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Entry version 190 (13 Feb 2019)
Sequence version 1 (01 Oct 1996)
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Protein

Dual specificity mitogen-activated protein kinase kinase 6

Gene

MAP2K6

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

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.8 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 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

Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.3 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 sitei82ATPPROSITE-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 sitei179Proton 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 bindingi59 – 67ATPPROSITE-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

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • MAP kinase kinase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB-KW

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, Tyrosine-protein kinase
Biological processApoptosis, Stress response, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.12.2 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-375170 CDO in myogenesis
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-5210891 Uptake and function of anthrax toxins
R-HSA-6811555 PI5P Regulates TP53 Acetylation
R-HSA-9020702 Interleukin-1 signaling

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

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SignaLinki
P52564

SIGNOR Signaling Network Open Resource

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SIGNORi
P52564

<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:
Dual specificity mitogen-activated protein kinase kinase 6 (EC:2.7.12.2)
Short name:
MAP kinase kinase 6
Short name:
MAPKK 6
Alternative name(s):
MAPK/ERK kinase 6
Short name:
MEK 6
Stress-activated protein kinase kinase 3
Short name:
SAPK kinase 3
Short name:
SAPKK-3
Short name:
SAPKK3
<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:MAP2K6
Synonyms:MEK6, MKK6, PRKMK6, SKK3
<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 17

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000108984.13

Human Gene Nomenclature Database

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HGNCi
HGNC:6846 MAP2K6

Online Mendelian Inheritance in Man (OMIM)

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MIMi
601254 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P52564

<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, Cytoskeleton, 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

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>Mutagenesisi207S → A: Inactivation. 1
Mutagenesisi207S → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675. 1
Mutagenesisi211T → A: Inactivation. 1
Mutagenesisi211T → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675. 1

Organism-specific databases

DisGeNET

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DisGeNETi
5608

Open Targets

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OpenTargetsi
ENSG00000108984

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA30591

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2171

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2067

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
MAP2K6

Domain mapping of disease mutations (DMDM)

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DMDMi
1709088

<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_00000863861 – 334Dual specificity mitogen-activated protein kinase kinase 6Add BLAST334

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 residuei207O-acetylserine; by Yersinia yopJ; alternate1 Publication1
Modified residuei207Phosphoserine; by MAP3K; alternate1 Publication1
Modified residuei211O-acetylthreonine; by Yersinia yopJ; alternate1 Publication1
Modified residuei211Phosphothreonine; by MAP3K; alternate1 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

Weakly autophosphorylated. Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.1 Publication
Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei14 – 15Cleavage; by anthrax lethal factor2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P52564

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P52564

MaxQB - The MaxQuant DataBase

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MaxQBi
P52564

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

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PaxDbi
P52564

PeptideAtlas

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PeptideAtlasi
P52564

PRoteomics IDEntifications database

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PRIDEi
P52564

ProteomicsDB human proteome resource

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ProteomicsDBi
56487
56488 [P52564-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P52564

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

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PhosphoSitePlusi
P52564

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
P52564

<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

Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.1 Publication

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000108984 Expressed in 203 organ(s), highest expression level in quadriceps femoris

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P52564 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P52564 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB007744
HPA031134

<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

Dimer. Interacts with Yersinia yopJ. Interacts (via its D domain) with its substrates MAPK11, MAPK12, MAPK13 and MAPK14 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2 (By similarity). Interacts with DCTN1. Interacts with EIF2AK2/PKR.By similarity4 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

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111594, 43 interactors

Database of interacting proteins

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DIPi
DIP-31346N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P52564

Protein interaction database and analysis system

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IntActi
P52564, 12 interactors

Molecular INTeraction database

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MINTi
P52564

STRING: functional protein association networks

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STRINGi
9606.ENSP00000468348

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P52564

<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

1334
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y8OX-ray1.95B4-17[»]
3ENMX-ray2.35A/B/C/D45-332[»]
3FMEX-ray2.26A47-334[»]
3VN9X-ray2.60A1-334[»]
5ETFX-ray2.40B4-17[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P52564

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

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SMRi
P52564

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
P52564

<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>Domaini53 – 314Protein kinasePROSITE-ProRule annotationAdd BLAST262

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni4 – 19D domainBy similarityAdd BLAST16
Regioni311 – 334DVD domainAdd BLAST24

<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 DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.1 Publication
The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates.By similarity

<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
KOG0984 Eukaryota
ENOG410XT3F LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000157836

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000234206

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG108518

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P52564

KEGG Orthology (KO)

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KOi
K04433

Identification of Orthologs from Complete Genome Data

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OMAi
WGTPFEQ

Database of Orthologous Groups

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OrthoDBi
688282at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P52564

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
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

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
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 (2+)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 2 <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 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P52564-1) [UniParc]FASTAAdd to basket
Also known as: MKK6b

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
MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA
60 70 80 90 100
DDLEPIMELG RGAYGVVEKM RHVPSGQIMA VKRIRATVNS QEQKRLLMDL
110 120 130 140 150
DISMRTVDCP FTVTFYGALF REGDVWICME LMDTSLDKFY KQVIDKGQTI
160 170 180 190 200
PEDILGKIAV SIVKALEHLH SKLSVIHRDV KPSNVLINAL GQVKMCDFGI
210 220 230 240 250
SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI WSLGITMIEL
260 270 280 290 300
AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSAEFVDF TSQCLKKNSK
310 320 330
ERPTYPELMQ HPFFTLHESK GTDVASFVKL ILGD
Length:334
Mass (Da):37,492
Last modified:October 1, 1996 - v1
<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:i4ECA8014522216AF
GO
Isoform 2 (identifier: P52564-2) [UniParc]FASTAAdd to basket
Also known as: MKK6

