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Aliases for MAP2K6 Gene

Aliases for MAP2K6 Gene

  • Mitogen-Activated Protein Kinase Kinase 6 2 3
  • PRKMK6 3 4 6
  • MEK6 3 4 6
  • MKK6 3 4 6
  • Stress-Activated Protein Kinase Kinase 3 3 4
  • MAPK/ERK Kinase 6 3 4
  • SAPK Kinase 3 3 4
  • EC 2.7.12.2 4 63
  • MAPKK 6 3 4
  • SAPKK-3 3 4
  • MAPKK6 3 6
  • SAPKK3 3 4
  • MEK 6 3 4
  • Protein Kinase, Mitogen-Activated, Kinase 6 (MAP Kinase Kinase 6) 3
  • Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 3
  • Kinase 6 (MAP Kinase Kinase 6) 2
  • MAP Kinase Kinase 6 4
  • Mitogen-Activated 2
  • Protein Kinase 2
  • SKK3 4

External Ids for MAP2K6 Gene

Previous HGNC Symbols for MAP2K6 Gene

  • PRKMK6

Previous GeneCards Identifiers for MAP2K6 Gene

  • GC17P067254
  • GC17P070371
  • GC17P067875
  • GC17P068007
  • GC17P064922
  • GC17P067410
  • GC17P062796

Summaries for MAP2K6 Gene

Entrez Gene Summary for MAP2K6 Gene

  • This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. [provided by RefSeq, Jul 2008]

GeneCards Summary for MAP2K6 Gene

MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6) is a Protein Coding gene. Among its related pathways are MAPK signaling pathway and GPCR Pathway. GO annotations related to this gene include protein serine/threonine kinase activity and protein tyrosine kinase activity. An important paralog of this gene is MAP2K7.

UniProtKB/Swiss-Prot for MAP2K6 Gene

  • 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.

Gene Wiki entry for MAP2K6 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP2K6 Gene

Genomics for MAP2K6 Gene

Regulatory Elements for MAP2K6 Gene

Genomic Location for MAP2K6 Gene

Start:
69,414,697 bp from pter
End:
69,543,331 bp from pter
Size:
128,635 bases
Orientation:
Plus strand

Genomic View for MAP2K6 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP2K6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP2K6 Gene

Proteins for MAP2K6 Gene

  • Protein details for MAP2K6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P52564-MP2K6_HUMAN
    Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 6
    Protein Accession:
    P52564
    Secondary Accessions:

    Protein attributes for MAP2K6 Gene

    Size:
    334 amino acids
    Molecular mass:
    37492 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for MAP2K6 Gene

    Alternative splice isoforms for MAP2K6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP2K6 Gene

Proteomics data for MAP2K6 Gene at MOPED

Post-translational modifications for MAP2K6 Gene

  • Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
  • 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.
  • Ubiquitination at Lys172
  • Modification sites at PhosphoSitePlus

Other Protein References for MAP2K6 Gene

Domains for MAP2K6 Gene

Gene Families for MAP2K6 Gene

HGNC:
  • MAP2K :Mitogen-activated protein kinase cascade / Kinase kinases
IUPHAR :

Graphical View of Domain Structure for InterPro Entry

P52564

UniProtKB/Swiss-Prot:

MP2K6_HUMAN :
  • P52564
Domain:
  • 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.
  • The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
genes like me logo Genes that share domains with MAP2K6: view

Function for MAP2K6 Gene

Molecular function for MAP2K6 Gene

GENATLAS Biochemistry: mitogen-activated protein kinase kinase 6,activated by TNFA,involved in TNFA mediated endothelial SCYA2 (MCP1) expression,activating PRKMK8 and p38 kinase (MAPK) and required for ABL1 induced apoptosis
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot Function: 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.
UniProtKB/Swiss-Prot Induction: Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF

Enzyme Numbers (IUBMB) for MAP2K6 Gene

Gene Ontology (GO) - Molecular Function for MAP2K6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity --
GO:0004702 receptor signaling protein serine/threonine kinase activity IBA --
GO:0004708 MAP kinase kinase activity IBA --
GO:0004713 protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with MAP2K6: view
genes like me logo Genes that share phenotypes with MAP2K6: view

