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Entry version 167 (16 Oct 2019)
Sequence version 2 (27 Apr 2001)
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Protein

Kelch-like protein 3

Gene

KLHL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity).By similarity6 Publications

Caution

The BCR(KLHL3) complex was initially thought to act by mediating ubiquitination of SLC12A3/NCC (PubMed:22406640). However, it was later shown that effects on SLC12A3/NCC are indirect and caused by impaired ubiquitination of WNK4 (PubMed:23387299).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActin-binding
Biological processUbl conjugation pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00143

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Kelch-like protein 3
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:KLHL31 PublicationImported
Synonyms:KIAA11291 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:6354 KLHL3

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
605775 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9UH77

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Pseudohypoaldosteronism 2D (PHA2D)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06750177A → E in PHA2D; impaired interaction with CUL3. 3 PublicationsCorresponds to variant dbSNP:rs199469623EnsemblClinVar.1
Natural variantiVAR_06750278M → V in PHA2D; impaired interaction with CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469624EnsemblClinVar.1
Natural variantiVAR_06750385E → A in PHA2D; impaired interaction with CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469625EnsemblClinVar.1
Natural variantiVAR_067504164C → F in PHA2D; impaired interaction with CUL3; de novo mutation. 3 PublicationsCorresponds to variant dbSNP:rs199469626EnsemblClinVar.1
Natural variantiVAR_067505228R → G in PHA2D. 1 Publication1
Natural variantiVAR_067506309Q → R in PHA2D; impaired interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469627EnsemblClinVar.1
Natural variantiVAR_067507322F → C in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469639EnsemblClinVar.1
Natural variantiVAR_067508336R → I in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469640EnsemblClinVar.1
Natural variantiVAR_067509340A → V in PHA2D; does not affect interaction with WNK1 or CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469628EnsemblClinVar.1
Natural variantiVAR_067510361V → M in PHA2D. 1 Publication1
Natural variantiVAR_067511362R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs200892557Ensembl.1
Natural variantiVAR_067512384R → Q in PHA2D; impaired interaction with WNK1. 2 PublicationsCorresponds to variant dbSNP:rs199469629EnsemblClinVar.1
Natural variantiVAR_067513384R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs951676369Ensembl.1
Natural variantiVAR_067514387L → P in PHA2D; abolished interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469630EnsemblClinVar.1
Natural variantiVAR_067515398A → V in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs387907155EnsemblClinVar.1
Natural variantiVAR_067516410S → L in PHA2D; impaired interaction with WNK1. 3 PublicationsCorresponds to variant dbSNP:rs199469641EnsemblClinVar.1
Natural variantiVAR_067517426P → L in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs387907156EnsemblClinVar.1
Natural variantiVAR_067518427M → T in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469642EnsemblClinVar.1
Natural variantiVAR_067519431R → Q in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469643EnsemblClinVar.1
Natural variantiVAR_067520432S → N in PHA2D; impaired interaction with WNK1. 3 PublicationsCorresponds to variant dbSNP:rs199469631EnsemblClinVar.1
Natural variantiVAR_067521433S → G in PHA2D; decreased interaction with WNK4. 2 Publications1
Natural variantiVAR_067522433S → N in PHA2D. 2 PublicationsCorresponds to variant dbSNP:rs199469632EnsemblClinVar.1
Natural variantiVAR_067524494A → T in PHA2D; does not affect interaction with WNK1 or CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469633EnsemblClinVar.1
Natural variantiVAR_079630498H → Y in PHA2D. 1 Publication1
Natural variantiVAR_067525500G → V in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs746774345Ensembl.1
Natural variantiVAR_067526501P → T in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469634EnsemblClinVar.1
Natural variantiVAR_067527528R → C in PHA2D; impaired interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469635EnsemblClinVar.1
Natural variantiVAR_067528528R → H in PHA2D; dominant negative effect due to homodimer formation; impaired interaction with WNK1 and WNK4 and impaired ubiquitination of WNK4. 6 PublicationsCorresponds to variant dbSNP:rs199469636EnsemblClinVar.1
Natural variantiVAR_067529529N → K in PHA2D; impaired interaction with WNK1. 2 Publications1
Natural variantiVAR_079631553S → L in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs1367184898Ensembl.1
Natural variantiVAR_067530557Y → C in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469645EnsemblClinVar.1
Natural variantiVAR_067531575R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469646EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi433S → E or D: Phosphomimetic mutant that shows decreased interaction with WNK4. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
26249

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...
GeneReviewsi
KLHL3

MalaCards human disease database

More...
MalaCardsi
KLHL3
MIMi614495 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000146021

