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Protein

Phospholipid-transporting ATPase IG

Gene

ATP11C

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

Functioni

Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. In the cell membrane of erythrocytes, it is required to maintain phosphatidylserine (PS) in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for splenic macrophages (PubMed:26944472). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Required for B cell differentiation past the pro-B cell stage (By similarity). Seems to mediate PS flipping in pro-B cells (By similarity). May be involved in the transport of cholestatic bile acids (By similarity).By similarity1 Publication

Catalytic activityi

ATP + H2O + phospholipid(Side 1) = ADP + phosphate + phospholipid(Side 2).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4124-aspartylphosphate intermediateBy similarity1
Metal bindingi819MagnesiumBy similarity1
Metal bindingi823MagnesiumBy similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • phospholipid-translocating ATPase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionTranslocase
Biological processLipid transport, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-936837 Ion transport by P-type ATPases

Protein family/group databases

TCDBi3.A.3.8.14 the p-type atpase (p-atpase) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid-transporting ATPase IG (EC:7.6.2.1)
Alternative name(s):
ATPase IQ
ATPase class VI type 11C
P4-ATPase flippase complex alpha subunit ATP11C
Gene namesi
Name:ATP11C
Synonyms:ATPIG, ATPIQ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101974.14
HGNCiHGNC:13554 ATP11C
MIMi300516 gene
neXtProtiNX_Q8NB49

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 – 66CytoplasmicSequence analysisAdd BLAST66
Transmembranei67 – 85HelicalSequence analysisAdd BLAST19
Topological domaini86ExtracellularSequence analysis1
Transmembranei87 – 107HelicalSequence analysisAdd BLAST21
Topological domaini108 – 290CytoplasmicSequence analysisAdd BLAST183
Transmembranei291 – 311HelicalSequence analysisAdd BLAST21
Topological domaini312 – 346ExtracellularSequence analysisAdd BLAST35
Transmembranei347 – 367HelicalSequence analysisAdd BLAST21
Topological domaini368 – 879CytoplasmicSequence analysisAdd BLAST512
Transmembranei880 – 900HelicalSequence analysisAdd BLAST21
Topological domaini901 – 908ExtracellularSequence analysis8
Transmembranei909 – 929HelicalSequence analysisAdd BLAST21
Topological domaini930 – 955CytoplasmicSequence analysisAdd BLAST26
Transmembranei956 – 976HelicalSequence analysisAdd BLAST21
Topological domaini977 – 995ExtracellularSequence analysisAdd BLAST19
Transmembranei996 – 1016HelicalSequence analysisAdd BLAST21
Topological domaini1017 – 1026CytoplasmicSequence analysis10
Transmembranei1027 – 1047HelicalSequence analysisAdd BLAST21
Topological domaini1048 – 1069ExtracellularSequence analysisAdd BLAST22
Transmembranei1070 – 1090HelicalSequence analysisAdd BLAST21
Topological domaini1091 – 1132CytoplasmicSequence analysisAdd BLAST42

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Hemolytic anemia, congenital, X-linked (HAXL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked hematologic disease characterized by shortened survival of erythrocytes due to congenital hemolysis that cannot be compensated by bone marrow activity. Clinical features are mild jaundice and anemia. Red cells morphology is normal.
See also OMIM:301015
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081016418T → N in HAXL; decreased phosphatidylserine translocation from the outer to the inner leaflet of erythrocytes cell membrane. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

DisGeNETi286410
MIMi301015 phenotype
OpenTargetsiENSG00000101974
PharmGKBiPA25103

Polymorphism and mutation databases

BioMutaiATP11C
DMDMi62512178

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463731 – 1132Phospholipid-transporting ATPase IGAdd BLAST1132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei445PhosphoserineCombined sources1
Modified residuei1108PhosphoserineCombined sources1
Modified residuei1116PhosphoserineCombined sources1
Modified residuei1126PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8NB49
MaxQBiQ8NB49
PaxDbiQ8NB49
PeptideAtlasiQ8NB49
PRIDEiQ8NB49
ProteomicsDBi72731
72732 [Q8NB49-2]
72733 [Q8NB49-3]
72734 [Q8NB49-4]

PTM databases

iPTMnetiQ8NB49
PhosphoSitePlusiQ8NB49
SwissPalmiQ8NB49

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000101974 Expressed in 198 organ(s), highest expression level in female gonad
ExpressionAtlasiQ8NB49 baseline and differential
GenevisibleiQ8NB49 HS