Animal Models for MAP2K6 Gene

MGI Knock Outs for MAP2K6:

miRNA for MAP2K6 Gene

miRTarBase miRNAs that target MAP2K6

No data available for Transcription Factor Targeting and HOMER Transcription for MAP2K6 Gene

Localization for MAP2K6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP2K6 Gene

Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Binds to microtubules.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP2K6 Gene COMPARTMENTS Subcellular localization image for MAP2K6 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 4

Gene Ontology (GO) - Cellular Components for MAP2K6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm TAS --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
genes like me logo Genes that share ontologies with MAP2K6: view

Pathways for MAP2K6 Gene

genes like me logo Genes that share pathways with MAP2K6: view

Gene Ontology (GO) - Biological Process for MAP2K6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade --
GO:0000187 activation of MAPK activity TAS --
GO:0001934 positive regulation of protein phosphorylation --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with MAP2K6: view

Compounds for MAP2K6 Gene

(19) ApexBio Compounds for MAP2K6 Gene

Compound Action Cas Number
AZD6244 (Selumetinib) Potent, selective, and ATP-uncompetitive MEK inhibitor
AZD8330 orally active, selective MEK inhibitor [869357-68-6]
BIX 02188 MEK5-selective inhibitor [1094614-84-2]
BIX 02189 blocks MEK5 and ERK5 catalytic activity [1094614-85-3]
Cobimetinib selective inhibitor of MEK [934660-93-2]
MEK inhibitor Potent MEK inhibitor, Antitumor agent. [334951-92-7]
MEK162 (ARRY-162, ARRY-438162) orally available inhibitor of MEK1/2 [606143-89-9]
PD0325901 MEK inhibitor [391210-10-9]
PD184352 (CI-1040) Selective MEK inhibitor [212631-79-3]
PD318088 inhibit MEK-1 and MEK-2. [391210-00-7]
PD98059 Inhibitor of MKK/MEK. [167869-21-8]
Pimasertib (AS-703026) highly selective and potent noncompetitive inhibitor of MEK1 and MEK2 [1236699-92-5]
PLX-4720 Potent and selective inhibitor of BRAF with V600E mutation [918505-84-7]
SCH772984 novel, potent and ATP-competitive inhibition of ERK1 and ERK2 [942183-80-4]
SL-327 Selective inhibitor of MEK1 and MEK2 [305350-87-2]
Trametinib (GSK1120212) Potent and selective MEK1 and MEK2 inhibitor [871700-17-3]
Trametinib DMSO solvate reversible, selective, allosteric MEK1/MEK2 kinase activity inhibitor [1187431-43-1]
U0126-EtOH Potent, selective, and uncompetitive MEK1/2 inhibitor [1173097-76-1]
Vemurafenib (PLX4032, RG7204) Potent and selective inhibitor of BRAF with V600E mutation [918504-65-1]

(2) HMDB Compounds for MAP2K6 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(10) Novoseek inferred chemical compound relationships for MAP2K6 Gene

Compound -log(P) Hits PubMed IDs
sb 203580 84.1 9
anisomycin 80.4 4
arsenite 41.5 3
tyrosine 32.1 4
mannitol 30.2 2
genes like me logo Genes that share compounds with MAP2K6: view

Transcripts for MAP2K6 Gene

Unigene Clusters for MAP2K6 Gene

Mitogen-activated protein kinase kinase 6:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K6 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13
SP1: - - -
SP2: -
SP3:

Relevant External Links for MAP2K6 Gene

GeneLoc Exon Structure for
MAP2K6
ECgene alternative splicing isoforms for
MAP2K6

Expression for MAP2K6 Gene

mRNA expression in normal human tissues for MAP2K6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP2K6 Gene

This gene is overexpressed in Whole Blood (11.0) and Muscle - Skeletal (7.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP2K6 Gene

SOURCE GeneReport for Unigene cluster for MAP2K6 Gene Hs.463978

mRNA Expression by UniProt/SwissProt for MAP2K6 Gene

P52564-MP2K6_HUMAN
Tissue specificity: Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.
genes like me logo Genes that share expressions with MAP2K6: view

