PROSITEiView protein in PROSITE
PS00661 FERM_2, 1 hit
PS50057 FERM_3, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 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 promoter usage. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O35346-1) [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
MAAAYLDPNL NHTPSSSTKT HLGTGTERSP GAMERVLKVF HYFESSNEPT
60 70 80 90 100
TWASIIRHGD ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV
110 120 130 140 150
DMGVSSVREK YELAHPPEEW KYELRIRYLP KGFLNQFTED KPTLNFFYQQ
160 170 180 190 200
VKSDYMLEIA DQVDQDIALK LGCLEIRRSY WEMRGNALEK KSNYEVLEKD
210 220 230 240 250
VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI LKFFEILSPV
260 270 280 290 300
YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFNQVQ
310 320 330 340 350
TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL
360 370 380 390 400
VNGATQSFII RPQKEGERAL PSIPKLANNE KQGMRTHAVS VSETDDYAEI
410 420 430 440 450
IDEEDTYTMP STRDYEIQRE RIELGRCIGE GQFGDVHQGV YLSPENPALA
460 470 480 490 500
VAIKTCKNCT SDSVREKFLQ EALTMRQFDH PHIVKLIGVI TENPVWIIME
510 520 530 540 550
LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK RFVHRDIAAR
560 570 580 590 600
NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT
610 620 630 640 650
SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT
660 670 680 690 700
LYSLMTKCWA YDPSRRPRFT ELKAQLSTIL EEEKVQQEER MRMESRRQAT
710 720 730 740 750
VSWDSGGSDE APPKPSRPGY PSPRSSEGFY PSPQHMVQTN HYQISGYPGS
760 770 780 790 800
HGIPAMAGSI YPGQASLLDQ TELWNHRPQE MSMWQPSVED SAALDLRGMG
810 820 830 840 850
QVLPPHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS RGSIDREDGS
860 870 880 890 900
FQGPTGNQHI YQPVGKPDPA APPKKPPRPG APGHLSNLSS ISSPAESYNE
910 920 930 940 950
GVKPWRLQPQ EISPPPTANL DRSNDKVYEN VTGLVKAVIE MSSKIQPAPP
960 970 980 990 1000
EEYVPMVKEV GLALRTLLAT VDETIPILPA STHREIEMAQ KLLNSDLGEL
1010 1020 1030 1040 1050
ISKMKLAQQY VMTSLQQEYK KQMLTAAHAL AVDAKNLLDV IDQARLKMLG

QTRPH
Length:1,055
Mass (Da):119,717
Last modified:January 1, 1998 - v1
Checksum:i3AFB4ED682D14A33
GO
Isoform 2 (identifier: O35346-2) [UniParc]FASTAAdd to basket
Also known as: FRNK

The sequence of this isoform differs from the canonical sequence as follows:
     1-692: Missing.

Show »
Length:363
Mass (Da):40,409
Checksum:i8BC926B7A78DBD50
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2KAT5A0A0G2KAT5_RAT
Focal adhesion kinase 1
Ptk2
1,067Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0421721 – 692Missing in isoform 2. CuratedAdd BLAST692

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020777 mRNA Translation: AAB72203.1
U43942 mRNA Translation: AAA86280.1
RefSeqiNP_037213.1, NM_013081.2 [O35346-1]
UniGeneiRn.2809

Genome annotation databases

EnsembliENSRNOT00000011219; ENSRNOP00000011219; ENSRNOG00000007916 [O35346-1]
GeneIDi25614
KEGGirno:25614
UCSCiRGD:3443 rat [O35346-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020777 mRNA Translation: AAB72203.1
U43942 mRNA Translation: AAA86280.1
RefSeqiNP_037213.1, NM_013081.2 [O35346-1]
UniGeneiRn.2809

3D structure databases

ProteinModelPortaliO35346
SMRiO35346
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247643, 5 interactors
CORUMiO35346
DIPiDIP-41330N
IntActiO35346, 6 interactors
MINTiO35346
STRINGi10116.ENSRNOP00000011219

Chemistry databases

ChEMBLiCHEMBL5773

PTM databases

iPTMnetiO35346
PhosphoSitePlusiO35346

Proteomic databases

PaxDbiO35346
PeptideAtlasiO35346
PRIDEiO35346

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000011219; ENSRNOP00000011219; ENSRNOG00000007916 [O35346-1]
GeneIDi25614
KEGGirno:25614
UCSCiRGD:3443 rat [O35346-1]

Organism-specific databases

CTDi5747
RGDi3443 Ptk2

Phylogenomic databases

eggNOGiKOG4257 Eukaryota
ENOG410ZH9Y LUCA
GeneTreeiENSGT00760000118799
HOGENOMiHOG000069938
HOVERGENiHBG004018
InParanoidiO35346
KOiK05725
PhylomeDBiO35346

Enzyme and pathway databases

BRENDAi2.7.10.2 5301
ReactomeiR-RNO-111465 Apoptotic cleavage of cellular proteins
R-RNO-2029482 Regulation of actin dynamics for phagocytic cup formation
R-RNO-354192 Integrin alphaIIb beta3 signaling
R-RNO-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-RNO-372708 p130Cas linkage to MAPK signaling for integrins
R-RNO-375165 NCAM signaling for neurite out-growth
R-RNO-3928662 EPHB-mediated forward signaling
R-RNO-418885 DCC mediated attractive signaling
R-RNO-4420097 VEGFA-VEGFR2 Pathway
R-RNO-5663213 RHO GTPases Activate WASPs and WAVEs
R-RNO-5673001 RAF/MAP kinase cascade
R-RNO-8874081 MET activates PTK2 signaling

Miscellaneous databases

PROiPR:O35346

Gene expression databases

BgeeiENSRNOG00000007916 Expressed in 10 organ(s), highest expression level in lung
ExpressionAtlasiO35346 baseline and differential
GenevisibleiO35346 RN

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
Gene3Di1.20.80.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR014352 FERM/acyl-CoA-bd_prot_sf
IPR035963 FERM_2
IPR019748 FERM_central
IPR000299 FERM_domain
IPR036137 Focal_adhe_kin_target_dom_sf
IPR005189 Focal_adhesion_kin_target_dom
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR029071 Ubiquitin-like_domsf
PfamiView protein in Pfam
PF00373 FERM_M, 1 hit
PF03623 Focal_AT, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
ProDomiView protein in ProDom or Entries sharing at least one domain
PD006413 Focal_adhesion_target_reg, 1 hit
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47031 SSF47031, 1 hit
SSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
SSF68993 SSF68993, 1 hit
PROSITEiView protein in PROSITE
PS00661 FERM_2, 1 hit
PS50057 FERM_3, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFAK1_RAT
AccessioniPrimary (citable) accession number: O35346
Secondary accession number(s): Q62900
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: September 12, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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