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
300525 Pseudohypoaldosteronism type 2D

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA30144

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
Q9UH77

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
KLHL3

Domain mapping of disease mutations (DMDM)

More...
DMDMi
13431657

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001191031 – 587Kelch-like protein 3Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei10Phosphoserine1 Publication1
Modified residuei295Phosphothreonine1 Publication1
Modified residuei375Phosphothreonine1 Publication1
Modified residuei376Phosphoserine1 Publication1
Modified residuei433Phosphoserine; by PKA2 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation at Ser-433 by PKA decreases the interaction with WNK4, Leading to inhibit WNK4 degradation by the BCR(KLHL3) complex (PubMed:26435498, PubMed:27727489). Phosphorylation at Ser-433 is increased by insulin (PubMed:26435498).2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q9UH77

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9UH77

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q9UH77

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9UH77

PeptideAtlas

More...
PeptideAtlasi
Q9UH77

PRoteomics IDEntifications database

More...
PRIDEi
Q9UH77

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
84282 [Q9UH77-1]
84283 [Q9UH77-2]
84284 [Q9UH77-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q9UH77

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q9UH77

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000146021 Expressed in 203 organ(s), highest expression level in cerebellar vermis

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9UH77 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9UH77 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA051291

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (PubMed:28052936).

Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable) (PubMed:23453970, PubMed:23576762, PubMed:23573258).

Interacts with SLC12A3 (PubMed:22406640).

Interacts with WNK1 and WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23573258, PubMed:23576762, PubMed:23665031, PubMed:26435498, PubMed:27727489).

Interacts with CLDN8 (By similarity).

By similarity9 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
Q136183EBI-8524663,EBI-456129

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
117637, 19 interactors

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
Q9UH77

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q9UH77

Protein interaction database and analysis system

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IntActi
Q9UH77, 7 interactors

Molecular INTeraction database

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MINTi
Q9UH77

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000312397

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1587
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9UH77

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini50 – 117BTBPROSITE-ProRule annotationAdd BLAST68
Domaini152 – 254BACKAdd BLAST103
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati302 – 347Kelch 1Add BLAST46
Repeati348 – 394Kelch 2Add BLAST47
Repeati396 – 441Kelch 3Add BLAST46
Repeati442 – 490Kelch 4Add BLAST49
Repeati491 – 537Kelch 5Add BLAST47
Repeati539 – 585Kelch 6Add BLAST47

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4441 Eukaryota
ENOG410XNX8 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000157891

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000230814

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9UH77

KEGG Orthology (KO)

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KOi
K10443

Identification of Orthologs from Complete Genome Data

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OMAi
MDVRKNC

Database of Orthologous Groups

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OrthoDBi
635140at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q9UH77

TreeFam database of animal gene trees

More...
TreeFami
TF329218

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.120.10.80, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF037037 Kelch-like_protein_gigaxonin, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50097 BTB, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform A (identifier: Q9UH77-1) [UniParc]FASTAAdd to basket
Also known as: KLHL3A1 Publication

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MEGESVKLSS QTLIQAGDDE KNQRTITVNP AHMGKAFKVM NELRSKQLLC
60 70 80 90 100
DVMIVAEDVE IEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT
110 120 130 140 150
LSKLIDYIYT AEIEVTEENV QVLLPAASLL QLMDVRQNCC DFLQSQLHPT
160 170 180 190 200
NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP EVMLGEEFLS LSLDQVCSLI
210 220 230 240 250
SSDKLTVSSE EKVFEAVISW INYEKETRLE HMAKLMEHVR LPLLPRDYLV
260 270 280 290 300
QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
310 320 330 340 350
KVMIVVGGQA PKAIRSVECY DFEEDRWDQI AELPSRRCRA GVVFMAGHVY
360 370 380 390 400
AVGGFNGSLR VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG
410 420 430 440 450
GFDGSTGLAS VEAYSYKTNE WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD
460 470 480 490 500
GASRQCLSTV EQYNPATNEW IYVADMSTRR SGAGVGVLSG QLYATGGHDG
510 520 530 540 550
PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY VVGGDDGSCN
560 570 580
LASVEYYNPV TDKWTLLPTN MSTGRSYAGV AVIHKSL
Length:587
Mass (Da):64,970
Last modified:April 27, 2001 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iC5026A246620BEA1
GO
Isoform B (identifier: Q9UH77-2) [UniParc]FASTAAdd to basket
Also known as: KLHL3B1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: Missing.

Show »
Length:555
Mass (Da):61,490
Checksum:i1FE9B061BD542347
GO
Isoform C (identifier: Q9UH77-3) [UniParc]FASTAAdd to basket
Also known as: KLHL3C1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-82: Missing.

