Names & Taxonomy
- Uniprot ID:
- P80192
- Entry Name:
- M3K9_HUMAN
- Status:
- reviewed
- Protein Names:
- Mitogen-activated protein kinase kinase kinase 9 (EC 2.7.11.25) (Mixed lineage kinase 1)
- Gene Names:
- MAP3K9 MLK1 PRKE1
- Gene Names Primary:
- MAP3K9
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1104
- Sequence:
- MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPYWTAVFEYEAAGEDELTLRLGDVVEVLSKDSQVSGDEGWWTGQLNQRVGIFPSNYVTPRSAFSSRCQPGGEDPSCYPPIQLLEIDFAELTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDEDISQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVNWAVQIARGMNYLHDEAIVPIIHRDLKSSNILILQKVENGDLSNKILKITDFGLAREWHRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLLWELLTGEVPFRGIDGLAVAYGVAMNKLALPIPSTCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFHCLQDNWKHEIQEMFDQLRAKEKELRTWEEELTRAALQQKNQEELLRRREQELAEREIDILERELNIIIHQLCQEKPRVKKRKGKFRKSRLKLKDGNRISLPSDFQHKFTVQASPTMDKRKSLINSRSSPPASPTIIPRLRAIQLTPGESSKTWGRSSVVPKEEGEEEEKRAPKKKGRTWGPGTLGQKELASGDEGSPQRREKANGLSTPSESPHFHLGLKSLVDGYKQWSSSAPNLVKGPRSSPALPGFTSLMEMEDEDSEGPGSGESRLQHSPSQSYLCIPFPRGEDGDGPSSDGIHEEPTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLGCGAVLAATGLGFDLLEAGKCQLLPLEEPEPPAREEKKRREGLFQRSSRPRRSTSPPSRKLFKKEEPMLLLGDPSASLTLLSLSSISECNSTRSLLRSDSDEIVVYEMPVSPVEAPPLSPCTHNPLVNVRVERFKRDPNQSLTPTHVTLTTPSQPSSHRRTPSDGALKPETLLASRSPSSNGLSPSPGAGMLKTPSPSRDPGEFPRLPDPNVVFPPTPRRWNTQQDSTLERPKTLEFLPRPRPSANRQRLDPWWFVSPSHARSTSPANSSSTETPSNLDSCFASSSSTVEERPGLPALLPFQAGPLPPTERTLLDLDAEGQSQDSTVPLCRAELNTHRPAPYEIQQEFWS
- Proteomes:
- UP000005640
Function
- Function:
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=62 uM for ATP
- Enzyme Regulation:
- ENZYME REGULATION: 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.
- Active Site:
- ACT_SITE 268 268 Proton acceptor.
- Gene Ontology Go:
- intracellular
ATP binding
JUN kinase kinase kinase activity
MAP kinase kinase activity
protein homodimerization activity
protein serine/threonine kinase activity
protein tyrosine kinase activity
activation of JNKK activity
activation of JUN kinase activity
apoptotic process
positive regulation of apoptotic process
protein autophosphorylation
protein phosphorylation
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Biological Process:
- activation of JNKK activity
activation of JUN kinase activity
apoptotic process
positive regulation of apoptotic process
protein autophosphorylation
protein phosphorylation
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Molecular Function:
- ATP binding
JUN kinase kinase kinase activity
MAP kinase kinase activity
protein homodimerization activity
protein serine/threonine kinase activity
protein tyrosine kinase activity - Gene Ontology Cellular Component:
- intracellular
- Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Apoptosis
Complete proteome
Kinase
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
SH3 domain
Serine/threonine-protein kinase
Stress response
Transcription
Transcription regulation
Transferase - Interacts With:
- P08238