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Protein

Mitogen-activated protein kinase 3

Gene

MAPK3

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

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.12 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei71ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei166Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi48 – 56ATPPROSITE-ProRule annotation9

<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 functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Host-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.24 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112409 RAF-independent MAPK1/3 activation
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-445144 Signal transduction by L1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5674499 Negative feedback regulation of MAPK pathway
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-73728 RNA Polymerase I Promoter Opening
R-HSA-74749 Signal attenuation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8939211 ESR-mediated signaling
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-982772 Growth hormone receptor signaling

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P27361

SIGNOR Signaling Network Open Resource

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SIGNORi
P27361

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

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MoonDBi
P27361 Predicted

<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:
Mitogen-activated protein kinase 3 (EC:2.7.11.24)
Short name:
MAP kinase 3
Short name:
MAPK 3
Alternative name(s):
ERT2
Extracellular signal-regulated kinase 1
Short name:
ERK-1
Insulin-stimulated MAP2 kinase
MAP kinase isoform p44
Short name:
p44-MAPK
Microtubule-associated protein 2 kinase
p44-ERK1
<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:MAPK3
Synonyms:ERK1, PRKM3
<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 16

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000102882.11

Human Gene Nomenclature Database

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HGNCi
HGNC:6877 MAPK3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
601795 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P27361

<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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

<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

Organism-specific databases

DisGeNET

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DisGeNETi
5595

Open Targets

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OpenTargetsi
ENSG00000102882

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA30622

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3385

Drug and drug target database

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DrugBanki
DB04604 5-iodotubercidin
DB01169 Arsenic trioxide
DB02733 Purvalanol
DB00605 Sulindac

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1494

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MAPK3

Domain mapping of disease mutations (DMDM)

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DMDMi
232066

<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 <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources1 Publication
<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_00001862512 – 379Mitogen-activated protein kinase 3Add BLAST378

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 residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei198PhosphothreonineCombined sources1
Modified residuei202Phosphothreonine; by MAP2K1 and MAP2K2Combined sources1
Modified residuei204Phosphotyrosine; by MAP2K1 and MAP2K2Combined sources2 Publications1
Modified residuei207Phosphothreonine; by autocatalysis1 Publication1

<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

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-204.By similarity5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P27361

MaxQB - The MaxQuant DataBase

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MaxQBi
P27361

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

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PaxDbi
P27361

PeptideAtlas

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PeptideAtlasi
P27361

PRoteomics IDEntifications database

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PRIDEi
P27361

ProteomicsDB human proteome resource

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ProteomicsDBi
54383
54384 [P27361-2]
54385 [P27361-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P27361

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

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PhosphoSitePlusi
P27361

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000102882 Expressed in 222 organ(s), highest expression level in right frontal lobe

CleanEx database of gene expression profiles

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CleanExi
HS_MAPK3

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P27361 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P27361 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB002683
HPA003995
HPA005700
HPA030069

<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

Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with TPR. Interacts with CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs upon heat shock (PubMed:10747973). Interacts with CAVIN4 (By similarity).By similarity13 Publications
(Microbial infection) Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity.1 Publication

<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

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111581, 201 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P27361

Database of interacting proteins

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DIPi
DIP-30985N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P27361

Protein interaction database and analysis system

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IntActi
P27361, 98 interactors

Molecular INTeraction database

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MINTi
P27361

STRING: functional protein association networks

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STRINGi
9606.ENSP00000263025

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P27361

<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

1379
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P27361

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

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SMRi
P27361

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P27361

<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>Domaini42 – 330Protein kinasePROSITE-ProRule annotationAdd BLAST289

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi202 – 204TXY3

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.1 Publication

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0660 Eukaryota
ENOG410XNY0 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000160691

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000233024

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG014652

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P27361

KEGG Orthology (KO)

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KOi
K04371

Identification of Orthologs from Complete Genome Data

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OMAi
KIAPFDH

Database of Orthologous Groups

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OrthoDBi
EOG091G08QL

Database for complete collections of gene phylogenies

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PhylomeDBi
P27361

TreeFam database of animal gene trees

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TreeFami
TF105097

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

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Pfami
View protein in Pfam
PF00069 Pkinase, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01770 ERK1ERK2MAPK

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 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>.<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.