Show »
Length:505
Mass (Da):55,927
Checksum:i0B4157AC6E474F70
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RH21D6RH21_HUMAN
Kelch-like protein 3
KLHL3
400Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6R9K4D6R9K4_HUMAN
Kelch-like protein 3
KLHL3
105Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAB97127 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAA86443 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti227T → N in AAF20938 (PubMed:10843806).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06750177A → E in PHA2D; impaired interaction with CUL3. 3 PublicationsCorresponds to variant dbSNP:rs199469623EnsemblClinVar.1
Natural variantiVAR_06750278M → V in PHA2D; impaired interaction with CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469624EnsemblClinVar.1
Natural variantiVAR_06750385E → A in PHA2D; impaired interaction with CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469625EnsemblClinVar.1
Natural variantiVAR_067504164C → F in PHA2D; impaired interaction with CUL3; de novo mutation. 3 PublicationsCorresponds to variant dbSNP:rs199469626EnsemblClinVar.1
Natural variantiVAR_067505228R → G in PHA2D. 1 Publication1
Natural variantiVAR_067506309Q → R in PHA2D; impaired interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469627EnsemblClinVar.1
Natural variantiVAR_067507322F → C in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469639EnsemblClinVar.1
Natural variantiVAR_067508336R → I in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469640EnsemblClinVar.1
Natural variantiVAR_067509340A → V in PHA2D; does not affect interaction with WNK1 or CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469628EnsemblClinVar.1
Natural variantiVAR_067510361V → M in PHA2D. 1 Publication1
Natural variantiVAR_067511362R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs200892557Ensembl.1
Natural variantiVAR_067512384R → Q in PHA2D; impaired interaction with WNK1. 2 PublicationsCorresponds to variant dbSNP:rs199469629EnsemblClinVar.1
Natural variantiVAR_067513384R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs951676369Ensembl.1
Natural variantiVAR_067514387L → P in PHA2D; abolished interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469630EnsemblClinVar.1
Natural variantiVAR_067515398A → V in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs387907155EnsemblClinVar.1
Natural variantiVAR_067516410S → L in PHA2D; impaired interaction with WNK1. 3 PublicationsCorresponds to variant dbSNP:rs199469641EnsemblClinVar.1
Natural variantiVAR_067517426P → L in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs387907156EnsemblClinVar.1
Natural variantiVAR_067518427M → T in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469642EnsemblClinVar.1
Natural variantiVAR_067519431R → Q in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469643EnsemblClinVar.1
Natural variantiVAR_067520432S → N in PHA2D; impaired interaction with WNK1. 3 PublicationsCorresponds to variant dbSNP:rs199469631EnsemblClinVar.1
Natural variantiVAR_067521433S → G in PHA2D; decreased interaction with WNK4. 2 Publications1
Natural variantiVAR_067522433S → N in PHA2D. 2 PublicationsCorresponds to variant dbSNP:rs199469632EnsemblClinVar.1
Natural variantiVAR_067523438V → I Found in a patient with hypertension; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs907779058Ensembl.1
Natural variantiVAR_067524494A → T in PHA2D; does not affect interaction with WNK1 or CUL3. 2 PublicationsCorresponds to variant dbSNP:rs199469633EnsemblClinVar.1
Natural variantiVAR_079630498H → Y in PHA2D. 1 Publication1
Natural variantiVAR_067525500G → V in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs746774345Ensembl.1
Natural variantiVAR_067526501P → T in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469634EnsemblClinVar.1
Natural variantiVAR_067527528R → C in PHA2D; impaired interaction with WNK1. 4 PublicationsCorresponds to variant dbSNP:rs199469635EnsemblClinVar.1
Natural variantiVAR_067528528R → H in PHA2D; dominant negative effect due to homodimer formation; impaired interaction with WNK1 and WNK4 and impaired ubiquitination of WNK4. 6 PublicationsCorresponds to variant dbSNP:rs199469636EnsemblClinVar.1
Natural variantiVAR_067529529N → K in PHA2D; impaired interaction with WNK1. 2 Publications1
Natural variantiVAR_079631553S → L in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs1367184898Ensembl.1
Natural variantiVAR_067530557Y → C in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469645EnsemblClinVar.1
Natural variantiVAR_067531575R → W in PHA2D. 1 PublicationCorresponds to variant dbSNP:rs199469646EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0028171 – 82Missing in isoform C. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_0028161 – 32Missing in isoform B. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF208068 mRNA Translation: AAF20938.1
AF208069 mRNA Translation: AAF20939.1
AF208070 mRNA Translation: AAF20995.1
AB032955 mRNA Translation: BAA86443.1 Different initiation.
AK314707 mRNA Translation: BAG37254.1
AC004021 Genomic DNA Translation: AAB97127.1 Sequence problems.
AC092318 Genomic DNA No translation available.
AC106775 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW62183.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS4192.1 [Q9UH77-1]
CCDS58969.1 [Q9UH77-3]
CCDS58970.1 [Q9UH77-2]

