Recombinant Human MKK6 Protein (207 Asp, 211 Asp)

Collections: Other recombinant proteins, Recombinant proteins

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Product Overview

Tag	211 Asp
Host Species	Human
Accession	P52564
Synonym	MAPKK6, MEK6, MKK6, PRKMK6, SAPKK-3, SAPKK3
Background	Dual specificity mitogen-activated protein kinase kinase 6, also known as MAP kinase kinase 6, MAPKK 6, MAPK / ERK kinase 6, SAPKK3, MAP2K6 and MKK6, is a protein which belongs to the?protein kinase superfamily, STE Ser / Thr protein kinase family and MAP kinase kinase subfamily. MAP2K6 / MKK6 contains one?protein kinase domain. Mitogen-activated protein kinases are members of a conserved cascade of kinases involved in many signal transduction pathways. They stimulate phosphorylation of transcription factors in response to extracellular signals such as growth factors, cytokines, ultraviolet light, and stress-inducing agents. MAP2K6 / MKK6 exists in a variety of alternatively spliced isoforms with distinct patterns of tissue expression. Isoform 2 of MAP2K6 / MKK6 is only expressed in skeletal muscle. Isoform 1 of MAP2K6 / MKK6 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.
Description	A DNA sequence encoding the human MAP2K6 (P52564-1) (Met 1-Asp 334, 207Asp, 211Asp) was expressed and purified with two additional amino acids (Gly & Pro ) at the N-terminus.
Source	Baculovirus-Insect Cells
Predicted N Terminal	Gly
AA Sequence	Met 1-Asp 334, 207Asp, 211Asp
Molecular Weight	The secreted recombinant human MAP2K6 consists of 336 a.a. and predicts a molecular mass of 37.7 KDa. The apparent molecular mass of the protein is approximately 38 KDa in SDS-PAGE under reducing conditions due to glycosylation.
Purity	>85% as determined by SDS-PAGE
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Formulation	Lyophilized from sterile 20mM Tris, 500mM NaCl, 10% glycerol, pH 8.0..
Stability	The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage	For Research Use Only
Storage	Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target 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.
Subcellular Location	Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Binds to microtubules.
Protein Families	Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily
Database References	HGNC: 6846 OMIM: 601254 KEGG: hsa:5608 STRING: 9606.ENSP00000468348 UniGene: Hs.463978
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.

Gene Functions References

Data show that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks. PMID: 27526785
acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure PMID: 29021624
Data indicate that mitogen-activated protein kinase kinase 6 (MKK6) levels were substantially higher in monocytes than in neutrophils. PMID: 25214442
Data show significant increase in the expression of MKK6 in Esophageal, Stomach, and Colon cancers as compared to controls. PMID: 25019214
uncover a new mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of FBXO31 in stress response PMID: 24936062
Serine phosphorylation of p66shc is carried out by active MKK6. beta-Amyloid-induced ROS production and apoptosis increased in the presence of MKK6 and p66shc, which directly associate. PMID: 24085465
The models confirmed the reaction order, revealed processivity in the phosphorylation of MEK6 by ASK1, and suggested that the order of phosphorylation is dictated by both binding and catalysis rates. PMID: 23744074
crystal structure of human non-phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at 2.6 A resolution and represents an auto-inhibition state of MAP2K6 PMID: 22383536
activation by mechanical stretch induces HMGB1 and cytokine expression in A549 cells PMID: 21926646
Results suggest that the p38alpha, MAPK, and MKK6 play prominent roles in IL-1beta and C/EBP-beta-mediated C3 gene expression in astrocytes. PMID: 21308746
Impaired cytokine production in natural killer (NK)T cells is demonstrated from MKK3-deficient6+/- mice. PMID: 21368234
we demonstrated that MKK6 has a role for regulation of dendricity in melanocytes. PMID: 20869211
MKK6 and other MAP2Ks are a distinct class of cellular redox sensors PMID: 21078955
MKK6 p38 alpha signaling pathway regulates the expression of RAGE induced by mechanical stretch in A549 cells. PMID: 19846005
Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation.( PMID: 20364819
active MKK6 in HepG2 cells enhanced basal activity or IL-6-induced transcriptional activation of a SOCS3 promoter PMID: 11727828
MKK6 is involved in a positive feedback loop regulating macrophage signaling with p38 MAP kinase PMID: 12509443
role in cardioprotection PMID: 15492008
PAK6 kinase activity was repressed by a p38 mitogen-activated protein (MAP) kinase antagonist and could be strongly stimulated by constitutively active MAP kinase kinase 6 (MKK6) PMID: 15550393
MKK6 promotes the development of cardiomyopathy by activation of a kinase cascade PMID: 15722372
MEK6E activates p38 and results in phosphorylation of its downstream substrate, heat shock protein 27 PMID: 15790570
selectivity pocket compounds prevent MKK6-dependent activation of p38alpha in addition to inhibiting catalysis by activated p38alpha PMID: 16342939
findings show that Yersinia YopJ acted as an acetyltransferase, using acetyl-coenzyme A (CoA) to modify the critical serine and threonine residues in the activation loop of MAPKK6 and thereby blocking phosphorylation PMID: 16728640
Conditional induction of a dominant active form of MAPK kinase 6, a direct upstream kinase of p38, in Langerhans cells induces up-regulation of costimulatory molecules & enhances their T-cell stimulatory capacity. PMID: 16960152
Data suggest that sequence variations of ASK1 and MAP2K6 lead to partially sex-specific changes in the levels and/or phosphorylation states of p38 and p38-regulated proteins that might contribute to the observed delaying effects in the age of onset of HD. PMID: 18327563
Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/DeltaN/DD and full-length unphosphorylated wild-type MEK6 in solution PMID: 19141286

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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