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mitogen-activated protein kinase kinase kinase 9 (MAP3K9, mixed lineage kinase [MLK] 1, MLK1, PRKE1)
Function:
- activates the JUN N-terminal pathway
- homodimerization via the leucine zipper domains is required for autophosphorylation & subsequent activation
- autophosphorylation on Ser & Thr within the activation loop plays a role in enzyme activation
- Thr-312 is likely to be the main autophosphorylation site
ATP + a protein ADP + a phosphoprotein
Cofactor: Mg+2
Structure:
- homodimer (putative)
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain contains 1 SH3 domain
Alternative splicing: named isoforms=2
Expression:
- expressed in epithelial tumor cell lines of colonic, breast & esophageal origin
General
mitogen-activated protein kinase kinase kinase (MAP3K) or MEK kinase (MEKK)
tyrosine kinase (protein tyrosine kinase, PTK)
Properties
SIZE: entity length = 1104 aa
MW = 122 kD
STATE: active state
MOTIF: alanine-rich region {12-42}
MOTIF: alanine residue (SEVERAL)
glutamate-rich region {30-38}
MOTIF: glutamate residue (SEVERAL)
src homology 3 [SH3] domain
SITE: 52-116
kinase domain
SITE: 144-412
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 150-158
ATP-binding site
NAME: ATP-binding site
SITE: 171-171
aspartate residue {D268}
Thr phosphorylation site {T304}
Ser phosphorylation site {S308}
Thr phosphorylation site {T312}
leucine zipper
SITE: 430-451
FOR-BINDING-VIA: leucine zipper
leucine zipper
SITE: 465-486
FOR-BINDING-VIA: leucine zipper
lysine-rich region {495-509}
MOTIF: lysine residue (SEVERAL)
Ser phosphorylation site {S552}
proline-rich region
SITE: 863-972
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S931}
Ser phosphorylation site {S934}
Ser phosphorylation site {S998}
serine-rich region {1011-1041}
MOTIF: serine residue (SEVERAL)
References
UniProt :accession P80192
Databases & Figures
OMIM 600136
UniProt P80192
PFAM correlations
Entrez Gene 4293
ENZYME 2.7.11.25
MAP kinase pathways