<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 in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

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 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P27361-1) [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
MAAAAAQGGG GGEPRRTEGV GPGVPGEVEM VKGQPFDVGP RYTQLQYIGE
60 70 80 90 100
GAYGMVSSAY DHVRKTRVAI KKISPFEHQT YCQRTLREIQ ILLRFRHENV
110 120 130 140 150
IGIRDILRAS TLEAMRDVYI VQDLMETDLY KLLKSQQLSN DHICYFLYQI
160 170 180 190 200
LRGLKYIHSA NVLHRDLKPS NLLINTTCDL KICDFGLARI ADPEHDHTGF
210 220 230 240 250
LTEYVATRWY RAPEIMLNSK GYTKSIDIWS VGCILAEMLS NRPIFPGKHY
260 270 280 290 300
LDQLNHILGI LGSPSQEDLN CIINMKARNY LQSLPSKTKV AWAKLFPKSD
310 320 330 340 350
SKALDLLDRM LTFNPNKRIT VEEALAHPYL EQYYDPTDEP VAEEPFTFAM
360 370
ELDDLPKERL KELIFQETAR FQPGVLEAP
Length:379
Mass (Da):43,136
Last modified:January 23, 2007 - v4
<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:iE6020CE413EC41F7
GO
Isoform 2 (identifier: P27361-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     259-302: Missing.

Show »
Length:335
Mass (Da):38,275
Checksum:i54DA760A09F1F2F5
GO
Isoform 3 (identifier: P27361-3) [UniParc]FASTAAdd to basket
Also known as: ERK1b

The sequence of this isoform differs from the canonical sequence as follows:
     340-379: PVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP → VGQSPAAVGLGAGEQGGT

Show »
Length:357
Mass (Da):40,088
Checksum:iF2C6D29C623AC072
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 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PJF0E9PJF0_HUMAN
Mitogen-activated protein kinase
MAPK3
316Annotation score:

Annotation score:2 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>
E9PQW4E9PQW4_HUMAN
Mitogen-activated protein kinase
MAPK3
339Annotation score:

Annotation score:2 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>
E9PBK7E9PBK7_HUMAN
Mitogen-activated protein kinase
MAPK3
311Annotation score:

Annotation score:2 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>
H0YDH9H0YDH9_HUMAN
Mitogen-activated protein kinase 3
MAPK3
87Annotation 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>
B3KR49B3KR49_HUMAN
Mitogen-activated protein kinase 3
MAPK3 hCG_1983753
265Annotation 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>
E9PRH7E9PRH7_HUMAN
Mitogen-activated protein kinase 3
MAPK3
136Annotation 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>
H0YEX6H0YEX6_HUMAN
Mitogen-activated protein kinase 3
MAPK3
121Annotation 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>

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 conflicti174I → S in CAA42744 (PubMed:7687743).Curated1
Sequence conflicti174I → S in AAK52329 (Ref. 2) Curated1

Natural variant

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_042253323E → K1 PublicationCorresponds to variant dbSNP:rs55859133Ensembl.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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_041906259 – 302Missing in isoform 2. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_041907340 – 379PVAEE…VLEAP → VGQSPAAVGLGAGEQGGT in isoform 3. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X60188 mRNA Translation: CAA42744.1
AY033607 mRNA Translation: AAK52329.1
DQ399291 mRNA Translation: ABD60302.1
EU332853 Genomic DNA Translation: ABY87542.1
AC012645 Genomic DNA No translation available.
CH471238 Genomic DNA Translation: EAW79912.1
CH471238 Genomic DNA Translation: EAW79915.1
BC013992 mRNA Translation: AAH13992.1
M84490 mRNA Translation: AAA36142.1
Z11696 mRNA Translation: CAA77754.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS10672.1 [P27361-1]
CCDS42148.1 [P27361-2]
CCDS42149.1 [P27361-3]

Protein sequence database of the Protein Information Resource

More...
PIRi
A48082

NCBI Reference Sequences

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RefSeqi
NP_001035145.1, NM_001040056.2 [P27361-3]
NP_001103361.1, NM_001109891.1 [P27361-2]
NP_002737.2, NM_002746.2 [P27361-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.861

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000263025; ENSP00000263025; ENSG00000102882 [P27361-1]
ENST00000322266; ENSP00000327293; ENSG00000102882 [P27361-2]
ENST00000395199; ENSP00000378625; ENSG00000102882 [P27361-3]
ENST00000395202; ENSP00000378628; ENSG00000102882 [P27361-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
5595