Organism-specific databases

HPAiHPA030830

Interactioni

Subunit structurei

Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit (Probable). Interacts with beta subunit TMEM30A.Curated1 Publication

Protein-protein interaction databases

BioGridi130370, 44 interactors
IntActiQ8NB49, 5 interactors
MINTiQ8NB49
STRINGi9606.ENSP00000332756

Structurei

3D structure databases

ProteinModelPortaliQ8NB49
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0206 Eukaryota
COG0474 LUCA
GeneTreeiENSGT00910000144008
HOVERGENiHBG050601
InParanoidiQ8NB49
KOiK01530
OMAiYVWQSNP
OrthoDBiEOG091G03B1
PhylomeDBiQ8NB49
TreeFamiTF326897

Family and domain databases

Gene3Di3.40.50.1000, 1 hit
InterProiView protein in InterPro
IPR030363 ATP11C
IPR023299 ATPase_P-typ_cyto_dom_N
IPR018303 ATPase_P-typ_P_site
IPR023298 ATPase_P-typ_TM_dom_sf
IPR008250 ATPase_P-typ_transduc_dom_A_sf
IPR036412 HAD-like_sf
IPR023214 HAD_sf
IPR006539 P-type_ATPase_IV
IPR032631 P-type_ATPase_N
IPR001757 P_typ_ATPase
IPR032630 P_typ_ATPase_c
PANTHERiPTHR24092 PTHR24092, 1 hit
PTHR24092:SF38 PTHR24092:SF38, 1 hit
PfamiView protein in Pfam
PF16212 PhoLip_ATPase_C, 1 hit
PF16209 PhoLip_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 1 hit
SSF81653 SSF81653, 1 hit
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 1 hit
TIGRFAMsiTIGR01652 ATPase-Plipid, 1 hit
TIGR01494 ATPase_P-type, 3 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8NB49-1) [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
MQMVPSLPPA SECAGEEKRV GTRTVFVGNH PVSETEAYIA QRFCDNRIVS
60 70 80 90 100
SKYTLWNFLP KNLFEQFRRI ANFYFLIIFL VQVTVDTPTS PVTSGLPLFF
110 120 130 140 150
VITVTAIKQG YEDCLRHRAD NEVNKSTVYI IENAKRVRKE SEKIKVGDVV
160 170 180 190 200
EVQADETFPC DLILLSSCTT DGTCYVTTAS LDGESNCKTH YAVRDTIALC
210 220 230 240 250
TAESIDTLRA AIECEQPQPD LYKFVGRINI YSNSLEAVAR SLGPENLLLK
260 270 280 290 300
GATLKNTEKI YGVAVYTGME TKMALNYQGK SQKRSAVEKS INAFLIVYLF
310 320 330 340 350
ILLTKAAVCT TLKYVWQSTP YNDEPWYNQK TQKERETLKV LKMFTDFLSF
360 370 380 390 400
MVLFNFIIPV SMYVTVEMQK FLGSFFISWD KDFYDEEINE GALVNTSDLN
410 420 430 440 450
EELGQVDYVF TDKTGTLTEN SMEFIECCID GHKYKGVTQE VDGLSQTDGT
460 470 480 490 500
LTYFDKVDKN REELFLRALC LCHTVEIKTN DAVDGATESA ELTYISSSPD
510 520 530 540 550
EIALVKGAKR YGFTFLGNRN GYMRVENQRK EIEEYELLHT LNFDAVRRRM
560 570 580 590 600
SVIVKTQEGD ILLFCKGADS AVFPRVQNHE IELTKVHVER NAMDGYRTLC
610 620 630 640 650
VAFKEIAPDD YERINRQLIE AKMALQDREE KMEKVFDDIE TNMNLIGATA
660 670 680 690 700
VEDKLQDQAA ETIEALHAAG LKVWVLTGDK METAKSTCYA CRLFQTNTEL
710 720 730 740 750
LELTTKTIEE SERKEDRLHE LLIEYRKKLL HEFPKSTRSF KKAWTEHQEY
760 770 780 790 800
GLIIDGSTLS LILNSSQDSS SNNYKSIFLQ ICMKCTAVLC CRMAPLQKAQ
810 820 830 840 850
IVRMVKNLKG SPITLSIGDG ANDVSMILES HVGIGIKGKE GRQAARNSDY
860 870 880 890 900
SVPKFKHLKK LLLAHGHLYY VRIAHLVQYF FYKNLCFILP QFLYQFFCGF
910 920 930 940 950
SQQPLYDAAY LTMYNICFTS LPILAYSLLE QHINIDTLTS DPRLYMKISG
960 970 980 990 1000
NAMLQLGPFL YWTFLAAFEG TVFFFGTYFL FQTASLEENG KVYGNWTFGT
1010 1020 1030 1040 1050
IVFTVLVFTV TLKLALDTRF WTWINHFVIW GSLAFYVFFS FFWGGIIWPF
1060 1070 1080 1090 1100
LKQQRMYFVF AQMLSSVSTW LAIILLIFIS LFPEILLIVL KNVRRRSARR
1110 1120 1130
NLSCRRASDS LSARPSVRPL LLRTFSDESN VL
Length:1,132
Mass (Da):129,477
Last modified:April 12, 2005 - v3
Checksum:i74B63B20A5C6E49D
GO
Isoform 2 (identifier: Q8NB49-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1100-1132: RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL → VHHLISSSA

