MAP2K6 - Dual specificity mitogen-activated protein kinase kinase 6 - human protein (Function)
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MAP2K6 »  Dual specificity mitogen-activated protein kinase kinase 6   [ EC ]  (MAPKK 6)
Protein also known as:  Stress-activated protein kinase kinase 3 (SAPKK3).
Gene name:  MAP2K6
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
MAP kinase kinase activitydefinition[GO:0004708] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
  • IPIIntAct
  • IPIUniProtKB
Protein kinase bindingdefinition[GO:0019901]  
  • IPIUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
  • IEAUniProtKB KW
Protein tyrosine kinase activitydefinition[GO:0004713]  
  • IEAUniProtKB KW
GO biological process 
Apoptotic processdefinition[GO:0006915] silver  
  • IEAOrtholog Compara
Cardiac muscle contractiondefinition[GO:0060048] silver  
  • IEAOrtholog Compara
Cell cycle arrestdefinition[GO:0007050]  
Cellular response to sorbitoldefinition[GO:0072709] silver  
  • IEAOrtholog Compara
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
  • IEAUniProtKB KW
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • IEAUniProtKB KW
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to ischemiadefinition[GO:0002931] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Amyotrophic lateral sclerosis (ALS)  hsa05014+5608  
Fc epsilon RI signaling pathway  hsa04664+5608  
GnRH signaling pathway  hsa04912+5608  
Influenza A  hsa05164+5608  
MAPK signaling pathway  hsa04010+5608  
Osteoclast differentiation  hsa04380+5608  
Toll-like receptor signaling pathway  hsa04620+5608  
Toxoplasmosis  hsa05145+5608  
According to Reactome, this protein belongs to the following pathways:
activated TAK1 mediates p38 MAPK activation  REACT_21399  
CDO in myogenesis  REACT_21402  
Interleukin-1 signaling  REACT_22442  
NOD1/2 Signaling Pathway  REACT_75776  
Oxidative Stress Induced Senescence  REACT_169436  


Biological process 
Apoptosis  definition   [KW-0053]
Stress response  definition   [KW-0346]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: MAP2K6
GenomeRNAi: 5608
PRO: PR:P52564