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:5595

UCSC genome browser

More...
UCSCi
uc002dws.4 human [P27361-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60188 mRNA Translation: CAA42744.1
AY033607 mRNA Translation: AAK52329.1
DQ399291 mRNA Translation: ABD60302.1
EU332853 Genomic DNA Translation: ABY87542.1
AC012645 Genomic DNA No translation available.
CH471238 Genomic DNA Translation: EAW79912.1
CH471238 Genomic DNA Translation: EAW79915.1
BC013992 mRNA Translation: AAH13992.1
M84490 mRNA Translation: AAA36142.1
Z11696 mRNA Translation: CAA77754.1
CCDSiCCDS10672.1 [P27361-1]
CCDS42148.1 [P27361-2]
CCDS42149.1 [P27361-3]
PIRiA48082
RefSeqiNP_001035145.1, NM_001040056.2 [P27361-3]
NP_001103361.1, NM_001109891.1 [P27361-2]
NP_002737.2, NM_002746.2 [P27361-1]
UniGeneiHs.861

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
2ZOQX-ray2.39A/B1-379[»]
4QTBX-ray1.40A/B1-379[»]
ProteinModelPortaliP27361
SMRiP27361
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111581, 201 interactors
CORUMiP27361
DIPiDIP-30985N
ELMiP27361
IntActiP27361, 98 interactors
MINTiP27361
STRINGi9606.ENSP00000263025

Chemistry databases

BindingDBiP27361
ChEMBLiCHEMBL3385
DrugBankiDB04604 5-iodotubercidin
DB01169 Arsenic trioxide
DB02733 Purvalanol
DB00605 Sulindac
GuidetoPHARMACOLOGYi1494

Protein family/group databases

MoonDBiP27361 Predicted

PTM databases

iPTMnetiP27361
PhosphoSitePlusiP27361

Polymorphism and mutation databases

BioMutaiMAPK3
DMDMi232066

Proteomic databases

EPDiP27361
MaxQBiP27361
PaxDbiP27361
PeptideAtlasiP27361
PRIDEiP27361
ProteomicsDBi54383
54384 [P27361-2]
54385 [P27361-3]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
5595
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263025; ENSP00000263025; ENSG00000102882 [P27361-1]
ENST00000322266; ENSP00000327293; ENSG00000102882 [P27361-2]
ENST00000395199; ENSP00000378625; ENSG00000102882 [P27361-3]
ENST00000395202; ENSP00000378628; ENSG00000102882 [P27361-2]
GeneIDi5595
KEGGihsa:5595
UCSCiuc002dws.4 human [P27361-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
5595
DisGeNETi5595
EuPathDBiHostDB:ENSG00000102882.11

GeneCards: human genes, protein and diseases

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GeneCardsi
MAPK3
HGNCiHGNC:6877 MAPK3
HPAiCAB002683
HPA003995
HPA005700
HPA030069
MIMi601795 gene
neXtProtiNX_P27361
OpenTargetsiENSG00000102882
PharmGKBiPA30622

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00940000160691
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP27361
KOiK04371
OMAiKIAPFDH
OrthoDBiEOG091G08QL
PhylomeDBiP27361
TreeFamiTF105097

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112409 RAF-independent MAPK1/3 activation
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-445144 Signal transduction by L1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5674499 Negative feedback regulation of MAPK pathway
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-73728 RNA Polymerase I Promoter Opening
R-HSA-74749 Signal attenuation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8939211 ESR-mediated signaling
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiP27361
SIGNORiP27361

Miscellaneous databases

EvolutionaryTraceiP27361

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
MAPK3

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

More...
GenomeRNAii
5595

Protein Ontology

More...
PROi
PR:P27361

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000102882 Expressed in 222 organ(s), highest expression level in right frontal lobe
CleanExiHS_MAPK3
ExpressionAtlasiP27361 baseline and differential
GenevisibleiP27361 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
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 nameiMK03_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: P27361
Secondary accession number(s): A8CZ58, B0LPG3, Q8NHX1
<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: August 1, 1992
Last sequence update: January 23, 2007
Last modified: December 5, 2018
This is version 216 of the entry and version 4 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, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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