Map2k6 mitogen-activated protein kinase kinase 6 [Mus musculus (house mouse)] - Gene

Summary

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Official Symbol: Map2k6provided by MGI
Official Full Name: mitogen-activated protein kinase kinase 6provided by MGI
Primary source: MGI:1346870
Locus tag: RP23-162E10.1
See related: Ensembl:ENSMUSG00000020623; Vega:OTTMUSG00000003325
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: MEK6; MKK6; Prkmk6; SAPKK3

Genomic context

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Location :: 11; 11 E1

Sequence :: Chromosome: 11; NC_000077.6 (110399122..110513637)

See Map2k6 in Epigenomics, MapViewer

Chromosome 11 - NC_000077.6 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Activation of distinct p38MAPK isoforms is regulated by the selective and synchronized action of two kinases, MKK3 and MKK6, in response to cell stress.
Title: Differential activation of p38MAPK isoforms by MKK6 and MKK3.
MKK6 appears mainly to facilitate p38 and MK2 colocalization in the nucleus rather than to phosphorylate p38.
Title: Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression.
MKK6-p38 and insulin growth factor 1 (IGF1)-induced PI3K/AKT pathways converge on the chromatin of muscle genes to target distinct components of the muscle transcriptosome.
Title: Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation.
These results suggest that p38 MAPK signaling plays a critical role in the survival of osteoclasts in inflammatory diseases.
Title: MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts.
MKK6 phosphorylation regulates production of superoxide by enhancing Rac GTPase activity.
Title: MKK6 phosphorylation regulates production of superoxide by enhancing Rac GTPase activity.
All these results suggest that DGK may play a role in glucose transport in the skeletal muscle cells through modulating a MKK3/6-p38 signaling pathway.
Title: A diacylglycerol kinase inhibitor, R59022, stimulates glucose transport through a MKK3/6-p38 signaling pathway in skeletal muscle cells.
increased activity of Sox9 accounts at least in part for the phenotype caused by constitutive activation of MKK6 in chondrocytes
Title: Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation.
p38alpha can negatively regulate the stability of the MKK6 mRNA and thus control the steady-state concentration of one of its upstream activators
Title: Negative feedback regulation of MKK6 mRNA stability by p38alpha mitogen-activated protein kinase.
MKK6 is one of three different protein kinases which activate p38 MAPK in vitro.
Title: Mechanism of p38 MAP kinase activation in vivo.
Involvement of MKK6 in apoptotic cell death in thymocytes.
Title: Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes.

Submit: New GeneRIF Correction See all (13)

Alleles

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Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (knock-out) (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:204953	BioGRID:204962	Map3k7		BioGRID	PubMed	Affinity Capture-Western
BioGRID:204953	BioGRID:204969	Mapk14		BioGRID	PubMed	Biochemical Activity

