MAP3K9 - Mitogen-activated protein kinase kinase kinase 9 - human protein (Function)
 
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MAP3K9 »  Mitogen-activated protein kinase kinase kinase 9   [ EC 2.7.11.25 ]
 
Protein also known as:  Mixed lineage kinase 1.
Gene name:  MAP3K9
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
JUN kinase kinase kinase activitydefinition[GO:0004706]  
  • ISSOrtholog Curator
MAP kinase kinase activitydefinition[GO:0004708]  
1
  • NASUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • ISSUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDAUniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713] silver  
  • IEAInterPro 2 GO
GO biological process 
Activation of JNKK activitydefinition[GO:0007256]  
  • ISSOrtholog Curator
Activation of JUN kinase activitydefinition[GO:0007257]  
1
  • ISSUniProtKB
Activation of MAPKK activitydefinition[GO:0000186]  
  • ISSOrtholog Curator
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • IEAUniProtKB KW
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.25: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
It is regulated in the following manner
Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-312 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-304 and Ser-308 have been shown to be of secondary importance in the activation of MAP3K9/MLK1. CEP-1347 and many indolocarbazole analogs have been shown to act as inhibitors of MAP3K9/MLK1 activity.  
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  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 62 uM for ATP
KM 7 uM for myelin basic protein (MBP) as substrate

Keywords

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]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAP3K9
GenomeRNAi: 4293
PRO: PR:P80192
Chemistry
GuidetoPHARMACOLOGY: 2084