NCBI Reference Sequences

More...
RefSeqi
NP_001244123.1, NM_001257194.1 [Q9UH77-2]
NP_001244124.1, NM_001257195.1 [Q9UH77-3]
NP_059111.2, NM_017415.2 [Q9UH77-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000309755; ENSP00000312397; ENSG00000146021 [Q9UH77-1]
ENST00000506491; ENSP00000424828; ENSG00000146021 [Q9UH77-3]
ENST00000508657; ENSP00000422099; ENSG00000146021 [Q9UH77-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
26249

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:26249

UCSC genome browser

More...
UCSCi
uc003lbr.6 human [Q9UH77-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208068 mRNA Translation: AAF20938.1
AF208069 mRNA Translation: AAF20939.1
AF208070 mRNA Translation: AAF20995.1
AB032955 mRNA Translation: BAA86443.1 Different initiation.
AK314707 mRNA Translation: BAG37254.1
AC004021 Genomic DNA Translation: AAB97127.1 Sequence problems.
AC092318 Genomic DNA No translation available.
AC106775 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW62183.1
CCDSiCCDS4192.1 [Q9UH77-1]
CCDS58969.1 [Q9UH77-3]
CCDS58970.1 [Q9UH77-2]
RefSeqiNP_001244123.1, NM_001257194.1 [Q9UH77-2]
NP_001244124.1, NM_001257195.1 [Q9UH77-3]
NP_059111.2, NM_017415.2 [Q9UH77-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4CH9X-ray1.84A/B298-587[»]
4HXIX-ray3.51A24-276[»]
5NKPX-ray2.80A/B298-587[»]
SMRiQ9UH77
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi117637, 19 interactors
CORUMiQ9UH77
ELMiQ9UH77
IntActiQ9UH77, 7 interactors
MINTiQ9UH77
STRINGi9606.ENSP00000312397

PTM databases

iPTMnetiQ9UH77
PhosphoSitePlusiQ9UH77

Polymorphism and mutation databases

BioMutaiKLHL3
DMDMi13431657

Proteomic databases

EPDiQ9UH77
jPOSTiQ9UH77
MassIVEiQ9UH77
PaxDbiQ9UH77
PeptideAtlasiQ9UH77
PRIDEiQ9UH77
ProteomicsDBi84282 [Q9UH77-1]
84283 [Q9UH77-2]
84284 [Q9UH77-3]

Genome annotation databases

EnsembliENST00000309755; ENSP00000312397; ENSG00000146021 [Q9UH77-1]
ENST00000506491; ENSP00000424828; ENSG00000146021 [Q9UH77-3]
ENST00000508657; ENSP00000422099; ENSG00000146021 [Q9UH77-2]
GeneIDi26249
KEGGihsa:26249
UCSCiuc003lbr.6 human [Q9UH77-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
26249
DisGeNETi26249

GeneCards: human genes, protein and diseases

More...
GeneCardsi
KLHL3
GeneReviewsiKLHL3
HGNCiHGNC:6354 KLHL3
HPAiHPA051291
MalaCardsiKLHL3
MIMi605775 gene
614495 phenotype
neXtProtiNX_Q9UH77
OpenTargetsiENSG00000146021
Orphaneti300525 Pseudohypoaldosteronism type 2D
PharmGKBiPA30144

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00940000157891
HOGENOMiHOG000230814
InParanoidiQ9UH77
KOiK10443
OMAiMDVRKNC
OrthoDBi635140at2759
PhylomeDBiQ9UH77
TreeFamiTF329218

Enzyme and pathway databases

UniPathwayiUPA00143
ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
KLHL3 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
KLHL3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
26249
PharosiQ9UH77

Protein Ontology

More...
PROi
PR:Q9UH77

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000146021 Expressed in 203 organ(s), highest expression level in cerebellar vermis
ExpressionAtlasiQ9UH77 baseline and differential
GenevisibleiQ9UH77 HS

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiKLHL3_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9UH77
Secondary accession number(s): B2RBK7
, Q9UH75, Q9UH76, Q9ULU0, Q9Y6V6
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: October 16, 2019
This is version 167 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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