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Show »
Length:278
Mass (Da):31,339
Checksum:i1EE7FC1B26B11AE4
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 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EIW3K7EIW3_HUMAN
Dual-specificity mitogen-activated ...
MAP2K6
128Annotation 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>
K7ELM6K7ELM6_HUMAN
Dual-specificity mitogen-activated ...
MAP2K6
84Annotation 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>
A0A0A0MRF7A0A0A0MRF7_HUMAN
Dual-specificity mitogen-activated ...
MAP2K6
68Annotation 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 conflicti125V → M in AAB03705 (PubMed:8621675).Curated1
Sequence conflicti125V → M in AAB03708 (PubMed:8621675).Curated1

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_0048821 – 56Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U39657 mRNA Translation: AAC50389.1
U39656 mRNA Translation: AAC50388.1
U49732 mRNA Translation: AAB05035.1
U39065 mRNA Translation: AAB03705.1
U39064 mRNA Translation: AAB03708.1
D87905 mRNA Translation: BAA13496.1
X96757 mRNA Translation: CAA65532.1
BC012009 mRNA Translation: AAH12009.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS11686.1 [P52564-1]
CCDS82194.1 [P52564-2]

Protein sequence database of the Protein Information Resource

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PIRi
S71631

NCBI Reference Sequences

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RefSeqi
NP_002749.2, NM_002758.3 [P52564-1]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.463978
Hs.49329

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000589647; ENSP00000467213; ENSG00000108984 [P52564-2]
ENST00000590474; ENSP00000468348; ENSG00000108984 [P52564-1]
ENST00000613873; ENSP00000477701; ENSG00000108984 [P52564-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
5608

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:5608

UCSC genome browser

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UCSCi
uc002jij.4 human [P52564-1]

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
U39657 mRNA Translation: AAC50389.1
U39656 mRNA Translation: AAC50388.1
U49732 mRNA Translation: AAB05035.1
U39065 mRNA Translation: AAB03705.1
U39064 mRNA Translation: AAB03708.1
D87905 mRNA Translation: BAA13496.1
X96757 mRNA Translation: CAA65532.1
BC012009 mRNA Translation: AAH12009.1
CCDSiCCDS11686.1 [P52564-1]
CCDS82194.1 [P52564-2]
PIRiS71631
RefSeqiNP_002749.2, NM_002758.3 [P52564-1]
UniGeneiHs.463978
Hs.49329

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y8OX-ray1.95B4-17[»]
3ENMX-ray2.35A/B/C/D45-332[»]
3FMEX-ray2.26A47-334[»]
3VN9X-ray2.60A1-334[»]
5ETFX-ray2.40B4-17[»]
ProteinModelPortaliP52564
SMRiP52564
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111594, 43 interactors
DIPiDIP-31346N
ELMiP52564
IntActiP52564, 12 interactors
MINTiP52564
STRINGi9606.ENSP00000468348

Chemistry databases

BindingDBiP52564
ChEMBLiCHEMBL2171
GuidetoPHARMACOLOGYi2067

PTM databases

iPTMnetiP52564
PhosphoSitePlusiP52564

Polymorphism and mutation databases

BioMutaiMAP2K6
DMDMi1709088

Proteomic databases

EPDiP52564
jPOSTiP52564
MaxQBiP52564
PaxDbiP52564
PeptideAtlasiP52564
PRIDEiP52564
ProteomicsDBi56487
56488 [P52564-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
5608
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000589647; ENSP00000467213; ENSG00000108984 [P52564-2]
ENST00000590474; ENSP00000468348; ENSG00000108984 [P52564-1]
ENST00000613873; ENSP00000477701; ENSG00000108984 [P52564-2]
GeneIDi5608
KEGGihsa:5608
UCSCiuc002jij.4 human [P52564-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
5608
DisGeNETi5608
EuPathDBiHostDB:ENSG00000108984.13

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MAP2K6
HGNCiHGNC:6846 MAP2K6
HPAiCAB007744
HPA031134
MIMi601254 gene
neXtProtiNX_P52564
OpenTargetsiENSG00000108984
PharmGKBiPA30591

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0984 Eukaryota
ENOG410XT3F LUCA
GeneTreeiENSGT00940000157836
HOGENOMiHOG000234206
HOVERGENiHBG108518
InParanoidiP52564
KOiK04433
OMAiWGTPFEQ
OrthoDBi688282at2759
PhylomeDBiP52564

Enzyme and pathway databases

BRENDAi2.7.12.2 2681
ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-375170 CDO in myogenesis
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-5210891 Uptake and function of anthrax toxins
R-HSA-6811555 PI5P Regulates TP53 Acetylation
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiP52564
SIGNORiP52564

Miscellaneous databases

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

More...
ChiTaRSi
MAP2K6 human
EvolutionaryTraceiP52564

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
MAP2K6

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

More...
GenomeRNAii
5608
PMAP-CutDBiP52564

Protein Ontology

More...
PROi
PR:P52564

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000108984 Expressed in 203 organ(s), highest expression level in quadriceps femoris
ExpressionAtlasiP52564 baseline and differential
GenevisibleiP52564 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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 nameiMP2K6_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: P52564
<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: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 13, 2019
This is version 190 of the entry and version 1 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 chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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