| Post Translational Modifications | 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. (Microbial infection) Acetylation of Ser-207 and Thr-211 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. |
| 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. |
| Protein Name | Dual Specificity Mitogen-Activated Protein Kinase Kinase 6Map Kinase Kinase 6Mapkk 6Mapk/Erk Kinase 6Mek 6Stress-Activated Protein Kinase Kinase 3Sapk Kinase 3Sapkk-3Sapkk3 |
| Database Links | Reactome: R-HSA-168638Reactome: R-HSA-2559580Reactome: R-HSA-450302Reactome: R-HSA-5210891 P52564-1Reactome: R-HSA-525793Reactome: R-HSA-6811555Reactome: R-HSA-9020702Reactome: R-HSA-9833482 |
| Cellular Localisation | NucleusCytoplasmCytoskeletonBinds To Microtubules |
| Alternative Protein Names | Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 proteinMap Kinase Kinase 6 proteinMapkk 6 proteinMapk/Erk Kinase 6 proteinMek 6 proteinStress-Activated Protein Kinase Kinase 3 proteinSapk Kinase 3 proteinSapkk-3 proteinSapkk3 proteinMAP2K6 proteinMEK6 proteinMKK6 proteinPRKMK6 proteinSKK3 protein |
Information sourced from Uniprot.org