Note: No experimental confirmation available.
Show »
Length:1,108
Mass (Da):126,710
Checksum:iADC1995E368B8C4E
GO
Isoform 3 (identifier: Q8NB49-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1100-1132: RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL → NPNLELPMLLSYKHTDSGYS

Show »
Length:1,119
Mass (Da):128,040
Checksum:i2F1EF15A73AB3947
GO
Isoform 4 (identifier: Q8NB49-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1100-1132: RNLSCRRASDSLSARPSVRPLLLRTFSDESNVL → VTKRLPSSGTSAIFMLSQTSSNHSFSWSE

Note: No experimental confirmation available.
Show »
Length:1,128
Mass (Da):128,933
Checksum:i5928DF8ED2988A7C
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A067XG54A0A067XG54_HUMAN
Phospholipid-transporting ATPase
ATP11C
1,113Annotation score:
H7C0E8H7C0E8_HUMAN
Phospholipid-transporting ATPase IG
ATP11C
202Annotation score:
H7C113H7C113_HUMAN
Phospholipid-transporting ATPase IG
ATP11C
165Annotation score:
A0A067XG57A0A067XG57_HUMAN
Phospholipid-transporting ATPase IG
ATP11C
172Annotation score:

Sequence cautioni

The sequence BAC03692 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC86172 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC86377 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD18440 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti537L → P in BAC86377 (PubMed:14702039).Curated1
Sequence conflicti873I → V in BAC86377 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021827114C → W1 PublicationCorresponds to variant dbSNP:rs2491014Ensembl.1
Natural variantiVAR_036501157T → I in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_081016418T → N in HAXL; decreased phosphatidylserine translocation from the outer to the inner leaflet of erythrocytes cell membrane. 1 Publication1
Natural variantiVAR_055546522Y → C. Corresponds to variant dbSNP:rs17281983Ensembl.1
Natural variantiVAR_036502931Q → P in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_061036972V → M. Corresponds to variant dbSNP:rs55724992Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0073091100 – 1132RNLSC…ESNVL → VHHLISSSA in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_0133731100 – 1132RNLSC…ESNVL → NPNLELPMLLSYKHTDSGYS in isoform 3. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_0133741100 – 1132RNLSC…ESNVL → VTKRLPSSGTSAIFMLSQTS SNHSFSWSE in isoform 4. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ580093 mRNA Translation: CAE30472.1
AJ580094 mRNA Translation: CAE30473.1
AL161777 Genomic DNA No translation available.
AL356785 Genomic DNA No translation available.
AL590077 Genomic DNA No translation available.
AK091552 mRNA Translation: BAC03692.1 Different initiation.
AK125474 mRNA Translation: BAC86172.1 Different initiation.
AK125986 mRNA Translation: BAC86377.1 Different initiation.
AK131262 mRNA Translation: BAD18440.1 Different initiation.
CCDSiCCDS14668.1 [Q8NB49-1]
CCDS35410.1 [Q8NB49-3]
RefSeqiNP_001010986.1, NM_001010986.2
NP_775965.2, NM_173694.4
UniGeneiHs.88252