Pathways from BioSystems

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Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
Activated TLR4 signalling, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Amyotrophic lateral sclerosis (ALS), organism-specific biosystem (from KEGG)
Amyotrophic lateral sclerosis (ALS), organism-specific biosystemAmyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord...
Amyotrophic lateral sclerosis (ALS), conserved biosystem (from KEGG)
Amyotrophic lateral sclerosis (ALS), conserved biosystemAmyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord...
CDO in myogenesis, organism-specific biosystem (from REACTOME)
CDO in myogenesis, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemcomputationally inferred pathway (not manually curated)
ESC Pluripotency Pathways, organism-specific biosystem (from WikiPathways)
ESC Pluripotency Pathways, organism-specific biosystemThe cytokine LIF and its downstream effector STAT3 are essential for maintenance of pluripotency in mouse ES cells. The requirement for the transcription factor Oct3/4 for ES cell pluripotency is als...
Epstein-Barr virus infection, organism-specific biosystem (from KEGG)
Epstein-Barr virus infection, organism-specific biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
Epstein-Barr virus infection, conserved biosystem (from KEGG)
Epstein-Barr virus infection, conserved biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
Fc epsilon RI signaling pathway, organism-specific biosystem (from KEGG)
Fc epsilon RI signaling pathway, organism-specific biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
Fc epsilon RI signaling pathway, conserved biosystem (from KEGG)
Fc epsilon RI signaling pathway, conserved biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
Focal Adhesion, organism-specific biosystem (from WikiPathways)
Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
GnRH signaling pathway, organism-specific biosystem (from KEGG)
GnRH signaling pathway, organism-specific biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
GnRH signaling pathway, conserved biosystem (from KEGG)
GnRH signaling pathway, conserved biosystemGonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnR...
IL-6 signaling Pathway, organism-specific biosystem (from WikiPathways)
IL-6 signaling Pathway, organism-specific biosystem
IL-6 signaling Pathway
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Influenza A, organism-specific biosystem (from KEGG)
Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Influenza A, conserved biosystem (from KEGG)
Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Insulin Signaling, organism-specific biosystem (from WikiPathways)
Insulin Signaling, organism-specific biosystem
Insulin Signaling
Integrin-mediated cell adhesion, organism-specific biosystem (from WikiPathways)
Integrin-mediated cell adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
Interleukin-1 signaling, organism-specific biosystem (from REACTOME)
Interleukin-1 signaling, organism-specific biosystemcomputationally inferred pathway (not manually curated)
MAP kinase activation in TLR cascade, organism-specific biosystem (from REACTOME)
MAP kinase activation in TLR cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
MAPK Cascade, organism-specific biosystem (from WikiPathways)
MAPK Cascade, organism-specific biosystemThe MAPK/ERK pathway is a signal transduction pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. In many cell types, activation of this pathway p...
MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, organism-specific biosystem (from KEGG)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, conserved biosystem (from KEGG)
MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. Converted from the humane pathway. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted inter...
MyD88 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
MyD88 cascade initiated on plasma membrane, organism-specific biosystemcomputationally inferred pathway (not manually curated)
MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
MyD88 dependent cascade initiated on endosome, organism-specific biosystemcomputationally inferred pathway (not manually curated)
MyD88-independent cascade, organism-specific biosystem (from REACTOME)
MyD88-independent cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Myogenesis, organism-specific biosystem (from REACTOME)
Myogenesis, organism-specific biosystemcomputationally inferred pathway (not manually curated)
NOD1/2 Signaling Pathway, organism-specific biosystem (from REACTOME)
NOD1/2 Signaling Pathway, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystem (from REACTOME)
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Osteoclast differentiation, organism-specific biosystem (from KEGG)
Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Osteoclast differentiation, conserved biosystem (from KEGG)
Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Signaling by Interleukins, organism-specific biosystem (from REACTOME)
Signaling by Interleukins, organism-specific biosystemcomputationally inferred pathway (not manually curated)
TGF-beta Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
TGF-beta Receptor Signaling Pathway, organism-specific biosystem
TGF-beta Receptor Signaling Pathway
TLR4 (Toll-like receptor 4) signaling pathway, organism-specific biosystem (from LIPID MAPS)
TLR4 (Toll-like receptor 4) signaling pathway, organism-specific biosystem
TLR4 (Toll-like receptor 4) signaling pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemcomputationally inferred pathway (not manually curated)
TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll Like Receptor signaling, organism-specific biosystem (from WikiPathways)
Toll Like Receptor signaling, organism-specific biosystem
Toll Like Receptor signaling
Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
Toll-Like Receptors Cascades, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Toxoplasmosis, organism-specific biosystem (from KEGG)
Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
Toxoplasmosis, conserved biosystem (from KEGG)
Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
activated TAK1 mediates p38 MAPK activation, organism-specific biosystem (from REACTOME)
activated TAK1 mediates p38 MAPK activation, organism-specific biosystemcomputationally inferred pathway (not manually curated)
p38 MAPK Signaling Pathway (BioCarta), organism-specific biosystem (from WikiPathways)
p38 MAPK Signaling Pathway (BioCarta), organism-specific biosystemp38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases...