Orthologs for MAP2K6 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP2K6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP2K6 35
  • 99.9 (n)
  • 100 (a)
MAP2K6 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MAP2K6 35
  • 89.62 (n)
  • 98.5 (a)
MAP2K6 36
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP2K6 35
  • 91.62 (n)
  • 97.9 (a)
MAP2K6 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map2k6 35
  • 91.02 (n)
  • 97.9 (a)
Map2k6 16
Map2k6 36
  • 98 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP2K6 36
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MAP2K6 36
  • 86 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map2k6 35
  • 90.32 (n)
  • 97.31 (a)
chicken
(Gallus gallus)
Aves MAP2K6 35
  • 84.63 (n)
  • 96.71 (a)
MAP2K6 36
  • 97 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP2K6 36
  • 94 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.717 35
tropical clawed frog
(Silurana tropicalis)
Amphibia map2k6 35
  • 78.64 (n)
  • 92.81 (a)
Str.6414 35
zebrafish
(Danio rerio)
Actinopterygii map2k3 35
map2k6 35
  • 75.25 (n)
  • 87.27 (a)
map2k6 36
  • 80 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta lic 36
  • 57 (a)
OneToMany
lic 37
  • 60 (a)
worm
(Caenorhabditis elegans)
Secernentea sek-1 35
  • 56.28 (n)
  • 52.47 (a)
sek-1 36
  • 51 (a)
OneToMany
F35C8.1 37
  • 34 (a)
VZC374L.1 37
  • 45 (a)
sek-1 37
  • 52 (a)
jkk-1 37
  • 39 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.2206 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3213 36
  • 61 (a)
OneToMany
Species with no ortholog for MAP2K6:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP2K6 Gene

ENSEMBL:
Gene Tree for MAP2K6 (if available)
TreeFam:
Gene Tree for MAP2K6 (if available)

Paralogs for MAP2K6 Gene

Paralogs for MAP2K6 Gene

genes like me logo Genes that share paralogs with MAP2K6: view

Variants for MAP2K6 Gene

Sequence variations from dbSNP and Humsavar for MAP2K6 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs707247 -- 69,430,471(-) TTCTT(A/T)CAGGC intron-variant
rs707248 -- 69,416,490(-) CTAAA(G/T)GCCAT intron-variant
rs731606 -- 69,430,375(-) TTCCA(A/T)TTGGC intron-variant
rs732322 -- 69,422,847(-) tggcc(C/T)aggag intron-variant
rs739559 -- 69,494,089(-) CCCTT(A/G)TTATT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP2K6 Gene

Variant ID Type Subtype PubMed ID
nsv2130 CNV Insertion 18451855
nsv520649 CNV Loss 19592680
esv2716154 CNV Deletion 23290073

Relevant External Links for MAP2K6 Gene

HapMap Linkage Disequilibrium report
MAP2K6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP2K6 Gene

Disorders for MAP2K6 Gene

(13) Novoseek inferred disease relationships for MAP2K6 Gene

Disease -log(P) Hits PubMed IDs
necrosis 30.9 2
shock 28 6
anthrax 16.8 1
tumors 13.4 3
neurofibrillary tangles 12.1 1

Relevant External Links for MAP2K6

Genetic Association Database (GAD)
MAP2K6
Human Genome Epidemiology (HuGE) Navigator
MAP2K6
genes like me logo Genes that share disorders with MAP2K6: view

No data available for UniProtKB/Swiss-Prot for MAP2K6 Gene

Publications for MAP2K6 Gene

  1. Characterization of the structure and function of a novel MAP kinase kinase (MKK6). (PMID: 8621675) Han J. … Ulevitch R.J. (J. Biol. Chem. 1996) 2 3 4 23
  2. MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. (PMID: 8622669) Raingeaud J. … Davis R.J. (Mol. Cell. Biol. 1996) 3 4 23
  3. Cloning and characterization of MEK6, a novel member of the mitogen- activated protein kinase kinase cascade. (PMID: 8626699) Stein B. … Barbosa M.S. (J. Biol. Chem. 1996) 3 4 23
  4. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. (PMID: 8663074) Moriguchi T. … Hagiwara M. (J. Biol. Chem. 1996) 3 4 23
  5. Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells. (PMID: 8861944) Cuenda A. … Nebreda A.R. (EMBO J. 1996) 3 4 23

Products for MAP2K6 Gene

Sources for MAP2K6 Gene

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