Genome annotation databases

EnsembliENST00000327569; ENSP00000332756; ENSG00000101974 [Q8NB49-1]
ENST00000361648; ENSP00000355165; ENSG00000101974 [Q8NB49-3]
GeneIDi286410
KEGGihsa:286410
UCSCiuc004faz.4 human [Q8NB49-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ580093 mRNA Translation: CAE30472.1
AJ580094 mRNA Translation: CAE30473.1
AL161777 Genomic DNA No translation available.
AL356785 Genomic DNA No translation available.
AL590077 Genomic DNA No translation available.
AK091552 mRNA Translation: BAC03692.1 Different initiation.
AK125474 mRNA Translation: BAC86172.1 Different initiation.
AK125986 mRNA Translation: BAC86377.1 Different initiation.
AK131262 mRNA Translation: BAD18440.1 Different initiation.
CCDSiCCDS14668.1 [Q8NB49-1]
CCDS35410.1 [Q8NB49-3]
RefSeqiNP_001010986.1, NM_001010986.2
NP_775965.2, NM_173694.4
UniGeneiHs.88252

3D structure databases

ProteinModelPortaliQ8NB49
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi130370, 44 interactors
IntActiQ8NB49, 5 interactors
MINTiQ8NB49
STRINGi9606.ENSP00000332756

Protein family/group databases

TCDBi3.A.3.8.14 the p-type atpase (p-atpase) superfamily

PTM databases

iPTMnetiQ8NB49
PhosphoSitePlusiQ8NB49
SwissPalmiQ8NB49

Polymorphism and mutation databases

BioMutaiATP11C
DMDMi62512178

Proteomic databases

EPDiQ8NB49
MaxQBiQ8NB49
PaxDbiQ8NB49
PeptideAtlasiQ8NB49
PRIDEiQ8NB49
ProteomicsDBi72731
72732 [Q8NB49-2]
72733 [Q8NB49-3]
72734 [Q8NB49-4]

Protocols and materials databases

DNASUi286410
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327569; ENSP00000332756; ENSG00000101974 [Q8NB49-1]
ENST00000361648; ENSP00000355165; ENSG00000101974 [Q8NB49-3]
GeneIDi286410
KEGGihsa:286410
UCSCiuc004faz.4 human [Q8NB49-1]

Organism-specific databases

CTDi286410
DisGeNETi286410
EuPathDBiHostDB:ENSG00000101974.14
GeneCardsiATP11C
HGNCiHGNC:13554 ATP11C
HPAiHPA030830
MIMi300516 gene
301015 phenotype
neXtProtiNX_Q8NB49
OpenTargetsiENSG00000101974
PharmGKBiPA25103
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0206 Eukaryota
COG0474 LUCA
GeneTreeiENSGT00910000144008
HOVERGENiHBG050601
InParanoidiQ8NB49
KOiK01530
OMAiYVWQSNP
OrthoDBiEOG091G03B1
PhylomeDBiQ8NB49
TreeFamiTF326897

Enzyme and pathway databases

ReactomeiR-HSA-936837 Ion transport by P-type ATPases

Miscellaneous databases

ChiTaRSiATP11C human
GenomeRNAii286410
PROiPR:Q8NB49
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101974 Expressed in 198 organ(s), highest expression level in female gonad
ExpressionAtlasiQ8NB49 baseline and differential
GenevisibleiQ8NB49 HS

Family and domain databases

Gene3Di3.40.50.1000, 1 hit
InterProiView protein in InterPro
IPR030363 ATP11C
IPR023299 ATPase_P-typ_cyto_dom_N
IPR018303 ATPase_P-typ_P_site
IPR023298 ATPase_P-typ_TM_dom_sf
IPR008250 ATPase_P-typ_transduc_dom_A_sf
IPR036412 HAD-like_sf
IPR023214 HAD_sf
IPR006539 P-type_ATPase_IV
IPR032631 P-type_ATPase_N
IPR001757 P_typ_ATPase
IPR032630 P_typ_ATPase_c
PANTHERiPTHR24092 PTHR24092, 1 hit
PTHR24092:SF38 PTHR24092:SF38, 1 hit
PfamiView protein in Pfam
PF16212 PhoLip_ATPase_C, 1 hit
PF16209 PhoLip_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 1 hit
SSF81653 SSF81653, 1 hit
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 1 hit
TIGRFAMsiTIGR01652 ATPase-Plipid, 1 hit
TIGR01494 ATPase_P-type, 3 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAT11C_HUMAN
AccessioniPrimary (citable) accession number: Q8NB49
Secondary accession number(s): Q5JT69
, Q5JT70, Q5JT71, Q5JT72, Q5JT73, Q6ZND5, Q6ZU50, Q6ZUP7, Q70IJ9, Q70IK0, Q8WX24
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: April 12, 2005
Last modified: November 7, 2018
This is version 155 of the entry and version 3 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

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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
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