General gene information

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Markers

D11Mit300 (e-PCR), detects polymorphism
- UniSTS:126510

UniSTS:224328 (e-PCR)
- UniSTS:224328

Map2k6 (e-PCR), detects polymorphism
- UniSTS:507044

Map2k6 (e-PCR), detects polymorphism
- UniSTS:143819

Homology

Homologs of the Map2k6 gene: The Map2k6 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, and C.elegans.
Map Viewer (Human, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
MAP kinase kinase activity	ISO Inferred from Sequence Orthology more info
kinase activity	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	IEA Inferred from Electronic Annotation more info
protein kinase binding	ISO Inferred from Sequence Orthology more info
protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
transferase activity	IEA Inferred from Electronic Annotation more info
transferase activity, transferring phosphorus-containing groups	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
MAPK cascade	IPI Inferred from Physical Interaction more info	PubMed
activation of MAPK activity	IDA Inferred from Direct Assay more info	PubMed
activation of MAPK activity	IMP Inferred from Mutant Phenotype more info	PubMed
apoptotic process	IEA Inferred from Electronic Annotation more info
cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	IEA Inferred from Electronic Annotation more info
regulation of transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
response to stress	IEA Inferred from Electronic Annotation more info
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytoskeleton	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 6

Names: dual specificity mitogen-activated protein kinase kinase 6; MEK 6; MAPKK 6; MAPK/ERK kinase 6; MAP kinase kinase 6; mitogen activated protein kinase kinase 6; protein kinase, mitogen activated, kinase 6

NP_036073.1

EC 2.7.12.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_011943.2 → NP_036073.1 dual specificity mitogen-activated protein kinase kinase 6

Status: PROVISIONAL

Source sequence(s)

AK043482

Consensus CDS

CCDS25592.1

UniProtKB/Swiss-Prot

P70236

UniProtKB/TrEMBL

Q543Z5

Related

ENSMUSP00000020949, OTTMUSP00000003317, ENSMUST00000020949, OTTMUST00000006983

Conserved Domains (2) summary

cd06617
Location:51 – 333
Blast Score: 1513

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, MAP kinase kinases 3 and 6

smart00220
Location:54 – 314
Blast Score: 611

S_TKc; Serine/Threonine protein kinases, catalytic domain

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 103

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm38.p1 C57BL/6J

Genomic

NC_000077.6 Reference GRCm38.p1 C57BL/6J

Range

110399122..110513637

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate Mm_Celera

Genomic

AC_000033.1 Alternate Mm_Celera

Range

122139172..122253133

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein	Strain
Heading	Accession and Version	Protein	Strain
genomic	AAHY01096284.1 (12056..20718)	None
genomic	AAHY01096285.1	None
genomic	AAHY01096286.1	None
genomic	AAHY01096287.1	None
genomic	AAHY01096288.1	None
genomic	AAHY01096289.1 (18603..53396)	None
genomic	AL691461.22 (32754..147269)	None	ZRU
genomic	CH466558.1	EDL34384.1	mixed
		EDL34385.1	mixed
		EDL34386.1	mixed
		EDL34387.1	mixed
mRNA	AK043482.1	BAC31556.1	C57BL/6J
mRNA	AK077712.1	BAC36972.1	C57BL/6J
mRNA	AK086722.1	BAC39729.1	C57BL/6J
mRNA	AK138757.1	BAE23771.1	C57BL/6J
mRNA	AK140289.1	None	C57BL/6J
mRNA	AK141708.1	BAE24808.1	C57BL/6J
mRNA	AK162671.1	BAE37014.1	C57BL/6J
mRNA	BC075652.1	AAH75652.1	C57BL/6
mRNA	U39066.1	AAB03709.1
mRNA	X97052.1	CAA65764.1
mRNA	X98067.1	CAA66670.1